Nephrolithiasis (Clinical)

Overview

Definition^[15,18]

Nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis (also known as kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis, urolithiasis, or urinary calculi) is the formation of stones anywhere along the urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy.

Classification^[1,2,15,18]

There are 5 main types of kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis:

• Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes oxalate stones:
  • Account for 70%–80% of all kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis (most common type)
  • Envelope Envelope Bilayer lipid membrane acquired by viral particles during viral morphogenesis. Although the lipids of the viral envelope are host derived, various virus-encoded integral membrane proteins, i.e. Viral envelope proteins are incorporated there. Virology or dumbbell-shaped crystals
• Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis stones:
  • Account for 8% of all kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
  • Associated with acidic urine
  • Rhomboid or rosette-shaped crystals
• Struvite Struvite The mineral magnesium ammonium phosphate with the formula NH4mgpo4. It is associated with urea-splitting organisms in a high magnesium, high phosphate, alkaline environment. Accumulation of crystallized struvite is found in the urinary tract as struvite calculi and as scale on sewage system equipment and wastewater pipes. Nephrolithiasis (ammonium magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes) stones:
  • Account for 1% of all kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
  • Associated with elevated ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance and urine pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance, which occurs with upper urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infection due to urease-producing organism
  •  “Coffin lid”-shaped crystals
• Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes stones:
  • Account for 15% of all kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
  • Associated with alkaline urine
  • Wedge-shaped prisms
• Cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis stones:
  • Account for 1%–2% of kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
  • Associated with cystinuria Cystinuria An inherited disorder due to defective reabsorption of cystine and other basic amino acids by the proximal renal tubules. This form of aminoaciduria is characterized by the abnormally high urinary levels of cystine; lysine; arginine; and ornithine. Mutations involve the amino acid transport protein gene slc3a1. Nephrolithiasis, a genetic disorder
  • Hexagonal crystals
  • Mnemonic: Pronounce cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis stones as “sixtine” stones (six-sided stones) to remember their shape.

Epidemiology^[18]

• More common in men than in women
• Most common in White, non-Hispanic men
• Peak incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 45–70 years old, but can occur at any age
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency increases with age, with notable increase after the age 40.

Etiology^[2,3,18]

Nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis occurs when normally soluble material supersaturates the urine and crystal formation begins.

Risk factors^[2,3,18]

• Family history Family History Adult Health Maintenance
• Medical conditions:
  • Urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (UTIs)
  • Cystinuria Cystinuria An inherited disorder due to defective reabsorption of cystine and other basic amino acids by the proximal renal tubules. This form of aminoaciduria is characterized by the abnormally high urinary levels of cystine; lysine; arginine; and ornithine. Mutations involve the amino acid transport protein gene slc3a1. Nephrolithiasis
  • Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout (high uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis)
  • Hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism (high calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes levels)
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension and diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus → metabolic changes increase stone risk
  • Inflammatory bowel disease (IBD) and short gut syndrome → malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion → increasing oxalate absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption and risk of calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes oxalate stones
• Diet:
  • High sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia: decreased sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia and calcium reabsorption Calcium reabsorption Tubular System in the proximal tubule Proximal tubule The renal tubule portion that extends from the bowman capsule in the kidney cortex into the kidney medulla. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the u-shaped loop of henle. Tubular System → hypercalciuria Hypercalciuria Excretion of abnormally high level of calcium in the urine, greater than 4 mg/kg/day. Nephrolithiasis
  • High calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes (supplements)
• Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration: causes an excessive concentration of urine solutes → stone formation
• Medications that induce metabolic abnormalities that alter urine composition:
  • Loop diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication (e.g., furosemide Furosemide A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for edema and chronic renal insufficiency. Loop Diuretics): inhibit calcium reabsorption Calcium reabsorption Tubular System → hypercalciuria Hypercalciuria Excretion of abnormally high level of calcium in the urine, greater than 4 mg/kg/day. Nephrolithiasis
  • Carbonic anhydrase Carbonic anhydrase A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of carbon dioxide from the tissues to the lung. Carbonic Anhydrase Inhibitors inhibitors → metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis which leads to increased urine pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance → calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes stone formation
    • Acetazolamide Acetazolamide One of the carbonic anhydrase inhibitors that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. Carbonic Anhydrase Inhibitors
    • Topiramate Topiramate A sulfamate-substituted fructose analog that was originally identified as a hypoglycemic agent. It is used for the treatment of epilepsy and migraine disorders, and may also promote weight loss. Second-Generation Anticonvulsant Drugs
  • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids
  • Laxatives Laxatives Laxatives are medications used to promote defecation. Most often, laxatives are used to treat constipation or for bowel preparation for certain procedures. There are 4 main classes of laxatives: bulk-forming, stimulant, osmotic, and emollient. Laxatives
• Medications that can form crystals in the urine:
  • Antiviral Antiviral Antivirals for Hepatitis B agents:
    • Acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles)
    • Atazanavir Atazanavir Anti-HIV Drugs
    • Indinavir Indinavir A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. Anti-HIV Drugs
    • Ritonavir Ritonavir An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits cytochrome p-450 cyp3a. Anti-HIV Drugs
  • Antibiotics:
    • Ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins
    • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones
    • Sulfa medications
  • Triamterene Triamterene A pteridinetriamine compound that inhibits sodium reabsorption through sodium channels in renal epithelial cells. Potassium-sparing Diuretics

