The relationship between renal injury and change in vitamin D metabolism in aged rats with insulin resistance or type 2 diabetes mellitus

Insulin resistance (IR), IR treated with vitamin D, IR treated with 1alpha-hydroxyvitamin D (1alpha-(OH)D), type 2 diabetes mellitus (T2DM), T2DM treated with vitamin D and T2DM treated with 1alpha-(OH)D were studied in animal models using aged Wistar rats. Glucose infusion rates and levels of urinary albumin (UA), serum 25-hydroxyvitamin D (25-(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. T2DM rats had higher UA than IR or normal rats, and levels of 25-(OH)D in all models weresimilar. IR rats had higher 1,25-(OH)2D levels than T2DM rats, and had lower 1,25-(OH)2D levels than normal rats. Treating IR or T2DM rats with vitamin D had no effect on 25-(OH)D or 1,25-(OH)2D. Administration of 1alpha-(OH)D significantly increased 1,25-(OH)2D in IR rats to above-normal levels, and significantly increased 1,25-(OH)2D in T2DM rats to normal levels. In IR or T2DM, abnormal vitamin D metabolism is characterized by 1,25-(OH)2D deficiency and is related to renal injury.     

Evidence that 1,25-dihydroxyvitamin D3 inhibits the hepatic production of 25-hydroxyvitamin D in man

Previous in vitro studies in rachitic rat liver suggested that 1,25-dihydroxyvitamin D inhibits the hepatic production of 25-hydroxyvitamin D (25-OHD). An investigation therefore was carried out in eight normal subjects to determine whether concomitant administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] would alter the response of serum 25-OHD to challenge with vitamin D. In control studies, vitamin D, 100,000 U/d for 4 d, significantly increased mean serum 25-OHD, from 26.3 +/- 2.9 to 66.7 +/- 12.6 ng/ml (P less than 0.01). In contrast, 1,25(OH)2D3, 2 micrograms/d for 4 d, completely prevented an increase in serum 25-OHD in response to the same dose of vitamin D in the same individuals (25.1 +/- 2.2 vs. 27.4 +/- 5.3 ng/ml, NS). In a post-control study in seven of the normal subjects, vitamin D again significantly increased mean serum 25-OHD, from 18.2 +/- 3.1 to 42.8 +/- 4.7 ng/ml (P less than 0.001). In each of the three studies, mean serum calcium, phosphorus, and creatinine did not change and remained within the normal range. Whereas mean urinary calcium did not change in response to vitamin D alone during the 4 d of the two control studies, it increased significantly in the study in which vitamin D and 1,25(OH)2D3 were given together. A dose-response inhibition of the response of serum 25-OHD to vitamin D by 1,25(OH)2D3 was demonstrated in two of the normal subjects. The results provide evidence that 1,25(OH)2D3 inhibits the hepatic synthesis of its precursor 25-OHD in man.     

2型糖尿病患者血25-羟维生素D水平的改变及其对血糖与骨量的影响

目的：研究2型糖尿病患者血25-羟维生素D[25（OH）D]水平的改变对血糖与骨量的影响。方法本研究收集621例复旦大学附属中山医院内分泌科2009年10月至2011年3月住院2型糖尿病患者的临床资料,将测得的血25（OH）D进行季节校正后纳入分析。以血25（OH）D等于50 nmol/L为界将患者分为25（OH）D缺乏组[25（OH）D＜50 nmol/L]及25（OH）D非缺乏组[25（OH）D≥50 nmol/L]两组,观察两组之间糖代谢指标[包括空腹血糖（FBS）、餐后2 h血糖（2 h PG）、糖化血红蛋白（HbA1c）、糖化白蛋白、空腹胰岛素（FINS）]及骨代谢指标[包括甲状旁腺激素（PTH）、碱性磷酸酶（ALP）、骨密度]的差异。结果（1）2型糖尿病患者25（OH）D的平均水平低于50 nmol/L,而且女性较男性更低（P＜0.001）;（2）维生素D缺乏组血空腹胰岛素水平高于维生素D非缺乏组（P＜0.05）,胰岛素抵抗指数（HOMA-IR）也高于维生素D非缺乏组（P＜0.001）。FPG、HbA1c及胰岛素分泌指数（HOMA-B）两组间无明显统计学差异;（3）维生素D缺乏组PTH高于维生素D非缺乏组（P＜0.05）;维生素D缺乏组腰椎、股骨颈和全髋骨密度均低于维生素D非缺乏组（P＜0.05）;钙磷乘积及ALP两组间无统计学意义差异。结论2型糖尿病患者普遍存在维生素D缺乏,在2型糖尿病人群中,胰岛素抵抗、骨量流失可能与血25（OH）D水平降低有关。     

