cholecalciferol and Diabetic-Nephropathies

Several studies found that vitamin D3 might alter glucose metabolism, protect kidney from injury and even proposed the mechanisms. But results from previous studies have been conflicting. The aim of this study was to evaluate the efficacy and safety of vitamin D3 in patients with diabetic nephropathy. The underlying mechanism of vitamin D3 decreasing proteinuria is also discussed.. We conducted a search of English and Chinese articles using database of Pubmed, Embase, Sinomed, CNKI, Wanfang and clinical trial register centers, for randomized controlled trials of vitamin D3 in diabetic nephropathy patients. Two reviewers performed independently. Meta-analysis was used when studies were homogeneous enough.. Twenty studies, including 1 497 patients with diabetic nephropathy, were involved in this systemic review. Vitamin D3-treated patients with diabetic nephropathy had a statistically significant reduction in 24-hour proteinuria (weighted mean difference -0.44, 95% CI -0.54 to -0.34, Z = 8.80, P < 0.000 01) and urine albumin/creatine ratio (standardized mean difference -0.29, 95% CI -0.48 to -0.10, Z = 2.96, P = 0.003). But vitamin D3 supplementation did not significantly reduce blood pressure and hemoglobin A1c compared with control group. The potential mechanisms about the renal protection of vitamin D3, including the inhibition of rennin-angiotensin system, the protection of kidney from inflammation, fibrosis and the structure change of kidney are discussed. In addition, vitamin D3 did not significantly increase the incidence of adverse effects, including total adverse effects, gastrointestinal adverse effects and fluctuation of blood pressure.. Vitamin D3 can ameliorate proteinuria and protect kidney from injury in patients with diabetic nephropathy. This renoprotective effect is independent of blood pressure and glucose reduction. And it does not increase any adverse effects than control, even in combination therapy with angiotensin converting enzyme inhibitors/angiotensin receptor blockers. But due to the limited randomized controlled trials of high quality, more clinical researches should be taken in the future.

Topics: Blood Pressure; Cholecalciferol; Diabetic Nephropathies; Humans; Proteinuria; Randomized Controlled Trials as Topic

The effect of daily vitamin D supplementation on the serum concentration of vitamin D (the parent compound) may offer insight into vitamin D disposition.. To assess the total serum vitamin D response to vitamin D3 supplementation and whether it varies according to participant characteristics. To compare results with corresponding results for total serum 25-hydroxyvitamin D [25(OH)D], which is used clinically and measured in supplementation trials.. Exploratory study within a randomized trial.. 2000 International Units of vitamin D3 per day (or matching placebo).. Community-based.. 161 adults (mean ± SD age 70 ± 6 years; 66% males) with type 2 diabetes.. Changes in total serum vitamin D and total serum 25(OH)D concentrations from baseline to year 2.. At baseline, there was a positive, nonlinear relation between total serum vitamin D and total serum 25(OH)D concentrations. Adjusted effects of supplementation were a 29.2 (95% CI: 24.3, 34.1) nmol/L increase in serum vitamin D and a 33.4 (95% CI: 27.7, 39.2) nmol/L increase in serum 25(OH)D. Among those with baseline 25(OH)D < 50 compared with ≥ 50 nmol/L, the serum vitamin D response to supplementation was attenuated (15.7 vs 31.2 nmol/L; interaction P-value = 0.02), whereas the serum 25(OH)D response was augmented (47.9 vs 30.7 nmol/L; interaction P-value = 0.05).. Vitamin D3 supplementation increases total serum vitamin D and 25(OH)D concentrations with variation according to baseline 25(OH)D, which suggests that 25-hydroxylation of vitamin D3 is more efficient when serum 25(OH)D concentration is low.

Topics: Aged; Cholecalciferol; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dietary Supplements; Fatty Acids, Omega-3; Female; Humans; Male; Middle Aged; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Low vitamin D levels can be associated with albuminuria, and vitamin D analogs are effective anti-proteinuric agents. The aim of this study was to investigate differences in vitamin D levels between those with micro- and those with macroalbuminuria, and to determine whether low dose cholecalciferol increases vitamin D levels and ameliorates albuminuria.. Two studies were performed in which 25-OH vitamin D(3) (25(OH)D(3)) concentrations were determined by electrochemiluminescence immunoassay: 1) a cross-sectional study of patients with type 2 diabetes mellitus (T2DM) (n = 481) and healthy controls (n = 78); and 2) a longitudinal study of T2DM patients with albuminuria treated with conventional doses, 800 IU, of cholecalciferol for 6 months (n = 22), and a control group (n = 24).. 1) Cross-sectional study: Compared to controls and T2DM patients with normoalbuminuria, serum 25(OH)D(3) concentrations were significantly lower in patients with macro-albuminuria, but not in those with micro-albuminuria. Serum 25(OH)D(3) levels were independently correlated with microalbuminuria. 2) Longitudinal study: Cholecalciferol significantly decreased microalbuminuria in the early stages of treatment, in conjunction with an increase in serum 25(OH)D(3) levels.. Low vitamin D levels are common in type 2 diabetic patients with albuminuria, particularly in patients with macroalbuminuria, but not in those with microalbuminuria. Conventional doses of cholecalciferol may have antiproteinuric effects on Chinese type 2 diabetic patients with nephropathy.

