Paeds · nephrology-urology-fluids-and-electrolytes
Polycystic kidney disease and inherited nephropathies
Also known as ARPKD · ADPKD · Alport syndrome · Nephronophthisis · Inherited cystic kidney disease · Ciliopathy
Fellowship guide to polycystic kidney disease and inherited nephropathies in children: the neonatal-onset ARPKD driven by PKHD1 and fibrocystin with bilateral enlarged echogenic kidneys and congenital hepatic fibrosis, the later-presenting ADPKD from PKD1 or PKD2 encoding polycystin with height-adjusted total kidney volume guiding tolvaptan therapy, Alport syndrome with its type IV collagen defect causing progressive haematuric nephropathy with sensorineural hearing loss and the ACE-inhibitor-at-diagnosis strategy, and nephronophthisis as the autosomal recessive ciliopathy causing tubulointerstitial fibrosis with disproportionate anaemia and ESKD in childhood.
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Red flags
- Bilateral massively enlarged echogenic kidneys in a neonate with respiratory distress from pulmonary hypoplasia and oligohydramnios
- A child with persistent microscopic haematuria, sensorineural hearing loss and a family history of kidney failure suggesting Alport syndrome
- Progressive anaemia developing out of proportion to the degree of kidney impairment, pointing to nephronophthisis
- Severe hypertension in an infant with bilateral cystic kidney disease risking cardiac failure and neurological complications
- Gastrointestinal bleeding from portal hypertension in a child with ARPKD and congenital hepatic fibrosis
- Rapid cyst growth or accelerating function decline in ADPKD warranting tolvaptan consideration before irreversible damage
Life stages
Care settings
Clinical exam formats
Board mappings
- Distinguishes ARPKD from ADPKD by inheritance, gene and age of presentation
- Recognises Alport syndrome from the combination of haematuria, hearing loss and family history
- Identifies nephronophthisis as a cause of ESKD with disproportionate anaemia in children
- Explains the ciliary and basement membrane mechanisms linking gene defects to cystogenesis and glomerular injury
- Justifies tolvaptan therapy in rapidly progressive ADPKD using height-adjusted total kidney volume
- Coordinates multidisciplinary management of hepatic fibrosis, hypertension and renal replacement in ARPKD
- Genes and inheritance patterns: PKHD1 for ARPKD, PKD1 and PKD2 for ADPKD, COL4A3 to COL4A5 for Alport, NPHP for nephronophthisis
- Clinical features distinguishing cystic disease, Alport and nephronophthisis in children
- Role of genetic testing, surveillance and when to involve specialist nephrology
- Long-case assessment of a child with inherited nephropathy including genetics, complications and transplantation planning
- Counselling families on inheritance risk, prognosis and reproductive options
- Recognising and managing acute complications of cystic kidney disease
- Level 1: Recognises the major inherited cystic and basement membrane nephropathies and their presentations
- Level 2: Applies genetic testing and surveillance strategies, initiates ACE inhibitor therapy in Alport syndrome
- Level 3: Leads multidisciplinary care including tolvaptan consideration and transplant pathway planning
- PKHD1, PKD1, PKD2, COL4A3, COL4A4, COL4A5 and NPHP genes and their protein products
- Clinical features and imaging findings of ARPKD, ADPKD, Alport syndrome and nephronophthisis
- Principles of management including tolvaptan and ACE inhibitor therapy
- Assessment of a child with suspected inherited nephropathy including family history and syndromic features
- Interpretation of renal ultrasound, audiometry and genetic test results
- Structured explanation of the management ladder from surveillance to transplantation
- Classification and genetics of polycystic kidney disease and inherited nephropathies in children
- Clinical presentation and diagnostic approach to ARPKD, ADPKD, Alport syndrome and nephronophthisis
- Principles of management including blood pressure control, tolvaptan and transplantation
