Ramprasad Elumalai

Association between end-stage diabetic nephropathy and MTHFR (C677T and A1298C) gene polymorphisms: MTHFR gene and diabetic nephropathy.

Methylenetetrahydrofolate reductase (MTHFR) is a regulatory enzyme of homocysteine metabolism. The C677T and A1298C polymorphism of the MTHFR gene has been reported to be associated with elevated plasma homocysteine in patients with Diabetic nephropathy. This study aimed to investigate the influence of the C677T and A1298C polymorphisms on the progression chronic kidney disease in diabetic nephropathy of south Indian population.

Role of endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism on the progression of renal disease in autosomal dominant polycystic kidney disease

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder, and it is mainly associated with renal cyst formation. Several studies have also shown that these mutations regulate the physiology of epithelial tissues and determine renal cyst formation and growth in polycystic kidney disease (PKD). Nitric oxide (NO) is also considered to be an important factor involved in the deterioration of renal function. Objectives: The aim of the current study is to determine the frequency of NOS3 27-bp VNTR in ADPKD patients and to investigate the role of NOS3 27-bp VNTR genotypes in the modification of progression of renal disease in ADPKD.Patients and Methods: The hypothesis was investigated by studying the South Indian population of 53 ADPKD patients and 94 unrelated healthy controls. The genotyping was performed by polymerase chain reaction and electrophoresis. Genotypes were compared between ADPKD and controls using the χ2-test. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on the progress of chronic kidney disease (CKD). A stratified analysis was also performed to assess the evidence of the modification of hypertension-CKD relationship among VNTR genotypes. Results: The NOS3 4a allele frequencies were 21.3% and 13.2% respectively for controls and ADPKD groups. The NOS3 VNTR genotypes and alleles were not associated with ADPKD. The univariate analysis showed that age, hypertension and NOS3 VNTR influenced the advancement of CKD. Conclusion: The present study confirms the significant association between the 27-bp VNTR and CKD advancement among the ADPKD patients in the South Indian population.

Fungal peritonitis in continuous ambulatory peritoneal dialysis patients; a study from South of India

Introduction: Fungal peritonitis is a potential life-threatening complication for patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Objectives: To assess the incidence and outcome of fungal peritonitis in CAPD patients. Patients and Methods: Dialysis records of all end-stage renal disease patients initiated on CAPD treatment were reviewed retrospectively. The study was conducted during January 2010 to December 2016. Mann–Whitney U test was applied for data analysis. Results: Out of 265 dialysis patients, a total of 36 fungal peritonitis were recorded. The incidence rate of fungal peritonitis was 13.6%. The majority of cases was affected by Candida albicans was 41.6%. Moreover, the major cause of end-stage renal disease (ESRD) in our study was diabetic nephropathy in 38.8% of cases. Conclusion: In this study, we found initiation of antifungal therapy and early removal of catheter reduced the mortality rate of fungal peritonitis in CAPD patients.

Aldosterone synthase gene is not a major susceptibility gene for progression of chronic kidney disease in patients with autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable kidney disease and is characterized by bilateral renal cysts. Hypertension is a frequent cause of chronic kidney disease (CKD) and mortality in patients with ADPKD. The aldosterone synthase gene polymorphisms of the renin-angiotensin-aldosterone system have been extensively studied as hypertension candidate genes. The present study is aimed to investigate the potential modifier effect of CYP11B2 gene on the progression of CKD in ADPKD. One hundred and two ADPKD patients and 106 healthy controls were recruited based on Ravine inclusion and exclusion criteria. The three tag-SNPs within CYP11B2 gene (rs3802230, rs4543, and rs4544) were genotyped using FRET-based KASPar method. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Mantel- Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. Of the three tag-SNPs genotyped, rs4544 polymorphism was monomorphic and rs3802230 deviated Hardy-Weinberg equilibrium. The CYP11B2 tag-SNPs did not show significant association with ADPKD or CKD. Further, these polymorphisms did not exhibit confounding effect on the relationship between CKD progression and hypertension. Our results suggest that aldosterone synthase gene is not a major susceptibility gene for progression of CKD in South Indian ADPKD patients.

Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD)

Background & objectives: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. Methods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. Results: All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. Interpretation & conclusions: The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients.