Abstract: PUB196
APOL1 Kidney Risk Variants and Outcomes in Children with Congenital Anomalies of the Kidney and Urinary Tract
Session Information
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Complex Kidney Traits
Authors
- Vendrig, Lisanne M., Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- Lim, Tze Yin, Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, United States
- Tanck, Michael Wt, Department of Epidemiology and Data Science, Amsterdam UMC, Amsterdam, Netherlands
- Ke, Juntao, Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, United States
- Martinelli, Elena, Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, United States
- Groothoff, Jaap, Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- Levtchenko, Elena, Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- Sanna-Cherchi, Simone, Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, United States
- Westland, Rik, Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Background
APOL1 high-risk variants “G1” and “G2” predispose to chronic kidney disease (CKD) in individuals of genetic African ancestry due to toxic effects on podocytes. Congenital anomalies of the kidney and urinary tract (CAKUT) encompass a spectrum of developmental defects with variable outcomes driven by podocyte injury due to glomerular hyperfiltration. We hypothesize that the outcome of children with CAKUT is influenced by APOL1 risk genotypes.
Methods
APOL1 genotype status was determined in a cohort of CAKUT patients from African and Latinx genetic ancestry using DNA microarray genotyping or exome sequencing. Data on CAKUT phenotype was collected, as well as prevalence of CKD stage ≥2 and kidney failure at last follow-up. For each outcome, we computed odds ratios between different APOL1 genotype carriers under the recessive model (HR vs. LR) and exploratory dominant and additive models using logistic regression and Cox proportional hazards.
Results
Clinical data were available for 318 individuals: 98 (31%) carried at least one risk allele, 20 (6%) were HR. 66% were male and 61% were of African ancestry. Median age at follow-up was 14.9 y (IQR 9.8, 19.6). CAKUT phenotypes included kidney anomalies (37%), obstructive uropathy (25%), lower urinary tract obstruction (17%), vesicoureteral reflux (15%), duplex collecting system (3%) and ectopic kidney (3%). No differences were observed between HR and LR individuals for CKD stage ≥2 (OR 0.88, 95% CI 0.38-2.04, p = 0.77), kidney failure (OR 1.16, 95% CI 0.49-2.78, p = 0.73) or time until development of kidney failure (RR 0.93, 95% CI 0.43-1.99, p = 0.85). Similarly, dominant and additive models did not uncover significant differences between categories.
Conclusion
This pilot study showed no significant associations between APOL1 risk variant carriers and kidney disease outcomes in CAKUT patients, under different genetic models, likely due to limited sample size and the genetic and clinical heterogeneity of CAKUT. With APOL1 disease modifying therapies emerging, larger and well characterized studies on CAKUT are needed to identify individuals who might benefit from multimodal treatment strategies.
Funding
- Private Foundation Support