Evidence for extrarenal metabolism of 25-hydroxyvitamin D3 in man

Metabolites of vitamin D3 were measured in the circulation of four patients on chronic haemodialysis (three of whom were surgically anephric) before and during daily ingestion of 40 000 i.u. of cholecalciferol. Circulating 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] was measurable, but abnormally low before treatment; its circulating concentration rose in a substrate dependent manner when serum 25-hydroxyvitamin D3 (25-OHD3) increased, but the response was reduced when compared with the normal relationship. Serum 1,25-hydroxyvitamin D3 [1,25-(OH)2D3] and calcidiol lactone (25-OHD3-lactone) were consistently unmeasurable in sera from these patients before administration of cholecalciferol. However, when serum 25-OHD3 rose with treatment, 1,25-(OH)2D3 became detectable in the sera of three of the four patients and 25-OHD3-lactone could be measured in all of them. These data indicate that extrarenal sites of synthesis of 24,25-(OH)2D3, 25-OHD3-lactone and 1,25-(OH)2D3 exist in chronically dialysed patients but require large amounts of substrate to be significant.     

Vitamin D and vitamin-D-binding protein kinetics in patients treated with continuous ambulatory peritoneal dialysis (CAPD)

Serum and dialysate levels of 25-hydroxycholecalciferol (25-OHD3), 1,25 dihydroxycholecalciferol (1,25-(OH)2D3), and vitamin-D-binding protein (DBP) were measured in 14 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Serum levels of 25-OHD3 and DBP were within normal range (29.1 +/- 22.9 nmol/L and 5.9 +/- 1.1 mumol/L, respectively). Serum levels of 1,25-(OH)2D3 were subnormal in all (less than 16 pmol/L) but one. In 5 patients, dialysate concentrations of 25-OHD3 were 2.3 +/- 0.9 nmol/L, the rest had levels less than 1.0 nmol/L. Small quantities of 1,25-(OH)2D3 were found in the dialysate effluents. DBP could be detected in the dialysate in all patients (0.24 +/- 0.06 mumol/L). Mass transfer (MT) of 25-OHD3 and DBP were respectively -10.4 +/- 8.3 nmol/24 h and -1.46 +/- 0.46 0.46 mumol/24 h. Peritoneal clearances of 25-OHD3 and DBP were low (0.40 +/- 0.37 mL/min and 0.18 +/- 0.06 mL/min, respectively. We conclude that CAPD leads to losses of 25-OHD3 and DBP. However, the peritoneal loss of DBP is well compensated and does not result in serum deficiency. Serum 25-OHD3 levels did not correlate with time on CAPD.     

Quantitation of the main metabolites of vitamin D in a single serum sample II. Determination by uv-absorption and competitive protein binding assays

The present report, together with extraction, separation and purification procedures described previously [1], constitutes a sensitive method for determination of vitamin D and its main metabolites in 2 ml of human serum. By omitting vitamin D itself, 25-OHD, 24,25-(OH)₂D, 25,26-(OH)₂D and 1,25-(OH) ₂D could be determined in less than 0.5 ml serum. The quantitation methods described have detection limits of 1.8 pmol for vitamin D, 20 fmol for 25-OHD, 24,25-(OH)₂D and 25,26-(OH)₂D, and 1 fmol for 1,25-(OH)₂D.     

