Seasonal variations in urinary calcium, volume, and vitamin D in kidney stone formers

ABSTRACT Objectives: To investigate the seasonal variations in urinary calcium, serum vitamin D, and urinary volume in patients with a history of nephrolithiasis. Materials and Methods: Patients included were those who completed a 24-hour urine metabolic evaluation on two occasions; one in summer (June-Aug) and one in winter (Nov-Jan), and who had not started any medications or been instructed on dietary modifications in the interval between the two tests that may have impacted the results. Patients were excluded if they were on thiazide diuretics or were taking calcium and / or Vitamin D supplementation. Welch's t-test was used to compare the difference in average summer and winter values. Unpaired Student t-test was used to compare baseline parameters (age, BMI), and Paired Student t-test was used to compare average seasonal measurements in men vs. women. Results: 136 patients were identified who were not taking calcium or vitamin D supplements or thiazide diuretics, and who were not instructed on dietary modifications in the interval between the two measured parameters. No significant differences were observed when comparing male to female baseline parameters of age or BMI (Table-1). Average 24-hour urine calcium was higher (226.60) in the winter than in summer (194.18) and was significant in males (p = 0.014) and females (p < 0.001). No significant seasonal difference was seen in 24-hour urine volume or serum vitamin D levels. Conclusions: Urinary calcium is higher in winter months compared to summer months. As such, tailoring medical preventative strategies to the time of year may be helpful.

Vitamin A and D intake in pregnancy, infant supplementation, and asthma development: the Norwegian Mother and Child Cohort.

Background: Western diets may provide excess vitamin A, which is potentially toxic and could adversely affect respiratory health and counteract benefits from vitamin D. Objective: The aim of this study was to examine child asthma at age 7 y in relation to maternal intake of vitamins A and D during pregnancy, infant supplementation with these vitamins, and their potential interaction. Design: We studied 61,676 school-age children (born during 2002-2007) from the Norwegian Mother and Child Cohort with data on maternal total (food and supplement) nutrient intake in pregnancy (food-frequency questionnaire validated against biomarkers) and infant supplement use at age 6 mo (n = 54,142 children). Linkage with the Norwegian Prescription Database enabled near-complete follow-up (end of second quarter in 2015) for dispensed medications to classify asthma. We used log-binomial regression to calculate adjusted RRs (aRRs) for asthma with 95% CIs. Results: Asthma increased according to maternal intake of total vitamin A [retinol activity equivalents (RAEs)] in the highest (≥2031 RAEs/d) compared with the lowest (≤779 RAEs/d) quintile (aRR: 1.21; 95% CI: 1.05, 1.40) and decreased for total vitamin D in the highest (≥13.6 µg/d) compared with the lowest (≤3.5 µg/d) quintile (aRR: 0.81; 95% CI: 0.67, 0.97) during pregnancy. No association was observed for maternal intake in the highest quintiles of both nutrients (aRR: 0.99; 95% CI: 0.83, 1.18) and infant supplementation with vitamin D or cod liver oil. Conclusions: Excess vitamin A (≥2.5 times the recommended intake) during pregnancy was associated with increased risk, whereas vitamin D intake close to recommendations was associated with a reduced risk of asthma in school-age children. No association for high intakes of both nutrients suggests antagonistic effects of vitamins A and D. This trial was registered at http://www.clinicaltrials.gov as NCT03197233.

Seasonal variations in urinary calcium, volume, and vitamin d in kidney stone formers.

