#1232 Integrating genotype and phenotype data is required for renal survival prediction in autosomal dominant polycystic kidney disease

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the cause for 5-10% of end stage kidney disease (ESKD) worldwide. Accurate renal prognosis is essential for effective disease management. Investigation of the prognostic value of combining genetic and phenotypic characteristics in a cohort of ADPKD patients is attempted. Method In 66 ADPKD patients (mean age 33 ± 12 years, 32 males) the genetic diagnosis (using targeted Next Generation, tNGS, or Sanger Sequencing or Multiplex ligation-dependent probe amplification, MLPA) and the Mayo Clinic Imaging Category (MCIC) (through Renal Magnetic Resonance Imaging, MRI, for Total Kidney Volume measurement) were assessed. The prediction of ESKD was performed using the Mayo Clinic formula (Irazabal MV et al JASN, 2015). The calculation incorporated variables such as sex, age, e-GFR, and the MCIC. The PROPKD score was derived by considering both phenotypic factors (sex, hypertension and urologic events before the age of 35 years) and genetic data (PKD1-truncating, PKD1-nontruncating and PKD2). Results Adjusted for age, the e-GFR was on average, 26 and 27 ml/min higher in PKD2 patients compared to ADPKD-PKD1-truncating and ADPKD-PKD1-non-truncating patients, respectively (p = 0.001). The median prediction of ESKD for ADPKD-PKD1-truncating, ADPKD-PKD1-non-truncating and PKD2 patients was 22 (11-31) years, 22 (11-34) years and 31 (21-59) years, respectively (NS). In patients categorized as high risk according to PROPKD (score 7-9) the predicted time to ESKD was 16 (9-30) years, for those at intermediate risk (score 4-6), 25 (13-34) years and for those at low risk (score 0-3), 28 (16-55) years (NS). Finally, the PROPKD score showed an inverse correlation to the years of ESKD prediction, as determined by the Mayo Clinic formula; a higher PROPKD score was associated with a shorter prediction period for ESKD (Spearman r = −0.3, p = 0.04). Conclusion Prognosis of renal survival in ADPKD patients requires not only a specific genetic diagnosis but also consideration of the phenotypic data, as incorporated in the PROPKD score, enhancing the accuracy of renal survival prediction.