Ashok Kumar Tripathi

Chronic kidney disease of unknown etiology (CKDu), manifested clinically as tubulo interstitial fibrosis, has emerged as the second major cause of chronic kidney disease (CKD) in the Indian subcontinent and various agrochemicals have been implicated in its occurance. Among the agrochemicals organochlorine pesticides particularly endosulfan is well known for its toxicity and recent residue analysis have shown its presence in the blood samples of general population. In this present study, we have investigated the consequences of endosulfan exposure at a concentration (0.01 μM) equivalent to their highest reported presence in human blood sample of some CKDu patients, to human renal proximal tubular epithelial (HK‐2) cell line with regard to ROS generation and expression of profibrotic and epithelial to mesenchymal (EMT) markers in order to find out endosulfan's ability to induce profibrotic changes in renal cell. We demonstrated a significant increase in intracellular ROS generation and increased expression of TGF‐β1 when cells were incubated with β‐endosulfan (0.01 μM) indicating occurrence of oxidative stress and fibrotic process. Again, decreased expression of epithelial marker E‐cadherin and increase in the expression of mesenchymal marker α‐smooth muscle actin (α‐SMA) suggest possible onset of EMT process. Pre‐treatment with 5 mM concentration of anti‐oxidant N‐acetyl cysteine partially attenuated the above process. In conclusion, these findings suggest possible involvement of β‐endosulfan in the development of CKDu through oxidative stress and profibrotic signaling.

Chronic kidney disease (CKD) contributes to a significant burden on the healthcare system and economy worldwide. In the last two decades, a new form of CKD: chronic kidney disease of unknown etiology (CKDu) in which the disease is not attributed to known causes has emerged as a major health issue in different geographical areas over the world mainly from farming community and has become a global concern today. Despite intense and numerous research works dedicated to CKDu, very little is known with certainty regarding its etiology and the pathophysiology behind its development. Recent evidences are emerging in favor of possible role of agrochemicals and pesticides in the pathogenesis of CKDu. Organochlorine pesticides (OCPs) due to their longer half-life and lipophilic nature persist long in the environment and are known to be biomagnified through food chain. Some study reports by the authors and a few others constitute the important body of evidences depicting the association between chronic exposures to OCPs and occurrence of CKDu through environmental contamination in farming as well as non-farming communities in different geographical areas around the globe.

Involvement 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. All 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. Increased 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. Increased blood level of certain organochlorine pesticides is associated with the development of chronic kidney disease of unknown etiology.

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

Aims: The aim of present study was to find out the prevalence of micro-albuminuria and its relationship with diabetic retinopathy in type 2 diabetes mellitus (T2DM) patients. Study Design: Cross-sectional study. Place and Duration of Study: Department of Biochemistry and Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, India, between September 2013 and August 2015. Methodology: Total 387 clinically diagnosed T2DM patients with age range 30-65 years were enrolled for the study. Morning spot urine samples were collected for analysis of urinary albumin and creatinine on two separate occasions. Serum and urine creatinine were carried out by alkaline picrate Jaffee´s kinetic method. Urine albumin was estimated by turbidometric method by using nephelometer (Nephstar®, Goldsite Diagnostics Inc., USA). On the basis of albumin/creatinine ratio (ACR), patients were classified as normo-albuminuric (albumin/creatinine ratio Results: Out of total 387 T2DM patients screened, 159 (41%) were normo-albuminuric, 162 (41.8%) were micro-albuminuric and 66 (17%) were macro-albuminuric. The overall prevalence of micro-albuminuria was 41.8%. The prevalence of micro-albuminuria was 51.2% among males and 48.8% among females. The percentage of patients having micro-albuminuria was found to be increased with increasing duration of diabetes. Micro-albuminuria showed significant correlation with duration of diabetes (pConclusions: The present study suggests that the onset of micro-albuminuria in T2DM patients is associated with increasing duration of diabetes, poor glycemic control and presence of diabetic retinopathy. Presence of micro-albuminuria in T2DM patients having <5 years of duration of diabetes suggest screening of micro-albuminuria would be beneficial for early detection of DN.

Aims: The present study was carried out to evaluate the effect of angiotensin converting enzyme inhibitor (ACEI) therapy on proteinuria and serum advanced glycation end products (AGEs) level in type 2 diabetes mellitus (T2DM) patients with nephropathy. Study Design: Single-arm prospective longitudinal study. Duration and Place of Study: The study subjects were enrolled from Diabetic and Nephrology clinic at University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, India, between September 2013 and July 2014. Methodology: The study subjects comprised of clinically diagnosed T2DM patients (n = 75) with evidence of persistent micro-albuminuria (ACR; 30-299 mg/g creatinine) or overt albuminuria (ACR; ≥300 mg/g creatinine) tested on two separate occasions. These patients were treated with ACE inhibitor; ramipril (5 mg to 20 mg /day) for 12 months. Effectiveness was assessed based on change in urinary albumin/creatinine ratio (ACR) and serum AGEs level. Results: Ramipril treatment produced significant fall in log urinary ACR (PPConclusions: Apart from antiproteinuric action, ramipril treatment has been found to lower serum AGEs level that may eventually arrest vascular complications in T2DM patients with nephropathy.

Oxidative stress has been proposed as one of the causes involved in idiopathic fetal growth restriction (IFGR). However, the exact relationship between oxidative stress and IFGR is not understood. This study aimed at understanding the role of oxidative stress and antioxidant status in IFGR materno-fetal dyads and matched controls. 75 materno-fetal dyads with IFGR were enrolled with equal number of normal low risk controls. Malondialdehyde (MDA) levels were measured as marker of oxidative stress, while paraoxonase-1 (PON1) activity and total antioxidant capacity (TAC) of serum were measured as markers of antioxidant status. MDA levels were increased in both maternal and cord blood of IFGR neonates as compared to controls (p < 0.001). TAC of serum were found to be decreased in IFGR (both maternal and cord blood) as compared to controls (p < 0.001; p < 0.05, respectively). PON1 activity was found to be decreased in the IFGR mothers while it was found increased in IFGR cord blood (p < 0.01; p < 0.001)). IFGR is a state of increased oxidative stress. Decreased PON1 enzymatic activity in mothers is also associated with IFGR.