Donor and recipient genetic variants in NLRP3 associate with early acute rejection following kidney transplantation.
NLRP3 (NOD-like receptor family, pyrin domain containing 3) is a member of the inflammasome family and is of special interest in renal disease. Experimental studies have shown that Nlrp3 plays a significant role in the induction of renal damage and dysfunction in acute and chronic renal injury. However, the role of NLRP3 in human renal disease is completely unknown. From a retrospective cohort study, we determined in 1271 matching donor and recipient samples if several NLRP3 single nucelotide polymorphisms (SNPs) were associated with primary non-function (PNF), delayed graft function (DGF), biopsy-proven acute rejection (BPAR) and death-censored graft and patient survival. NLRP3 gain-of-function SNP (rs35829419) in donors was associated with an increased risk of BPAR while NLRP3 loss-of-function SNP (rs6672995) in the recipient was associated with a decreased risk of BPAR in the first year following renal transplantation (HR 1.91, 95% CI 1.38-2.64, P < 0.001 and HR 0.73, 95% CI 0.55-0.97, P = 0.03 resp.). NLRP3 SNPs in both donor and recipient were not associated with PNF, DGF, graft survival or patient survival. We conclude that genetic variants in the NLRP3 gene affect the risk of acute rejection following kidney transplantation.
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Mark C
MC
Dessing
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Jesper
J
Kers
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Jeffrey
J
Damman
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Gerjan J
GJ
Navis
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
Sandrine
S
Florquin
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Jaklien C
JC
Leemans
D000328:Adult; D001706:Biopsy; D051799:Delayed Graft Function; D005260:Female; D006084:Graft Rejection / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics / Q000628:therapy*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D014019:Tissue Donors
D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human