Synergistic Effect of Inflammatory Cytokines and Body Adiposity on Insulin Resistance and Endothelial Markers in Patients With Stages 3-5 Chronic Kidney Disease.

BACKGROUND: High body adiposity, inflammatory cytokines, insulin resistance (IR), and the endothelial markers-soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1)-are among cardiovascular risk factors observed in chronic kidney disease (CKD). Synergistic interaction of inflammatory cytokines with adiposity on IR, sICAM-1, and sVCAM-1 has not been reported in nondialysis-dependent CKD (NDD-CKD) patients. Thus the study aim was to evaluate the interaction of inflammatory cytokines on the association of body adiposity with the cardiometabolic risk factors-IR, sICAM-1, and sVCAM-1-in NDD-CKD patients. Cytokines association with estimated glomerular filtration rate (eGFR) and body adiposity was also examined. DESIGN AND METHODS: A cross-sectional study was conducted in an interdisciplinary outpatient Nephrology Clinic. SUBJECTS AND MEASUREMENTS: NDD-CKD adults with eGFR ≤60 mL/minute/1.73 m2 under regular treatment. Inflammatory cytokines, homeostasis model assessment of insulin resistance (HOMA-IR), sICAM-1, sVCAM-1, eGFR (by CKD-Epidemiology collaboration equation)-EPI equation, and body composition assessed by dual-energy X-ray absorptiometry and anthropometry were evaluated. Synergistic effects of inflammatory markers with body adiposity on studied cardiometabolic risk factors were assessed by interaction and mediation analysis. RESULTS: The study cohort comprised 241 NDD-CKD patients (54.8% men; eGFR = 29.4 ± 12.9 mL/minute/1.73 m2). Variables evaluated: Inflammatory cytokines were not associated with eGFR and not different among CKD stages. Percentage of total body adiposity (%TBA) was independently associated with tumor necrosis factor-alpha (TNFα) and HOMA-IR. Waist-to-height ratio was independently associated with TNFα, interleukin-8, monocyte chemoattractant protein-1 (MCP1), and HOMA-IR. Interaction analysis showed TNFα, interleukin-8, and MCP1 as independent mediators of the effects of high percentage of total body adiposity and waist-to-height ratio on HOMA-IR (P < .0001). Body adiposity did not associate with sICAM-1 and sVCAM-1. TNFα (ß = 0.40) and MCP1 (ß = 0.31) were independently associated with sVCAM-1 (P < .01). CONCLUSIONS: In NDD-CKD patients, inflammatory cytokines synergistically mediated the effects of body adiposity, enhancing the cardiometabolic risk. Inflammation was associated with sVCAM-1, but not with eGFR.

Vitamin D status in renal transplant recipients living in a low-latitude city: association with body fat, cardiovascular risk factors, estimated glomerular filtration rate and proteinuria.

Recent evidence suggests that vitamin D deficiency is associated with CVD, impaired kidney function and proteinuria. To date, no study has evaluated these associations in renal transplant recipients (RTR) adjusting for body adiposity assessed by a 'gold standard' method. This study aimed to evaluate the vitamin D status and its association with body adiposity, CVD risk factors, estimated glomerular filtration rate (eGFR) and proteinuria in RTR, living in Rio de Janeiro, Brazil (a low-latitude city (22°54'10"S)), taking into account body adiposity evaluated by dual-energy X-ray absorptiometry (DXA). This cross-sectional study included 195 RTR (114 men) aged 47·6 (sd 11·2) years. Nutritional evaluation included anthropometry and DXA. Risk factors for CVD were hypertension, diabetes mellitus, dyslipidaemia and the metabolic syndrome. eGFR was evaluated using the Chronic Kidney Disease Epidemiology Collaboration equation. Serum 25-hydroxyvitamin D (25(OH)D) concentration was used to define vitamin D status as follows: 10 % (n 19) had vitamin D deficiency (30 ng/ml). Percentage of body fat (DXA) was significantly associated with vitamin D deficiency independently of age, sex and eGFR. Lower 25(OH)D was associated with higher odds of the metabolic syndrome and dyslipidaemia after adjustment for age, sex and eGFR, but not after additional adjustment for body fat. Hypertension and diabetes were not related to 25(OH)D. Lower serum 25(OH)D was associated with increasing proteinuria and decreasing eGFR even after adjustments for age, sex and percentage of body fat. This study suggests that in RTR of a low-latitude city hypovitaminosis D is common, and is associated with excessive body fat, decreased eGFR and increased proteinuria.