Polycystic Kidney Disease (ADPKD)

The answer first

ADPKD is the commonest monogenic kidney disease — an autosomal dominant disorder that replaces both kidneys with cysts over decades, and the one inherited nephropathy where you now have a disease-modifying drug to offer. Five rules carry the DWE and the long-case defence ^{[7] [20]}:

1. The gene sets the tempo. PKD1 families (about 85%) reach end-stage kidney disease around two decades earlier than PKD2 families (about 15%) — median ESKD in the late 50s versus the late 70s. Genotype is destiny on average, but within a family the course still varies, so never quote a fixed sentence to a patient ^{[6] [7]}.
2. No family history does not exclude it. Up to about one in five genotyped patients reports no affected parent — de novo variants, parental mosaicism, hypomorphic alleles and quietly mild PKD2 ancestors all break the "dominant, so someone must have it" reflex ^[11].
3. Measure progression before you treat progression. Height-adjusted total kidney volume plotted against age (the Mayo Imaging Classification) separates typical classes 1A to 1E; classes 1C to 1E are the rapid progressors who benefit from tolvaptan. eGFR alone lies for years because hyperfiltration masks cyst growth — kidneys grow before function falls ^{[4] [8]}.
4. Tolvaptan is for rapid progressors, not everyone. TEMPO 3:4 and REPRISE established slower kidney growth and slower eGFR decline, at the price of aquaresis and scheduled liver-function monitoring for idiosyncratic hepatotoxicity. Selection, consent and monitoring are the exam — not the drug name ^{[1] [2] [19]}.
5. Think outside the kidney. Polycystic liver disease, intracranial aneurysms, valvular disease, hernias and diverticulosis travel with the genotype. Screen for aneurysms selectively — family history of aneurysm or subarachnoid haemorrhage, prior rupture, high-risk occupation, pre-transplant — not universally ^{[12] [19]}.

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References21ShowHide

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