Effect of underground working on vitamin D levels and bone mineral densities in coal miners: a controlled study

The aim of this study was to determine the effect of underground working on 25-hydroxyvitamin D (25-OHD) levels and bone mineral density (BMD) values in coal miners. Fifty coal miners working underground and 50 surface workers as controls, matched for age and body mass index, from Zonguldak, Turkey, were recruited to the study. Levels of 25-OHD, biochemical bone markers, and lumbar spine and femur BMD values were measured in all study participants. Lumbar spine and femur BMD values were significantly higher in underground workers compared with surface workers, but there was no significant difference in 25-OHD levels between the two groups. Duration of underground working, age, 25-OHD levels, cigarette consumption and dietary calcium intake were not correlated with BMD values. Underground physical working does not seem to be a significant risk factor for low 25-OHD levels or low BMD values.     

25-hydroxycholecalciferol stimulation of muscle metabolism.

Intact diaphragms from vitamin D-deficient rats were incubated in vitro with [3H]leucine. Oral administration of 10 mug (400 U) of cholecalciferol 7 h before incubation increased leucine incorporation into diaphragm muscle protein by 136% (P less than 0.001) of the preparation from untreated animals. Nephrectomy did not obliterate this response. ATP content of the diaphragm muscle was also enhanced 7 h after administration of the vitamin. At 4 h after administration of cholecalciferol, serum phosphorus concentration was reduced by 0.7 mg/100 ml (P less than 0.025) and the rate of inorganic 32PO4 accumulation by diaphragm muscle was increased by 18% (P less than 0.025) over the untreated animals. Increasing serum phosphate concentration of the vitamin D-deficient animals by dietary supplementation with phosphate for 3 days failed to significantly enhance leucine incorporation into protein. However, supplementation of the rachitogenic, vitamin D-deficient diet with phosphorus for 3 wk stimulated the growth of the animal and muscle ATP levels. This increase in growth and muscle ATP content attributed to the addition of phosphorus to the diet was less than the increase in growth and muscle ATP levels achieved by the addition of both phosphorus and vitamin D to the diet. To eliminate systemic effects of the vitamin, the epitrochlear muscle of the rat foreleg of vitamin D-depleted rats was maintained in tissue culture. Addition of 20 ng/ml of 25-hydroxycholecalciferol (25-OHD3) to the medium enhanced ATP content of the muscle and increased leucine incorporation into protein. Vitamin D3 at a concentration of 20 mug/ml and 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) at a concentration of 500 pg/ml were without effect. Analysis of muscle cytosol in sucrose density gradients revealed a protein fraction which specifically bound 25-OHD3 and which demonstrated a lesser affinity for 1,25-(OH)2D3. These studies suggest that 25-OHD3 may influence directly the intracellular accumulation of phosphate by muscle and thereby play an important role in the maintenance of muscle metabolism and function.     

Calcium and vitamin D. Diagnostics and therapeutics

Vitamin D is neither a vitamin nor a nutrient if adequate exposure to sunlight is available to produce adequate quantities of vitamin D3 in the skin. It is well known that an adequate supply of vitamin D, either from the diet or from the skin, is important for maximum bone health throughout life. The new revelation that 25(OH)D can be metabolized to 1,25(OH)2D in the colon, prostate, and skin opens a new chapter in the vitamin D story. It is quite possible that there are two levels of vitamin D sufficiency. One level requires that the serum 25(OH)D levels be at least 20 ng/mL to satisfy the body's requirement for the renal production of 1,25(OH)2D that regulates calcium absorption, and bone calcium mobilization and bone mineralization. The second level may need higher circulating levels of 25(OH)D for maximum cellular health because of the conversion of 25(OH)D to 1,25(OH)2D in extrarenal tissues, such as the prostate, colon, and skin.     

糖尿病肾病患者血清1，25-二羟维生素D3水平及临床意义

目的探讨血清1,25-二羟维生素D。水平在糖尿病肾病（diabeticnephropathy,DN）进展中的作用。方法131例2型糖尿病患者分为单纯糖尿病组（DM组）30例、早期DN组（EDN组）32例、临床DN组（CDN组）35例与DN终末期组（ESDN组）34例,选择体检健康者30例为对照组,各组采用ELISA法检测血清1,25-二羟维生素D3和25-羟维生素D。水平。结果糖尿病及DN各组血清1,25-二羟维生素D3及25-羟维生素D。水平均明显低于对照组（P〈0．01）,且随DN逐渐进展二者水平均逐渐降低（P〈0．05）;糖尿病患者血清1,25-二羟维生素D3水平与尿微量白蛋白排泄率呈负相关（r=0．452,P=0．034）,与肾小球滤过率呈正相关（r=0．390,P=0．006）。结论血清1,25-二羟维生素D3水平检测可能有利于DN的早期发现和病情判断。     

