EpiRPCter - Epidemiology of Autosomal Dominant Polycystic Kidney Disease among patients incident on first renal replacement therapy between 1990-2020, in a major University Hospital in the Northwest of Portugal

Abstract

Background and hypothesis Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic kidney disease, being the cause of the kidney failure (KF) in 5-10% of incident patients in renal replacement therapy (RRT). ADPKD is genetically heterogenous, but pathogenic variants in the genes encoding polycystin-1 ('PKD1') and polycystin-2 ('PKD2') explain most cases (respectively ~78% and ~15%). Clinical experience at São João University Hospital Centre (CHUSJ) suggests that the relative prevalence of ADPKD-'PKD2' is significantly higher than reported, mainly due to a polycystin-2 truncating mutation - 'PKD2' p.(Gln61*). The purpose of this study was to describe the epidemiology of ADPKD among patients starting RRT at CHUSJ, and to compare ADPKD-'PKD1' to ADPKD-'PKD2'. Methods Medical reports for RRT initiation (MR-RRT) issued at the CHUSJ between 01/01/1990-31/12/2020 were systematically reviewed to identify patients diagnosed with ADPKD. Genotyping data were obtained from the Genetics Laboratory of the Faculty of Medicine, University of Porto. For patients who not been directly tested, the genotype was inferred from genealogical analysis. Data from non-ADPKD patients starting RRT between 2010-2020 were collected for selected comparisons with the general RRT population. Results Out of 6244 medical reports reviewed, 376 ADPKD patients were identified; of the latter, 125 (33.2%) had genotyping information available, which was imputed in 79 (63.2%). Among genotyped patients, prevalences of ADPKD-'PKD1' and ADPKD-'PKD2' were, respectively, 65.6% and 29.8%. Mean age at RRT initiation was 53.6 years for ADPKD-'PKD1' patients and 68.0 years for ADPKD-'PKD2'. Heterozygosity for the 'PKD2' p.Gln61* allele was identified in 30 patients. Between 2010-2020, prevalence of ADPKD was 7.19% at CHUSJ and 4.71% nationwide (p<.001). Conclusion Prevalence of ADPKD among patients incident on RRT at CHUSJ was significantly higher than nationwide. ADPKD-'PKD1' was associated with KF significantly earlier than ADPKD-'PKD2'. 'PKD2' p.(61Gln*) was the most prevalent pathogenic variant identified in our cohort.