Glomerular Filtration

The kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys are primarily in charge of the maintenance of water and solute homeostasis through the processes of filtration, reabsorption, secretion, and excretion. Glomerular filtration is the process of converting the systemic blood supply into a filtrate, which will ultimately become the urine. Complex regulatory processes ensure that only the appropriate substances in the systemic blood are lost in the urine and that the urine flow is satisfactorily balanced to maintain adequate systemic volume status. Abnormalities of the glomerulus can cause several clinically important conditions.

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Renal Anatomy and Physiology Overview

Overview

The GFR is the rate of filtration of plasma through the glomerular membrane. Filtration is 1 of 4 primary mechanisms involved in the regulation of water, 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, and waste excretion:

  1. Filtration: Plasma is filtered in the glomerular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries, creating a filtrate that passes through the renal tubules.
  2. Reabsorption: Desirable solutes and water are reabsorbed from the tubule lumens back into the blood.
  3. Secretion: Waste products are intentionally secreted.
  4. Excretion: Remaining filtrate is excreted as urine.

Other renal functions:

  • Hemodynamic regulation (renin, prostaglandins, bradykinin)
  • RBC production (erythropoietin)
  • Bone metabolism Bone metabolism Bone is the primary storage site of calcium in the body; thus, bone metabolism plays a critical role in maintaining normal calcium levels. Bone metabolism (and thus calcium levels) are primarily regulated by 3 hormones, namely, calcitonin, parathyroid hormone (PTH), and vitamin D. Bone Metabolism
Overview of the glomerulus

Overview of the glomerulus:
Blood and filtrate flow through the glomerulus. Blood enters through the afferent arteriole, and as it moves through the glomerular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries (which are closely associated with filtering podocytes), a portion of the plasma is filtered across the glomerular barrier into Bowman’s space. The filtrate (which becomes the urine) then moves out through the proximal tubule, while the blood that was not filtered (and remains in the vessels) leaves through the efferent arteriole.

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Kidney layers

  • Cortex: 
    • Outer layer
    • Location of the glomeruli and proximal and distal convoluted tubules
    • Lowest osmolality (approximately 300 mOsm/kg)
  • Outer medulla: middle layer, between the cortex and inner medulla
  • Inner medulla:
    • Deepest layer
    • Contains the loops of Henle
    • Highest osmolality (up to 1200 mOsm/kg)
Renal circulation (diagram)

Renal circulation

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Blood flow

The renal blood flow is as follows (in order):

  • Aorta → renal artery → interlobar artery → arcuate artery → interlobular artery  
  • Afferent arteriole  
  • Glomerular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries:  
    • Blood is filtered in the glomerular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries.
    • The filtrate enters Bowman’s space (ultimately becomes urine).
  • Efferent arteriole  
  • Peritubular and vasa recta capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries:  
    • Peritubular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: surround the proximal and distal tubules
    • Vasa recta: surround the loops of Henle
    • Peritubular and vasa recta capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries are the beginning of venous circulation.
  • Interlobular vein → arcuate vein → interlobar vein → renal vein → vena cava
Renal circulation

Renal circulation

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Nephrons

Nephrons are the functional units of the kidney

  • Nephron segments (in the order through which the filtrate flows):
    • Bowman’s capsule
    • Proximal convoluted tubule
    • Proximal straight tubule
    • Loop of Henle, further divided into:
      • Thin descending limb
      • Thin ascending limb
      • Thick ascending limb
    • Distal convoluted tubule
    • Collecting duct
  • Types of nephrons:
    • Cortical (or superficial): Loops of Henle penetrate only as deep as the outer medulla.
    • Juxtamedullary: 
      • Nephrons whose loops penetrate all the way into the inner medulla
      • Allow for ↑ concentration of the urine (due to ↑ osmolality in the inner medulla)
Nephron anatomy

Nephron anatomy

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Definitions

  • Renal blood flow (RBF):
    • Rate at which systemic blood is delivered to the kidney
    • Roughly equals 1000 mL/min, or 20%–25% of the cardiac output 
    • The entire blood volume is delivered to the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys about every 5 minutes.
  • Renal plasma flow (RPF):
    • Portion of RBF that is only plasma (not cells or proteins)
    • This portion of the blood is filtered across the glomerular membrane.
    • RPF (approximate) = RBF × (1 – hematocrit)
    • Approximately 600 mL/min (assuming an RBF of 1000 mL/min and a hematocrit of 40%)
  • Filtration fraction (FF):
    • Fraction of the RPF that actually moves across the glomerular membrane 
    • FF = GFR / RPF 
    • Approximately 20% under normal circumstances

Glomerular Filtration Rate

Glomerular filtration rate

The GFR is the volume of plasma filtered by the glomerulus per unit of time. It is the most important laboratory indicator of kidney function.