Pathophysiology

Underlying medical (including genetic) and environmental factors affect mechanisms that lead to formation of stones.^[15]

Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes oxalate stones^[14,15]

• Idiopathic Idiopathic Dermatomyositis normocalcemic hypercalciuria Hypercalciuria Excretion of abnormally high level of calcium in the urine, greater than 4 mg/kg/day. Nephrolithiasis (most common cause)
• Ethylene glycol Ethylene glycol A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins. Nephrolithiasis (antifreeze) ingestion:
  • Ethylene glycol Ethylene glycol A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins. Nephrolithiasis is metabolized to oxalate by alcohol dehydrogenase Alcohol dehydrogenase A zinc-containing enzyme which oxidizes primary and secondary alcohols or hemiacetals in the presence of nad. In alcoholic fermentation, it catalyzes the final step of reducing an aldehyde to an alcohol in the presence of nadh and hydrogen. Ethanol Metabolism and aldehyde dehydrogenase.
  • Oxalate filtered in the urine binds to urinary calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes and produces calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes oxalate crystals.
• Decreased urine pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance:
  • Excessive H⁺ ions bind BIND Hyperbilirubinemia of the Newborn to citrate, resulting in hypocitraturia.
  • Urinary calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes can no longer bind BIND Hyperbilirubinemia of the Newborn to citrate and binds to oxalate instead, producing calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes oxalate crystals. 
• Excessive vitamin C Vitamin C A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. Water-soluble Vitamins and their Deficiencies (ascorbic acid) ingestion: decreases urine pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance resulting in calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes oxalate crystals
• Crohn disease or small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy resection:
  • Decreased absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of fat due to damaged mucosa (Crohn disease) or small surface area ( small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy resection)
  • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes in the GI lumen binds to fat, resulting in increased free oxalate absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption from the GI tract. 
  • Oxalate filtered across the glomeruli binds to urinary calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes, producing calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes oxalate crystals. 

Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis stones^[14,15]

• Decreased urine pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance:
  • Excessive H⁺ binds to urate and forms uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis.
  • Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis moieties coalesce to form uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis crystals.
• Arid climate:
  • Excessive sweating causes volume depletion Volume depletion Volume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids. Volume Depletion and Dehydration.
  • Volume depletion Volume depletion Volume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids. Volume Depletion and Dehydration concentrates urine, allowing uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis moieties to coalesce and form crystals.
• Hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout: Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis crystals are formed because of increased filtered uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis.
• Increased cell turnover (e.g., lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum, leukemia):
  • Purine breakdown in the cell nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles produces uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis.
  • Excessive uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis is filtered across glomeruli and forms uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis crystals.
• Diet:
  • Diets high in purines Purines A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. Nucleic Acids (red meat, seafood) and fructose can elevate uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis levels.
  • Excessive intake of alcohol can contribute to hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout and stone formation.