Topics: Administration, Oral; Adult; Albuminuria; Cholecalciferol; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Longitudinal Studies; Male; Middle Aged

We aimed to determine the effect of a monthly oral vitamin D on the serum 25-hydroxyvitamin D levels and iPTH levels in patients with CKD.. This was a prospective controlled trial of 48 patients with CKD stage 3-4. Patients were divided into two groups Group1 the cholecalciferol treatment group, Group 2, the control group. One patient in Group 1, and 3 patients in Group2 were excluded after the baseline 25(OH)D levels were determined to be greater than 30ng/ml. Two patients in Group1, and one patient in Group 2 were excluded after the baseline iPTH was determined to be less than 70 pg/ml and greater than 300 pg/ml. Five patients in both groups were lost to follow-up. Thus, a total of 16 patients in Group 1 and 15 patients in Group2 completed the three month study. Group1 patients received 300,000 IU month oral cholecalciferol.. The mean serum 25(OH)D concentration of the group1 was significantly higher at baseline (P=0.039). At the end of the three months; serum 25 (OH) D level increased significantly in Group1 (P=0.001). iPTH level of Group1 was significantly lower at baseline (P=0.034). The values of the group1 before and end of third month was compared, serum Ca (P=0.011), P (P=0.013) level showed significant increase, but no significant increase in the Group 2 (P>0.05). The groups had not a clinically significant change in serum Ca and P level (P>0.05).. Oral cholecalciferol supplementation can be used safely and effective in reducing iPTH levels and correcting vitamin D insufficiency/deficiency in patients with CKD.

Topics: Administration, Oral; Adult; Aged; Bone Density Conservation Agents; Cholecalciferol; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Follow-Up Studies; Glomerulonephritis; Humans; Hyperparathyroidism; Hypertension; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Treatment Outcome; Vitamin D

To investigate the effect of vitamin D/vitamin D receptor (VDR)/Atg16L1 signaling on podocyte autophagy and survival in diabetic nephropathy.. Diabetic rat models were induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) and treated with and without gavage of 0.1 μg/kg/d active vitamin D3 (aVitD3; 1,25- OH vitamin D3) and kidney tissues assessed by histopathology and immunohistochemistry. The murine podocyte cell line MPC-5 was cultured under hyperglycemic conditions in the absence or presence of 100 nmol/L calcitriol to investigate podocyte injury and autophagy. Cell survival rates were analyzed using Cell Counting Kit-8 (CCK-8) assays and the numbers of autophagosomes were determined after transduction with the mRFP-GFP-LC3 autophagy reporter construct. The expression of autophagy-related proteins (LC3-II, beclin-1, Atg16L1) and podocyte-related proteins (nephrin, podocin, synaptopodin, and desmin) was determined by Western blotting.. VDR expression and autophagy were decreased in diabetic nephropathy. Calcitriol treatment repressed renal injury in rat diabetic kidneys and reduced high glucose-induced damage to cultured podocytes. Mechanistically, Atg16L1 was identified as a functional target of VDR, and siRNA-mediated knockdown of VDR and Atg16L1 blocked the protective effects of aVitD3 against podocyte damage.. Autophagy protects podocytes from damage in DN and is modulated by VitD3/VDR signaling and downstream regulation of Atg16L1 expression.

Topics: Animals; Autophagy; Autophagy-Related Proteins; Calcitriol; Cholecalciferol; Diabetes Mellitus; Diabetic Nephropathies; Female; Humans; Male; Mice; Podocytes; Rats; Receptors, Calcitriol

The aim of this study is to evaluate the association between urinary megalin, renal function, blood pressure, lipid profile, vitamin D and glycemic control in patients with type 2 diabetes mellitus (T2DM).. . This was a cross-sectional study which recruited 209 patients with T2DM. Urinary megalin was positively associated with systolic blood pressure (SBP) (r=0.218, p=0.04) but negatively with glomerular filtration rate (GFR) (r=-0.16, p=0.023). The levels of urinary albumin, triglycerides (TGs) and glycosylated hemoglobin (HbA1c) were higher in the "high-megalin" group, compared to those in "low-megalin" group. Moreover, there was a significant inverse association between vitamin D3 levels and megalin levels in urine (OR=0.281, p=0.047).. Our study showed for the first time that megalin is associated with progression factors of diabetic nephropathy as well as vitamin D deficiency (Tab. 3, Fig. 1, Ref. 15).