  • Normal GFR = 90–120 mL/min in healthy people
    • Varies with age, sex, and muscle mass
    • Often standardized for body surface area 
    • Is the sum of all filtration rates in all functioning nephrons:
      • Is a rough assessment of the number of functioning nephrons
      • ↓ GFR indicates renal disease.
  • Process: 
    • Plasma moves from the glomerular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries through the glomerular barrier.
    • The resulting filtrate (the primary urine) collects in Bowman’s space and exits through the tubule lumen.
    • The remaining blood within the capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries exits through the efferent arteriole.
  • Equation 1: GFR = RPF × FF
    • Assume normal parameters: 
      • RPF = 600 mL/min
      • FF = 20%
    • GFR = RPF × FF →  600 mL/min × 20% = 120 mL/min
  • GFR is a function of:
    • Renal capillary forces (Starling forces): hydrostatic and oncotic pressure within the capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries and Bowman’s space
    • Properties of the glomerular barrier 

Starling forces

Equation 2: GFR = Kf [ (PGC – PBS) – (πGC – πBS) ]:

  • Kf: filtration barrier; measure of surface area and glomerular permeability
  • PGC: glomerular capillary hydrostatic pressure
  • PBS: Bowman’s space hydrostatic pressure
  • πGC: glomerular capillary oncotic pressure
  • πBS: Bowman’s space oncotic pressure

Glomerular barrier

The glomerular barrier is the filtration structure of the nephron that surrounds the glomerular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries and includes the following 3 layers:

  • Capillary endothelium: 
    • Walls of the capillary vessels
    • Fenestrated: contain small windows, approximately 100 nm in size
    • Coated with anionic glycosaminoglycans and glycoproteins
  • Glomerular basement membrane (GBM): 
    • Intermediate layer formed by the capillary endothelial and podocyte basal laminas
    • Negatively charged → favors filtration of cations
  • Epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium (podocytes): 
    • Attached to the GBM with multiple foot processes
    • Foot processes interdigitate, forming gaps (or pores) approximately 40 nm in size.
    • Pores are covered by a membrane called the slit diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm:
      • A unique form of intercellular junction
      • Consists of multiple proteins, including nephrin 
      • Assists in filtration function
Glomerular barrier

Diagram of the glomerular barrier:
A: Fenestrated endothelium of the glomerular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries
B: Basal membrane
C: Epithelial layer demonstrating podocyte foot processes and structural proteins creating the slit diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm

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Regulation of the Glomerular Filtration Rate

The kidney has multiple levels of regulatory mechanisms on the GFR: 

  • Autoregulation of the renal blood flow overall
  • Relative constriction and dilation of the afferent and efferent arterioles
  • Tubuloglomerular feedback
  • Fine-tuning mechanisms: paracrine, endocrine, and neural

Autoregulation of Renal Blood Flow

Renal blood flow is autoregulated through a localized reflexive process called the myogenic response. 

  • Myogenic response: BP stretches afferent arterioles → activates inward-directed ion channels → depolarization → arteriole contraction
    • ↑ Systemic BP → afferent arteriole vasoconstriction → ↓ RBF
    • ↓ Systemic BP  → afferent arteriole vasodilation → ↑ RBF
  • Maintains relatively constant RBF within a range of normal mean arterial BPs (the autoregulatory range)
  • Stable RBF allows the other regulatory mechanisms (rather than systemic BP) to regulate the GFR.
Impact of mean arterial blood pressure on the flow rate of renal blood flow (rbf) and glomerular filtration rate (gfr)

Impact of mean arterial blood pressure on the flow rate of renal blood flow (RBF) and glomerular filtration rate (GFR):
Notice that within the autoregulatory range, GFR and RBF remain relatively constant.

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Glomerular hemodynamics

The primary regulation of glomerular filtration occurs within the glomerulus itself by constricting and dilating the afferent and efferent arterioles. This affects the hydrostatic pressure within the glomerular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries.