OBJECTIVES: To investigate the seasonal variations in urinary calcium, serum vitamin D, and urinary volume in patients with a history of nephrolithiasis. MATERIALS AND METHODS: Patients included were those who completed a 24-hour urine metabolic evaluation on two occasions; one in summer (June-Aug) and one in winter (Nov-Jan), and who had not started any medications or been instructed on dietary modifications in the interval between the two tests that may have impacted the results. Patients were excluded if they were on thiazide diuretics or were taking calcium and / or Vitamin D supplementation. Welch's t-test was used to compare the difference in average summer and winter values. Unpaired Student t-test was used to compare baseline parameters (age, BMI), and Paired Student t-test was used to compare average seasonal measurements in men vs. women. RESULTS: 136 patients were identified who were not taking calcium or vitamin D supplements or thiazide diuretics, and who were not instructed on dietary modifications in the interval between the two measured parameters. No significant differences were observed when comparing male to female baseline parameters of age or BMI (Table-1). Average 24-hour urine calcium was higher (226.60) in the winter than in summer (194.18) and was significant in males (p = 0.014) and females (p < 0.001). No significant seasonal difference was seen in 24-hour urine volume or serum vitamin D levels. CONCLUSIONS: Urinary calcium is higher in winter months compared to summer months. As such, tailoring medical preventative strategies to the time of year may be helpful.

Vitamin D and renal outcome: the fourth outcome of CKD-MBD? Oshima Award Address 2015.

Bone fracture, cardiovascular events, and mortality are three outcomes of chronic kidney disease-mineral and bone disorder (CKD-MBD), and the umbrella concept originally described for dialysis patients. The reported association of serum phosphorus or fibroblast growth factor 23 (FGF23) levels with renal outcome suggests that the fourth relevant outcome of CKD-MBD in predialysis patients is renal outcome. We found that proteinuria of 2+ or greater with a dipstick test was associated with low vitamin D status due to urinary loss of 25-hydroxyvitamin D (25D). Moreover, active vitamin D or its analogues decrease proteinuria. Given our finding that maxacalcitol does not repress renin, the reduction of proteinuria by this agent is likely due to direct upregulation of the nephrin and podocin in podocytes. Moreover, this agent downregulates the mesenchymal marker desmin in podocytes and blocks transforming growth factor-beta autoinduction, leading to attenuation of renal fibrosis in a unilateral ureteral obstructive (UUO) model. These facts are reminiscent of the suppression of epithelial-mesenchymal transition (EMT) by vitamin D. EMT blockage may explain our finding that vitamin D prescription in renal transplant recipients is associated with a lower incidence of cancer. We also reported that low vitamin D status and high FGF23 levels predict a worse renal outcome. However, administration of massive doses of 25D exacerbates renal fibrosis in UUO kidneys in 1alpha-hydroxylase knockout mice. Moreover, FGF23 inhibits 1alpha-hydroxylase in proximal tubules and monocytes. Taken together, local 1,25(OH)2D in the kidney tissue but not 25D seems to protect the kidney.

Effects of cholecalciferol supplementation on serum and urinary vitamin D metabolites and binding protein in HIV-infected youth.

Vitamin D insufficiency is widespread in HIV-infected patients. HIV and/or antiretroviral therapy (ART), particularly efavirenz (EFV), may interfere with vitamin D metabolism. However, few data from randomized, controlled trials exist. Here, we investigate changes in vitamin D metabolites and binding protein (VDBP) after 6 months of supplementation in a randomized, active-control, double-blind trial investigating 2 different monthly cholecalciferol (vitamin D3) doses [60,000 (medium) or 120,000 (high) IU/month] vs. a control arm of 18,000 IU/month in 8-25year old HIV-infected youth on ART with HIV-1 RNA <1000 copies/mL and baseline 25-hydroxycholecalciferol (25(OH)D3) ≤30ng/mL. A matched healthy uninfected group was enrolled in a similar parallel study for comparison. Changes after 6 months were analyzed as intent-to-treat within/between groups [control group (low dose) vs. combined supplementation doses (medium+high)]. At 6 months, 55% vs. 82% of subjects in control and supplementation groups, respectively, reached 25(OH)D3 ≥30ng/mL (P=0.01) with no difference between medium and high doses (both 82% ≥30ng/mL). There were few differences for those on EFV vs. no-EFV, except serum VDBP decreased in EFV-treated subjects (both within- and between-groups P≤0.01). There were no significant differences between the HIV-infected vs. healthy uninfected groups. The major finding of the present study is that cholecalciferol supplementation (60,000 or 120,000 IU/month) effectively raises serum 25(OH)D3 in the majority of HIV-infected subjects, regardless of EFV use. Notably, response to supplementation was similar to that of uninfected subjects.