Struvite Struvite The mineral magnesium ammonium phosphate with the formula NH4mgpo4. It is associated with urea-splitting organisms in a high magnesium, high phosphate, alkaline environment. Accumulation of crystallized struvite is found in the urinary tract as struvite calculi and as scale on sewage system equipment and wastewater pipes. Nephrolithiasis stones^[14,15]

• UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections (UTIs) with urease-positive Urease-positive Helicobacter bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology
• Urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis breaks down urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle into ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance and CO₂.
• Ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance binds to magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes and phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes forming struvite Struvite The mineral magnesium ammonium phosphate with the formula NH4mgpo4. It is associated with urea-splitting organisms in a high magnesium, high phosphate, alkaline environment. Accumulation of crystallized struvite is found in the urinary tract as struvite calculi and as scale on sewage system equipment and wastewater pipes. Nephrolithiasis stones.
• Commonly implicated bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology:
  • Proteus mirabilis Proteus mirabilis A species of gram-negative, facultatively anaerobic, rod-shaped bacteria that is frequently isolated from clinical specimens. Its most common site of infection is the urinary tract. Proteus (most common)
  • Ureaplasma urealyticum
  • Staphylococcus saprophyticus Staphylococcus saprophyticus A species of gram-positive bacteria in the family staphylococcaceae. It commonly causes urinary tract infections in humans. Staphylococcus
  • Klebsiella pneumoniae Klebsiella Pneumoniae Gram-negative, non-motile, capsulated, gas-producing rods found widely in nature and associated with urinary and respiratory infections in humans. Aminoglycosides
• Can form large staghorn stone/s which fill up the renal pelvis Renal pelvis Kidneys: Anatomy and calyces, causing obstruction and recurrent infections Recurrent infections Common Variable Immunodeficiency (CVID)

Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes stones^[14,15]

• Increased urine pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance results in high levels of monohydrogen phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes anions Anions Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. Electrolytes.
• Monohydrogen phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes binds to calcium-forming calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes crystals.

Cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis stones^[14,15]

• Cystinuria Cystinuria An inherited disorder due to defective reabsorption of cystine and other basic amino acids by the proximal renal tubules. This form of aminoaciduria is characterized by the abnormally high urinary levels of cystine; lysine; arginine; and ornithine. Mutations involve the amino acid transport protein gene slc3a1. Nephrolithiasis: autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance defect in sodium-dibasic amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids cotransporter
• Results in decreased tubular reabsorption of cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis, ornithine Ornithine An amino acid produced in the urea cycle by the splitting off of urea from arginine. Urea Cycle, arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle, and lysine
• Cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis moieties are retained in the urine, coalesce, and form cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis stones.

Summary

Sites of obstruction and complications^[14,15,22]

• Kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis can lodge into any of the 3 natural narrowings along the ureter:
  • Ureteropelvic junction Ureteropelvic junction Urinary Tract: Anatomy (junction of the renal pelvis Renal pelvis Kidneys: Anatomy and ureter)
  • Ureter at the pelvic inlet Pelvic inlet Pelvis: Anatomy (site of ureteral crossing of the iliac vessels)
  • Ureterovesical junction (junction of the ureter and urinary bladder Urinary Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters (ureter), and is held there until urination. Urinary Tract: Anatomy) 
• A stone lodged at any of the 3 locations can cause obstruction and consequent proximal complications:
  • Acute pyelonephritis Acute pyelonephritis Inflammation of the kidney involving the renal parenchyma (the nephrons); kidney pelvis; and kidney calices. It is characterized by abdominal pain; fever; nausea; vomiting; and occasionally diarrhea. Imaging of the Urinary System:
    • Obstruction of the urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy, which allows for proximal overgrowth of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology
    • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the renal pelvis Renal pelvis Kidneys: Anatomy (kidney parenchyma results)
    • Presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, urinary frequency, urgency, dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary Tract Infections (UTIs), and costovertebral angle tenderness
  • Hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis:
    • Obstruction causes proximal accumulation of urine.
    • Results in the dilation of the renal pelvis Renal pelvis Kidneys: Anatomy and calyces (visible on ultrasound)

Clinical Presentation and Diagnosis

Clinical presentation^[14,15,17]

• Depends on the size, number, and location of the stones
• Small stones or those within the renal pelvis Renal pelvis Kidneys: Anatomy and bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess may be asymptomatic.
• Symptoms are usually associated with acute ureteral obstruction Ureteral obstruction Blockage in any part of the ureter causing obstruction of urine flow from the kidney to the urinary bladder. The obstruction may be congenital, acquired, unilateral, bilateral, complete, partial, acute, or chronic. Depending on the degree and duration of the obstruction, clinical features vary greatly such as hydronephrosis and obstructive nephropathy. Vesicoureteral Reflux:
  • Severe unilateral, colicky abdominal pain Abdominal Pain Acute Abdomen due to intermittent ureteral peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility:
    • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways radiates to the groin Groin The external junctural region between the lower part of the abdomen and the thigh. Male Genitourinary Examination, testes Testes Gonadal Hormones, or labia majora Labia majora Vagina, Vulva, and Pelvic Floor: Anatomy.
    • Causes costovertebral angle tenderness
    • Usually associated with inability to lie still
  • Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma (gross or microscopic) due to ureteral trauma
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and/or vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever suggests associated infection or pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess.
• With persistent ureteral stones, neither pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways nor hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis is consistently present.

