Renal dysplasia (ORPHA:93108)
A rare renal malformation in which the kidney(s) are present but their development is abnormal, leading to malformation of histologic architecture of the kidney and presence of embryological tissue such as mesenchymal collarettes or other forms of undifferentiated and metaplastic tissues. Renal dysplasia can be unilateral or bilateral, segmental, and of variable severity.
Epidemiology
Prevalence and incidence are not known due to the highly variable presentation and asymptomatic unilateral cases. In Europe, the prevalence at birth is estimated 1 / 2,300. Renal aplasia/hypoplasia/dysplasia are the most frequent underlying pathology in children requiring renal replacement therapy (13.5%).
Clinical description
Renal dysplasia is usually asymptomatic, but an abnormal kidney sonographic appearance may be detected during routine antenatal ultrasonography (US), US for urinary tract infections (in children) or renal disease (in children and adults). The severity of dysplasia is variable with renal aplasia at the extreme end. In cases of unilateral renal aplasia, consequences are similar to having a solitary functioning kidney, potentially resulting in hypertension and proteinuria, and possible kidney failure in adulthood. In cases of bilateral renal dysplasia, chronic kidney disease and kidney failure can occur during childhood. Bilateral renal dysplasia may limit kidney function to such an extent that oligohydramnios occurs during pregnancy, which is associated with the Potter sequence. In such cases, neonates may die shortly after birth due to respiratory failure; those with residual renal function may develop complications of chronic kidney disease: failure to thrive, growth retardation, anemia, hypertension, proteinuria and kidney failure.
Etiology
The etiology of renal dysplasia is multi-factorial. Generally, it may occur as an isolated condition or as a component of numerous rare syndromes, either secondary due to antenatal urine obstruction or due to primary maldevelopment of nephrogenic tissues. Isolated renal dysplasia has been reported in families with mutations in HNF1B (17q12). Incomplete penetrance and variable expressivity are very common in CAKUT (congenital anomalies of kidney and urinary tract); thus, genes involved in multi-organ syndromes ( such as EYA1, GATA3, GREBI1L, PAX2, PBX1, SALL1, FRAS1, FREM2, and GRIP1) may possibly lead to an isolated renal phenotype (dysplasia/hypoplasia/agenesis). Other forms of renal dysplasia may be caused by embryotoxic drugs such as angiotensin converting enzyme inhibitors or prenatal programming triggers such as hypoxia or diabetes mellitus.
Diagnostic methods
Diagnosis is based on ultrasonography, showing an abnormal appearing kidney with absent or poor corticomedullary differentiation with or without cysts and increased echogenicity. Kidneys may be of normal size or small. Renography shows decreased renal uptake of DMSA-tracer. Histology shows disorganized primitive ducts surrounded by mesenchymal stroma. Genetic analysis may identify variants in one of the previously mentioned genes in a minority of cases.
Differential diagnosis
Differential diagnoses of an abnormally differentiated kidney on ultrasound include renal hypoplasia, polycystic kidney disease, vascular insults, and renal post-infectious damage. Renal dysplasia may occur as part of recognized syndromes such as Kallmann, Bardet-Biedl, Beckwith-Wiedemann, diGeorge, Fraser, and renal coloboma syndromes as well as HNF1B-related autosomal dominant tubulointerstitial kidney disease.
Antenatal diagnosis
Antenatal diagnosis is possible from midway through gestation. The condition is dynamic and can evolve during pregnancy and after birth; therefore, repeated assessments are necessary.
Genetic counseling
Families may benefit from genetic counseling in case of renal dysplasia as part of a multi-organ syndrome, in familial cases or in bilateral cases with chronic kidney disease. The recurrence risk in families may be elevated, but data remain scarce.
Management and treatment
Regular evaluation of the remaining kidney function is recommended. Due to an increased risk of hypertension and/or proteinuria, a long-term follow-up is recommended. In severe cases, kidney replacement therapy may be needed.
Prognosis
Infants with pulmonary hypoplasia show substantial mortality in the neonatal period. Survivors may develop chronic renal failure in childhood. In unilateral renal dysplasia, the risk of kidney failure in childhood is minimal but patients may develop hypertension, proteinuria and kidney failure as adults.

                            Last update: 
                            July 2020


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


                                * European Reference Network