cholecalciferol and Proteinuria

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

Dysregulation of CD4+ T cell subsets participates in the pathogenesis of immunoglobulin A nephropathy (IgAN). Vitamin D has immunomodulatory functions. This study aims to investigate the regulatory effect of vitamin D3 on T helper- regulatory T (Th17-Treg) cells balance in rats with IgAN.. Sprague-Dawley rats were randomly assigned to a normal group (n = 6), an IgAN model group (n = 5), a prednisone treatment IgAN group (n = 6), a 1,25-dihydroxyvitamin D3 IgAN group (n = 6), and prednisone plus 1,25-dihydroxyvitamin D3 treatment group (n = 6). At week 12, the 24-hour urine protein excretion and erythrocyte count and renal pathological changes were determined, and serum interleukin-17 and Treg cell levels were measured in blood.. The urine protein content and the number of erythrocytes were lower in the vitamin D group than in the model group (P < .01), but higher than in the prednisone groups (P < 0.01). The pathological impairments in the glomerular mesangium, renal tubule, and renal interstitium decreased in response to treatment with prednisone with and without 1,25-dihydroxyvitamin D3. Serum interleukin-17 level in the vitamin D and prednisone plus vitamin D groups was lower than in the prednisone group (P < .05). The Treg cells in the vitamin D and prednisone plus vitamin D groups showed higher levels than in the prednisone group (P < .01).. Vitamin D3 can regulate the Th17/Treg balance and reduce the level of protein and blood in the urine of rats with IgAN.

Topics: Animals; Cholecalciferol; Erythrocytes; Glomerulonephritis, IGA; Interleukin-17; Kidney; Proteinuria; Rats; Rats, Sprague-Dawley; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Treatment Outcome; Vitamins

Vitamin D deficiency is common in glomerular disease. Supplementation may be ineffective due to ongoing urinary losses of vitamin D binding protein. We sought to determine if daily cholecalciferol supplementation would increase vitamin D concentrations in children with glomerular disease and persistent proteinuria, without adverse effects.. Eighteen participants at least 5 years of age with primary glomerular disease and urine protein:creatinine ratio ≥ 0.5 were enrolled from four pediatric nephrology practices to receive cholecalciferol supplementation: 4,000 IU or 2,000 IU per day for serum 25 hydroxyvitamin vitamin D (25OHD) concentrations < 20 ng/mL and 20 ng/mL to < 30 ng/mL, respectively. Measures of vitamin D and mineral metabolism were obtained at baseline and weeks 6 and 12. Multivariable generalized estimating equation (GEE) regression estimated mean percent changes in serum 25OHD concentration.. Median baseline 25OHD was 12.8 ng/mL (IQR 9.3, 18.9) and increased to 27.8 ng/mL (20.5, 36.0) at week 6 (p < 0.001) without further significant increase at week 12. A total of 31% of participants had a level ≥ 30 ng/mL at week 12. Supplementation was stopped in two participants at week 6 for mildly elevated calcium and phosphorus, respectively, with subsequent declines in 25OHD of > 20 ng/mL. In the adjusted GEE model, 25OHD was 102% (95% CI: 64, 141) and 96% (95% CI: 51, 140) higher versus baseline at weeks 6 and 12, respectively (p < 0.001).. Cholecalciferol supplementation in vitamin D deficient children with glomerular disease and persistent proteinuria safely increases 25OHD concentration. Ideal dosing to fully replete 25OHD concentrations in this population remains unknown.. NCT01835639. A higher resolution version of the Graphical abstract is available as Supplementary information.

Topics: Child; Cholecalciferol; Dietary Supplements; Humans; Kidney Diseases; Proteinuria; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

Body stores of vitamin D are measured as "total" serum 25-hydroxy vitamin D (25(OH)D). Its largest component is protein bound and lost in urine in nephrotic syndrome (NS). Our study investigates whether "free" 25(OH)D levels are a better guide to bone health and need for vitamin D supplementation in patients with steroid-sensitive NS (SSNS).. A cross-sectional study was performed in children with SSNS and healthy controls. Blood was tested for albumin, creatinine, calcium, phosphate, ALP, total and free (by direct ELISA) 25(OH)D, iPTH, and urine for protein-creatinine ratio.. These results confirm that total 25(OH)D levels are low in NS and related to degree of proteinuria. However levels of free 25(OH)D, ALP, and iPTH did not change in relapse or remission in comparison with healthy controls. Our results suggest that in proteinuric renal diseases, free 25(OH)D rather than total 25(OH)D levels should be used to diagnose vitamin D deficiency and guide therapy.

