A Pre-Post Study of Vitamin D Supplement Effects on Urinary Megalin: The Emerging Predictive Role of Megalin in Diabetic Nephropathy Progression.

INTRODUCTION: Megalin is a renal proximal tubular protein that reabsorbs vitamin D from glomerular filtrates. Previous studies found significantly higher levels of urinary megalin in chronic microvascular complications of diabetes with associated metabolic derangements. This study aimed at testing the effect of vitamin D supplements on urinary megalin levels in diabetic nephropathy (DN) patients with vitamin D hypovitaminosis. METHODS: Sixty-three participants with vitamin D deficiency and diabetic nephropathy (DN) were enrolled in the pre-post study; urinary megalin levels with various clinical parameters and serum levels of vitamin D3 were measured and compared to the baseline at 3- and 6-month intervals. RESULTS: Interestingly, a supplementation related increase in serum vitamin D3 levels at 3- and 6- month interventions affected a constellation of ameliorations in the DN progression of clinical and metabolic factors. There was a decrease in ACR with a concomitant decrease in urinary megalin and a decrease in blood pressure, fasting plasma glucose (FPG), and low-density lipoprotein - cholesterol (LDL-C) - but an increase in glomerular filtration rate (GFR). Principally, pellet urinary megalin associated positively (p < 0.05) with vitamin D hypovitaminosis and the albumin-to-creatinine ratio (ACR) but negatively (p < 0.05) with Ca2+ and body mass index (BMI). CONCLUSION: Vitamin D supplementation could elucidate underlying pathophysiological mechanisms and a prognostic significance of urinary megalin association with DN, obesity/MetS-related dyslipidemia, and hyperglycemia modification. Megalin is a putative sensitive and precise predictive marker and an emerging therapeutic target of renal anomalies.

Impact of three different daily doses of vitamin D3 supplementation in healthy schoolchildren and adolescents from North India: a single-blind prospective randomised clinical trial.

In India, there is a lack of information about the adequate daily dose of vitamin D3 supplementation in school children. Hence, we undertook this study to evaluate the adequacy and efficacy of different doses of vitamin D3 in schoolchildren. A total of 1008 vitamin D-deficient (VDD) children, aged 6-16 years with serum 25-hydroxyvitamin D (25(OH)D) levels <50nmol/l, were cluster randomised into three groups (A-344, B-341 and C-232) for supplementation (600, 1000 and 2000 IU daily) of vitamin D3 under supervision for 6 months. Of the 1008 subjects who completed the study, 938 (93 %) were compliant. Baseline and post-supplementation fasting blood and urine samples were evaluated for Ca, phosphates, alkaline phosphatase, 25(OH)D and parathormone and urine Ca:creatinine ratio. The mean age of the subjects was 11·7 (sd 2·4) years, and the overall mean baseline serum 25(OH)D level was 24·3 (SD 9·5)nmol/l. Post-supplementation rise in serum 25(OH)D in compliant group was maximum with 2000 IU (70·0 (SD 30·0)nmol/l), followed by 1000 IU (46·8 (SD 22·5)nmol/l) and 600 IU (36·5 (SD 18·5)nmol/l), and serum 25(OH)D levels of ≥50nmol/l were achieved in 71·5, 81·8 and 92·9 % by groups A, B and C, respectively. Secondary hyperparathyroidism decreased from 31·7 to 8·4 % post-supplementation. Two participants developed hypercalciuria, but none developed hypercalcaemia. Children with VDD benefit maximum with the daily supplementation of 2000 IU of vitamin D3. Whether recommendations of 400 IU/d by Indian Council of Medical Research or 600 IU by Indian Academy of Pediatrics or Institute of Medicine would suffice to achieve vitamin D sufficiency in children with VDD remains debatable.

Association of Serum Level of 25-Hydroxy Vitamin D Deficiency and Pulmonary Function in Healthy Individuals.