  • Main parameters:
    • RBF
    • Ultrafiltrate pressure (PUF), which correlates with glomerular capillary hydrostatic pressure (PGC)
    • GFR
    • Tubular flow: refers to filtered primary urine leaving Bowman’s space
  • Afferent arteriole: 
    • Think in terms of how changing the inflow of blood affects forward pressure.
    • Constriction: 
      • Decreases all parameters 
      • ↓ Inflow → ↓ RBF → ↓ PUF →↓ GFR → ↓ tubular flow
    • Dilation: 
      • Increases all parameters 
      • ↑ Inflow → ↑ RBF → ↑ PUF → ↑ GFR → ↑ tubular flow
  • Efferent arteriole: 
    • Think in terms of how changing outflow affects backward pressure
    • Constriction: ↓ outflow → ↑ PUF →  ↑ GFR → ↑ tubular flow but ↓ RBF
    • Dilation: ↑ outflow → ↓ PUF  → ↓ GFR → ↓ tubular flow but ↑ RBF
  • Renin–angiotensin–aldosterone system (RAAS):
    • ↓ BP → ↓ afferent arteriole stretch → triggers release of renin from the juxtaglomerular cells within the afferent arterioles
    • ↑ Renin → ↑ angiotensin I → ↑ angiotensin II:
      • Systemic vasoconstriction → ↑ BP to maintain RBF
      • Vasoconstriction of both the afferent and efferent arterioles but with more constriction of the efferent → ↑ PGC → ↑ GFR but ↓ in RBF
      • Stimulates aldosterone → ↑ Na and water reabsorption → ↑ in systemic BP and RBF
    • ↑ BP has the opposite effects.

Tubuloglomerular feedback

Macula densa cells within the tubules can sense tubular flow and adjust secretion of substances that affect GFR. This process is called tubuloglomerular feedback.

  • Macula densa cells (located in distal tubules):
    • Sense the relative flow of NaCl, which correlates directly with GFR
    • ↑ NaCl flow = ↑ GFR
    • Macula densa cells can:
      • Secrete adenosine
      • Independently stimulate juxtaglomerular cells to secrete renin (activate the RAAS)
  • Adenosine: ↓ GFR
    • Constricts afferent arterioles 
    • Dilates efferent arterioles 
  • Renin: ↑ GFR (see RAAS above)
  • Examples:
    • ↑ GFR → ↑ tubular NaCl flow → macula densa cells sense ↑ flow → release adenosine (and inhibit renin) → GFR ↓ (normalizes)
    • ↓ GFR → ↓ tubular NaCl flow → macula densa cells sense ↓ flow → stimulate the release of renin (and inhibit adenosine) → GFR ↑ (normalizes)
Metabolic responses of the kidney to high and low tubule flow

Metabolic responses of the kidney to high and low tubule flow
AA: afferent arteriole
EA: efferent arteriole
JG: juxtaglomerular

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Fine-tuning mechanisms

  • Paracrine mechanisms:
    • Arteriole vasoconstrictors (↓ RBF):
      • Endothelins
      • Leukotrienes
    • Arteriole vasodilators (↑ RBF):
      • NO
      • Prostaglandins
  • Endocrine mechanisms:
    • Angiotensin II: ↑ glomerular hydrostatic pressure due to preferential constriction of the efferent arteriole → ↑ GFR but ↓ RBF
    • Atrial natriuretic peptide (ANP): vasodilation of the afferent arteriole → ↑ GFR and ↑ RBF
  • Neural mechanisms:
    • Sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System–mediated vasoconstriction of arterioles → ↓ RBF
    • Epinephrine, norepinephrine

Clearance

Clearance describes the amount of plasma volume that is completely cleared of a particular substance per unit of time. Clearance equals GFR with substances that are freely filtered (not blocked by the glomerular barrier), not reabsorbed, and not secreted.

Renal clearance formula

Cx = Ux ⋅ V/Px 

  • Cx is the clearance of substance x (e.g., creatinine).
  • Ux is the urine concentration of substance x.
  • Px is the plasma concentration of substance x.
  • V is the urine flow rate.