Topics: Case-Control Studies; Child; Child, Preschool; Cholecalciferol; Cross-Sectional Studies; Dietary Supplements; Ergocalciferols; Female; Glucocorticoids; Humans; Male; Nephrotic Syndrome; Proteinuria; Risk Factors; Serum Albumin, Human; Severity of Illness Index; Vitamin D Deficiency

In this study, we evaluated the relationship between serum homocysteine level and proteinuria, parathyroid hormone, vitamin D, and bone mineral density in kidney transplant recipients (KTR).. A total of 117 stable KTR older than 18 years was followed in our outpatient clinic. Demographic data were recorded. Simultaneously biochemical parameters, including glucose, blood urea nitrogenous, creatinine, calcium, phosphorus, sodium, potassium, albumin, parathormone, vitamin D. DEXA measurements were normal, osteoporotic, and osteopenic (12.3%, 36.3%, and 51.3%, respectively). There was a relationship between the serum homocysteine and usage of rapamycin (P = .05), statins (P = .057), and beta blockers (P = .01), DEXA measurements were not related with serum homocysteine levels and immunosuppressive drugs used. Serum homocysteine levels correlated negatively with blood urea nitrogen (P = .002), creatinine (P = .001), vitamin B. The bone mineral density decreased in more than 87% of our KTR. We did not find any relationship between DEXA measurements and levels of homocysteine, vitamin D, parathormone, and immunosuppressive drugs. It should be noted that some drugs used may affect serum homocysteine levels. Interestingly, there was a relationship between proteinuria and serum levels of homocysteine and vitamin D. Therefore, serum levels of homocysteine and vitamin D should be evaluated for preventing renal damage in KTR.

Topics: Absorptiometry, Photon; Bone Density; Calcineurin Inhibitors; Cholecalciferol; Female; Homocysteine; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Parathyroid Hormone; Proteinuria

Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D3 deficiency as a result of reduced renal 1α-hydroxylase activity. Vitamin D treatment to reduce proteinuria remains controversial, although there is an inverse correlation between vitamin D levels and proteinuria. Herein, we showed that 1,25-vitamin D3-deficient 25-hydroxy-vitamin-D3-1α-hydroxylase knockout mice and 1,25-vitamin D3-deficient rats develop podocyte injury and renal dysfunction. Glomerular injury was characterized by proteinuria and partial podocyte foot process effacement. Expression of nephrin, podocin, desmin, and transient receptor potential channel C6 in the podocyte was significantly altered in 1,25-vitamin D3-deficient animals. Supplementation with 1,25-vitamin D3 or 1,25-vitamin D2 prevented podocyte effacement or reversed glomerular and tubulointerstitial damage in 1,25-vitamin D3-deficient animals, thereby preserving and restoring renal function, respectively. The effect of 1,25-vitamin D3 deficiency and 1,25-vitamin D3 and 1,25-vitamin D2 repletion on proteinuria could not be explained by hypocalcemia, changes in parathyroid hormone, or fibroblast growth factor 23. This study demonstrates that 1,25-vitamin D3 deficiency directly leads to renal injury in rodents. Translated to human subjects, this would underline the need for early vitamin D supplementation in patients with glomerular disease and chronic renal insufficiency, which might inhibit or potentially reverse renal injury.

Topics: Albuminuria; Animals; Cholecalciferol; Kidney Diseases; Kidney Glomerulus; Mice, Inbred C57BL; Mice, Knockout; Parathyroid Hormone; Podocytes; Proteinuria; Rats; Rats, Wistar