BACKGROUND: Besides the extensive regulatory role in growing number of biologic processes, vitamin D has been recently considered essential for lungs function as well as protective against exacerbation of chronic obstructive pulmonary diseases. We assessed the correlation between vitamin D serum levels with pulmonary function in healthy individuals. METHODS: In a cross-sectional study, healthy volunteer (n = 92) participants underwent the following laboratory procedures: a blood test, a 24-hour urine collection test, and the serum level of 25-hydroxy vitamin D before undergoing spirometry. Linear correlation coefficient was calculated to detect the association between serum level of 25-hydroxy vitamin D and pulmonary volumes. RESULTS: The mean age of participants was 39.95 ± 9.98 years. 48% of participants showed different levels of 25-hydroxy vitamin D deficiency. We recognized a consistent direct positive correlation between serum levels of 25-hydroxy vitamin D and lung function volumes. The coefficient for forced vital capacity, forced expiratory volume in 1 second, forced expiratory flow 25-75%, and forced expiratory volume in 1 second/forced vital capacity ratio were 0.610, 0.509, 0.454, and 0.551, respectively. CONCLUSIONS: Our findings suggest correlation between higher serum levels of 25-hydroxy vitamin D and improved pulmonary function. Accordingly, supplemental vitamin D might significantly improve treatment response.

Calcium intake in winter pregnancy attenuates impact of vitamin D inadequacy on urine NTX, a marker of bone resorption.

PURPOSE: Pregnancy is characterised by increased bone turnover, but high bone turnover with resorption exceeding formation may lead to negative maternal bone remodelling. Recent studies are conflicting regarding the effect of calcium on skeletal health in pregnancy. The aim of this study was to examine the seasonal effect of serum 25-hydroxyvitamin D (25OHD) and dietary calcium on a marker of bone resorption. METHODS: This was prospective study of 205 pregnant women [two cohorts; early pregnancy at 13 weeks (n = 96), and late pregnancy at 28 weeks (n = 109)]. Serum 25OHD and urine cross-linked N-telopeptides of type I collagen (uNTX) were measured at both time points. Intakes of vitamin D and calcium were recorded using 3-day food diaries at each trimester. RESULTS: Compared to summer pregnancies, winter pregnancies had significantly lower 25OHD and significantly higher uNTX. Higher calcium intakes were negatively correlated with uNTX in winter, but not summer. In late pregnancy, compared to those reporting calcium intakes ≥1000 mg/day, intakes of <1000 mg/day were associated with a greater increase in uNTX in winter pregnancies than in summer (41.8 vs. 0.9%). Increasing calcium intake in winter by 200 mg/day predicted a 13.3% reduction in late pregnancy uNTX. CONCLUSIONS: In late pregnancy, during winter months when 25OHD is inadequate, intakes of dietary calcium <1000 mg/day were associated with significantly increased bone resorption (uNTX). Additional dietary calcium is associated with reduced bone resorption in late pregnancy, with greater effect observed in winter. Further research regarding optimal dietary calcium and 25OHD in pregnancy is required, particularly for women gestating through winter.

Vitamin D Repletion in Kidney Stone Formers: A Randomized Controlled Trial.

PURPOSE: Vitamin D deficiency is often detected during metabolic evaluation in the nephrolithiasis population. Multiple vitamin D repletion protocols exist, although their differing impact on urinary stone formation risk factors is unclear. MATERIALS AND METHODS: Patients with a history of calcium stones and vitamin D deficiency (less than 30 ng/ml) were randomized to receive either 1,000 IU daily or 50,000 IU weekly of vitamin D supplementation for 6 weeks. Patients completed a pretreatment and posttreatment serum vitamin D level evaluation and 24-hour urine collections to assess the response and any changes in urine stone formation risk parameters. RESULTS: A total of 21 patients completed the study, including 8 who received 1,000 IU daily and 13 who received 50,000 IU weekly. The 50,000 IU weekly group showed a significant increase in median serum vitamin D levels of 23 ng/ml (135%, p <0.01), while the 1,000 IU daily group showed a nonsignificant median increase of 9 ng/ml (49%, p = 0.12). Post-repletion 24-hour urine analysis demonstrated no significant change in urine calcium between the groups, including a median change of -11 mg (IQR -143-29) in patients receiving 1,000 IU and -16 mg (IQR -42-66) in those receiving 50,000 IU. Between the groups there was no significant difference in the supersaturation of calcium oxalate or calcium phosphate. CONCLUSIONS: High dose and low dose vitamin D repletion had no effect on urine calcium excretion or the supersaturation of calcium salts in known stone formers. The higher dosing regimen, which had superior repletion, may be the optimal protocol in patients with vitamin D deficiency.