Diagnosis

• Imaging:
  • Low-dose, noncontrast CT of the abdomen and pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy:^[16,20]
    • Gold-standard for imaging for kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
    • Can show location and size of the stone
    • Can detect hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis
  • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity ( BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity > 30 kg/m²): standard-dose, noncontrast CT
  • Recommendations for CT scans:
    • American College of Radiology: helical Helical Computed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures. Computed Tomography (CT) ( spiral Spiral Computed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures. Computed Tomography (CT)) noncontrast CT (low-dose protocol) has the highest (> 95%) sensitivity and specificity Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. Epidemiological Values of Diagnostic Tests for urolithiasis.^[19]
    • UK quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement statement (NICE): Adults with suspected renal colic have low-dose non-contrast CT within 24 hours of presentation.^[16]
    • The US “Choosing Wisely” initiative of the American Board of Internal Medicine (ABIM):^[13]
      • Avoid ordering CT of the abdomen/ pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy in otherwise healthy patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship < age 50 with known histories of kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis and uncomplicated renal colic presentation (no worsening of symptoms, no fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever or history of severe obstruction).
      • CT scans of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship in the ED with symptoms of recurrent kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis usually do not change the management and their use further increases cost and radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma exposure. 
  • Abdominal ultrasound: used in pregnant women and children to avoid radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma
  • Abdominal X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests: can detect large stones
• Laboratory studies:^[14,16,20]
  • Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children and urine dipstick:
    • Useful for detecting microscopic hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma
    • Determines urine pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance and helps determine the type of stone
    • Urine pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance <5.5 may suggest uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis or cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis stones, whereas pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance >7.5 may suggest struvite Struvite The mineral magnesium ammonium phosphate with the formula NH4mgpo4. It is associated with urea-splitting organisms in a high magnesium, high phosphate, alkaline environment. Accumulation of crystallized struvite is found in the urinary tract as struvite calculi and as scale on sewage system equipment and wastewater pipes. Nephrolithiasis (infection) stones.
  • Urine microscopy: evaluates the shape of the crystals
  • Blood tests:
    • Serum calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes and electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes
    • BUN and creatinine
    • Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis level
  • Additional tests:^[11,12]
    • Urine culture Urine culture Urinary Tract Infections (UTIs) if there are signs (clinical and laboratory) of infection
    • If primary hyperparathyroidism Primary hyperparathyroidism A condition of abnormally elevated output of parathyroid hormone due to parathyroid hyperplasia or parathyroid neoplasms. It is characterized by the combination of hypercalcemia, phosphaturia, elevated renal 1, 25-dihydroxyvitamin d3 synthesis, and increased bone resorption. Hyperparathyroidism is suspected, obtain serum parathyroid Parathyroid The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands: Anatomy hormone (PTH).
    • For recurrent or high-risk stone formers, metabolic testing includes: 24-hr urine collection analyzed for volume, pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance, calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes, oxalate, uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis, citrate, sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia, potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia, creatinine
    • Obtain stone analysis when able.

Management

US and UK Guidelines

• US: American Urological Association (AUA) guideline for the medical management of kidney stones^[12]
• US: AUA guideline for the surgical management of kidney stones^[11]
• UK: National Institute for Health and Care Excellence (NICE) guidelines on renal and ureteric stones in children and adults^[16]
• Europe: European Association of Urology (EAU) guidelines on nephrolithiasis^[20]

Size-based approach^[17]

• ≤ 5 mm:
  • Observation only (spontaneous passage is likely)
  • Symptomatic management with hydration and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways control
  • Strain urine
• 6–10 mm: alpha-blockers Alpha-blockers Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma. Antiadrenergic Drugs or dihydropyridine Dihydropyridine Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers ( alpha-blockers Alpha-blockers Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma. Antiadrenergic Drugs are preferred because calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers have lower passage rates and more complications)
• 10–20 mm: extracorporeal shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock wave lithotripsy (ESWL) or ureterorenoscopy/ureteroscopy (URS)
• > 20 mm or staghorn stone: percutaneous nephrolithotomy  (PCNL)