Calcium and phosphorus metabolism and lithogenic factors in patients with osteoporotic fracture.

OBJECTIVES: To demonstrate the attendance of mineral metabolism disorders and lithogenic factors in patients' urine with osteoporotic fracture without previously known stones MATERIAL AND METHODS: 67 patients with osteoporotic fractures surgically treated in trauma service are included. The area of the fracture site, fracture mechanism and the presence of osteoporosis were the factors taken into account to diagnose osteoporotic fracture. Mineral metabolism, calciuria, oxaluria, uricosuria and citraturia in 24hours urine were analyzed. The presence of abnormal calcium and phosphorus metabolism was proved comparing hypercalciuria patients with normocalciuria ones. RESULTS: 12 men and 55 women with mean age 68.8±14.5 years old were included. Mean Body Mass Index (BMI) was 27.4±4.1kg/m2. 42% of patients showed hypercalciuria, 34% hyperoxaluria, 34% hypocitraturia and 7% hyperuricosuria. Statistically significant differences were observed only in fasting calcium/creatinine ratio (0.17 vs. 0.08; P<.0001) when comparing patients with hypercalciuria with those with normocalciuria. CONCLUSIONS: Patients with osteoporotic fractures show different lithogenic factors in urine, mainly hypercalciuria, always in fasting conditions.

Dietary resistant starch prevents urinary excretion of vitamin D metabolites and maintains circulating 25-hydroxycholecalciferol concentrations in Zucker diabetic fatty rats.

BACKGROUND: Type 2 diabetes (T2D) is the leading cause of nephropathy in the United States. Renal complications of T2D include proteinuria and suboptimal serum 25-hydroxycholecalciferol (25D) concentrations. 25D is the major circulating form of vitamin D and renal reabsorption of the 25D-vitamin D-binding protein (DBP) complex via megalin-mediated endocytosis is believed to determine whether 25D can be activated to 1,25-dihydroxycholecalciferol (1,25D) or returned to circulation. We previously demonstrated that excessive urinary excretion of 25D-DBP and albuminuria occurred in rats with type 1 diabetes (T1D) and T2D. Moreover, feeding rats with T1D high-amylose maize partially resistant to digestion [resistant starch (RS)] prevented excretion of 25D-DBP without significantly affecting hyperglycemia. OBJECTIVE: We used Zucker diabetic fatty (ZDF) rats, a model of obesity-related T2D, to determine whether feeding RS could similarly prevent loss of vitamin D and maintain serum 25D concentrations. METHODS: Lean control Zucker rats (n = 8) were fed a standard semi-purified diet (AIN-93G) and ZDF rats were fed either the AIN-93G diet (n = 8) or the AIN-93G diet in which cornstarch was replaced with RS (550 g/kg diet; 35% resistant to digestion) (n = 8) for 6 wk. RESULTS: RS attenuated hyperglycemia by 41% (P < 0.01) and prevented urinary DBP excretion and albuminuria, which were elevated 3.0- (P < 0.01) and 3.6-fold (P < 0.01), respectively, in control diet-fed ZDF rats. Additionally, urinary excretion of 25D (P = 0.01) and 1,25D (P = 0.03) was higher (89% and 97%, respectively), whereas serum 25D concentrations were 31% lower (P < 0.001) in ZDF rats fed the control diet compared with RS-fed ZDF rats. Histopathologic scoring of the kidney revealed that RS attenuated diabetes-mediated damage by 21% (P = 0.12) despite an ∼50% decrease in megalin protein abundance. CONCLUSIONS: Taken together, these data provide evidence that suggests vitamin D balance can be maintained by dietary RS through nephroprotective actions in T2D, which are independent of vitamin D supplementation and renal expression of megalin.

Serum vitamin D increases with weight loss in obese subjects 6 months after Roux-en-Y gastric bypass.

