Log in to add personal notes on this page.
Bilateral renal cysts on imaging. The differential collapses quickly around age at presentation, cyst pattern (diffuse versus corticomedullary), kidney size, and which extrarenal features cluster with the cysts.
Three discriminators do most of the work: age (neonate, infant, child, adult), kidney size and parenchymal pattern (massively enlarged versus normal or small), and extrarenal phenotype (liver, retina, brain, pancreas, hearing, polydactyly).
Adult-onset, large bilateral kidneys
- Autosomal dominant polycystic kidney disease: PKD1 (~85%, earlier ESRD) and PKD2 (~15%, later ESRD). Hundreds to thousands of cysts of varying size. Liver cysts (very common), berry aneurysms (5-10%), mitral valve prolapse, colonic diverticula. ESRD by the 50s for PKD1, 70s for PKD2. Tolvaptan slows progression in selected patients.
Neonatal or infant, massive echogenic kidneys
- Autosomal recessive polycystic kidney disease: PKHD1. Antenatal oligohydramnios with Potter sequence in severe cases. Congenital hepatic fibrosis with portal hypertension dominates the older phenotype. Survivors of infancy often present with portal hypertension and esophageal varices before progressing to ESRD.
Cysts plus diabetes plus uterine anomalies
- HNF1B-related disease (RCAD, MODY5): HNF1B. Bilateral renal cysts (often present antenatally), MODY5 diabetes, Mullerian anomalies, hyperuricemia and early-onset gout, pancreatic atrophy, magnesium wasting. The renal phenotype can mimic ARPKD or hypoplasia depending on age.
Tuberous sclerosis cysts and angiomyolipomas
- TSC1, TSC2. Renal angiomyolipomas are pathognomonic; some patients have polycystic-appearing kidneys. TSC2-PKD1 contiguous deletion syndrome causes a severe early polycystic phenotype on top of the TSC features.
Renal cysts plus retinal angioma plus cerebellar hemangioblastoma
- Von Hippel-Lindau syndrome: VHL. Cysts plus clear cell RCC, pheochromocytoma, pancreatic cysts and neuroendocrine tumors, endolymphatic sac tumors.
Nephronophthisis and ciliopathies
- Nephronophthisis (NPHP genes): corticomedullary cysts with tubulointerstitial fibrosis. Progressive CKD with normal-sized or small kidneys (not enlarged). Syndromic forms: Senior-Loken (plus retinitis pigmentosa), Joubert syndrome (cerebellar molar tooth sign), Cogan oculomotor apraxia.
- Bardet-Biedl syndrome (ciliopathy): cysts plus obesity plus polydactyly plus retinitis pigmentosa plus hypogonadism plus cognitive impairment.
- Meckel-Gruber syndrome: lethal ciliopathy. Cystic kidneys plus occipital encephalocele plus polydactyly.
- "Big bilateral cystic kidneys in an adult with liver cysts and a relative on dialysis" is ADPKD until proven otherwise.
- "Massively enlarged echogenic kidneys on the prenatal ultrasound" is ARPKD; parental ultrasound is normal (recessive parents).
- "Cysts plus diabetes plus a bicornuate uterus" is the HNF1B trifecta.
- Corticomedullary cysts with shrinking kidneys (not enlarging) point to nephronophthisis, not ADPKD.
- Renal ultrasound on the patient and on first-degree relatives in suspected ADPKD (age-adjusted criteria).
- PKD1/PKD2 sequencing in young or de novo cases.
- HNF1B deletion/sequencing for cysts plus diabetes plus uterine anomalies.
- VHL testing for cysts plus retinal angioma or cerebellar hemangioblastoma.
- Genetic kidney panel for ambiguous early-onset cases or syndromic features.
- Adult bilateral cystic kidneys plus liver cysts equals ADPKD.
- Neonatal massive bilateral kidneys equals ARPKD.
- Cysts plus diabetes plus a uterine anomaly equals HNF1B; remember the magnesium wasting and the gout.
- Shrinking (not growing) kidneys with corticomedullary cysts equals nephronophthisis, not ADPKD.