leptin and Glomerulonephritis

Increased evidence suggests that obesity-related glomerulopathy and chronic kidney diseases should be identified as isolated complications of obesity. It is questioned if the numerous adipose tissue productions could play a role in the initiation/maintenance of such kidney diseases. This review will provide a sum-up of recent advances on fat cell metabolism and adipose tissue physiology. The adipose tissue behaves as an endocrine organ with multiple activities. It is secreting hormones (leptin, adiponectin, apelin) and numerous factors with autocrine, paracrine and systemic effects. These secretions are coming from adipocytes themselves or from cells present in the stroma-vascular fraction of the adipose tissue. When expanding, the adipose tissue of the obese is infiltrated by immune cells such as macrophages and lymphocytes; the role of which is not fully clarified. An attempt will be done to delineate if alterations of lipid storage/fatty acid release or of the secretion potencies of adipose tissue could contribute to kidney lipotoxicity and other chronic kidney diseases described in the obese.

Topics: Adipocytes; Adiponectin; Adipose Tissue, White; Apelin; Biomarkers; Body Mass Index; Cytokines; Evidence-Based Medicine; Glomerulonephritis; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Obesity; Renal Insufficiency, Chronic

Some angiotensin receptor blockers (ARBs), including irbesartan, increase the peroxisome proliferator-activated receptor (PPAR)-g activity in vitro. The aim of this study was to evaluate the interactions between obesity and the effects of irbesartan on inflammatory cytokines in chronic glomerulonephritis patients without diabetes.. The anti-inflammatory effects of irbesartan were evaluated in 29 hypertensive chronic glomerulonephritis patients without diabetes in a prospective, single-arm study.. Following treatment with irbesartan for 26 weeks, blood pressure and proteinuria significantly decreased, as previously reported (blood pressure decreased from 142±1/87±1 to 131±1/81±1 mmHg and the urine protein/creatinine ratio decreased from 1030±143 to 779±121 mg/g Cr). BMI did not significantly change after the study. Among the inflammatory parameters, the concentrations of adiponectin and high-sensitivity C-reactive protein (hsCRP) significantly improved after treatment; however, the changes in the concentrations of interleukin-6 (IL-6), tumor necrosis factor (TNF)-a and leptin did not reach statistical significance. Moreover, the changes in these five parameters following treatment were moderately correlated with the BMI values obtained at the initiation of the study, and the improvements were particularly prominent in those with a BMI greater than 25. Improvements in proteinuria were significantly correlated with increases in the adiponectin concentration, but not with BMI. There was also a moderate correlation between the changes in the adiponectin and insulin concentrations.. Irbesartan improves metabolic parameters in nondiabetic hypertensive chronic glomerulonephritis patients, especially those with a high BMI. Improving the adiponectin concentration may be important for reducing proteinuria.

Topics: Adiponectin; Angiotensin II Type 1 Receptor Blockers; Anti-Inflammatory Agents, Non-Steroidal; Biphenyl Compounds; Body Mass Index; C-Reactive Protein; Chronic Disease; Cytokines; Female; Glomerulonephritis; Humans; Hypertension; Inflammation Mediators; Interleukin-6; Irbesartan; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Proteinuria; Tetrazoles; Tumor Necrosis Factor-alpha

Altered regulation of adiponectin and leptin may be relevant to endothelial dysfunction and cardiovascular complications in patients with chronic glomerulonephritis.. The relationship between the levels of plasma adiponectin, leptin and proteinuria, glomerular filtration rate and metabolic risk factors was investigated in 38 patients with chronic glomerulonephritis.. Plasma adiponectin was much higher in patients with heavy proteinuria (38.8 +/- 27.8 microg/mL) than in patients with mild proteinuria (13.3 +/- 5.1 microg/mL, P < 0.001) and with moderate proteinuria (18.1 +/- 8.0 microg/mL, P < 0.01). The levels of serum leptin were not changed among these groups. Proteinuria and lipoprotein(a) were a strong and direct correlate of plasma adiponectin (r = 0.75, P < 0.0001), while serum albumin and the glomerular filtration rate correlated inversely with this protein (r = -0.56, P = 0.0002; r = 0.38, P = 0.02). Body mass index and triglyceride were direct correlates (r = 0.37, P = 0.02 and r = 0.37, P = 0.02, respectively) of plasma leptin in patients with glomerulonephritis.. Plasma adiponectin but not plasma leptin levels correlate with proteinuria in patients with chronic glomerulonephritis.

