Pawan Kumar Kare

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients

AIM To investigate the role of genetic variants of angiotensin converting enzyme (ACE) and angiotensinogen (AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy (DN) patients. METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor (ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio (ACR) in urine. Genotyping of ACE I/D and AGT M235T polymorphisms were performed by using primer specific polymerase chain reaction (PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients (responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric (≥ 30 and < 300 mg/g creatinine) or macro-albuminuric (≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients (55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response (72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235T polymorphisms.

Organochlorine pesticide level in patients with chronic kidney disease of unknown etiology and its association with renal function

BackgroundInvolvement of agrochemicals have been suggested in the development of chronic kidney disease of unknown etiology (CKDu). The association between CKDu and blood level of organochlorine pesticides (OCPs) in CKDu patients has been examined in the present study.MethodsAll the recruited study subjects (n = 300) were divided in three groups, namely, healthy control (n = 100), patients with chronic kidney disease of unknown etiology (n = 100), and patients with chronic kidney disease of known etiology (CKDk) (n = 100). Blood OCP levels of all three study groups were analyzed by gas chromatography.ResultsIncreased level of OCPs, namely α-HCH, aldrin, and β-endosulfan, were observed in CKDu patients as compared to healthy control and CKD patients of known etiology. The levels of these pesticides significantly correlated negatively with the estimated glomerular filtration rate (eGFR) and positively with urinary albumin of CKD patients. Logistic regression analysis revealed association of γ-HCH, p, p′-DDE, and β-endosulfan with CKDu on adjustment of age, sex, BMI, and total lipid content.ConclusionsIncreased blood level of certain organochlorine pesticides is associated with the development of chronic kidney disease of unknown etiology.

RAGE gene polymorphism and expression: risk factor for vascular complications in type 2 diabetes mellitus

Background Advanced glycation end products (AGEs) are formed due to hyperglycemia in T2DM. Interaction of AGEs with its receptor RAGE induces signal transduction that culminates in vascular complications, the major cause of morbidity and mortality in diabetic subjects. Some functional polymorphism of this gene show differential activity of this receptor and therefore may be associated with the development of diabetic complications. In the present study we investigated the association of expression of RAGE gene and its polymorphism namely -374T/A and -429T/C in the promoter region and Gly82Ser polymorphism in the exon 3 region with vascular complications in T2DM patients.