Pathophysiological role and therapeutic implications of inflammation in diabetic nephropathy

Diabetes mellitus and its complications are becoming one of the most important health problems in the world. Diabetic nephropathy is now the main cause of end-stage renal disease. The mechanisms leading tothe development and progression of renal injury are not well known. Therefore, it is very important to f ind new pathogenic pathways to provide opportunities for early diagnosis and targets for novel treatments. At the present time, we know that activation of innate immunity with development of a chronic low grade inflammatory response is a recognized factor in the pathogenesis of diabetic nephropathy. Numerous experimental and clinical studies have shown the participation of different inflammatory molecules and pathways in the pathophysiology of this complication.

What is the optimal level of vitamin D in non-dialysis chronic kidney disease population?

AIM To evaluate thresholds for serum 25(OH)D concentrations in relation to death, kidney progression and hospitalization in non-dialysis chronic kidney disease(CKD) population.METHODS Four hundred and seventy non-dialysis 3-5 stage CKD patients participating in OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into 3 groups according to 25(OH)D levels at enrollment(less than 20 ng/mL, between 20 and 29 ng/mL, and at or above 30 ng/mL), considering 25(OH)D between 20 and 29 ng/mL as reference group. Association between 25(OH)D levels and death(primary outcome), and time to first hospitalization and renal progression(secondary outcomes) over a 3-year followup, were assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. To identify 25(OH)D levels at highest risk for outcomes, receiver operating characteristic(ROC) curves were performed.RESULTS Over 29 ± 12 mo of follow-up, 46(10%) patients dead, 156(33%) showed kidney progression, and 126(27%) were hospitalized. After multivariate adjustment, 25(OH)D < 20 ng/mL was an independent predictor of all-cause mortality(HR = 2.33; 95%CI: 1.10-4.91; P = 0.027) and kidney progression(HR = 2.46; 95%CI: 1.63-3.71; P < 0.001), whereas the group with 25(OH)D at or above 30 ng/mL did not have a different hazard for outcomes from the reference group. Hospitalization outcomes were predicted by 25(OH) levels(HR = 0.98; 95%CI: 0.96-1.00; P = 0.027) in the unadjusted Cox proportional hazards model, but not after multivariate adjusting. ROC curves identified 25(OH)D levels at highest risk for death, kidney progression, and hospitalization, at 17.4 ng/mL [area under the curve(AUC) = 0.60; 95%CI: 0.685-0.69; P = 0.027], 18.6 ng/mL(AUC = 0.65; 95%CI: 0.60-0.71; P < 0.001), and 19.0 ng/m L(AUC = 0.56; 95%CI: 0.50-0.62; P = 0.048), respectively.CONCLUSION25(OH)D < 20 ng/mL was an independent predictor of death and progression in patients with stage 3-5 CKD, with no additional benefits when patients reached the levels at or above 30 ng/m L suggested as optimal by CKD guidelines.