To investigate whether an increase in vitamin D levels in patients with systemic lupus erythematosus (SLE) was associated with improvement in disease activity.. A total of 1,006 SLE patients were monitored over 128 weeks. SLE patients with low levels of 25-hydroxyvitamin D (25[OH]D; <40 ng/ml) were given supplements of 50,000 units of vitamin D2 weekly plus 200 units of calcium/vitamin D3 twice daily. Longitudinal regression models were used to estimate the association between levels of 25(OH)D and various measures of disease activity.. The SLE patients had the following characteristics: 91% were female, their mean age was 49.6 years, and their ethnicity was 54% Caucasian, 37% African American, and 8% other. For those with levels of 25(OH)D <40 ng/ml, a 20-unit increase in the 25(OH)D level was associated with a mean decrease of 0.22 (95% confidence interval [95% CI] -0.41, -0.02) (P = 0.032) in the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This corresponded to a 21% decrease in the odds of having a SELENA-SLEDAI ≥5 (95% CI 1, 37). The mean urine protein-to-creatinine ratio decreased by 2% (95% CI -0.03, -0.01) (P = 0.0001), corresponding to a 15% decrease in the odds of having a ratio >0.5 (95% CI 2, 27).. We found that a 20-ng/ml increase in the 25(OH)D level was associated with a 21% decrease in the odds of having a high disease activity score and a 15% decrease in the odds of having clinically important proteinuria. Although these associations were statistically significant, the clinical importance is relatively modest. There was no evidence of additional benefit of 25(OH)D beyond a level of 40 ng/ml.

Topics: Adult; Calcium; Cholecalciferol; Cohort Studies; Creatinine; Ergocalciferols; Female; Humans; Longitudinal Studies; Lupus Erythematosus, Systemic; Male; Middle Aged; Proteinuria; Severity of Illness Index; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Increasing evidence indicates that vitamin D deficiency exacerbates chronic kidney injury, but its effects on renal enlargement in polycystic kidney disease (PKD) are not known. In this study, male Lewis polycystic kidney disease (LPK) rats received a normal diet (ND; AIN-93G) supplemented with or without cholecalciferol (vitamin D-deficient diet, VDD; both 0.5% calcium), commenced at either postnatal week 3 (until weeks 10-20; study 1) or from week 10 (until week 20; study 2). Levels of 25-hydroxy vitamin D were reduced in groups receiving the VDD (12 ± 1 nmol/l vs. 116 ± 5 in ND; P < 0.001). In study 1, food intake and weight gain increased by ∼25% in LPK rats receiving the VDD ad libitum, and at week 20 this was associated with a mild reduction in the corrected serum calcium (SCa(2+), 7.4%) and TKW:BW ratio (8.8%), and exacerbation of proteinuria (87%) and hypertension (19%; all P < 0.05 vs. ND). When LPK rats were pair-fed for weeks 3-10, there was a further reduction in the SCa(2+) (25%) and TKW:BW ratio (22%) in the VDD group (P < 0.05 vs. ND). In study 2, the VDD did not alter food intake and body weight, reduced SCa(2+) (7.7%), worsened proteinuria (41.9%), interstitial monocyte accumulation (26.4%), renal dysfunction (21.4%), and cardiac enlargement (13.2%, all P < 0.05), but there was a trend for a reduction in the TKW:BW ratio (13%, P = 0.09). These data suggest that chronic vitamin D deficiency has adverse long-term actions on proteinuria, interstitial inflammation, renal function, and cardiovascular disease in PKD, and these negate its mild inhibitory effect on kidney enlargement.

Topics: Animals; Calcium, Dietary; Cardiovascular Diseases; Cholecalciferol; Dietary Supplements; Disease Progression; Kidney; Male; Phosphates; Polycystic Kidney Diseases; Proteinuria; Rats; Rats, Inbred Lew; Vitamin D Deficiency

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure in the world. Currently there are no treatments to prevent kidney due to ADPKD. Vitamin D is traditionally known for its role in maintaining calcium balance and normal bone health, but it is being increasingly being recognised for a number of other important physiological functions, including reducing blood pressure and proteinuria as well as kidney inflammation andfibrosis. Vitamin D deficiency is associated with proteinuria, increased mortality and may mediate the progression to kidney failure. Recent data from an Australian cohort study (AusDiab) reveals that vitamin D deficiency and insufficiency are common conditions, affecting 26.6% and 42.1% of the Australian community respectively. Preclinical studies from our laboratory have identified that vitamin D deficiency exacerbates proteinuria and hypertension in experimental PKD, and that this is reversed by treatment with vitamin D receptor agonist. In this manuscript, we report the rational and design of an open-label observational study of humans with ADPKD (eGFR>30 ml/min/1.73m2). All subjects will undergo screening for vitamin D levels at the beginning of study, and those that are found to be either deficient (<50 nmol/L) or insufficient (<75 nmol/L) will be repleted with oral cholecalciferol for 6 months. We predict that cholecalciferol will attenuate hypertension, proteinuria and reduce the urinary excretion of a biomarker, monocyte chemoattractant protein-1 (MCP-1, a surrogate inflammatory marker of progression in ADPKD). This study will provide evidence as to whether a simple intervention such as vitamin D repletion, in either deficient or insufficient states, is a treatment to prevent kidney failure in ADPKD.