Evidence for alteration of the vitamin D-endocrine system in blacks

As compared with values in white subjects, bone mass is known to be increased and urinary calcium to be diminished in black individuals. To evaluate the possibility that these changes are associated with alterations in the vitamin D-endocrine system, an investigation was performed in 12 black subjects, 7 men and 5 women, and 14 white subjects, 8 men and 6 women, ranging in age from 20 to 35 yr. All of them were hospitalized on a metabolic ward and were given a constant daily diet containing 400 mg of calcium, 900 mg of phosphorus, and 110 meq of sodium. Whereas mean serum calcium, ionized calcium, and phosphate were the same in the two groups, mean serum immunoreactive parathyroid hormone (350 +/- 34 vs. 225 +/- 26 pg/ml, P less than 0.01) and mean serum 1,25-dihydroxyvitamin D (1,25(OH)2D) (41 +/- 3 vs. 29 +/- 2 pg/ml, P less than 0.01) were significantly higher, and mean serum 25-hydroxy-vitamin D (25-OHD) was significantly lower in the blacks than in the whites (6 +/- 1 vs. 20 +/- 2 ng/ml, P less than 0.001). Mean urinary sodium and 24-h creatinine clearance were the same in the two groups, whereas mean urinary calcium was significantly lower (101 +/- 14 vs. 166 +/- 13 mg/d, P less than 0.01) and mean urinary cyclic AMP was significantly higher (3.11 +/- 0.47 vs. 1.84 +/- 0.25 nM/dl glomerular filtrate, P less than 0.01) in the blacks. Further, the blacks excreted an intravenous calcium load, 15 mg/kg body weight, as efficiently as the whites (49 +/- 3 vs. 53 +/- 3%, NS). Mean serum Gla protein was lower in blacks than in whites (14 +/- 2 vs. 24 +/- 3 ng/ml, P less than 0.02), and increased significantly in both groups in response to 1,25(OH)2D3, 4 micrograms/d for 4 d. There was a blunted response of urinary calcium to 1,25(OH)2D3 in the blacks, and mean serum calcium did not change. The results indicate that alteration of the vitamin D-endocrine system with enhanced renal tubular reabsorption of calcium and increased circulating 1,25(OH)2D as a result of secondary hyperparathyroidism may contribute to the increased bone mass in blacks. Their low serum 25-OHD is attributed to diminished synthesis of vitamin D in the skin because of increased pigment.     

ApaI polymorphisms of the vitamin D receptor predict bone density of the lumbar spine and not racial difference in bone density in young men

A number of previous investigations showed significant associations between polymorphisms of the vitamin D receptor (VDR) gene and bone mineral density (BMD). BMD is influenced by hormones and the rate of skeletal remodeling. A study was performed to investigate the possible relationship between Apa I, Bsm I, Taq I, and Fok I polymorphisms of the VDR gene and serum 1,25-dihydroxyvitamin D (1,25[OH]2D), osteocalcin, and propeptide of type I collagen (PICP)-markers of bone turnover, total body calcium, and BMD of the total body, radius, lumbar spine, trochanter, and femoral neck-in 39 young adult black men of 20 to 40 years of age and 44 age-, height-, and weight-matched white men. The distribution of each of the four alleles of the VDR genotypes was similar in the two racial groups. The Apa I VDR genotype was associated with serum PICP (P =.0494) but not with serum 1,25(OH)2D or serum osteocalcin. A significant association between the Apa I VDR genotype and BMD of the lumbar spine (P =.0291) was also observed. However, the Bsm I, Taq I, and Fok I genotypes were not significantly associated with BMD or serum osteocalcin, PICP, or 1,25(OH)2D. Multivariate stepwise analysis indicated that (1) the Apa I VDR genotype was associated with BMD of the lumbar spine in the two groups together; with total body calcium and BMD of the total body, radius, trochanter, and femoral neck in the black men; and with BMD of the radius in the white men; analysis also indicated that (2) race was significantly associated with total body calcium and BMD of the total body, lumbar spine, and femoral neck. In summary, the Apa I VDR genotype is associated with serum PICP and BMD at a number of sites but does not contribute to or account for racial differences in BMD in young adult men.     

