Late Reoccurrence of Collapsing FSGS After Transplantation of a Living-Related Kidney Bearing APOL 1 Risk Variants Without Disease Evident in Donor Supports the Second Hit Hypothesis

Roberto S Kalil; Richard J Smith; Prerna Rastogi; Daniel A Katz; Christie P Thomas

doi:10.1097/TXD.0000000000000697

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Late Reoccurrence of Collapsing FSGS After Transplantation of a Living-Related Kidney Bearing APOL 1 Risk Variants Without Disease Evident in Donor Supports the Second Hit Hypothesis

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Late Reoccurrence of Collapsing FSGS After Transplantation of a Living-Related Kidney Bearing APOL 1 Risk Variants Without Disease Evident in Donor Supports the Second Hit Hypothesis

Roberto S Kalil, Richard J Smith, Prerna Rastogi, Daniel A Katz and Christie P Thomas

Transplantation Direct, Vol.3(8), pp.e185-e185

2017

DOI: 10.1097/TXD.0000000000000697

PMCID: PMC5540623

PMID: 28795137

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Abstract

Recent studies indicate that living kidney donors have higher rate of end-stage renal disease (ESRD) over their lifetime after donation compared with well-matched controls, with a much higher risk in African Americans (AA).1-3 Over the past decade, our understanding of the genetic underpinnings of chronic kidney disease (CKD) in the AA population has been enhanced by the discovery of common variants G1 and G2 in the apolipoprotein L1 gene (APOL1) that are associated both with higher rates of CKD and faster progression to ESRD.4 The G1 allele consists of missense variants in linkage disequilibrium, Ser342Gly and Ile384Met, and the G2 allele is a 2-amino acid deletion, delAsn388/Tyr389. 13% of the AA population carries 2 risk alleles (G1/G1, G1/G2, or G2/G2) and the inheritance of 2 risk alleles increases risk of hypertension-associated renal disease 7- to 10-fold and the risk of focal segmental glomerulosclerosis (FSGS) 10- to 17-fold. These risk alleles also appear to adversely affect renal allograft outcomes with deceased donor kidneys carrying 2 risk alleles having an approximately twofold increased risk of graft failure, whereas recipient genotype has no impact.5-7 We report a patient with FSGS and a strong family history of ESRD who received a kidney from a sibling. He developed abrupt and severe nephrotic syndrome with collapsing FSGS 10 years posttransplant unresponsive to plasmapheresis that rapidly progressed to ESRD. Although both recipient and donor carry 2 APOL 1 risk variants, the donor remains free of hypertension or proteinuria.

Kidney Transplantation

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Title: Subtitle: Late Reoccurrence of Collapsing FSGS After Transplantation of a Living-Related Kidney Bearing APOL 1 Risk Variants Without Disease Evident in Donor Supports the Second Hit Hypothesis
Creators: Roberto S Kalil - Department of Surgery, Organ Transplant Center, Carver College of Medicine, Iowa City, IA
Richard J Smith - Department of Surgery, Organ Transplant Center, Carver College of Medicine, Iowa City, IA
Prerna Rastogi - Department of Surgery, Organ Transplant Center, Carver College of Medicine, Iowa City, IA
Daniel A Katz - Department of Surgery, Organ Transplant Center, Carver College of Medicine, Iowa City, IA
Christie P Thomas - University of Iowa, Internal Medicine
Resource Type: Journal article
Publication Details: Transplantation Direct, Vol.3(8), pp.e185-e185
DOI: 10.1097/TXD.0000000000000697
PMID: 28795137
PMCID: PMC5540623
NLM abbreviation: Transplant Direct
ISSN: 2373-8731
eISSN: 2373-8731
Publisher: Lippincott Williams & Wilkins
Language: English
Date published: 2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Surgery; Obstetrics and Gynecology; Otolaryngology; Internal Medicine
Record Identifier: 9983986376002771

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