Topics: Adolescent; Adult; Aged; Australia; Biomarkers; Chemokine CCL2; Cholecalciferol; Disease Progression; Female; Humans; Hypertension; Male; Middle Aged; Polycystic Kidney, Autosomal Dominant; Proteinuria; Research Design; Vitamin D; Vitamin D Deficiency; Young Adult

To investigate the effects of lead and cadmium on the metabolic pathway of vitamin D3.. Blood and urinary cadmium and urinary total proteins were measured in 59 smelter workers occupationally exposed to lead and cadmium. In 19 of these workers, the plasma vitamin D3 metabolites, (25-hydroxycholecalciferol (25 OHD3), 24R, 25-dihydroxycholecalciferol (24R,25(OH)2D3) and 1 alpha,25-dihydroxycholecalciferol (1 alpha, 25(OH)2D3)) were measured together with blood lead. Vitamin D3 metabolites were measured by radioimmunoassay, (RIA), lead and cadmium by atomic absorption spectrophotometry, and total proteins with a test kit.. Ranges for plasma 25(OH)D3, 24R,25(OH)2D3 and 1 alpha,25(OH)2D3 were 1.0-51.9 ng/ml, 0.6-5.8 ng/ml, and 0.1-75.7 pg/ml, respectively. Ranges for blood lead were 1-3.7 mumol/l, (21-76 micrograms/dl), blood cadmium 6-145 nmol/l, and urinary cadmium 3-161 nmol/l. Total proteins in random urine samples were 2.1-32.6 mg/dl. Concentrations of lead and cadmium in blood showed no correlation (correlation coefficient -0.265) but there was a highly significant correlation between blood and urinary cadmium. Concentrations for 24R,25(OH)2D3 were depressed below the normal range as blood and urinary cadmium increased, irrespective of lead concentrations. High cadmium concentrations were associated with decreased plasma 1 alpha,25(OH)2D3 when lead concentrations were < 1.9 mumol/l and with above normal plasma 1 alpha,25(OH)2D3 when lead concentrations were > 1.9 mumol/l, Kruskal-Wallis analysis of variance (K-W ANOVA) chi 2 = 10.3, p = 0.006. Plasma 25(OH)D3 was negatively correlated with both urinary total proteins and urinary cadmium, but showed no correlation with plasma 24R,25(OH)2D3, 1 alpha,25(OH)2D3, blood lead, or blood cadmium.. Continuous long term exposure to cadmium may result in a state of equilibrium between blood and urinary cadmium. Cadmium concentrations in blood could be predicted from the cadmium concentration of the urine, (regression coefficient +0.35 SE 0.077). Exposure to cadmium alone decreased the concentrations of 1 alpha,25(OH)2D3 and 24R,25(OH)2D3, whereas exposure to both cadmium and lead increased the concentrations of 1 alpha,25(OH)2D3. It has been suggested that cadmium and lead interact with renal mitochondrial hydroxylases of the vitamin D3 endocrine complex. Perturbation of the vitamin D metabolic pathway by cadmium may result in health effect, such as osteoporosis or osteomalacia, risks which are possibly increased in the presence of lead.

Topics: 24,25-Dihydroxyvitamin D 3; Analysis of Variance; Cadmium; Calcifediol; Calcitriol; Cholecalciferol; Humans; Lead; Male; Metallurgy; Occupational Exposure; Proteinuria

Mercuric chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway (BN) rats. This syndrome is the consequence of T cell-dependent polyclonal B cell activation and autoantibody production. We have previously shown that HgCl2-induced autoimmune perturbations can be prevented in BN rats by the administration of cyclosporin A (CsA). The most potent vitamin D3 metabolite 1,25(OH)2 D3 (Vit D3) shares certain immunomodulatory properties with CsA. We therefore chose to compare the effects of Vit D3 to those of CsA in BN rats treated with HgCl2 in order to establish whether Vit D3 either alone or in combination with CsA can attenuate an autoimmune syndrome in vivo.. BN rats were treated with HgCl2 according to a standard protocol. Subgroups of rats were also given CsA alone, Vit D3 or synthetic analogues of Vit D3 alone, or combinations of both agents. Different doses and routes of administration were compared. The following markers of disease activity were evaluated: mortality, peak proteinuria, serum IgE concentrations, and renal immunoglobulin deposition.. Disease activity was markedly attenuated in all rats treated with CsA alone. Vit D3 and certain of its synthetic analogues administered alone also tempered the autoimmune process, but to a lesser extent than did CsA. The effect of CsA alone was so potent, that no additive or synergistic effects could be demonstrated when CsA was administered in combination with Vit D3.. Despite similar described immunomodulatory effects in vitro, CsA is clearly more effective than Vit D3 in preventing HgCl2 autoimmune disease in BN rats. This suggests that there is a difference in the cellular targets of these two agents in vivo, and/or a difference in the potency with which HgCl2-triggered immune activation is suppressed.