Chronic 1,25-dihydroxyvitamin D3 administration in the rat reduces the serum concentration of 25-hydroxyvitamin D by increasing metabolic clearance rate.

Administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can lower the serum concentration of 25-hydroxyvitamin (25-OH-D). To determine if 1,25(OH)2D3 lowers serum 25-OH-D by increasing clearance or reducing production, we directly measured the metabolic clearance rate (MCR) of 25-OH-D in rats chronically infused with 1,25(OH)2D3. Chronic 1,25(OH)2D3 administration (0 to 75 pmol/d) reduced, in a time- and dose-dependent fashion, the serum concentrations of 25-OH-D3 and 24,25(OH)2D3 from 18 +/- 2 to 9 +/- 1 ng/ml and from 4.8 +/- 0.7 to 1.3 +/- 0.3 ng/ml, respectively, and increased sevenfold the in vitro conversion of 25-OH-D to 24,25(OH)2D3 by kidney homogenates. The reduction in serum 25-OH-D3 was completely accounted for by an increase in MCR. No change in production occurred. The influence of 1,25(OH)2D3 on serum 25-OH-D3 and 24,25(OH)2D3 was shown not to be dependent on induction of hypercalcemia. These data suggest that chronic 1,25(OH)2D3 administration lowers serum 25-OH-D by increasing the metabolic clearance of 25-OH-D3 and not by decreasing its production.     

The effect of the dihydroxylated metabolites of vitamin D and dietary phosphate restriction on bone disease in uraemic rats

Uraemic rats maintained on either a high or a low phosphate diet for 12 weeks were allocated to one of the following oral vitamin D treatment groups and received: 1,25-dihydroxycholecalciferol [1, 25-(OH)2D3], 24,25-dihydroxycholecalciferol [24,25-(OH)2D3], both 1,25-(OH)2D3 and 24,25-(OH)2D3, or no vitamin D supplements. Mean serum creatinine concentrations were elevated to a similar extent in all groups. Mean serum concentrations of calcium, phosphate and alkaline phosphatase were not significantly different from normal in any of the groups. In the group receiving the high phosphate diet and no vitamin D supplements, calcified bone area measured by quantitative computerized histomorphometry was significantly lower than in the group receiving the low phosphate diet and no vitamin D supplements (0.01 greater than P greater than 0.001), and in the groups receiving high phosphate diet and either 1,25-(OH)2D3 (0.01 greater than P greater than 0.001) or 24,25-(OH)2D3 (0.01 greater than P greater than 0.001). We conclude that uraemic rats maintained on a high phosphate diet for 12 weeks develop skeletal demineralization, this process does not occur in rats on a low phosphate diet, and a decrease in calcified bone area may be prevented by treatment with either 1,25-(OH)2D3 or 24,25-(OH)2D3.     

Evidence for extrarenal production of 1 alpha ,25-dihydroxyvitamin D in man.

Recent studies provide evidence for extrarenal production of 1 alpha ,25-dihydroxyvitamin D [1 alpha ,25(OH)2D]. To investigate this possibility, serum vitamin D, 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha ,25(OH)2D were measured in eight adult anephric subjects. All were undergoing hemodialysis and three of them were receiving vitamin D, 50,000 or 100,000 U/d. Serum vitamin D was elevated in two of the patients given vitamin D and was abnormally low in the others. Mean serum 25-OHD was increased in patients given vitamin D (94.0 +/- 7.6 ng/ml) and was normal in the others (16.4 +/- 0.9 ng/ml, P less than 0.001). Mean serum 24,25(OH)2D was normal in patients given vitamin D (1.38 +/- 0.27 ng/ml) and was low in the others (0.25 +/- 0.08 ng/ml, P less than 0.001). Serum 24,25(OH)2D correlated significantly with serum 25-OHD (r = 0.848, P less than 0.01). Mean serum 1 alpha ,25(OH)2D determined by receptor assay was 5.8 +/- 1.9 pg/ml in patients who were not given vitamin D and was 14.1 +/- 0.6 in those who were given vitamin D (P less than 0.001). Serum 1 alpha ,25(OH)2D correlated significantly with serum 25-OHD (r = 0.911, P less than 0.01). Mean serum 1 alpha ,25(OH)2D, measured by bioassay, was 8.3 +/- 1.9 pg/ml in patients who were given vitamin D and was 15.9 +/- 2.4 pg/ml in those who were given vitamin D (P less than 0.05). There was a significant correlation between the values for serum 1 alpha ,25(OH)2D obtained with the two methods (r = 0.728, P less than 0.01). The results (a) provide evidence in man for extrarenal production of both 24,25(OH)2D and, by two independent assays, of 1 alpha , 25(OH)2D, and (b) indicate that serum values of the two dihydroxy metabolites of vitamin D in anephric subjects vary with the serum concentration of the precursor 25-OHD.     