Substances used to measure clearance

  • Inulin: 
    • A nonendogenous polysaccharide (must be given IV)
    • An ideal indicator for GFR because it is:
      • Freely filtered 
      • Not reabsorbed
      • Not secreted
    • Used for research purposes, but not commonly used in clinical practice
  • Creatinine:
    • A by-product of muscle metabolism
    • Good indicator for GFR:
      • Freely filtered
      • Not reabsorbed
      • Small amount secreted: slight tendency to overestimate GFR (because some is cleared by secretion rather than filtration)
    • Clinical standard for GFR estimation and overall kidney function:
      • Endogenous product of muscle metabolism
      • Easily measured on routine blood tests (e.g., basic metabolic panel)
      • Can easily adjust for slight inaccuracy from secretion effect  
  • Para-amino hippurate (PAH): 
    • Ideal indicator for RPF (freely filtered, not reabsorbed, fully secreted)
    • Not endogenous (must be given IV)
    • Not commonly used in practice
Properties of inulin as a measure of clearance

Properties of inulin as a measure of clearance

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Clinical Assessment of GFR

24-hour urine collection for creatinine clearance

  • Clinical gold standard for GFR assessment 
  • Can be impractical: 
    • Patient must be motivated to collect all urine for 24 hours.
    • Takes several days to get results
    • Common to have incomplete urine collections, which are difficult to interpret
  • Sometimes done if very accurate GFR measurement is desired (e.g., prior to starting dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Overview and Types of Dialysis)

Serum creatinine

Serum creatinine is typically what is used for GFR determination, owing to its ease of collection and rapid turnaround time.

  • An inverse logarithmic relationship exists between serum creatinine and GFR.
    • Increase in Cr from 1 to 2 = approximately 50% decrease in GFR, but
    • Increase in Cr from 4 to 5 = relatively small decrease in GFR 
    • Clinical implications:
      • Small changes in serum creatinine must be attended to vigilantly.
      • Dialysis/transplantation are often considered once serum creatinine is consistently > 4 mg/dL.
  • Serum creatinine can be falsely elevated: will not have corresponding ↑ in serum BUN
    • ↑ Tubular secretion of creatinine: trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim, cimetidine
    • Lab assay interference: acetoacetate (in diabetic ketoacidosis Diabetic ketoacidosis Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises ( DKA DKA Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises)), cefoxitin, flucytosine Flucytosine Flucytosine is a pyrimidine analog that disrupts fungal DNA and RNA synthesis. Flucytosine is always used in combination with other antifungal agents and is primarily used to treat cryptococcal meningitis. Flucytosine, Griseofulvin, and Terbinafine
    • ↑ Production of creatinine: excessive intake of creatine (dietary supplement), injury to skeletal muscle
  • Serum creatinine can have true changes in several common circumstances other than AKI AKI 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 or CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease:
    • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care:
      • Decreases slightly during 1st and 2nd trimesters
      • Returns to prepregnancy value in 3rd trimester
    • Aging: 
      • Rises very slowly with age
      • GFR can decrease by 0.5–1 mL/min/year in healthy adults.
    • Diabetes:
      • Serum creatinine decreases early in the disease course owing to hyperfiltration.
      • Over time, hyperfiltration causes damage and results in elevated serum creatinine.
    • Very low muscle mass: cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis, malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries, amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation
      • Often have serum creatinine < 0.5 at baseline
      • GFR equations will overestimate true kidney function.
      • Small changes (e.g., serum creatinine 0.5 → 1) represent severe AKI AKI 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 in these patients (commonly missed by clinicians).
Relationship between creatinine and gfr

Relationship between creatinine and GFR
eGFR: estimated GFR

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Estimated glomerular filtration rate from serum creatinine

  • Most common clinical indicator of GFR
  • Several formulas have been developed and validated: 
    • Cockcroft–Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease Epidemiology Collaboration ( CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease-EPI)
    • Input variables: serum creatinine, age, sex, race (correlates with muscle mass)
    • Formulas are accurate only in steady-state conditions: 
      • Accurate in CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
      • Not accurate in AKI AKI 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
    • In practice, simple online calculators are used for this formula.
  • eGFR is used to stage chronic kidney disease:
    • Stage 1: GFR ≥ 90 mL/min/1.73 m2
    • Stage 2: GFR 60–89 mL/min/1.73 m2
    • Stage 3: GFR 30–59 mL/min/1.73 m2
    • Stage 4: GFR 15–29 mL/min/1.73 m2
    • Stage 5: GFR < 15 mL/min/1.73 m2
  • eGFR is also commonly used to adjust drug dosages for kidney function.