Topics: Animals; Autoimmune Diseases; Autoimmunity; Calcium; Cholecalciferol; Cyclosporine; Drug Therapy, Combination; Female; Glomerulonephritis; Immunoglobulin E; Immunosuppressive Agents; Lymphoproliferative Disorders; Male; Mercuric Chloride; Proteinuria; Rats; Rats, Inbred BN; Serum Albumin

We examined the immunoregulating effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3 (22-oxa-1 alpha,25(OH)2D3), a synthetic analogue of vitamin D3 with an oxygen atom at C22 in the side chain skeleton, on spontaneously developing autoimmune disorders in MRL/Mp-lpr/lpr (MRL/l) mice. The oral administration of the compound significantly prolonged the average life span of the mice and showed a significant reduction in proteinuria. Histopathological investigations also revealed that pathological conditions such as renal arteritis, granuloma or arthritis of the knee joints were much lighter in the treated group than in the untreated group. Furthermore, the lymphocyte phenotypes in thymus, lymphnode, and spleen were partially normalized and became similar to those found in young control animals by the treatment with 22-oxa-1 alpha,25(OH)2D3. These results suggest that this compound inhibits the development of lupus nephritis in MRL/l mice and may be therapeutically effective on the mice.

Topics: Animals; Antigens, Surface; Antineoplastic Agents; Autoimmune Diseases; Calcitriol; Cholecalciferol; Kidney; Knee Joint; Male; Mice; Mice, Inbred Strains; Organ Specificity; Proteinuria; Specific Pathogen-Free Organisms

Plasma concentrations of 25-hydroxy-cholecalciferol (25-OHD3) and vitamin-D-binding globulin (V.D.B.G.) were significantly reduced in ten nephrotic subjects. V.D.B.G., which is undetectable in normal urine, was present in substantial amounts in the urine of each nephrotic subject. Administration of 3H-labelled cholecalciferol to three subjects resulted in the rapid appearance of the labelled vitamin in the urine, mainly as the 25-hydroxylated metabolite bound to V.D.B.G. in amounts which could largely account for the low plasma-25-OHD3. The plasma half-life of 25-OHD3 was substantially reduced in the nephrotic syndrome.

Topics: Adult; Aged; Alkaline Phosphatase; Cholecalciferol; Chromatography; Female; Globulins; Half-Life; Humans; Isotope Labeling; Male; Middle Aged; Nephrotic Syndrome; Protein Binding; Proteinuria; Serum Albumin; Serum Globulins; Tritium; Vitamin D

The absorption and metabolism of vitamin D(3)-(3)H was studied in eight patients with chronic renal failure. Although the intestinal absorption of vitamin D(3)-(3)H was normal, the metabolic fate of the vitamin was abnormal as characterized by a twofold increase in fractional turnover rate, an abnormal accumulation of biologically inactive lipid-soluble metabolites, and the urinary excretion of both vitamin D(3)-(3)H and biologically inactive metabolites. Neither alterations in water-soluble vitamin D(3) metabolites nor qualitative abnormalities in protein-binding of vitamin D(3) were observed in the uremic subjects. Although hemodialysis proved ineffectual in reversing the observed abnormalities in vitamin D(3) metabolism and excretion, renal homotransplantation was completely successful in this regard. These experiments support the conclusion that the resistance to therapeutic doses of vitamin D often seen in patients with chronic renal failure and renal osteodystrophy results from an acquired defect in the metabolism and excretion of vitamin D.

Topics: Adult; Alkaline Phosphatase; Animals; Biological Assay; Blood Urea Nitrogen; Chloroform; Cholecalciferol; Chromatography; Electrophoresis; Feces; Female; Glomerulonephritis; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Nephrotic Syndrome; Proteinuria; Pyelonephritis; Rats; Renal Dialysis; Transplantation, Homologous; Tritium