Alport Syndrome Outcomes Linked to Genotype and Proteinuria in RaDaR Study

New data from the UK National Registry of Rare Kidney Diseases (RaDaR) provide the most detailed longitudinal analysis to date of kidney function decline in Alport syndrome (AS), reinforcing the critical role of genotype and proteinuria control in predicting long-term outcomes.

Presented at the 62nd European Renal Association (ERA 2025) Congress by Daniel Gale, MBChB, PhD, director of the RaDaR Registry, the study included 1175 individuals with genetically or biopsy-confirmed AS and used national linkage data with multi-level modeling to track eGFR slope and proteinuria progression across chronic kidney disease (CKD) stages, with results stratified by genotype.

“In RaDaR, we’ve now got about 1100 people with Alport Syndrome, of whom over 500 we've got genetic information on. And we wanted to ask some of the same questions that we'd previously asked in [focal segmental glomerulosclerosis], obviously a smaller number of patients,” said Gale, in an interview with HCPLive.

Among 535 patients with genetic data, those with classical AS genotypes, including male X-linked, autosomal recessive, or digenic, exhibited significantly faster eGFR decline compared to heterozygous genotypes. The difference was most pronounced in CKD stage 4, with classical genotypes losing kidney function at –9.1 mL/min/1.73 m² per year (95% CI, –10.9 to –7.3) versus –3.8 mL/min/1.73 m² per year (95% CI, –5.5 to –2.1) for heterozygotes.

Proteinuria increased with CKD progression across the cohort, but a significant upward trajectory was observed only in male X-linked and autosomal recessive cases. Critically, patients with higher proteinuria levels before reaching eGFR thresholds of 90, 60, or 45 mL/min/1.73 m² had substantially worse kidney survival. Hazard ratios for kidney failure in patients above the median proteinuria were 5.3, 3.6, and 6.5, respectively, at those eGFR cutoffs.

In an interview at ERA 2025, Gale emphasized the importance of these findings not only for understanding disease progression in AS but also for clinical trial design. To learn more about how RaDaR is shaping research and accelerating trial readiness in rare kidney diseases like AS, watch our full interview with Dr Gale from ERA 2025.

Relevant disclosures for Gale include Novartis, Alexion, Calliditas, Britannia, Vifor, Judo Bio, Adnovate, Sanofi, Anlylam, Boehringer Ingelheim, and Bayer.

Reference:

Wong K, Pitcher D, Rogers D, et al. Kidney outcomes and effects of proteinuria in Alport Syndrome: a longitudinal analysis of 1175 patients from the UK National Registry of Rare Kidney Diseases (RaDaR). Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.