Vitamin D deficiency is prevalent among idiopathic stone formers, but does correction pose any risk?

While vitamin D (vitD) deficiency is thought to contribute to poor health in a variety of ways and should be corrected, there is still concern about giving vitD supplements to patients with a history of nephrolithiasis. The aim is to study the prevalence of vitD deficiency and the effect on stone risk of cholecalciferol (vitD3) supplementation in a cohort of idiopathic stone formers (ISF). We screened for vitD deficiency and urinary measures of stone risk, comparing vitD deficient (serum 25-OH vitD ≤30 nmol/L; ≤12 ng/mL) with vitD insufficient (31-75 nmol/L; 13-30 ng/mL) or vitD replete (>75 nmol/L; >30 ng/mL); we investigated the effect of giving vitD3 (20,000 IU orally, weekly for 4 months) to 37 of the vitD deficients. Thirty-one percent (142/456) were vitD deficient, 57% (259/456) vitD insufficient, and the rest (12%) vitD replete (55/456). Comparison among the groups showed that baseline 24-h urinary measures related to stone risk expressed as concentration ratios over urine creatinine (Cr), such as U. Calcium/Cr, U. Oxalate/Cr, U. Citrate/Cr, and U. Uric acid/Cr were not significantly different. VitD3 supplementation did significantly increase serum 25-OH vitD levels and U. Phosphate/Cr ratios, as well as reduce serum parathyroid hormone (PTH) concentrations. Following vitD3 supplementation, there was an overall rise in 24-h urine calcium excretion, but it failed to reach statistical significance (p = 0.06). U. Calcium/Cr increased in 22 out of 37 patients (average increase +0.07 mmol/mmol), decreased in 14 (average decrease -0.13 mmol/mmol), and remained unchanged in 1; 6 out of 26 initially normocalciuric ISF developed hypercalciuria; and 6 out of 9 patients who became vitD replete were hypercalciuric after supplementation. It is appropriate to monitor urinary Ca excretion in vitD-supplemented stone formers, because it may reveal underlying hypercalciuria in some treated patients.

Vitamin D3 seems more appropriate than D2 to sustain adequate levels of 25OHD: a pharmacokinetic approach.

BACKGROUND/OBJECTIVES: The superiority of cholecalciferol (D3) over ergocalciferol (D2) in sustaining serum 25-hydroxy vitamin D (25OHD) levels is controversial. To compare D2 with D3 we performed a single-blind, placebo-controlled randomized trial spanning 11 weeks. SUBJECTS/METHODS: Healthy volunteers (n=33, aged 33.4±6 years) were divided into three groups (n=11, each): D2, D3 and placebo. Treatment started with a loading dose (100,000 IU) followed by 4800 IU/day (d) between d7 and d20 and follow-up until d77. Serum samples were obtained at baseline and at days 3, 7, 14, 21, 35, 49, 63 and 77. RESULTS: Baseline 25OHD values in the D2 group were lower than those in the D3 and placebo groups (P<0.01). Placebo 25OHD levels never changed. As after the loading dose both D2 and D3 groups had reached similar 25OHD levels, we tested equivalence of the area under the concentration × time curve (AUC) between d7 and d77. The AUC was 28.6% higher for D3 compared with D2, and both were higher with respect to placebo. At d77, D2 25OHD levels were higher than those at baseline, but similar to placebo; both were lower than D3 (P<0.04). According to raw data, the elimination half-life of 25OHD was 84 and 111 days under D2 and D3 supplementation, respectively; after subtracting the placebo values, the corresponding figures were 33 and 82 days. CONCLUSIONS: D2 and D3 were equally effective in elevating 25OHD levels after a loading dose. In the long term, D3 seems more appropriate for sustaining 25OHD, which could be relevant for classic and non-classic effects of vitamin D.

