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Clinical phenotype of APOL1 nephropathy in young relatives of patients with end-stage renal disease

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Abstract

Background

Two coding variants—G1 and G2—in the apolipoprotein L-1 (APOL1) gene are associated with increased incidence of end-stage renal disease (ESRD) in the adult African American population. These variants associate with hypertension-attributed renal disease, focal segmental glomerulosclerosis (FSGS), and HIV-associated nephropathy. We hypothesized that as a genetic disease, APOL1 nephropathy has a pediatric phenotype.

Methods

We investigated the incidence of APOL1 variants in young African Americans with hypertension or FSGS and a family history of ESRD by conducting a case–control study of 93 pediatric and young adult African Americans with hypertension or FSGS to determine the association with APOL1 risk variants, G1, and G2 using custom-made TaqMan-based allelic discrimination assays.

Results

Forty of the 61 cases (66 %) with a family history of kidney disease had two APOL1 risk variants, significantly higher than the prevalence in controls and the general African American population (p < 0.001); 24 of 29 patients with hypertension-attributed kidney disease had two APOL1 risk variants, while none of nine hypertensive patients without kidney disease had more than one risk allele.

Conclusions

Although it was a small study cohort, our findings strongly suggest for the first time that two APOL1 risk alleles in young hypertensive African Americans with a family history of ESRD are strongly associated with kidney disease.

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Acknowledgments

We acknowledge the assistance of Mary Hoffmann, clinical research coordinator, Kidney Translational Research Core (KTRC), Washington University School of Medicine, Masato Hoshi: Senior Scientist, Jain Lab, Washington University School of Medicine, and Jie Zheng Division of Biostatistics, Washington University School of Medicine.

Sources of support

This work was supported by a Genzyme (Sanofi) fellowship grant (EA), the National Institutes of Health (NIH) George M. O’Brien Center for Kidney Disease Research (P30-DK079333), and CTSA-ICTS Tissue Procurement and Molecular Phenotyping and Center for Biomedical Informatics Cores (NCRR UL1 RR024992) to Washington University, Children Discovery Institute grants MDII2009177 (S.J.).

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Authors and Affiliations

  1. Department of Pediatrics (Pediatric Nephrology), Washington University School of Medicine, 5th Fl MPRB, 660 South Euclid Avenue, Campus Box 8208, St. Louis, MO, 63110, USA

    Elizabeth I. Anyaegbu & Keith A. Hruska

  2. Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8126, St. Louis, MO, 63110, USA

    Andrey S. Shaw & Sanjay Jain

  3. Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA

    Keith A. Hruska & Sanjay Jain

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  1. Elizabeth I. Anyaegbu
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  2. Andrey S. Shaw
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Correspondence to Keith A. Hruska or Sanjay Jain.

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Anyaegbu, E.I., Shaw, A.S., Hruska, K.A. et al. Clinical phenotype of APOL1 nephropathy in young relatives of patients with end-stage renal disease. Pediatr Nephrol 30, 983–989 (2015). https://doi.org/10.1007/s00467-014-3031-0

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