Indications for hospitalization Hospitalization The confinement of a patient in a hospital. Delirium^[12]

• Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock or pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess: start empiric antibiotic therapy
• Urinary obstruction requiring surgical decompression
• Acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury
• Anuria Anuria Absence of urine formation. It is usually associated with complete bilateral ureteral (ureter) obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present. Acute Kidney Injury
• Intractable pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways or vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia

Indications for urology referral^[11]

• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship requiring hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
• Stone that does not pass after 4 weeks
• Persistent pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
• Stone > 10 mm
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and other signs or symptoms of infection need IV antibiotics and emergency urologic consultation for drainage.

Medical management^[12,14,15]

General supportive care:

• IV hydration Iv Hydration Crush Syndrome and advice on fluid intake if being managed on an outpatient basis
• Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways control:^[5]
  • NSAIDs NSAIDS Primary vs Secondary Headaches: may be sufficient to control pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship; associated with less vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia than treatment with opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics^[16,20]
    • Ketorolac 30 mg IV every 6 hours as needed, maximum: 120 mg/day
    • Indomethacin Indomethacin A non-steroidal anti-inflammatory agent (nsaid) that inhibits cyclooxygenase, which is necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. Nonsteroidal Antiinflammatory Drugs (NSAIDs) 25–50 mg orally up to 3 times a day as needed
    • Diclofenac Diclofenac A non-steroidal anti-inflammatory agent (nsaid) with antipyretic and analgesic actions. It is primarily available as the sodium salt. Nonsteroidal Antiinflammatory Drugs (NSAIDs) sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia immediate-release 50 mg orally up to 3 times a day
    • Avoid NSAIDs NSAIDS Primary vs Secondary Headaches in renal insufficiency, volume depletion Volume depletion Volume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids. Volume Depletion and Dehydration, GI bleeding risk, and in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care. 
  • Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics:
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to NSAIDs NSAIDS Primary vs Secondary Headaches; GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests < 30 mL/min/1.73 m²
    • Morphine Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Opioid Analgesics 1–4 mg IV every 1–4 hours as needed (for opioid-naive)
• Antiemetic if needed: ondansetron Ondansetron A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties. Antiemetics 4 mg IV or orally every 8–12 hours 
• Treat UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections (UTIs) if present with empiric antibiotics; send urine for culture
• Strain urine to send stone for lab analysis.
• Resolution of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways does not necessarily correlate with stone passage; follow-up imaging is needed if spontaneous passage has not occurred.^[3]

Medical expulsive therapy ( MET MET Preoperative Care):^{[6,9,10,16,17]}

• Given to facilitate spontaneous stone passage by smooth muscle relaxation in the ureteral tract
• Most evidence exists for distal ureteral stones.
• Alpha blockers are used only for stones 6–10 mm in diameter.
• Ureteral stone passage has been shown to be significantly more likely with alpha blocker therapy (for up to 4 weeks) than with conservative treatment alone.^[7,9,10] 
• Available alpha blockers (given up to 4 weeks; discontinue after stone expulsion):
  • Tamsulosin Tamsulosin A sulfonamide derivative and adrenergic alpha-1 receptor antagonist that is used to relieve symptoms of urinary obstruction caused by benign prostatic hyperplasia. Antiadrenergic Drugs 0.4 mg daily (generally recommended)
  • Alternatives:
    • Terazosin Terazosin Antiadrenergic Drugs 2–5 mg daily in evening 
    • Doxazosin Doxazosin A prazosin-related compound that is a selective alpha-1-adrenergic blocker. Antiadrenergic Drugs 4 mg daily in evening
    • Alfuzosin 10 mg once daily
    • Silodosin 8 mg once daily 
• Other agents:
  • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blocker: nifedipine Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) 30 mg daily (inferior to tamsulosin Tamsulosin A sulfonamide derivative and adrenergic alpha-1 receptor antagonist that is used to relieve symptoms of urinary obstruction caused by benign prostatic hyperplasia. Antiadrenergic Drugs; rarely used)
  • Phosphodiesterase type-5 inhibitor (used in combination with tamsulosin Tamsulosin A sulfonamide derivative and adrenergic alpha-1 receptor antagonist that is used to relieve symptoms of urinary obstruction caused by benign prostatic hyperplasia. Antiadrenergic Drugs in some studies):
    • Tadalafil Tadalafil A carboline derivative and phosphodiesterase 5 inhibitor that is used primarily to treat erectile dysfunction; benign prostatic hyperplasia and primary pulmonary hypertension. Phosphodiesterase Inhibitors 10 mg daily^[4]
    • Considered as adjunctive therapy in select patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship; not recommended as first-line monotherapy