Normocalcemic hyperparathyroidism in patients with recurrent kidney stones: a disease entity or vitamin D deficiency?

This retrospective data analysis was undertaken to examine the biochemical differences between renal stone formers with normocalcemic hyperparathyroidism (NHPT) and those with normal parathyroid hormone (PTH) levels. Our goal was to ascertain whether 25-hydroxyvitamin D (25(OH)D) status related to PTH levels in this patient cohort. Our findings among 74 patients with NHPT indicate that stone formers with NHPT had significantly lower 25(OH)D levels compared to 192 controls (p = 0.0001) and that 25(OH)D is positively correlated with 1,25-dihydroxyvitamin D values (R = 0.736, p = 0.015). Sequential measurements (after 3 - 5 years), among 11 patients with NHPT who did not receive vitamin D (VitD) preparations, showed a significant increase in urinary calcium (3.43 ± 1.96 vs. 5.72 ± 3.95, p = 0.0426) without a significant change in PTH levels. VitD supplementation, to 3 patients resulted in significant PTH decrease (11.8 ± 1.8 vs. 9.8 ± 1.3, p = 0.003). Prospective studies are needed to confirm the role of vitamin supplementation in renal stone formers with NHPT.

An effective oral vitamin D replacement therapy in persons with spinal cord injury.

BACKGROUND/OBJECTIVE: Vitamin D deficiency is prevalent in chronic spinal cord injury (SCI). A 3-month course of oral vitamin D(3) to 'normalize' serum vitamin D levels was investigated. DESIGN: Prospective drug-intervention study. SETTING: VA Medical Center; private rehabilitation facility. METHODS: Seven individuals with chronic SCI and vitamin D deficiency completed 3 months of oral vitamin D(3) (i.e. cholecalciferol) supplementation. At screening, baseline, and months 1 and 3, blood was collected for serum calcium, 25 hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), and N-telopeptide (NTx); 24-hour urine for calcium, creatinine, and NTx was performed. Oral vitamin D(3) (2000 IU daily) and elemental calcium (1.3 g daily) were prescribed for 90 days. The results are expressed as mean ± standard deviation (SD). Analysis of variance with a Fisher's post-hoc analysis was performed to test for differences between study visits. Subjects were classified as deficient (<20 ng/ml), relatively deficient (20-30 ng/ml), or not deficient (>30 ng/ml) in 25(OH)D. RESULTS: Serum 25(OH)D levels were greater at months 1 and 3 than at baseline (26 ± 6 and 48 ± 17 vs. 14 ± 2 ng/ml; P = 0.005). Six of seven subjects were no longer deficient [25(OH)D >30 ng/ml] by month 3. Serum iPTH levels were significantly decreased at month 1 and month 3; serum NTx levels were significantly lower at month 3 than at baseline. Serum and urinary calcium levels remained within the normal range. CONCLUSION: A daily prescription of 2000 IU of oral vitamin D(3) for 3 months safely raised serum 25(OH)D levels into the normal range in persons with chronic SCI on calcium supplementation.

Presence of impaired intestinal calcium absorption in chronic hypovitaminosis D and its change after cholecalciferol supplementation: assessment by the calcium load test.

