Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Laura M Vilander,Ville Pettilä,Suvi T Vaara,Mari A Kaunisto

doi:10.3390/jcm8030342

Abstract

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEXTM Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89–1.28, p = 0.51) and 0.92 (95% CI 0.80–1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.

Highlights

Acute kidney injury (AKI) is a syndrome that often complicates critical illness and is associated with significant mortality and morbidity [1,2]
In our systematic review in 2014 we found that evidence about genetic predisposition to AKI was heterogeneous, the studies were of inadequate size and the findings were generally not replicated [3]
We found no variation in single nucleotide polymorphisms (SNPs) rs2069842 and rs2069830 in interleukin 6 (IL6); rs10499563 in IL6 was not in Hardy–Weinberg Equilibrium (HWE) (p = 0.034)

Summary

Introduction

Acute kidney injury (AKI) is a syndrome that often complicates critical illness and is associated with significant mortality and morbidity [1,2]. Efforts to distinguish patients at risk for AKI are justifiable, but despite the advances in the understanding of the pathophysiology of AKI, reliable prediction of developing AKI in different clinical scenarios remains a challenge. In our systematic review in 2014 we found that evidence about genetic predisposition to AKI was heterogeneous, the studies were of inadequate size and the findings were generally not replicated [3]. Based on these findings, we analyzed 27 common genetic variants that situate in genes previously associated with AKI in a Finnish sample of critically ill patients

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