Stone-specific management^[12,14]

• All stone formers are recommended to have adequate fluid intake, enough to produce at least 2.5 L of urine output per day.
• Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes stones with hypercalciuria Hypercalciuria Excretion of abnormally high level of calcium in the urine, greater than 4 mg/kg/day. Nephrolithiasis:
  • Low-sodium diet to increase concomitant sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia and calcium reabsorption Calcium reabsorption Tubular System in proximal tubules
  • Thiazide Thiazide Heterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters and are used as diuretics. Hyponatremia diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication to increase calcium reabsorption Calcium reabsorption Tubular System in the distal tubule → ↓ calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes in the urine (continue treatment until urinary calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes normalizes)
    • Chlorthalidone Chlorthalidone A benzenesulfonamide-phthalimidine that tautomerizes to a benzophenones form. It is considered a thiazide-like diuretic. Thiazide Diuretics 25 mg daily, or
    • Hydrochlorothiazide Hydrochlorothiazide A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. Thiazide Diuretics 25 mg twice daily, or 50 mg daily
    • Indapamide Indapamide A benzamide-sulfonamide-indole derived diuretic that functions by inhibiting sodium chloride symporters. Hypertension Drugs 2.5 mg once daily
  • Citrate given to those with low urine citrate; citrate will increase urinary citrate excretion which in turn, inhibits calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes stone formation:
    • Potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia citrate 10–30 mEq 3 times daily (maximum: 100 mEq/day)
• Stones with hyperoxaluria:
  • Limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation oxalate-rich foods (e.g., spinach, rhubarb etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC))
  • Calcium carbonate Calcium carbonate Carbonic acid calcium salt. An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. Hypocalcemia (or citrate) 1–4 g per day taken with meals (to bind BIND Hyperbilirubinemia of the Newborn oxalate in the intestine), or
  • Potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia citrate 10–30 mEq 3 times daily, or
  • Magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes oxide 400–800 mg 2–3 times daily
• Struvite Struvite The mineral magnesium ammonium phosphate with the formula NH4mgpo4. It is associated with urea-splitting organisms in a high magnesium, high phosphate, alkaline environment. Accumulation of crystallized struvite is found in the urinary tract as struvite calculi and as scale on sewage system equipment and wastewater pipes. Nephrolithiasis stones:
  • Antibiotic therapy to eliminate the causative microbe 
  • Urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis inhibitor: acetohydroxamic acid 250 mg 3–4 times daily (rarely the first-line, unless in inoperable cases or patient is too ill)
• Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis stones:
  • Urine alkalinization  to dissolve uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis crystals:
    • Potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia citrate 10–30 mEq 3 times daily 
    • Alternative: sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes 4 g orally initially, followed by 1–2 g every 4–6 hours; maximum: 16 g/day
  • Xanthine oxidase Oxidase Neisseria inhibitor to decrease uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis production (if alkali therapy and ↑ fluid intake fail):
    • Allopurinol Allopurinol A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. Gout Drugs 100–300 mg daily
    • Alternative: febuxostat Febuxostat A thiazole derivative and inhibitor of xanthine oxidase that is used for the treatment of hyperuricemia in patients with chronic gout. Gout Drugs 40–80 mg daily
• Cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis stones:
  • Limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation intake of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia (↓ cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis excretion) and animal proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis.
  • Urine alkalinization:
    • Potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia citrate 10–30 mEq 3 times daily 
  • Thiol binding agent/ cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis chelator:
    • Tiopronin 800 mg/day in 3 divided doses, or
    • Penicillamine Penicillamine 3-mercapto-d-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in wilson’s disease. Wilson Disease 250 mg 4 times daily (up to 4 g/day)
• Follow-up:
  • Repeat 24-hour urine studies within 6 months to check on response to dietary and medical therapy.
  • Repeat stone analysis if there is no response.

