Congenital Renal Abnormalities

Disorders of the Renal Parenchyma

Introduction

Renal embryologic disorders affecting the size, the shape, or the structure of kidney parenchyma (renal dysgenesis):

• Renal agenesis: absence of renal tissue due to a disruption during embryologic renal development
• Renal hypoplasia: small 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 with a decreased number of functioning nephrons
• Renal dysplasia: focal or diffuse abnormalities of the nephron architecture; can be:
  • Non-cystic (simple renal dysplasia)
  • Cystic dysplasia: characterized by the formation of cysts
    • Multicystic dysplastic 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 (MCDK): cystic dysplasia involving the entire kidney
    • Autosomal recessive polycystic kidney disease Autosomal Recessive Polycystic Kidney Disease Polycystic kidney disease (PKD) is an inherited genetic disorder leading to the development of numerous fluid-filled cysts in the kidneys. Autosomal recessive polycystic kidney disease is primarily characterized by cystic dilatations of the renal collecting ducts and intrahepatic bile duct dilatation with hepatic fibrosis. Autosomal Recessive Polycystic Kidney Disease ( ARPKD ARPKD Polycystic kidney disease (PKD) is an inherited genetic disorder leading to the development of numerous fluid-filled cysts in the kidneys. Autosomal recessive polycystic kidney disease is primarily characterized by cystic dilatations of the renal collecting ducts and intrahepatic bile duct dilatation with hepatic fibrosis. Autosomal Recessive Polycystic Kidney Disease)

Renal agenesis

• Pathophysiology:
  • Interruption of the embryologic development of the ureteric bud, or metanephric blastema 
  • True renal agenesis includes an absent ipsilateral ureter and bladder hemitrigone.
  • Bilateral renal agenesis is incompatible with life.
• Epidemiology:
  • Incidence of unilateral renal agenesis: ~1 in 500–1,000 births
  • ↑ in infants with a single umbilical artery.
  • Boys ＞ girls
  • Common associations include:
    • Boys: absent ipsilateral vas deferens
    • Girls: Müllerian duct abnormalities 
• Etiology:
  • Genetic predisposition (e.g., mutations in genes responsible for renal development, RET and GDNF)
  • Syndrome association:
    • Associated with vertebral anomalies, anal atresia, and cardiac anomalies (VACTERL)
    • Mayer-Rokitanski-Kuster-Hauser: vaginal aplasia, uterine abnormalities
    • DiGeorge’s syndrome: palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Oral Cavity: Palate defects, cardiac abnormalities, absent thymus
  • Associated maternal risk factors:
    • Maternal diabetes
    • Maternal 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
    • Young maternal age
    • Maternal smoking
    • Maternal ethanol consumption during 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
    • Teratogen exposure (e.g., retinoic acid, cocaine)
• Clinical presentation: 
  • Prenatal:
    • Routine-monitoring ultrasound findings include oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios and an absent bladder and kidney.
    • Genetic testing in cases with a high prenatal index of suspicion
    • Left kidney is more often absent.
  • Postnatal:
    • Often discovered during evaluation for other anomalies 
    • Incidental discovery on ultrasound
    • May have recurrent urinary tract infections Urinary tract infections 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) or 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
    • Pulmonary hypoplasia Pulmonary hypoplasia Pulmonary hypoplasia is the lack of normal fetal development of the pulmonary parenchyma. The condition is characterized by a decreased number of alveoli and bronchial generations. Oligohydramnios is a notable cause, but conditions that restrict lung development or lead to fetal lung compression can also result in pulmonary hypoplasia. Pulmonary Hypoplasia due to a lack of amniotic fluid production may be a sign.
  • Potter’s syndrome: 
    • Bilateral renal agenesis, pulmonary hypoplasia resulting from oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios 
    • Facial abnormalities: widely separated eyes, prominent epicanthal folds, broad and compressed nose Nose The nose is the human body's primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Anatomy of the Nose, and low-set ears 
    • Other abnormalities: club foot, leg Leg The lower leg, or just "leg" in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg bowing, diaphragmatic hernia, eye anomalies (e.g., cataract, lens prolapse), cardiovascular abnormalities (e.g., ventricular septal defect, patent ductus arteriosus Patent ductus arteriosus The ductus arteriosus (DA) allows blood to bypass pulmonary circulation. After birth, the DA remains open for up to 72 hours and then constricts and involutes, becoming the ligamentum arteriosum. Failure of this process to occur results in patent ductus arteriosus (PDA), a condition that causes up to 10% of congenital heart defects. Patent Ductus Arteriosus (PDA), tetralogy of Fallot Tetralogy of Fallot Tetralogy of Fallot is the most common cyanotic congenital heart disease. The disease is the confluence of 4 pathologic cardiac features: overriding aorta, ventricular septal defect, right ventricular outflow obstruction, and right ventricular hypertrophy. Tetralogy of Fallot)
    • Potter’s syndrome may also be associated with cystic renal dysplasia, obstructive uropathy, ARPKD ARPKD Polycystic kidney disease (PKD) is an inherited genetic disorder leading to the development of numerous fluid-filled cysts in the kidneys. Autosomal recessive polycystic kidney disease is primarily characterized by cystic dilatations of the renal collecting ducts and intrahepatic bile duct dilatation with hepatic fibrosis. Autosomal Recessive Polycystic Kidney Disease, renal hypoplasia, and medullary dysplasia.  
• Management: 
  • Children with a solitary kidney have a high risk for 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):
    • Monitor the contralateral kidney for hypertrophy.
    • Long-term follow-up for 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 proteinuria
    • Kidney function testing
  • Avoiding contact sports is controversial.