Are tuberculous patients at a great risk from hypercalcemia?

The risk of tuberculous patients to develop hypercalcemia was investigated in 33 patients aged 19 to 80. Twenty-two of the 33 received no vitamin D supplements. Before antituberculous chemotherapy serum calcium corrected for albumin and urinary calcium levels were normal, serum 25-hydroxyvitamin D (25(OH)D) levels were low, but serum 1,25(OH)2D levels, oral calcium load test and intestinal 47Ca absorption were normal. After 17 to 34 days of chemotherapy serum calcium corrected for albumin and 1,25(OH)2D levels were lower without change in serum D-binding protein. In 11 patients 25(OH)D, 50 micrograms/day, was given orally for two months. 25(OH)D given three days before chemotherapy in five patients induced an increase of levels of 1,25(OH)2D which was greater than in 10 control patients with similar serum levels of 25(OH)D. When chemotherapy was added to 25(OH)D, the five patients showed high normal 1,25(OH)2D levels. The last six patients received 25(OH)D together with or after starting chemotherapy. None of the 33 patients developed hypercalcemia, even when supplemented with 25(OH)D for two months. It appears that hypercalcemia is uncommon in tuberculosis.     

1,25-Dihydroxyvitamin D3 increases serum and tissue accumulation of aluminum in rats

We examined the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in both hypercalcemic and hypocalcemic rat models and the effect of exogenous 25-hydroxyvitamin D3 (25(OH)D3) on serum and tissue aluminum (Al) burdens. Rats fed a 0.2% Al diet received daily subcutaneous injections of either 1,25(OH)2D3 (80.9 ng/kg, n = 5 and 809 ng/kg, n = 8), 25 (OH)D3 (809 ng/kg, n = 4, and 8090 ng/kg, n = 8) or propylene glycol vehicle for 18 days. Rats given 809 ng/kg of 1,25(OH)2D3 were hypercalcemic and when compared with pair-fed controls had higher serum (33.1 vs. 14.3 micrograms/L, P less than 0.01), bone (21.2 vs. 13.2 micrograms/gm, P less than 0.01), and kidney (6.5 vs. 2.0 micrograms/gm, P less than 0.01) but not brain (1.2 vs. 1.5 micrograms/gm) or liver (0.9 vs. 0.8 micrograms/gm dry tissue) Al concentration. The lower dose of 1,25(OH)2D3 had no effect on serum or tissue Al. Treatment with 25(OH)D3 did not increase serum Ca and Al or tissue Al concentration. To dissociate a specific effect of exogenous 1,25(OH)2D3 from the concurrent hypercalcemia, endogenous production of 1,25(OH)2D3 was stimulated. Animals were fed a low Ca diet until hypocalcemia developed and were then divided into four groups: one given low Ca (n = 7) for 21 days, one given low Ca plus 0.2% Al (n = 7) for 21 days, one returned to a normal Ca diet (n = 4) for 30 days, and one returned to a normal Ca diet for 9 days and continued with a normal diet plus 0.2% Al (n = 5) for 21 days. Hypocalcemic rats fed the Al diet, when compared with hypocalcemic controls, had higher serum (143.6 vs. 31.8 micrograms/L, P less than 0.01), bone (16.0 vs. 2.9 micrograms/gm, P less than 0.01), and kidney (8.2 vs. 2.8 micrograms/gm, P less than 0.005) but not brain (3.4 vs. 2.3 micrograms/gm) or liver (3.8 vs. 2.3 micrograms/gm) Al concentrations. Serum, bone, and kidney Al concentration was also significantly higher than that in normocalcemic rats fed the Al diet. These results indicate that pharmacologic doses of 1,25(OH)2D3 and dietary hypocalcemia enhance gastrointestinal Al absorption and serum, kidney, and bone Al concentration.     