Management of obstruction and infection^[20,21]

• Obstructed kidney with anuria Anuria Absence of urine formation. It is usually associated with complete bilateral ureteral (ureter) obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present. Acute Kidney Injury and/or infection → urologic emergency
• Obstruction:^[11]
  • Treat with decompression (dependent on institutional resources, anatomy, and urologic availability):
    • Ureteric stent or surgical removal
    • Percutaneous nephrostomy by an interventional radiologist
  • If infection is present, antibiotics are given and definitive stone removal is delayed until infection resolves.
• Infection:
  • Treat infected hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis (infection proximal to the stone) with systemic symptoms (requiring hospitalization Hospitalization The confinement of a patient in a hospital. Delirium) initially with IV antibiotics.
    • Choice of antibiotics depends on local resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing data, previous use of antibiotics, individual risk factors and severity of presentation.
    • Ultimately, tailor regimen to susceptibility studies.
  • For the critically ill ( sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock, multiorgan dysfunction) and/or with urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy obstruction: antipseudomonal coverage ( carbapenem Carbapenem The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam) + vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides
    • Imipenem Imipenem Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. Carbapenems and Aztreonam 500 mg IV every 6 hours + vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides 15–20 mg/kg every 12 hours
    • Meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam 1 g IV every 8 hours + vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides
  • For hospitalized patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (not critically ill) without risk of multidrug resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing:
    • Ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins 1–2 g IV every 24 hours
    • Piperacillin Piperacillin Semisynthetic, broad-spectrum, ampicillin derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics. Penicillins– tazobactam Tazobactam A penicillanic acid and sulfone derivative and potent beta-lactamase inhibitor that enhances the activity of other anti-bacterial agents against beta-lactamase producing bacteria. Cephalosporins 3.375 g IV every 6 hours
    • Levofloxacin Levofloxacin The l-isomer of ofloxacin. Fluoroquinolones 750 mg IV or orally daily
    • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones 400 mg IV every 12 hours
  • For hospitalized patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (not critically ill) with risk of multidrug resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing:
    • Piperacillin Piperacillin Semisynthetic, broad-spectrum, ampicillin derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics. Penicillins– tazobactam Tazobactam A penicillanic acid and sulfone derivative and potent beta-lactamase inhibitor that enhances the activity of other anti-bacterial agents against beta-lactamase producing bacteria. Cephalosporins 3.375 g IV every 6 hours
    • Cefepime Cefepime A fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against pseudomonas aeruginosa and may also be used in the empiric treatment of febrile neutropenia. Cephalosporins 2 g IV every 12 hours
    • Imipenem Imipenem Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. Carbapenems and Aztreonam 500 mg IV every 6 hours
    • Meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam 1 g IV every 8 hours

Surgical management^[11,16,20]

Indications: 

• Stones ≥ 10 mm 
• Failed medical therapy (stones < 10 mm that have not passed even after 4–6 weeks):
  • Uncontrolled symptoms (e.g., ongoing intolerable pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways)
  • Persistent obstruction
  • Failure to pass stone
  • Stone unlikely to pass

Procedures:

• ESWL:
  • Stone fragmentation Fragmentation Chronic Apophyseal Injury with sound waves
  • Not routinely performed in obese patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship because of poor penetration Penetration X-rays of sound waves
  • Least morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and least complication rate among procedures (non-invasive but often will need multiple sessions)
  • Carries the risk of ureteral blockage by stone fragments
  • Not for large kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis or those on the lower pole of the kidney (as clearing of the stone fragments in this location would be difficult)
• Ureteroscopy (URS):
  • A transurethral endoscopic procedure to visualize the entire urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy and retrieve the kidney stone
  • Associated with better stone-free rates than ESWL
  • Recommended for those with mid or distal ureteral stones (which failed medical therapy)
  • Recommended for suspected cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis and uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis stones (which failed medical therapy)
  • A treatment option for pregnant patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with ureteral stone (in whom medical therapy failed)
  • A ureteral stent is sometimes placed to prevent obstruction (from ureteral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema or stone fragment).
• Percutaneous nephrolithotomy (PCNL):
  • Minimally invasive surgical procedure with skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions incision 
  • More complications than URS or ESWL (which include bleeding, perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis of the renal pelvis Renal pelvis Kidneys: Anatomy, hydrothorax Hydrothorax A collection of watery fluid in the pleural cavity. Edema)
  • Usually reserved for:
    • Intrarenal and proximal ureteric stones 
    • Large stones (≥ 20 mm) 
    • Stones unresponsive to ESWL and ureteroscopy
    • Stones associated with complex renal anatomy
• Laparoscopic, open, or robot-assisted stone removal:
  • For large or complex kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
  • Open surgery is performed only if the stone (or stones) cannot be removed with less invasive procedures.
• Nephrectomy Nephrectomy Excision of kidney. Renal Cell Carcinoma: performed if kidney with the stones has negligible function

