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Background <p><i>APOL1</i> high-risk variants predispose to chronic kidney disease (CKD) in individuals of African genetic ancestry due to podocyte toxicity. As congenital anomalies of the kidney and urinary tract (CAKUT) have variable outcomes potentially driven by podocyte injury, we hypothesize that the outcome of children with CAKUT is influenced by <i>APOL1</i> risk genotypes.</p> Methods <p><i>APOL1</i> risk status was determined in children and adults with CAKUT from African genetic ancestry using DNA microarrays or exome sequencing. Phenotypic information and CKD outcomes at last follow-up were collected. We computed odds ratios (OR) and hazard ratios between <i>APOL1</i>-high risk (HR) vs. low risk (LR) carriers under different models using logistic regression and Cox proportional hazards.</p> Results <p>Clinical data were available for 195 patients (median age 15.35&#xa0;years, [IQR 11.01–19.87]), including 20 (10.3%) carrying <i>APOL1</i>-HR. Under a recessive model, <i>APOL1</i>-HR vs. LR showed no differences in proteinuria or hypertension (OR 0.24, 95% CI 0.04–1.30, <i>p</i> = 0.10 and OR 0.99, 95% CI 0.38–2.54, <i>p</i> = 0.98, respectively), nor in CKD stage ≥ G2 risk (OR 0.71, 95% CI 0.29–1.78, <i>p</i> = 0.47). Median time until kidney failure for <i>APOL1</i> risk groups was 11.59&#xa0;years [IQR 7.15–21.47] and 14.35&#xa0;years ([IQR 9.16–17.20]; <i>p</i> = 0.73) for HR and LR, respectively. Additional exploratory analyses showed comparable outcomes between HR and LR variant carriers.</p> Conclusions <p>This pilot study identified no association between <i>APOL1</i> risk genotypes and kidney outcomes in patients with CAKUT across genetic models. With <i>APOL1</i>-targeted therapies emerging, large-scale prospective studies are needed to identify individuals with CAKUT who may benefit from these treatment strategies.</p> Graphical Abstract <p></p>

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APOL1 kidney risk variants and outcomes in children with congenital anomalies of the kidney and urinary tract

  • 期刊论文

  • 发表日期：

    2026年1月14日

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  • Lisanne M. Vendrig,
  • Juntao Ke,
  • Michael W. T. Tanck,
  • Tze Y. Lim,
  • Elena Martinelli,
  • Monica Bodria,
  • Valentina Capone,
  • Claudia Izzi,
  • Claudio La Scola,
  • Umberto Maggiore,
  • Pierluigi Marzuillo,
  • Giuseppe Masnata,
  • Frank D. Mentch,
  • Giovanni Montini,
  • Isabella Pisani,
  • Huiqi Qu,
  • Matthew G. Sampson,
  • Ana Cristina Simões-e-Silva,
  • Alexandria Thomas,
  • Jaap W. Groothoff,
  • Hakon Hakonarson,
  • Gian Marco Ghiggeri,
  • Miguel Verbitsky,
  • Elena N. Levtchenko,
  • Simone Sanna-Cherchi,
  • Rik Westland

摘要

Background

APOL1 high-risk variants predispose to chronic kidney disease (CKD) in individuals of African genetic ancestry due to podocyte toxicity. As congenital anomalies of the kidney and urinary tract (CAKUT) have variable outcomes potentially driven by podocyte injury, we hypothesize that the outcome of children with CAKUT is influenced by APOL1 risk genotypes.

Methods

APOL1 risk status was determined in children and adults with CAKUT from African genetic ancestry using DNA microarrays or exome sequencing. Phenotypic information and CKD outcomes at last follow-up were collected. We computed odds ratios (OR) and hazard ratios between APOL1-high risk (HR) vs. low risk (LR) carriers under different models using logistic regression and Cox proportional hazards.

Results

Clinical data were available for 195 patients (median age 15.35 years, [IQR 11.01–19.87]), including 20 (10.3%) carrying APOL1-HR. Under a recessive model, APOL1-HR vs. LR showed no differences in proteinuria or hypertension (OR 0.24, 95% CI 0.04–1.30, p = 0.10 and OR 0.99, 95% CI 0.38–2.54, p = 0.98, respectively), nor in CKD stage ≥ G2 risk (OR 0.71, 95% CI 0.29–1.78, p = 0.47). Median time until kidney failure for APOL1 risk groups was 11.59 years [IQR 7.15–21.47] and 14.35 years ([IQR 9.16–17.20]; p = 0.73) for HR and LR, respectively. Additional exploratory analyses showed comparable outcomes between HR and LR variant carriers.

Conclusions

This pilot study identified no association between APOL1 risk genotypes and kidney outcomes in patients with CAKUT across genetic models. With APOL1-targeted therapies emerging, large-scale prospective studies are needed to identify individuals with CAKUT who may benefit from these treatment strategies.

Graphical Abstract