BACKGROUND: Malabsorptive surgical procedures lead to deficiencies in fat-soluble vitamins. However, results concerning serum vitamin D (25OHD) after gastric bypass (GBP) are controversial. The aim of the study was to assess the influence of GBP on 25OHD and calcium metabolism. METHODS: Parameters of calcium metabolism were evaluated in 202 obese subjects before and 6 months after GBP. Thirty of them were matched for age, gender, weight, skin color, and season with 30 subjects who underwent sleeve gastrectomy (SG). A multivitamin preparation that provides 200 to 500 IU vitamin D3 per day was systematically prescribed after surgery. RESULTS: In the 202 patients after GBP, serum 25OHD significantly increased from 13.4 ± 9.1 to 22.8 ± 11.3 ng/ml (p < 0.0001), whereas parathyroid hormone (PTH) did not change. Despite a decrease in calcium intake (p < 0.0001) and urinary calcium/creatinine ratio (p = 0.015), serum calcium increased after GBP (p < 0.0001). Preoperatively, 91 % of patients had 25OHD insufficiency (< 30 ng/ml), 80% deficiency (< 20 ng/ml), and 19% secondary hyperparathyroidism (> 65 pg/ml) vs. 76, 44, and 17%, respectively, following GBP. Serum 25OHD was negatively correlated with BMI at 6 months after GBP (R = -0.299, p < 0.0001). In the two groups of 30 subjects, serum 25OHD and PTH did not differ at 6 months after GBP or SG. CONCLUSIONS: At 6 months after GBP, serum 25OHD significantly increased in subjects supplemented with multivitamins containing low doses of vitamin D. These data suggest that weight loss at 6 months after surgery has a greater influence on vitamin D status than malabsorption induced by GBP.

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.

Vitamin D status and clinical outcomes in incident dialysis patients: results from the NECOSAD study.

BACKGROUND: The majority of dialysis patients suffer from vitamin D deficiency, which might contribute to an adverse health outcome. We aimed to elucidate whether European dialysis patients with low 25-hydroxyvitamin D (25(OH)D) levels are at increased risk of mortality and specific fatal events. METHODS: This was a prospective cohort study of incident dialysis patients in the Netherlands (the NECOSAD). We selected all patients with measured 25(OH)D at 12 months after the start of dialysis, the baseline for our study. By Cox regression analyses, we assessed the impact of 25(OH)D levels on short-term (6 months of follow-up) as well as longer-term mortality (3 years of follow-up). Associations of 25(OH)D levels with cardiovascular and non-cardiovascular mortality were also determined. RESULTS: The data from 762 patients (39% females, age 59 ± 15 years, 25(OH)D = 18 ± 11 ng/mL) were available. Fifty-one and 213 patients died during a follow-up of 6 months and 3 years, respectively. After adjustments for possible confounders, the hazard ratio (HR) (with 95% CI) for mortality was 2.0 (1.0-3.8) for short-term and 1.5 (1.0-2.1) for longer-term mortality when comparing patients with 25(OH)D levels ≤ 10 ng/mL with those presenting with 25(OH)D levels > 10 ng/mL. Adjusted HRs for cardiovascular mortality were 2.7 (1.1-6.5) and 1.7 (1.1-2.7) for short- and longer-term mortality, respectively. For non-cardiovascular mortality, we observed no relevant association overall. The impact of 25(OH)D levels on clinical events was modified by parathyroid hormone (PTH) status, with low 25(OH)D levels meaningfully affecting outcomes only in patients with PTH levels above the median of 123 pmol/L. CONCLUSIONS: Vitamin D deficiency in dialysis patients is associated with an adverse health outcome, in particular with short-term cardiovascular mortality. Intervention studies are urgently needed to evaluate whether vitamin D supplementation improves health outcomes of dialysis patients.

Biochemical markers of bone turnover associated with calcium supplementation in children with juvenile rheumatoid arthritis: results of a double-blind, placebo-controlled intervention trial.