1,25-(OH)_2D_3减轻糖尿病大鼠炎症因子的排泄及podocin表达缺失

目的:观察1,25-(OH)2D3对糖尿病大鼠尿液炎症因子单核细胞趋化蛋白- 1(MCP-1)、肿瘤坏死因子-α(TNF-α)、干扰素-λ(IFN-λ)及podocin表达水平的影响。方法:雄性Wistar大鼠随机分为对照组和糖尿病模型组;后者经链脲菌素诱导糖尿病模型成功后再随机分为糖尿病组和1,25-(OH)2D3组。给予1,25-(OH)2D3第6周测定大鼠尿红细胞、24小时尿蛋白、MCP-1、TNF-α、IFN-λ排泄及血糖水平。肾组织光镜电镜、肾小球podocin免疫组化及荧光染色定量分析检测podocin的表达。结果:与对照组相比,1,25-(OH)2D3组及糖尿病组尿红细胞、尿蛋白、MCP-1、TNF-α、IFN-λ、血糖明显升高(P<0.01),podocin蛋白表达明显下降(P<0.01)。与糖尿病组相比,1,25-(OH)2D3组尿红细胞、尿蛋白、MCP-1、TNF-α、IFN-λ、血糖明显降低(P<0.05或P<0.01),podocin蛋白表达明显增加(P<0.01)。结论:1,25-(OH)2D3可减轻糖尿病大鼠血尿、蛋白尿,减轻尿液炎症因子的排泄,恢复podocin的表达而有肾保护作...     

慢性肾脏病3～5期非透析患者25(OH)D与1,25(OH)2D水平的相关性及影响因素

目的 调查慢性肾脏病(chronic kidney disease,CKD)3～5期非透析人群25(OH)D与1,25(OH).D缺乏的情况,探讨25(OH)D与1,25(OH)2D水平的相关性及影响因素.方法 采用放射免疫法检测82例CKD 3～5期非透析患者的血浆25(OH)D与1,25(OH)2D水平,采用自动生化分析仪测定血钙、磷、碱性磷酸酶(alkaline phosphatase,ALP)、血清肌酐(serum creat inine,SCr)、白蛋白(albumin,Alb)、肝功能、血糖等.采用单因素相关分析探讨25(OH)D及1,25(OH)2D水平的相关因素并探讨二者的相关性.采用多因素回归分析探讨25(OH)D水平及1,25(OH).D水平的独立影响因素.结果 82例CKD3～5期非透析人群25(OH)D水平中位数8.81 ng/ml,全距0.34~37.69 ng/ml;血浆1,25(OH)2D水平中位数17.14 pg/ml,全距1.10～65.40 pg/ml.82例患者中25(OH)D不足占15.0%,缺乏占81.3%;1,25(OH)2D缺乏发生率44.0%.CKD 3～5期间25(OH)D的水平及缺乏比例差异均无统计学意义(均P＞0.05),但是1,25(OH)2D的水平及缺乏比例差异均有统计学意义(均P＜0.05).单因素相关分析提示:血浆25(OH)D水平与血浆Alb和24 h尿蛋白定量相关;1,25(OH)2D水平与估算肾小球滤过率(estimated glomerular filtration rate,eGFR)正相关,与合并糖尿病、血磷负相关;1,25(OH)2D水平与25(OH)D水平正相关.多因素回归分析结果提示:血浆Alb是25(OH)D水平的独立影响因素;血浆25(OH)D水平和eGFR是1,25(OH)2D水平的独立影响因素.结论 CKD 3～5非透析患者普遍存在25(OH)D和1,25(OH)2D缺乏.25(OH)D水平与1,25(OH)2D水平具有相关性.血浆Alb是25(OH)D水平的独立影响因素.血浆25(OH)D水平,eGFR是1,25(OH)2D水平的独立影响因素.