BACKGROUND: Hypovitaminosis D is common in Asian Indians and its functional significance is currently under investigation. Previous studies have reported on the effect of low serum 25(OH)D levels (<50 nmol L(-1)) on bone mineral density and serum parathyroid hormone values. The present study assessed the effect of chronic hypovitaminosis D in Asian Indians on intestinal calcium absorption and its change after cholecalciferol supplementation. METHODS: Subjects included 29 healthy volunteers [mean (SD) age, 28.4 +/- 6.4 years] with low serum 25(OH)D levels on screening. Intestinal calcium absorption was assessed by the 'calcium load test' with 1 g of oral elemental calcium. Subjects were put on a calcium restricted diet 1 week prior to the test. The calcium load test was repeated in 26 of them after 8 weeks of supplementation with oral cholecalciferol (60 000 IU week(-1)). RESULTS: The mean urinary calcium/creatinine ratio of the study subjects was 0.027 +/- 0.023 mg mg(-1) under fasting conditions and increased to 0.035 +/- 0.032 mg mg(-1) after calcium loading (delta change = 29.6%, P = 0.33). After 8 weeks of cholecalciferol supplementation, the mean serum 25(OH)D increased from 18.9 +/- 11.9 to 84.4 +/- 34.9 nmol L(-1) (P < 0.0001). Concomitantly, the mean urinary calcium/creatinine ratio of the study subjects increased from 0.030 +/- 0.024 mg mg(-1) under fasting conditions to 0.059 +/- 0.045 mg mg(-1) after calcium loading (delta change = 96.6%, P = 0.008). CONCLUSIONS: The results obtained in the present study show that chronic hypovitaminosis D in Asian Indians has functional relevance in terms of its effect on intestinal calcium absorption, which improves with cholecalciferol supplementation. These findings support the need for improving the vitamin D status of Asian Indians through dietary supplementation and exposure to sunshine.

[Neonatal vitamin D status and calcium-phosphorus homeostasis in the third week of life]. / Zasoby ustrojowe witaminy D a homeostaza wapniowo-fosforowa u noworodków donoszonych w 3 tygodniu zycia.

AIM: Assessment of vitamin D status and calcium -phosphorus homeostasis in term newborns before routine supplementation. MATERIAL AND METHOD: Calcidiol (25OHD), calcium, phosphorus and alkaline phosphatase in serum and Ca (urine)/creatinine (urine) ratio (mg/mg), P (urine)/creatinine (urine) ratio (mg/mg) and tubular phosphate reabsorption rate (TRP= [1-(P(urine) / P(serum). creatinine serum/urine)].100%) in 3rd week of life in 56 appropriate for gestational age term neonates was measured. First group contains 35 newborns (62.5%) with normal 25OHD values and second group 21 newborns (37.5%) with hypovitaminosis D (25OHD < 11 ng/ml). RESULT: Mean 25OHD concentration was 15.23 ng/ml + 8.57 ng/ml. Maternal vitamin D supplementation (10 ug/day) for more than 4 months of pregnancy was similar in both groups (55.9% vs. 52.4%) (p>0.05). There were 51.43% breastfed newborns in group one and 85.71% in group two (p=0.009). Median 25OHD concentration in breastfed newborns was 11.2 ng/ml and 18.5 ng/ml in formula fed babies (p=0.017). There were no statistical differences between groups in calcium (2.44 vs. 2.41 mmol/l), phosphorus (2.27 vs. 2.22 mmol/l) and alkaline phosphatase (261 vs. 266 U/L) blood concentration and Ca (urine)/creatinine (urine) ratio (0,34 vs. 0,25mg/mg) and TRP (86% vs. 88%) (p>0.05). The P (urine) /creatinine (urine) ratio in the first group was 2.3mg/mg and 1.42 mg/mg in the second group (p=0.048). CONCLUSIONS: Neonatal vitamin D stores in the 3rd week of life are not more dependent on maternal vitamin D supplementation during pregnancy. Breastfed infants are at greater risk of hypovitaminosis D than formula fed infants, therefore earlier vitamin D supply should be considered. The hypovitaminosis D has no influence on basic parameters of Ca-P homeostasis in the 3rd week of life.

Different responses of free and peptide-bound cross-links to vitamin D and calcium supplementation in elderly women with vitamin D insufficiency.