OBJECTIVE: To determine the effects of calcium supplementation on bone physiology in corticosteroid-free children with juvenile rheumatoid arthritis (JRA) by measuring serum and urinary bone-related hormones, minerals, and markers of bone formation and resorption. METHODS: In this double-blind trial, patients were randomized to receive daily oral supplementation with 1,000 mg of calcium and 400 IU of vitamin D or with placebo and 400 IU of vitamin D for 24 months. The effect of calcium supplementation on bone physiology was determined periodically using markers of bone turnover. RESULTS: One hundred ninety-eight patients met the inclusion criteria and were followed up in the study. At baseline, there were no differences in markers of bone turnover between the groups. Patients with < or = 4 joints with active disease had higher serum levels of calcium and parathyroid hormone (PTH). Calcium-treated patients with < or =4 joints with active disease had lower levels of osteocalcin (OC). At followup, levels of 1,25-dihydroxyvitamin D3, PTH, OC, and urine phosphorus were lower in the group receiving calcium supplementation. Hypercalciuria, as determined by the urinary calcium-to-creatinine ratio, was not noted in 24-hour urine studies. CONCLUSION: Levels of markers of bone physiology were significantly decreased in children with JRA receiving calcium supplementation. The physiologic changes were noted as early as 12 months into calcium supplementation. The hypercalciuria noted on spot testing of the urinary calcium-to-creatinine ratio was not demonstrated on further evaluation, nor did it lead to renal pathology. These findings suggest that the calcium supplementation met physiologic needs and caused an increased calcium loss in urine.

Influence of anionic salts on bone metabolism in periparturient dairy goats and sheep.

The purpose of the present study was to investigate the influence of diets supplemented with anionic salts on bone metabolism of dairy goats and sheep. Twelve Saanen goats and 12 Ostfrisean milk sheep (fourth lactation) were divided into 2 groups each [sheep control (SC), goat control (GC); sheep anionic salts (SA), goat anionic salts (GA)]. Each group was fed a different diet in the last 10 d of gestation. Groups SC and GC received a normal diet according to the requirements of goats and sheep in this stage of gestation. Groups SA and GA received supplemental anionic salts. The dietary cation-anion difference (DCAD) was +524 (SC) and +515 (GC) vs. -163 (SA) and -164 (GA) mEq/kg of dry matter. Blood and urine samples were collected daily until parturition. Serum Ca, P, Mg, serum crosslaps (CTX), osteocalcin, 1,25-dihydroxy-vitamin D (VITD), urinary pH, and urinary Ca concentrations were analyzed. Bone mineral density and bone mineral content were measured with peripheral quantitative computer tomography. The bone resorption marker CTX showed significant differences between the animals supplemented with anionic salts and the control animals in goats, but not in sheep. The goats receiving anionic salts had greater CTX concentrations throughout the administration of the salts. In sheep, a difference was only observed on the day of parturition. Similar observations were made in VITD concentrations, although a significant difference between the goat groups was only observed 3 d prepartum. The bone formation marker osteocalcin was lower prepartum in the animals supplemented with anionic salts. The urinary pH was lower in the SA and GA animals, whereas urinary Ca concentrations were greater. Bone mineral content and bone mineral density decreased in all groups around parturition. In conclusion, this experiment showed that the addition of anionic salts in goats led to greater bone resorption rates while on this feeding regimen. It can be concluded that the anionic salts induced a mild metabolic acidosis with all its effects on calcium metabolism. These effects were not evident in milk sheep.

Self-reported dietary supplement use is confirmed by biological markers in the Norwegian Mother and Child Cohort Study (MoBa).

BACKGROUND/AIMS: A food frequency questionnaire (FFQ) and a database for dietary supplements were developed for use in the Norwegian Mother and Child Cohort Study (MoBa). The aim of the present study was to investigate the relation between reported use and biomarkers in supplement and non-supplement users and to validate self-reported intake of dietary supplements in mid pregnancy. METHOD: 120 women were recruited from MoBa, and 119 subjects completed the MoBa FFQ and a 4-day weighed food diary. Information on supplement use was collected by both methods. Venous blood specimens and 24-hour urine samples were obtained for measurement of dietary biomarkers. RESULTS: Biomarker concentration/excretion and intake differed significantly between supplement and non-supplement users for vitamin D, carotenoids, folate, the n-6/n-3 fatty acid ratio and iodine (p < 0.05 for all variables). Flavonoid excretion was higher in flavonoid-supplement users (p < 0.05). Significant correlations between total dietary intake (food and supplements) and biomarker concentration/excretion were found for vitamin D (r = 0.45, p < 0.001), folate (r = 0.26, p = 0.005), the n-6/n-3 fatty acid ratio (r = 0.36, p < 0.001) and iodine (r = 0.42, p < 0.001). CONCLUSION: The biochemical indicators examined in this study confirmed differences in self-reported micronutrient intake between supplement and non-supplement users for vitamin D, beta-carotene, folate, n-3 fatty acids, flavonoids and iodine.