Topics: Albuminuria; Cholecalciferol; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Low Density Lipoprotein Receptor-Related Protein-2; Triglycerides; Vitamin D Deficiency

Studies indicated that imbalance of proinflammatory and anti-inflammatory cytokines may contribute to development of type 2 diabetes mellitus (T2DM). We hypothesized that sitagliptin and VitD3 may exert more anti-inflammatory effects on the regulation of cytokine balance in T2DM. Nonnephropathic and nephropathic T2DM patients were divided into the subgroups, based on treatments. The effect of 8 months sitagliptin, alone or together with 2 months of VitD3, on serum IFN-γ, IL-4, IL-17, IL-6, IL-21, TGF-β, and IL-37 levels was determined using enzyme-linked immunosorbent assay. Increased levels of interferon (IFN)-γ and IL-17 in untreated (without sitagliptin and VitD3) nephropathic and nonnephropathic patients and decreased levels of IL-37 in untreated nephropathic patients were observed compared with healthy controls. Treatment with sitagliptin plus VitD3 reduced the levels of IFN-γ and IL-17 in both nonnephropathic and nephropathic patients compared with untreated patients. The level of IL-37 was enhanced in patients treated with sitagliptin or sitagliptin plus VitD3, compared with untreated patients. Sitagliptin plus VitD3 treatment increased the levels of IL-4 in nonnephropathic patients. These findings indicated that the sitagliptin plus VitD3 was more effective to reduce the increased proinflammatory IFN-γ and IL-17 cytokines in T2DM patients.

Topics: Adult; Anti-Inflammatory Agents; Cholecalciferol; Cytokines; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Combinations; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Sitagliptin Phosphate; Young Adult

Renal podocytes form the main filtration barrier possessing unique phenotype maintained by proteins including podocalyxin and nephrin, which are modulated in pathological conditions. In diabetic nephropathy (DN), podocytes become structurally and functionally compromised. Nephrin, a structural backbone protein of the slit diaphragm, acts as regulator of podocyte intracellular signalling with renoprotective role. Vitamin D

Topics: Animals; Bone Density Conservation Agents; Cell Survival; Cholecalciferol; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Ergocalciferols; Glucose; Kidney Glomerulus; Membrane Proteins; Podocytes; Rats, Wistar; Sialoglycoproteins; Signal Transduction; Tissue Culture Techniques

Two new clinical trials highlight refinements in the use of vitamin D and its analogs in the treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD), and the treatment of proteinuria in diabetics. In patients with ESRD, alfacalcidol is as effective as paricalcitol in suppressing parathyroid hormone; the occurrence of hypercalcemia and hyperphosphatemia is infrequent and similar with the two analogs. Oral cholecalciferol reduces albuminuria and urinary transforming growth factor-β1 in patients with type 2 diabetes mellitus and proteinuria.

Topics: Albuminuria; Cholecalciferol; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Hyperparathyroidism, Secondary; Male; Renal Dialysis; Renin-Angiotensin System; Transforming Growth Factor beta1

The anti-inflammatory, antifibrotic, and antiproteinuric properties of vitamin D have been defined in studies using active vitamin D analogs. In this prospective observational study we determined whether nutritional vitamin D repletion can have additional beneficial effects in patients with type 2 diabetic nephropathy already established on renin-angiotensin-aldosterone system inhibition. During a 7-month period, 63 patients were enrolled and those with low levels of 25(OH)D were treated with oral cholecalciferol for 4 months. Baseline serum 25(OH)D and 1,25(OH)(2)D showed no significant correlation with baseline urinary MCP-1, TGF-β1, or albuminuria measured as the urinary albumin-to-creatinine ratio. Of the 63 patients, 54 had insufficient or deficient levels of serum 25(OH)D and 49 complied with cholecalciferol therapy and follow-up. Both 25(OH)D and 1,25(OH)(2)D were significantly increased at 2 and 4 months of treatment. Albuminuria and urinary TGF-β1 decreased significantly at both time points compared to their baseline values, while urinary MCP-1 did not change. Thus, in the short term, dietary vitamin D repletion with cholecalciferol had a beneficial effect in delaying the progression of diabetic nephropathy above that due to established renin-angiotensin-aldosterone system inhibition.

Topics: Administration, Oral; Aged; Albuminuria; Chemokine CCL2; Cholecalciferol; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Male; Middle Aged; Prospective Studies; Renin-Angiotensin System; Transforming Growth Factor beta1; Vitamin D; Vitamin D-Binding Protein