Effect of genotype on renal outcome among the patients with inherited cystic kidney disease

초록

Background and Aims: Inherited cystic kidney disease is a constellation of heterogenous genetic diseases that commonly share renal cystic phenotype. We have analyzed renal outcome (annual change of estimated glomerular filtration rate (eGFR) and total kidney volume (TKV)) among Korean genetic cohort of inherited cystic kidney disease. Method: Primary genetic analysis was conducted using a targeted gene panel including 89 ciliopathy-associated genes. A total of 1319 patients were included in the cross-sectional analysis. A total of 502 patients with longitudinal data without history of Tolvaptan treatment were included in the renal outcome analysis. Genotypes were classified into PKD1, PKD2, or minor genotypes. Results: PKD1 group showed younger age at diagnosis of cystic kidney disease and hypertension, and higher proportion of rapid progressor. Interestingly, the patients with minor genotypes showed a significantly higher rate of diabetes (11.6%) and proteinuria (3.6 ± 25.4 g/g) compared to other genotypes. In addition, the minor genotype group showed smaller kidneys (858 ± 913 mL) with atypical cystic phenotype (Mayo class 2). In longitudinal analysis, PKD1 genotype showed faster eGFR decline (−2.44 ± 6.1 mL/min/1.73 m2/yr) compared to PKD2 (−1.09 ± 8.5 mL/min/1.73 m2/yr) and minor genotypes (−0.5 ± 5.4 mL/min/1.73 m2/yr, P = 0.037). PKD1 group showed faster growth of kidneys (40.2 ± 188.2 mL per year) while PKD2 (9.6 ± 315.2 mL per year) and minor genotype group (13.4 ± 55.7 mL per year) demonstrated minimal TKV growth during study period (P = 0.635). Conclusion: PKD1 genotype demonstrated poorer renal outcome compared to other genotypes. Minor genotypes showed favorable renal outcome with minimal growth of TKV.