Recent findings have shown that bisphosphonates had different effects on the urinary excretion of free and peptide-bound cross-links. Because of this discrepancy, we investigated the effects of another antiresorptive therapy, i.e. vitamin D (vitD) and calcium (Ca) supplementation (800 IU vit D3 and 1 g elemental calcium daily for 6 months) in elderly women (n = 21, age: 83.5 +/- 1.5 yr) with vitD insufficiency and secondary hyperparathyroidism (mean level 25 hydroxy vitamin D = 3.17 +/- 1.2 ng/mL, mean level of intact parathormone = 45.3 +/- 22.7 pg/mL) on the urinary excretion of free and peptide-bound cross-links. A group of free-living, healthy elderly women (n = 25, age: 76.6 +/- 3.1 yr) with a normal vitD status (mean level of 25 OH D = 23.4 +/- 8.9 ng/mL, intact parathormone = 30.2 +/- 11.2 pg/mL) was simultaneously studied. Bone resorption was assessed by total (T), free (F), peptidyl (P) hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) measured with high performance liquid chromatography, by F-LP determined with enzyme linked immunosorbent assay (iF-LP) and by the N- and C-terminal telopeptides of type I collagen (NTX and Cross-laps) before and after (3 and 6 months) therapy. Comparison of the two groups of elderly women at baseline showed that the urinary excretion of pyridinoline cross-links (T, F, and peptide-bound forms) and of telopeptide fragment of type I collagen were all increased in patients with a low vitD status. Highly significant differences were seen principally for T-HP, F-HP, and F-LP (P < 0.001). Correlation studies between each marker showed that the values of pyridinoline cross-links (T and peptide-bound forms) and of the telopeptide fragments of type I collagen correlated well, but the correlation was slightly less pronounced between free pyridinolines and the other markers. After treatment, the response to therapy was greatest for peptide-bound cross-links assessed by high performance liquid chromatography and for telopeptide fragments of type I collagen (percent change at 6 months: -21% for P-HP P < 0.05, -26% for P-LP P < 0.05, -31% for NTX P < 0.01, and -51% for CLaps P < 0.001). In contrast, free pyridinolines excretion (F-HP and F-LP) assessed by high performance liquid chromatography as well as by immunoassay remained unchanged at 3 and 6 months. Because marked and significant changes were seen with peptide-bound cross-links only and not with free forms, we conclude that vitD and Ca therapy has the same effects as bisphosphonates on the urinary excretion of free and peptide-bound cross-links. So far, no rational mechanism can be given to explain this discrepancy, and further studies are needed before routine application of these bone collagen degradation products as bone resorption markers.

Effect of dietary calcium supplementation with lactose on bone in vitamin D-deficient rats.

The relationship between plasma calcium and bone length, chemical and histomorphometric bone parameters was studied in vitamin D-deficient rats in order to determine whether the effects of vitamin D on bone could be attributed to the effect of vitamin D on serum calcium. Plasma calcium was varied over a wide range of dietary manipulation. Four groups of vitamin D-deficient rats were given for 6 weeks: a vitamin D-deficient diet (D-, n = 6), the D--diet with calcium supplementation (D-Ca+, n = 6), the D-Ca+-diet with lactose substituted for dextrose (D-Ca+lac, n = 6) or a normal diet (D+, n = 8). After 6 weeks the mean plasma calcium concentrations were 6.1; 7.0; 9.8; and 10.4 mg/dl, respectively. In the vitamin D-deficient rats (groups D-, D-Ca+, D-Ca+lac) plasma calcium was correlated with bone length, bone ash, volumetric density of osteoid in the metaphysis of the tibia, and volumetric density of trabecular bone in the same bone section. In the D-Ca+lac group these bone parameters approximated the values of the D+ group, but were still significantly lower. It is concluded that in vitamin D-deficient rats longitudinal bone growth, bone mineral content and bone histomorphometry can be brought close to normal by supplying additional dietary calcium with lactose, without vitamin D repletion. The study does not exclude the possibility that residual amounts of vitamin D are required to obtain this effect.

Urinary calcium excretion in pregnancy.

