Calcitriol regulates angiotensin-converting enzyme and angiotensin converting-enzyme 2 in diabetic kidney disease.

To investigate the effects of calcitriol on angiotensin-converting enzyme (ACE) and ACE2 in diabetic nephropathy. Streptozotocin (STZ) induced diabetic rats were treated with calcitriol for 16 weeks. ACE/ACE2 and mitogen activated protein kinase (MAPK) enzymes were measured in the kidneys of diabetic rats and rat renal tubular epithelial cells exposed to high glucose. Calcitriol reduced proteinuria in diabetic rats without affecting calcium-phosphorus metabolism. ACE and ACE2 levels were significantly elevated in diabetic rats compared to those in control rats. The increase in ACE levels was greater than that of ACE2, leading to an elevated ACE/ACE2 ratio. Calcitriol reduced ACE levels and ACE/ACE2 ratio and increased ACE2 levels in diabetic rats. Similarly, high glucose up-regulated ACE expression in NRK-52E cells, which was blocked by the p38 MAPK inhibitor SB203580, but not the extracellular signal-regulated kinase (ERK) inhibitor FR180204 or the c-Jun N-terminal kinase (JNK) inhibitor SP600125. High glucose down-regulated ACE2 expression, which was blocked by FR180204, but not SB203580 or SP600125. Incubation of cells with calcitriol significantly inhibited p38 MAPK and ERK phosphorylation, but not JNK phosphorylation, and effectively attenuated ACE up-regulation and ACE2 down-regulation in high glucose conditions. The renoprotective effects of calcitriol in diabetic nephropathy were related to the regulation of tubular levels of ACE and ACE2, possibly by p38 MAPK or ERK, but not JNK pathways.

Effect of fish oil supplement in maintenance hemodialysis patients: a systematic review and meta-analysis of published randomized controlled trials.

PURPOSE: The purpose of this study was to systematically assess the efficacy of fish oil therapy on maintenance hemodialysis patients (MHD). METHODS: Electronic databases, including PubMed, Cochrane library, EMBase, and Web of Science, were searched for randomized controlled trials (RCTs) of fish oil versus placebo or no treatment in MHD patients. The study selection and data extraction were conducted independently by two reviewers, and statistical analysis was performed using RevMan software, version 5.2. RESULTS: A total of thirteen eligible RCTs involving 916 subjects (461 in the experimental group and 455 in the control group) were included. The meta-analysis showed that fish oil significantly reduced arteriovenous graft (AV-graft) events [risk ratio (RR) 0.71, 95 % confidence interval (CI) were (0.52, 0.97)] and cardiovascular events [RR (95 %CI) were 0.41 (0.26, 0.66)] in the fish oil group. In addition, compared with the control group, fish oil significantly decreased the Beck Depression Inventory (BDI) score [weighted mean difference (WMD) (95 %CI) were -11.91 (-15.88, -7.95)], serum intact parathyroidism (iPTH), C-reactive protein (CRP), and triglycerides (TG) [standard mean difference (SMD) (95 %CI) were -0.56 (-0.89, -0.23); -0.36 (-0.63, -0.09), and -0.41 (-0.68, -0.14), respectively]. However, the fish oil group did not differ significantly from the control group in albumin (ALB), hemoglobin (Hb), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and mortality. CONCLUSIONS: Fish oil reduced the risk of AV-graft events and cardiovascular events, and alleviated depression symptoms in MHD patients. It can also improve secondary hyperparathyroidism, micro-inflammation, and hypertriglyceridemia. But there is no evidence that fish oil can improve nutritional status and renal anemia.

[Efficacy and safety of active vitamin D3 supplement in maintenance hemodialysis patients: a meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of active vitamin D3 treatment in maintenance hemodialysis patients (MHD). METHODS: We conducted a comprehensive search of the following databases: PubMed, Embase, Google scholar, CNKI, VIP, Wanfang data and CBM, to identify randomized controlled trials (RCTs) of active vitamin D3 supplementation in MHD patients up to November 2014. Meanwhile, we manually searched the reference lists of identified studies. The selection of studies, assessment of methodological quality and data extraction were performed independently by two researchers. Statistical analyses were performed using RevMan software, version 5.0. RESULTS: A total of 10 trials were included. There was a significant improvement in serum albumin (ALB) and an associated decline in PTH, alkaline phosphatase (ALP), C-reactive protein (CRP) and interleukin-6 (IL-6) in active vitamin D3-treated group (standardized mean difference (SMD) or weighted mean difference (95% CI): 0.47 (0.06, 0.88), -2.49 (-3.96, -1.02), -50.55 (-83.91, -17.19), -1.53 (-1.93, -1.12) and -4.71 (-7.48, -1.94), respectively). There was no statistical difference in the incidence of hyperphosphatemia, adverse events and mortality between the treatment and control group (RR (95% CI): 1.31 (0.96, 1.79), 0.85 (0.55, 1.32), 1.49 (0.80, 2.74), respectively). But there was a significant increase in serum calcium and calcium-phosphorus product in treatment group (RR (95% CI): 2.10 (1.18, 3.75) and 3.65 (1.45, 9.17), respectively). CONCLUSIONS: Currently available evidence suggests that active vitamin D3 is effective in treating secondary hyperparathyroidism, renal osteodystrophy, and improving malnutrition and microinflammation in MHD patients, without obvious adverse events. However, the occurrence of calcium and phosphate abnormalities should be closely monitored.

Effect of Vitamin D on Urinary Albumin Excretion in Diabetic Nephropathy Patients: A Meta-analysis of Randomized Controlled Trials.

It remains controversial, whether vitamin D reduces urinary albumin excretion in patients with diabetic nephropathy (DN). This metaanalysis was designed to evaluate the therapeutic effect of vitamin D, on urinary albumin excretion, in DN patients. Electronic databases, including PubMed, Embase, Web of Science, and Cochrane library were searched for randomized controlled trials (RCTs), regarding the effect of vitamin D on urinary albumin excretion in DN patients. The study selection and data extraction were conducted by two reviewers independently, and statistical analysis was performed using RevMan software, version 5.2. A total of nine RCTs including 1547 subjects were qualified. There were 815 participants in the study group and 732 in the control group. The fixed-effect model was used to analyze urinary albumin creatinine ratio (UACR) and urinary albumin excretion ratio (UAER), and the pooled standard mean difference (SMD) was -0.24 (95% CI: -0.39 to -0.09), P = .002, and -0.57 (95% CI: -0.71 to -0.43), P < .00001; respectively. These findings indicated that vitamin D-treated patients had a statistically significant reduction in UACR and UAER. High-quality RCTs are still required.  DOI: 10.52547/ijkd.7107.