Prevention^[2,12]

• Adequate hydration
• Dietary modifications as recommended based on stone analysis.
• Evaluate the patient for possible underlying causes of stone disease and treat accordingly.

Differential Diagnosis

• Acute appendicitis Appendicitis Appendicitis is the acute inflammation of the vermiform appendix and the most common abdominal surgical emergency globally. The condition has a lifetime risk of 8%. Characteristic features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. Appendicitis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy caused by impaction of a fecalith Fecalith Imaging of the Intestines in adults, or by lymphoid hyperplasia Lymphoid hyperplasia Common Variable Immunodeficiency (CVID) in children. The initial presentation is diffuse periumbilical pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, which localizes to the RLQ. In contrast, nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis causes flank pain Flank pain Pain emanating from below the ribs and above the ilium. Renal Cell Carcinoma. The diagnosis of appendicitis Appendicitis Appendicitis is the acute inflammation of the vermiform appendix and the most common abdominal surgical emergency globally. The condition has a lifetime risk of 8%. Characteristic features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. Appendicitis is clinical and supported by imaging; treatment is usually surgical. 
• Testicular torsion Testicular torsion Testicular torsion is the sudden rotation of the testicle, specifically the spermatic cord, around its axis in the inguinal canal or below. The acute rotation results in compromised blood flow to and from the testicle, which puts the testicle at risk for necrosis. Testicular Torsion: the spermatic cord Spermatic Cord Either of a pair of tubular structures formed by ductus deferens; arteries; veins; lymphatic vessels; and nerves. The spermatic cord extends from the deep inguinal ring through the inguinal canal to the testis in the scrotum. Testicles: Anatomy twisting caused by increased testicular mobility in the scrotal sac. The presentation includes erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, swelling Swelling Inflammation, absent cremasteric reflex Cremasteric Reflex Male Genitourinary Examination, and sudden-onset, severe testicular pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. In contrast, nephrolithiasis-induced pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways originates in the flank and later radiates to the groin Groin The external junctural region between the lower part of the abdomen and the thigh. Male Genitourinary Examination. Diagnosis of testicular torsion Testicular torsion Testicular torsion is the sudden rotation of the testicle, specifically the spermatic cord, around its axis in the inguinal canal or below. The acute rotation results in compromised blood flow to and from the testicle, which puts the testicle at risk for necrosis. Testicular Torsion is via Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) ultrasound. Treatment is manual, or surgical detorsion with bilateral orchiopexy Orchiopexy A surgical procedure in which an undescended testicle is sutured inside the scrotum in male infants or children to correct cryptorchidism. Orchiopexy is also performed to treat testicular torsion in adults and adolescents. Cryptorchidism. 
• Biliary colic: cramp-like RUQ pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways caused by intermittent obstruction of the cystic Cystic Fibrocystic Change duct by a gallstone. Presentation is episodic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, typically after ingestion of a fatty meal. In contrast, pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways due to nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis is not related to eating. Diagnosis is based on the combination of clinical signs and RUQ ultrasound findings. Unless the patient develops acute cholecystitis Acute cholecystitis Acute inflammation of the gallbladder wall. It is characterized by the presence of abdominal pain; fever; and leukocytosis. Gallstone obstruction of the cystic duct is present in approximately 90% of the cases. Cholecystitis, treatment is observation.
• Diverticulitis Diverticulitis Inflammation of a diverticulum or diverticula. Diverticular Disease: an inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of diverticula caused by impaction of a fecalith Fecalith Imaging of the Intestines. Presentation may include LLQ pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, moderate to high fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and bloody stools. In contrast, nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis is not characterized by bloody stools. Diverticulitis Diverticulitis Inflammation of a diverticulum or diverticula. Diverticular Disease is diagnosed with a CT scan of the abdomen, and most cases are treated with IV antibiotics.