Renal hypoplasia

• Pathophysiology:
  • Small 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 (＜50% than expected for age) 
  • Fewer-than-normal nephrons and calyces
  • Large glomeruli and tubules (hypertrophy to compensate)
  • Over time, patients develop end-stage renal disease (ESRD).
• Epidemiology:
  • Incidence of 1 in 400 live births
• Etiology:
  • Vascular abnormalities: 
    • Renal hypoperfusion in utero leads to hypoplasia.
  • Genetic disorders: 
    • Over 200 associated syndromes
    • Mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in key regulatory genes in renal development
• Clinical presentation:
  • Unilateral: 
    • Diagnosed incidentally during evaluation for 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 or urinary complaints
    • Neonates may present with failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive.
  • Bilateral:
    • History of polyuria, polydipsia, and/or urinary abnormalities 
    • Development of ESRD in the 1st decade of life
• Diagnosis: 
  • Prenatal: 
    • Found through routine screening ultrasound by 3 months’ gestation
  • Postnatal: 
    • Renal ultrasound of suspected cases
    • Can be further confirmed by histology but rarely performed
• Management:
  • Unilateral:
    • Periodic follow-up by ultrasound and urinalysis to monitor compensatory hypertrophy of the unaffected kidney
  • Bilateral:
    • May require human growth hormone (rHGH) to allow appropriate growth
    • Angiotensin-converting enzyme (ACE) inhibitors to slow the progression to ESRD
    • Renal transplant for patients with advanced disease

Renal dysplasia

• Epidemiology:
  • 2–4 per 1,000 births
  • Boys-to-girls ratio:
    • Bilateral 1.3:1
    • Unilateral 2:1
• Classification:
  • Simple renal dysplasia
  • Cystic renal dysplasia
• Etiology: 
  • Primarily due to the incorrect differentiation of renal tissue caused by:
    • Embryonic ureteral buds arise in incorrect locations, leading to the incorrect differentiation of renal tissue.
    • Obstructive uropathy in gestation
• Clinical presentation:
  • Unilateral: 
    • Diagnosed incidentally during evaluation for another dysmorphism
  • Bilateral:
    • Found to have renal failure at birth or will develop renal failure soon after
    • Associated urinary abnormalities lead to frequent 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, hematuria, and abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain.
• Diagnosis: 
  • Prenatal: 
    • Found through routine screening ultrasound by 3 months’ gestation
  • Postnatal: 
    • Renal ultrasound of suspected cases 
• Management:
  • At risk for 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:
    • Blood pressure should be closely monitored.
    • Yearly urinalysis
    • Urine function tests in patients with proteinuria/ 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
• MCDK:
  • Most common cause of an abdominal mass in newborns
  • Usually unilateral (polycystic kidney disease is often bilateral)
  • Bilateral is incompatible with life.
  • May be diagnosed during prenatal ultrasound
  • May be asymptomatic and diagnosed incidentally on imaging
  • Complete cyst regression occurs by 7 years in half of cases.
  • Annual follow-up with ultrasound and blood pressure monitoring is recommended.