- Defines the major inherited nephropathies and identifies their genetic basis
- Initiates appropriate work-up including imaging, genetic testing and family screening
- Coordinates long-term surveillance and transition to adult nephrology care
- Canadian approach to genetic testing and counselling in inherited cystic kidney disease
- Management of complications and timing of transplantation in ARPKD and ADPKD
- Coordination of transition from paediatric to adult nephrology and hepatology services
Overview & Definition
A newborn is found on antenatal ultrasound to have bilateral massively enlarged echogenic kidneys. He is born with respiratory distress from pulmonary hypoplasia, and within days his blood pressure climbs and his creatinine rises. This is autosomal recessive polycystic kidney disease, one of a family of inherited conditions in which a single gene defect in a kidney structural protein slowly destroys renal architecture. The inherited nephropathies share three things: a genetic cause, a progressive course toward kidney failure, and the need for lifelong surveillance that begins in childhood and spans generations. [1]
These diseases are best understood by what is broken. In the polycystic kidney diseases, the defective protein sits on the primary cilium of the tubular epithelial cell, the antenna-like sensory organelle that lines every nephron, and its failure turns orderly tubules into disorganised cysts. In Alport syndrome, the defective protein is type IV collagen, the meshwork that forms the glomerular basement membrane, and its failure makes the filter fragile and leaky. In nephronophthisis, the defective protein is a ciliary or centrosomal protein that triggers tubular cell death and interstitial fibrosis. Each gene, each protein, each mechanism produces a recognisable clinical picture, and the exam reward lies in matching the gene to the phenotype. [3]
References12ShowHide
- [1]Guay-Woodford LM, Bissler JJ, Braun MC, Bockenhauer D, et al Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J Pediatr, 2014.PMID 25015577
- [2]Torres VE, Ahn C, Barten TRM, Brosnahan G, et al KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD): executive summary. Kidney Int, 2025.PMID 39848746
- [3]Bergmann C, Guay-Woodford LM, Harris PC, Horie S, et al Polycystic kidney disease. Nat Rev Dis Primers, 2018.PMID 30523303
- [4]Mekahli D, Guay-Woodford LM, Cadnapaphornchai MA, Greenbaum LA, et al Tolvaptan for Children and Adolescents with Autosomal Dominant Polycystic Kidney Disease: Randomized Controlled Trial. Clin J Am Soc Nephrol, 2023.PMID 36719158
- [5]Dachy A, Van Loo L, Mekahli D Autosomal Dominant Polycystic Kidney Disease in Children and Adolescents: Assessing and Managing Risk of Progression. Adv Kidney Dis Health, 2023.PMID 37088526
- [6]Kashtan CE, Gross O Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Pediatr Nephrol, 2021.PMID 33159213
- [7]Torra R, Lipska-Zietkiewicz B, Acke F, et al Diagnosis, management and treatment of the Alport syndrome - 2024 guideline on behalf of ERKNet, ERA and ESPN. Nephrol Dial Transplant, 2025.PMID 39673454
- [8]Wolf MTF, Bonsib SM, Larsen CP, Hildebrandt F Nephronophthisis: a pathological and genetic perspective. Pediatr Nephrol, 2024.PMID 37930417
- [9]Gimpel C, Avni EF, Breysem L, et al Imaging of Kidney Cysts and Cystic Kidney Diseases in Children: An International Working Group Consensus Statement. Radiology, 2019.PMID 30599104
- [10]Kapogiannis C, Dimakopoulos G, Kapogiannis A, et al Comparison of genetic profile and kidney outcomes between very early-onset and non-very-early-onset autosomal dominant polycystic kidney disease in children: a systematic review and meta-analysis. BMC Nephrol, 2026.PMID 42401882
- [11]Savige J, Lipska-Zietkiewicz BS, Watson E, et al Guidelines for Genetic Testing and Management of Alport Syndrome. Clin J Am Soc Nephrol, 2022.PMID 34930753
- [12]Brinkert F, Lehnhardt A, Montoya C, et al Combined liver-kidney transplantation for children with autosomal recessive polycystic kidney disease (ARPKD): indication and outcome. Transpl Int, 2013.PMID 23582048