scholarly journals Polymorphism in the GATM Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 834
Author(s):  
Špela Šalamon ◽  
Sebastjan Bevc ◽  
Robert Ekart ◽  
Radovan Hojs ◽  
Uroš Potočnik
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Failure ◽  
Association Studies ◽  
Genetic Difference ◽  
Genome Wide Association Studies ◽  
Healthy Controls ◽  
Genome Wide ◽  
Stage Renal Disease ◽  
End Stage

The ten most statistically significant estimated glomerular filtration rate (eGFRcrea)-associated loci from genome-wide association studies (GWAs) are tested for associations with chronic kidney disease (CKD) in 208 patients, including dialysis-independent CKD and dialysis-dependent end-stage renal disease (kidney failure). The allele A of intergenic SNP rs2453533 (near GATM) is more frequent in dialysis-independent CKD patients (n = 135, adjusted p = 0.020) but not dialysis-dependent kidney failure patients (n = 73) compared to healthy controls (n = 309). The allele C of intronic SNP rs4293393 (UMOD) is more frequent in healthy controls (adjusted p = 0.042) than in CKD patients. The Allele T of intronic SNP rs9895661 (BCAS3) is associated with decreased eGFRcys (adjusted p = 0.001) and eGFRcrea (adjusted p = 0.017). Our results provide further evidence of a genetic difference between dialysis-dialysis-independent CKD and dialysis-dependent kidney failure, and add the GATM gene locus to the list of loci associated only with dialysis-independent CKD. GATM risk allele carriers in the dialysis-independent group may have a genetic susceptibility to higher creatinine production rather than increased serum creatinine due to kidney malfunction, and therefore, do not progress to dialysis-dependent kidney failure. When using eGFRcrea for CKD diagnosis, physicians might benefit from information about creatinine-increasing loci.

scholarly journals Use of the Kidney Failure Risk Equation to Determine the Risk of Progression to End-stage Renal Disease in Children With Chronic Kidney Disease

2018 ◽  
Vol 172 (2) ◽  
pp. 174 ◽  
Author(s):  
Erica Winnicki ◽  
Charles E. McCulloch ◽  
Mark M. Mitsnefes ◽  
Susan L. Furth ◽  
Bradley A. Warady ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Failure ◽  
End Stage Renal Disease ◽  
Risk Equation ◽  
Failure Risk ◽  
Risk Of Progression ◽  
Stage Renal Disease ◽  
End Stage

scholarly journals Urine Osmolarity and Risk of Dialysis Initiation in a CKD Cohort

2015 ◽  
Vol 66 (Suppl. 3) ◽  
pp. 14-17 ◽  
Author(s):  
Lise Bankir ◽  
Max Plischke ◽  
Nadine Bouby ◽  
Martin Haas
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Association Studies ◽  
Experimental Studies ◽  
Dialysis Initiation ◽  
Hazards Model ◽  
Baseline Creatinine ◽  
Stage Renal Disease ◽  
End Stage ◽  
Disease Stages

Background: Several experimental studies in rats and a few association studies in humans suggest that the antidiuretic action of vasopressin may accelerate the progression of chronic kidney disease. We undertook a retrospective analysis in a monocentric cohort of 273 patients with chronic kidney disease stages 1-4, focusing on a strong variable of interest, urinary osmolarity, and a strong endpoint, dialysis initiation. Data was analyzed in a multivariate proportional sub-distribution hazards model for competing risk data with appropriate co-variates. Main Results: Over a median follow-up period of 92 months, dialysis was initiated in 105 patients. After adjustments for baseline creatinine clearance, and other confounding factors, a higher risk for initiation of dialysis was found in patients with higher urinary osmolarity. After 72 months, the estimated adjusted cumulative incidence probability for dialysis initiation was 15, 24, and 34% in patients with baseline urinary osmolarity of 315, 510, and 775 mosm/l, respectively (p = 0.033). Key Messages: In this retrospective, longitudinal study, a higher baseline urinary osmolarity was strongly associated with a higher risk of end-stage renal disease (after appropriate adjustments). Further, prospective studies are required to evaluate the possible benefit of interventions aiming at reducing urinary osmolarity as a potential treatment for slowing chronic kidney disease progression.