Topics: Adiponectin; Adult; Aged; Chronic Disease; Female; Glomerulonephritis; Humans; Leptin; Male; Middle Aged; Proteinuria

Adiponectin (ADPN) has been shown to protect against cardiovascular disease for the general population with problematic metabolic syndrome. However, it remains unclear whether ADPN is associated with mortality in patients on maintenance hemodialysis (HD). METHODS, PATIENTS OR MATERIALS: We selected 85 HD patients [51 men/34 women; mean age, 64+/-2 years; underlying kidney diseases, diabetic nephropathy in 36 patients (42.3%), chronic glomerulonephritis in 29 (34.1%), hypertensive nephrosclerosis in 10 (11.8%), and others in 10 (11.8%)] who survived for more than 3 months after the start of HD. We first measured serum ADPN levels and prospectively followed patients for the next 3 years.. We were able to follow 74 of 85 patients; 59 survived, and 15 died. Serum log-transformed ADPN levels were negatively correlated with BMI (r=-0.43, p<0.01). Despite a similar BMI (20.7+/-0.8 vs. 20.3+/-0.4 kg/m(2)), the expired patients had significantly higher ADPN compared with the surviving patients (20.5 microg/ml [14.0-23.5] vs. 14.2 microg/ml [9.7-21.3], p<0.05). Cox-hazards multivariate regression analysis adjusted for conventional case-mix features (age, sex, and underlying kidney disease) revealed that serum ADPN became a significant determinant of all-cause mortality. There was a 10.3% risk increment for each 1-microg/ml increase in ADPN during the follow-up. Kaplan-Meier analysis revealed that patients with higher ADPN levels (> or =15 microg/ml) had a significantly lower survival rate compared with those with lower ADPN levels (<15 microg/ml) (76 vs. 92%, p<0.05).. These results indicated that high rather than low ADPN independently predict total mortality in HD patients.

Topics: Adiponectin; Blood Urea Nitrogen; Body Mass Index; C-Reactive Protein; Creatinine; Diabetic Nephropathies; Female; Follow-Up Studies; Glomerulonephritis; Humans; Kaplan-Meier Estimate; Leptin; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Nephrosclerosis; Predictive Value of Tests; Prospective Studies; Regression Analysis; Renal Dialysis; Survival Rate

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. Markedly elevated leptin levels have been documented in uremic patients, especially in those who are treated by peritoneal dialysis (PD). However, the role of hyperleptinemia in uremic patients is not clear, and it is not known whether elevated leptin levels contribute to uremic anorexia and changes in body composition. In this prospective study, serum leptin, C-reactive protein (CRP), plasma insulin, and body composition (dual-energy x-ray absorptiometry) were measured in 36 patients (53 +/- 1 yr) close to start and after about 1 yr of PD. In addition, markers of dialysis adequacy and urea kinetics were followed during treatment with PD. During PD, the total body fat mass (20.5 +/- 1.0 to 22.9 +/- 1.3 kg; P < 0.01), truncal fat mass (11.5 +/- 0.7 to 13. 2 +/- 0.9 kg; P < 0.001), and serum leptin levels (20.1 +/- 3.8 to 35.6 +/- 6.8 ng/ml; P < 0.01) increased markedly, especially in patients with diabetes mellitus. Twenty-five PD patients that lost lean body mass during PD had significantly (P < 0.05) elevated initial CRP levels (14 +/- 2 mg/L) compared to 11 patients (<10 mg/L) who gained lean body mass during PD. A significant increase in serum leptin levels (20.9 +/- 4.2 to 42.7 +/- 4.0 ng/ml; P < 0.001) was observed in those patients who lost lean body mass, whereas no such change (18.4 +/- 8.4 to 19.2 +/- 6.4 ng/ml) was observed in the patients that gained lean body mass during PD treatment. The present longitudinal results demonstrate that serum leptin level and body fat content increase markedly during PD, especially in diabetic patients. Patients that lost lean body mass during PD had higher initial CRP levels and increased their serum leptin levels significantly during PD compared to those patients that gained lean body mass. Additional studies are therefore needed to elucidate the role of hyperleptinemia and inflammation in causing anorexia, protein-malnutrition, and changes in body composition during treatment with PD.

Topics: Absorptiometry, Photon; Body Composition; C-Reactive Protein; Diabetic Nephropathies; Female; Glomerulonephritis; Humans; Insulin; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nephritis; Peritoneal Dialysis; Prospective Studies