Kidney Week

Abstract: SA-PO573

Effect of Genotype on Kidney Outcomes among Patients with Inherited Cystic Kidney Disease

Session Information

• Cystic Kidney Diseases: Genetic Causes, Modifiers, and Extrarenal Manifestations
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Park, Hayne C., Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea (the Republic of)

Hayne C. Park, MD, PhD

• Im, Dha Woon, Eulji University Uijeongbu Eulji Medical Center, Uijeongbu, Gyeonggi-do, Korea (the Republic of)

Dha Woon Im, MD

• Kim, Yong Chul, Seoul National University Hospital, Seoul, Korea (the Republic of)

Yong Chul Kim, MD, PhD

• Kim, Yaerim, Keimyung University Dongsan Medical Center, Daegu, Korea (the Republic of)

Yaerim Kim, MD, PhD

• Oh, Yun Kyu, Seoul National University Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea (the Republic of)

Yun Kyu Oh, MD, PhD

Background

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.

Methods

Primary genetic analysis was conducted using a targeted gene panel including 89 ciliopathy-associated genes. A total of 705 patients were included in the cross-sectional analysis. A total of 375 patients with longitudinal data without history of Tolvaptan treatment were included in the renal outcome analysis. Genotypes were classified into PKD1, PKD2, minor genotypes, or double variants (DV).

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 better renal function but smaller kidneys than PKD1 group. The DV group demonstrated similar profiles with PKD1 group. PKD1 genotype showed faster eGFR decline (-2.69± 9.2 mL/min/1.73m²/yr) compared to PKD2 (-0.15 ± 8.1 mL/min/1.73m²/yr) and minor genotypes (0.68 ± 9.5 mL/min/1.73m²/yr, p=0.03). The DV group demonstrated faster eGFR decline rate than PKD1 genotype (-3.53 ± 7.4 mL/min/1.73m²/yr). PKD1 group (59.2 ± 93.0 mL per year) and PKD2 group (47.5 ± 79.5 mL per year) demonstrated TKV growth during study period while minor genotypes showed shrinkage of kidneys (-8.6 ± 55.8 mL per year, p=0.052).

Conclusion

PKD1 genotype demonstrated poorer renal outcome compared to other genotypes. Minor genotypes showed favorable renal outcome with shrinkage of kidneys.

Renal outcome according to genotypes

Minor genotypes: COL4A5, HNF1β, TSC1, COL4A3, GANAB, UMOD, DYNC2H1, TSC2, AHI1, AVP, COL4A1, CPLANE1, HSPA6, NEK8, PAX2, PRKCSH, SEC31B, TRPV1, WFS1

Funding

• Government Support – Non-U.S.