scholarly journals PNPLA3 gene and kidney disease

2020 ◽  
Vol 1 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Alessandro Mantovani ◽  
Chiara Zusi
Keyword(s):  
Kidney Disease ◽  
Association Studies ◽  
Liver Steatosis ◽  
Kidney Injury ◽  
Future Perspective ◽  
Genome Wide Association Studies ◽  
Alcoholic Fatty Liver ◽  
Liver And Kidney ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease (CKD) is a disease regularly seen in clinical practice. At present, CKD is described as a change of kidney structure and/or function and it is classified in relation to cause, values of glomerular filtration rate and albuminuria category. Seeing that CKD is closely linked to the development of end-stage renal disease and other comorbidities, the determination of additional independent predictors for CKD is clinically necessary. At present, there is evidence associating non-alcoholic fatty liver disease (NAFLD) with CKD, thereby suggesting that NAFLD patients may require intensive surveillance to reduce their risk of CKD. In 2008, genome-wide association studies documented an association between the variant rs738409 (C > G p.I148M) in the patatin-like phospholipase domain containing 3 (PNPLA3) gene (mainly implicated in the lipid regulation) and the entire spectrum of NAFLD (i.e., liver steatosis, non-alcoholic steatohepatitis, fibrosis, and hepatocellular carcinoma). In the last years, accumulating epidemiological evidence suggests the existence of a relationship between PNPLA3 rs738409 and risk of CKD, indicating that rs738409 may also contribute to the kidney injury. This is of particular scientific interest, as such association may explain, at least in part, the epidemiological association between liver and kidney disease. In this narrative review, we will discuss the accumulating evidence regarding the association between PNPLA3 rs738409 and risk of CKD, the putative biological mechanisms underpinning such relationship, and the possible future perspective.

scholarly journals Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ngan K. Tran ◽  
Rodney A. Lea ◽  
Samuel Holland ◽  
Quan Nguyen ◽  
Arti M. Raghubar ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Principal Components ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Functional Variants ◽  
Genome Wide ◽  
Norfolk Island

AbstractChronic kidney disease (CKD) is a persistent impairment of kidney function. Genome-wide association studies (GWAS) have revealed multiple genetic loci associated with CKD susceptibility but the complete genetic basis is not yet clear. Since CKD shares risk factors with cardiovascular diseases and diabetes, there may be pleiotropic loci at play but may go undetected when using single phenotype GWAS. Here, we used multi-phenotype GWAS in the Norfolk Island isolate (n = 380) to identify new loci associated with CKD. We performed a principal components analysis on different combinations of 29 quantitative traits to extract principal components (PCs) representative of multiple correlated phenotypes. GWAS of a PC derived from glomerular filtration rate, serum creatinine, and serum urea identified a suggestive peak (pmin = 1.67 × 10–7) that mapped to KCNIP4. Inclusion of other secondary CKD measurements with these three kidney function traits identified the KCNIP4 locus with GWAS significance (pmin = 1.59 × 10–9). Finally, we identified a group of two SNPs with increased minor allele frequencies as potential functional variants. With the use of genetic isolate and the PCA-based multi-phenotype GWAS approach, we have revealed a potential pleotropic effect locus for CKD. Further studies are required to assess functional relevance of this locus.

Abstract P350: Association of Plasma Levels of Soluble Receptor for Advanced Glycation End Products and Risk of Kidney Disease is Explained by Baseline Kidney Function

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Casey M Rebholz ◽  
Brad C Astor ◽  
Morgan E Grams ◽  
Marc K Halushka ◽  
Mariana Lazo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Failure ◽  
End Stage Renal Disease ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Stage Renal Disease ◽  
End Stage

Introduction: Advanced glycation end products and their cell-bound receptors (RAGE) are thought to mediate the adverse effects of dysglycemia and vascular disease through oxidative stress, inflammation, and endothelial dysfunction. The soluble form of RAGE (sRAGE) is a 48-kDa, positively-charged cleavage product of RAGE. There is limited evidence on the role of sRAGE in the pathogenesis of kidney disease. Methods: We conducted cross-sectional and prospective analyses of a case-cohort study nested within the ARIC Study. Plasma sRAGE was measured at baseline (1990-92) in a cohort random sample (n=1,218) and three case groups of participants with incident chronic kidney disease [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 and ≥25% eGFR decline; n=151], incident end-stage renal disease [U.S. Renal Data System registry; n=152], and incident kidney failure (eGFR <15 mL/min/1.73 m 2 , U.S. Renal Data System registry, or kidney failure-related hospitalization or death; n=266). Results: Baseline sRAGE levels were inversely related to baseline eGFR (r = -0.13). After adjusting for age, sex, and race, one interquartile range increase in log 10 -transformed sRAGE was associated with development of end-stage renal disease [hazard ratio: 1.97; 95% confidence interval (CI): 1.47, 2.64; p<0.001], kidney failure (hazard ratio: 1.59; 95% CI: 1.27, 2.00; p<0.001), and chronic kidney disease (odds ratio: 1.39; 95% CI: 1.06, 1.83; p=0.02). However, none of these associations were significant after additional adjustment for eGFR (all p>0.10; Figure). Conclusions: High sRAGE levels are associated with decreased kidney function. The association of sRAGE with kidney disease risk may be explained by its partial clearance by the kidney.

scholarly journals Genome-wide association studies in pediatric chronic kidney disease

2015 ◽  
Vol 31 (8) ◽  
pp. 1241-1252 ◽  
Author(s):  
Jayanta Gupta ◽  
Peter A. Kanetsky ◽  
Matthias Wuttke ◽  
Anna Köttgen ◽  
Franz Schaefer ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide
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