Renal hypoplasia (ORPHA:93101)
A congenital renal malformation characterized by abnormally small kidney(s) (kidney volume below two standard deviations of that of age-matched normal individuals or a combined kidney volume of less than half of what is normal for the patient's age) with normal corticomedullary differentiation and reduced number of nephrons.
Epidemiology
Isolated renal hypoplasia is considered rare and, given the difficulty to distinguish it from renal dysplasia that may also result in small kidneys, its prevalence and incidence are unknown. Both renal dysplasia and renal hypoplasia account for a significant proportion of chronic kidney disease in children and of inborn causes of chronic kidney disease in adults.
Clinical description
Isolated, unilateral renal hypoplasia is usually asymptomatic. It may be detected in a prenatal ultrasound screening, after a urinary tract infection in children, or with hypertension, proteinuria (generally symptoms of chronic kidney disease) in children and adults. Disease severity depends on the degree of reduction in the number of nephrons, the involvement of the other kidney, and whether other congenital anomalies of the kidney and urinary tract (CAKUT) are present. The disease may lead to glomerular hyperfiltration associated with hypertension, proteinuria and, in the long term, with chronic kidney failure.
Etiology
The occurrence of renal hypoplasia may be caused by mutations in kidney developmental genes (HNF1B, PAX2, PBX1) and/or multiple environmental factors such as intrauterine growth restriction, maternal diseases (diabetes, hypertension), maternal drug intake (inhibitors of the renin-angiotensin system or non-steroidal anti-inflammatory drugs (NSAIDs)) and intoxication (smoking and alcohol). Variants in multiple additional genes or genomic alterations have been linked to kidney hypoplasia or dysplasia but their specific role for hypoplasia is not clearly understood (EYA1, GATA3, GREB1L, SALL1, large copy number variations). Premature birth (before the 36th week) is also a risk factor due to incomplete nephrogenesis. Generally, kidney hypoplasia is seen as a defect in nephron endowment.
Diagnostic methods
The clinical diagnosis is typically based on ultrasonography. On fetal or postnatal ultrasound, renal hypoplasia is defined as a kidney volume of below two standard deviations or a combined kidney volume of less than half of age-related normal kidney volume. Corticomedullary differentiation typically is normal. Postnatal renography with technetium-99m-labeled dimercaptosuccinic acid shows smooth kidney outline.
Differential diagnosis
Differential diagnoses include all forms of kidney dysplasia. Although the definite differentiation can only be made on histological grounds, in clinical practice ultrasonography is used to distinguish normal appearing small kidneys (hypoplasia) from abnormal appearing small kidneys with disturbed corticomedullary differentiation and/or increased echogenicity, and/or cysts. Oligomeganephronia represents a severe variant of hypoplasia in which nephron number is reduced by 80% and nephrons are markedly hypertrophied
Antenatal diagnosis
Antenatal ultrasonographic screening is becoming routine and allows detection of renal hypoplasia from midway through gestation.
Genetic counseling
Most cases are sporadic. Familial cases have been observed with an autosomal dominant mode of inheritance with incomplete penetrance and variable expressivity and thus the recurrence risk of is up to 50% in such cases.
Management and treatment
Management largely depends on the degree of chronic kidney disease and whether or not there are additional CAKUT. Therefore, assessment of renal function (blood pressure, estimate of the glomerular filtration rate and proteinuria) should be obtained to evaluate the function of the remaining nephrons. Due to an increased risk of hypertension and/or proteinuria, individuals with renal hypoplasia deserve long-term follow-up. In extreme cases, kidney replacement therapy may be needed.
Prognosis
The risk of end stage chronic kidney disease in childhood is low but kidney failure may occur in severe cases.

                            Last update: 
                            April 2020


                            - Expert reviewer(s): 
                            Dr Stefan KOHL | ERKNet*


                                * European Reference Network