Diabetic tubulopathy: effect of toll-like receptor 2, toll-like receptor 4, and nuclear factor κb in elderly type 2 diabetes mellitus patients

Abstract

Objective The aims of the current study were to investigate the role of toll-like receptor (TLR)2, TLR4, and nuclear factor κB (NF-κB) expression in the pathogenesis of diabetic nephropathy (DN) in elderly type 2 diabetics, and also to determine the functional role of TLR2, TLR4, and NF-κB in tubular inflammation. Background Chronic kidney disease is one of the major complications of type 2 diabetes mellitus (T2DM) and is the leading cause of end-stage renal disease. There is growing evidence indicating that chronic low-grade inflammatory response is a recognized factor in the pathogenesis and progression of diabetic renal injury. Patients and methods Our study included a human part and an animal part, in the human part, participants were divided into four groups; old patients: 30 T2DM patients aged 65 years and above with documented DN in stage 2 incipient nephropathy and stage 3 overt nephropathy, old control: 20 age- matched and sex-matched healthy persons aged 65 years and above serving as a control group, young patients: 30 T2DM patients aged less than 65 years with documented DN in stage 2 incipient nephropathy and stage 3 overt nephropathy and young control: 20 age-matched and sex-matched healthy persons aged less than 65 years serving as a control group. We took a full history of all patients and concluded complete physical examination. Mean arterial pressure, BMI and fundus examination were done. We measured fasting plasma glucose, 2 h postprandial plasma glucose, glycated haemoglobin, complete urine analysis, serum creatinine, blood urea nitrogen, C-reactive protein, urinary albumin/creatinine ratio, estimated glomerular filtration rate using Modification of Diet in Renal Disease Abbreviated Equation, level of TLR2, TLR4, and nuclear NF-κB. In the animal part, the study was conducted on 20 aged (1.5-year old) male wistar rats, the rats were divided into two main groups; group I (control): 10 normal healthy male rats, group II (diabetic): 10 rats with high-fat diet)/streptozotocin-induced diabetes. Blood samples were collected for the determination of fasting plasma glucose, fasting serum insulin, insulin resistance was assessed by calculating the homeostatic model assessment of insulin resistance, blood urea nitrogen, serum creatinine and C-reactive protein and analysis of TLR2, TLR4, and NF-κB in renal tissue was done. Results In the human part of our study: the level of TLRs2, TLR4, and NF-κB was significantly higher in old diabetic patients group than young diabetic patients group and control group. In the animal part of our study: the level of TLRs2 and 4 and NF-κB was significantly higher in diabetic rat group than healthy rat control group. Conclusion TLRs2, TLR4, and NF-κB were higher in old diabetic patients compared with young diabetic patients and normal individuals. These observations significantly added to the emerging role of TLRs in T2DM development and its possible role in the pathogenesis and progression of DN. Also, the present study showed that the TLR system was closely related to the ageing of the kidneys.