ARPKD ARPKD Polycystic kidney disease (PKD) is an inherited genetic disorder leading to the development of numerous fluid-filled cysts in the kidneys. Autosomal recessive polycystic kidney disease is primarily characterized by cystic dilatations of the renal collecting ducts and intrahepatic bile duct dilatation with hepatic fibrosis. Autosomal Recessive Polycystic Kidney Disease

• Epidemiology: 
  • Incidence varies from 1:10,000 to 1:40,000 live births.
• Etiology:
  • An autosomal recessive disorder caused by the polycystic kidney and hepatic disease 1 (PKHD1) gene 
  • Affects: 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, lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs, and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver; rarely, the brain
• Clinical presentation:
  • Neonatal period or early infancy:
    • Typically presents with abdominal distension with bilateral flank masses 
    • Other associations: pulmonary hypoplasia and respiratory distress, spontaneous pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax, Potter’s syndrome, 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, impaired renal function, failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive, polyuria, polydipsia, ESRD
  • Infants and children:
    • Typically has a mixed renal-hepatic presentation
    • Often present with hepatosplenomegaly, signs of portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension (prominent periumbilical veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins, thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, and gastroesophageal varices), ascending cholangitis, choledochal cysts
    • Renal manifestations may be absent or similar to those in the neonatal period.
• Diagnosis:
  • Prenatal ultrasound: 
    • Oligohydramnios
    • Absence of urine in the bladder
  • Postnatal ultrasound:
    • Bilaterally enlarged, uniformly hyperechogenic 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 with poor corticomedullary differentiation and multiple cysts
    • Hepatosplenomegaly with a hyperechoic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver and dilatation of the peripheral intrahepatic and main bile ducts
  • Molecular genetic testing confirms the diagnosis.
• Management:
  • Aggressive ventilatory support
  • Supportive treatment with the multidisciplinary team:
    • Antihypertensive medications (ACE inhibitors)
    • Diuretics for 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
    • Osteopenia management
    • Palliative unilateral/bilateral nephrectomy
    • 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
    • Renal and/or hepatic transplantation
  • Pre-implantation genetic testing with in vitro fertilization Fertilization To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. Fertilization and First Week in families with a history of ARPKD ARPKD Polycystic kidney disease (PKD) is an inherited genetic disorder leading to the development of numerous fluid-filled cysts in the kidneys. Autosomal recessive polycystic kidney disease is primarily characterized by cystic dilatations of the renal collecting ducts and intrahepatic bile duct dilatation with hepatic fibrosis. Autosomal Recessive Polycystic Kidney Disease

Disorders of Renal Positioning

Renal ectopia and non-rotation

• Definition:
  • Renal ectopia: abnormal ascent of 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 during embryonic development
  • Renal non-rotation: abnormal rotation of 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
• Epidemiology:
  • Incidence of renal ectopia: 1 in 900 births
  • Incidence of renal non-rotation: 1 in 2,000 autopsies
• Clinical presentation:
  • Usually asymptomatic
  • May have a higher incidence of 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, urinary obstruction, or kidney stones
  • Ectopic kidney may be found in the 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, the thorax, or the contralateral side. 
  • Blood supply is variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables.
• Diagnosis:
  • Antenatal or postnatal renal ultrasound
  • Voiding cystourethrogram (VCUG) and serial serum creatinine may be necessary if there is evidence of kidney injury.

Kidney fusion

• Definition: fusion of the lower poles of the kidney (horseshoe kidney)
• Epidemiology:
  • Incidence of 1 in 400–500 births 
  • Associated with Turner’s syndrome
  • Wilms’ tumor, stone disease, 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, and MCDK are more common in horseshoe 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.
• Clinical presentation and management:
  • Hydronephrosis is a common finding (80% of cases).
  • Many patients are asymptomatic and require no treatment.