Necrotizing enterocolitis increases the bone resorption in premature infants.

BACKGROUND: Necrotizing enterocolitis is a common neonatal gastrointestinal disease that affects approximately 10% of premature infants less than 1500 g. The average mortality is 20-40% and survivors may present with diarrhea or malabsorption, intestinal strictures and fistulas, feeding abnormalities and failure to thrive. It is not clear whether the higher incidence of this gastrointestinal disease in premature infants contributes to the risk of osteopenia of prematurity. AIM: To examine bone turnover state in premature infants who had a necrotizing enterocolitis attack during postnatal period. STUDY DESIGN AND SUBJECTS: We examine the bone turnover markers in infants with necrotizing enterocolitis and compare them with infants with sepsis. Forty-one premature infants participated in the study and were divided into three groups. In group I, there were 14 premature infants who developed necrotizing enterocolitis with negative blood culture during their hospitalization. In group II, there were 12 premature infants who developed sepsis during their hospitalization. Age-matched 15 premature infants who were given parenteral nutrition served as control group (group III). Blood samples and 6-h urine samples were obtained for bone turnover markers and calcium, phosphorous, creatinine and 25-hydroxy vitamin D between the day 20 and 25. Bone osteoblastic activity was assessed by measurement of serum osteocalcin. Bone resorption was assessed by measurement of serum levels of beta-CrossLaps and urinary deoxypyridinoline. RESULTS: There were no significant differences in bone osteoblastic activity among the groups, but bone resorption markers were significantly higher in infants with necrotizing enterocolitis compared to other groups (p < 0.016). CONCLUSION: Necrotizing enterocolitis increases the bone resorption in premature infants. It may be related with reduced glucagon like peptide-2 levels, a new intestinal hormone that is primary secreted from distal small intestine.

Minimal vitamin D and high calcium and phosphorus needs of preterm infants receiving parenteral nutrition.

Preterm infants (birth weight, 1,089 +/- 91 g; gestational age, 28.9 +/- 0.7 weeks; mean +/- SEM) with mixed medical and surgical indications for parenteral nutrition (PN) were observed to determine the adequacy of infusates with fixed, low-dose vitamin D (25 IU/dl) and two combinations of calcium and phosphorus. The duration of low-dose vitamin D PN ranged from 5 to 52 days, with a median of 27 days. Twelve infants were randomly assigned to low (standard) Ca and P doses (5 mM each; 20 mg/dl of Ca and 15.5 mg/dl of P) and 13 high Ca and P doses (15 mM each; 60 mg/dl of Ca and 46.5 mg/dl of P). The maximum daily vitamin D intake was similar for both groups (31 +/- 1.3 versus 33 +/- 1.2 IU/kg). Vitamin D status in either group, as indicated by serum 25-hydroxyvitamin D (25-OHD) concentrations, was normal. There was no significant difference in observed changes of serial measurements of serum calcium, magnesium, phosphorus, alkaline phosphatase, creatinine (Cr), 25-OHD, and vitamin D-binding protein concentrations or urinary Ca:Cr and Mg:Cr ratios. In the low-dose Ca and P group, the serum P level was consistently less than 4 mg/dl in five infants, serum 1,25-dihydroxyvitamin D concentrations were higher, and tubular reabsorption of phosphorus was consistently greater than 95% and significantly higher than in the high-dose Ca and P groups. Severe bone demineralization apparent on X-ray occurred in two infants, with a fractured distal left ulna in one of the two infants.(ABSTRACT TRUNCATED AT 250 WORDS)