Abstract
Chronic kidney disease (CKD) is characterized by an increased risk of kidney failure and end-stage renal disease (ESRD). Aging and comorbidities as cardiovascular diseases, metabolic disorders, infectious diseases, or tumors, might increase the risk of dialysis. In addition, genetic susceptibility factors might modulate kidney damage evolution. We have analyzed, in a group of ESRD patients and matched controls, a set of SNPs of genes (Klotho rs577912, rs564481, rs9536314; FGF23 rs7955866; IGF1 rs35767; TNFA rs1800629; IL6 rs1800795; MIF rs755622, rs1007888) chosen in relation to their possible involvement with renal disease and concomitant pathologies. Analysis of the raw data did indicate that IL6 rs180795 and MIF rs755622 SNPs might be markers of genetic susceptibility to ESRD. In particular, the C positive genotypes of MIF rs755622, (dominant model) seem to be an independent risk factor for ESDR patients (data adjusted for age, gender, and associated pathologies). Stratifying results according to age MIF rs755622 C positive genotype frequencies are increased in both the two age classes considered (<59 and ≥59-year-old subjects). Analyses of data according to gender allowed us to observe that ESRD women shoved a significantly reduced frequency of genotypes bearing IL6 rs180795 C allele. In addition, MIF rs755622 might interact with diabetes or hypercholesterolemia in increasing susceptibility to ESRD. In conclusion, our data indicate that some polymorphisms involved in the regulation of both renal function and inflammatory response can influence the evolution of chronic kidney disease and suggest that the modulation of the activities of these and other genes should also be considered as therapeutic targets on to intervene with innovative therapies.
Highlights
Our results indicate that macrophage inhibiting factor (MIF) rs755622 might influence the susceptibility to ESDR both as an independent risk factor and in presence of comorbidities
Chronic kidney disease (CKD) might be considered a paradigm of the multifactorial diseases in which preexisting pathological conditions and genetic susceptibility factors might interplay with each other, resulting in different trajectories of damage evolution to the final stage as end-stage renal disease (ESRD)
Our data indicate that some polymorphisms, IL6
Summary
Chronic kidney disease (CKD) is characterized by a progressive decrease of renal function with an increased risk of kidney failure and end-stage renal disease (ESRD), the disease stage where dialysis and transplantation are needed [1]. Foundation’s Kidney Disease Outcomes Quality Initiative (K/DOQI) has defined the stage of chronic kidney disease (CKD) based on the value of glomerular filtration rate (GFR) [2]. According to this classification, a GFR ≤ 59 mL/min/1.73 m2 or less defines a moderate to severe decrease in renal function. Genes coding for these mediators are highly polymorphic and the effect of their interactions on the pathogeneses of different diseases might be influenced by the different individual genetic backgrounds [5]
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