Urinary calcium excretion and creatinine clearance studies have been conducted in 50 women at 36 weeks of pregnancy and 50 normal controls. Of the pregnant women, 25 had been administered 600,000 IU vitamin D in the 24-26 weeks of pregnancy (supplemented group). The non-supplemented group showed significant hypocalcaemia (even after accounting for low plasma protein levels) and hypocalciuria, while the supplemented group showed normocalcaemia as well as significantly greater 24-hour urinary calcium excretion than the controls. 24-hour creatinine clearance was increased in both groups of pregnant women. It was concluded that, due to increased GFR, urinary calcium excretion tends to increase in pregnancy provided the subject is not deficient in vitamin D. Occurrence of hypocalciuria in pregnancy suggests vitamin D deficiency and should not be considered a physiological adaptation.

Interactions between vitamin D deficiency and phosphorus depletion in the rat.

To evaluate the role of vitamin D in the physiologic response to phosphorus depletion (P depleton) and the response to vitamin D administration in P depletion, we studied vitamin D-deficient (-D) rats, fed either a normal or low phosphorus diet and then injected intraperitoneally on alternate days with replacement vitamin D(3), 1.25 mug qod (D(3)); 1.25-dihydroxy-vitamin D(3)[1,25(OH)(2)D(3)] in physiologic, 54 ng qod (LD), and pharmacologic doses, 400 ng qod (HD); or vehicle alone (-D). The following results were obtained: (a) With P depletion, urinary excretion of inorganic phosphorus (Pi) fell to almost undetectable levels in -D rats, and two physiologic features of P depletion a calcemic effect and hypercalciuria, ensued. (b) With administration of vitamin D(3) or 1,25(OH)(2)D(3) in either doses to P-depleted rats, the renal retention of Pi was unaltered despite a significant elevation of serum Pi. (c) The calcemic response to P depletion was accentuated by vitamin D sterols, and the hypercalciuria of P depletion was reduced by 1,25(OH)(2)D(3), HD > LD > D(3). (d) In -D animals receiving normal Pi (+P), D(3), and 1,25(OH)(2)D(3), both LD and HD produced a significant calcemic and phosphatemic effect. (e) Urinary Pi excretion in +P animals was reduced slightly by vitamin D(3) whereas 1,25(OH)(2)D(3), both LD and HD, lowered urinary Pi markedly despite an increased serum Pi. (f) The serial values of serum Ca and Pi and urinary Ca in PD rats and the sequential values for urinary and serum Pi in +P rats indicated more rapid effects of 1,25(OH)(2)D(3), both HD and LD, compared with D(3). We conclude that: (a) The renal adaptation and physiologic response to PD does not require the presence of vitamin D. (b) 1,25(OH)(2)D(3) may directly enhance the renal tubular reabsorption of Pi even as serum Pi rises. (c) A hypocalciuric action of 1,25(OH)(2)D(3) in rats on low phosphorus diet could be direct or occur as a consequence of an increase in serum Pi produced by 1,25(OH)(2)D(3). The different sequential renal response to D(3) compared with 1,25-(OH)(2)D(3) raises the possibility that other natural forms of vitamin D(3) [i.e., 25(OH)D(3), 24,25(OH)(2)D(3), etc.] which may be present in vitamin D-fed rats but not those given only 1,25(OH)(2)D(3), could modify the actions of 1,25(OH)(2)D(3).

Urinary excretion of adenosine 3'5' monophosphate in vitamin D deficiency.

Urinary cyclic adenosine 3'5' monophosphate (AMP) excretion has been determined by radioimmunoassay in children with rickets and in control children. Cyclic AMP was greatly increased in children with rickets. The excretion of cyclic AMP correlated significantly with parathyroid hormone levels (PTH) and alkaline phosphatase, but not with age, calcaemia and serum inorganic phosphate. Calcium infusion led to a decrease in the excretion of cyclic AMP. The data are consistent with following hypothesis. During vitamin D deficiency, high PTH levels can increase the renal excretion of cyclic AMP. The effects of PTH on bone resorption fail to maintain the levels of serum calcium due to the lack of vitamin D. The mechanism by which the secondary hyperparathyroidism develops during vitamin D deficiency remains to be investigated.