Advances in genetic testing and clinical awareness have made inherited kidney diseases — autosomal dominant polycystic kidney disease (ADPKD), Alport syndrome, Fabry disease, and the tubulopathies — increasingly treatable, with disease-specific therapy now available for several.
ADPKD
Tolvaptan remains the only approved disease-modifying therapy, slowing eGFR decline in rapidly progressive disease (as shown in REPRISE), at the cost of aquaresis and a need for liver monitoring. The 2025 KDIGO ADPKD guideline recommends it for patients with rapidly progressive disease and preserved eGFR, alongside high water intake and blood-pressure control (ideally with RAAS blockade). Comprehensive genetic testing helps distinguish ADPKD from other, rarer cystic diseases.
Alport syndrome
Early genetic testing for COL4A3/4/5 variants is now recommended in persistent hematuria, proteinuria, or unexplained CKD. RAAS inhibition, started at the onset of proteinuria (or earlier), slows progression and delays kidney failure, and SGLT2 inhibitors add further protection in proteinuric adults. Sparsentan is under investigation for Alport-related nephropathy.
Fabry disease
Beyond the established enzyme replacement therapies (agalsidase alfa and beta) and the oral chaperone migalastat (for amenable mutations), a newer option has arrived: pegunigalsidase alfa (Elfabrio), a PEGylated, plant-cell-derived enzyme replacement with a longer half-life and potentially reduced immunogenicity, approved in 2023 on the basis of the BALANCE, BRIDGE, and BRIGHT trials and offering both every-2-week and every-4-week dosing. Gene-therapy approaches are in early trials.
Gitelman syndrome
Management remains magnesium and potassium repletion with liberalized sodium and fluid intake; SGLT2 inhibitors are being used in patients with comorbid diabetes and may aid metabolic control.
| Disease | Key therapy | Status |
|---|---|---|
| ADPKD | Tolvaptan | Only disease-modifying therapy (2025 KDIGO) |
| Alport | RAAS inhibition, SGLT2 inhibitors | Standard; sparsentan investigational |
| Fabry | ERT, migalastat, pegunigalsidase alfa | Pegunigalsidase alfa approved 2023 |
| Gitelman | Electrolyte repletion | Supportive; SGLT2i if diabetic |
Further reading: REPRISE tolvaptan (Torres et al., NEJM 2017) and 2025 KDIGO ADPKD guideline; 2024 ERKNet/ERA/ESPN COL4A3/4/5 guideline; pegunigalsidase alfa in Fabry disease (BALANCE/BRIDGE/BRIGHT).