Clinical Relevance

Glomerular filtration is most commonly used to assess overall kidney function and to stratify CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease into stages. Additionally, there are specific disease processes of the glomerulus that impair filtration. Diseases are typically categorized as nephrotic (primarily proteinuria) or nephritic (primarily hematuria).

  • ANCA vasculitis: This vasculitis is a necrotizing vasculitis affecting small vessels, including the capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries of the glomerulus.
  • Alport syndrome Alport Syndrome Alport syndrome, also called hereditary nephritis, is a genetic disorder caused by a mutation in the genes encoding for the alpha chains of type IV collagen, resulting in the production of abnormal type IV collagen strands. Patients present with glomerulonephritis, hypertension, edema, hematuria, and proteinuria, as well as with ocular and auditory findings. Alport Syndrome: a genetic condition resulting in abnormal type IV collagen, which affects the GBM, in addition to the cochlea and eye, leading to progressive renal dysfunction, sensorineural hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss and ocular abnormalities.
  • Anti-GBM disease (Goodpasture’s disease): This rare small-vessel vasculitis with polyclonal circulating antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins directed against antigens within the GBM results in a rapidly progressive glomerulonephritis Rapidly Progressive Glomerulonephritis Rapidly progressive glomerulonephritis (RPGN) is a syndrome of severe glomerular disease with progressive loss of kidney function within weeks to months. Histologically, crescents (the proliferation of epithelial cells and the infiltration of monocytes/macrophages in the Bowman space) are found in the glomeruli and arise from immunologic injury. Rapidly Progressive Glomerulonephritis and/or alveolar hemorrhage.
  • Minimal change disease Minimal change disease Minimal change disease (MCD), also known as lipoid nephrosis, is the most common cause of nephrotic syndrome in children. The designation "minimal change" comes from the very little changes noticed in kidney biopsies under light microscopy. Hallmark clinical findings include edema, proteinuria, hypoalbuminemia, and hyperlipidemia. Minimal Change Disease: a major cause of nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome caused by fusion (retraction, widening, and shortening) of the foot processes in podocytes: The underlying cause of minimal change disease is unclear, but evidence suggests that T-cell dysfunction may play a causative role. Treatment generally involves 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.
  • Membranous nephropathy: a common cause of nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome resulting from thickening of the GBM due to immune deposits of IgG antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins directed against antigens on the podocyte foot processes.

References

  1. Inker LA, Astor BC, Fox CH, et al. (2014). KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease. American Journal of Kidney Diseases 63:713–735. https://doi.org/10.1053/j.ajkd.2014.01.416
  2. Inker LA, Perrone RD. (2020). Assessment of kidney function. UpToDate. Retrieved March 7, 2021, from https://www.uptodate.com/contents/assessment-of-kidney-function
  3. Inker LA, Perrone RD. (2020).  Drugs that elevate the serum creatinine concentration. UpToDate. Retrieved March 7, 2021, from https://www.uptodate.com/contents/drugs-that-elevate-the-serum-creatinine-concentration
  4. Kidney Disease: Improving Global Outcomes (KDIGO). (2012). Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease ( CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease). https://kdigo.org/guidelines/ckd-evaluation-and-management/
  5. Renal functions, basic processes, and anatomy. (2018). In Eaton DC, Pooler JP (Eds.), Vander’s Renal Physiology, 9th ed. McGraw-Hill. 
  6. Renal blood flow and glomerular filtration. (2018). In Eaton DC, Pooler JP (Eds.), Vander’s Renal Physiology, 9th ed. McGraw-Hill.
  7. Schwandt A, Denkinger M, Fasching P, et al. (2017). Comparison of MDRD, CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease-EPI, and Cockcroft-Gault equation in relation to measured glomerular filtration rate among a large cohort with diabetes. Journal of Diabetes and Its Complications 31:1376–1383. https://doi.org/10.1016/j.jdiacomp.2017.06.016
  8. Thadhani RI, Maynard SE. (2020). Maternal adaptations to pregnancy: renal and 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 physiology. UpToDate. Retrieved March 7, 2021, from https://www.uptodate.com/contents/maternal-adaptations-to-pregnancy-renal-and-urinary-tract-physiology

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