Switching from conventional therapy to burosumab injection has the potential to prevent nephrocalcinosis in patients with X-linked hypophosphatemic rickets.

OBJECTIVES: X-linked hypophosphatemic rickets (XLH) is a congenital fibroblast growth factor (FGF)23-related metabolic bone disease that is treated with active vitamin D and phosphate as conventional therapies. Complications of these therapies include nephrocalcinosis (NC) caused by excessive urine calcium and phosphate concentrations. Recently, an anti-FGF23 antibody, burosumab, was developed and reported to be effective in poorly-controlled or severe XLH patients. This study aimed to reveal the impact of switching treatments in relatively well-controlled XLH children with the Rickets Severity Scale less than 2.0. METHODS: The effects of the two treatments in eight relatively well-controlled XLH children with a mean age of 10.4 ± 1.9 years were compared retrospectively for the same treatment duration (31 ± 11 months) before and after the baseline. RESULTS: Actual doses of alfacalcidol and phosphate as conventional therapy were 150.9 ± 43.9 ng/kg and 27.5 ± 6.3 mg/kg per day, respectively. Renal echography revealed spotty NC in 8/8 patients, but no aggravation of NC was detected by switching treatments. Switching treatments increased TmP/GFR (p=0.002) and %TRP (p<0.001), and improved the high urine calcium/creatinine ratio to the normal range (p<0.001) although both treatments controlled disease markers equally. Additionally, low intact parathyroid hormone during conventional therapy was increased within the normal range by switching treatments. CONCLUSIONS: Our results suggest that a high dose of alfacalcidol was needed to control the disease, but it caused hypercalciuria and NC. We concluded that switching treatments in relatively well-controlled XLH children improved renal phosphate reabsorption and decreased urine calcium extraction, and may have the potential to prevent NC.

Importance of magnesium sulfate supplementation in the prevention of hypomagnesemia and hypocalcemia during chemoradiation in head and neck cancer.

In advanced squamous cell carcinoma of the head and neck, concomitant radiotherapy with cisplatin and/or cetuximab is frequently combined with cisplatin-based induction chemotherapy, which can cause severe hypomagnesemia, hypocalcemia, and hypokalemia. The aim of our study was to analyze the effects of magnesium sulfate supplementation on the incidence of hypomagnesemia, hypokalemia, and hypocalcemia during four cycles of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy followed by concomitant radiotherapy (CRT) with cisplatin and cetuximab. Twenty-five patients included in a phase II prospective study received routine magnesium sulfate infusions before each cycle of cisplatin, and additional supplementation based on laboratory findings. During TPF, the incidence of grade 1/2 and grade 3/4 hypomagnesemia was 16% and 4%, respectively; and increased despite magnesium supplementation during CRT to 72% and 8%, respectively. During TPF, a grade 2 and grade 4 hypocalcemia occurred in 8% and 4%, respectively; and during CRT, it reached 36% (grade 1/2). Grade 1 hypokalemia only was observed during TPF (4%) and CRT (8%). The median amounts of supplemented magnesium sulfate during TPF and CRT were 20 mEq and 50 mEq, respectively. It appears that a low incidence of grade 3/4 hypomagnesemia and hypocalcemia in our patients resulted from intensive magnesium supplementation. Thorough measurements of magnesium and calcium during cisplatin-based chemoradiation protocols in patients with head and neck cancer are crucial in preventing the development of grade 3/4 hypomagnesemia and hypocalcemia.

Zinc Inhibits Phosphate-Induced Vascular Calcification through TNFAIP3-Mediated Suppression of NF-κB.

Background The high cardiovascular morbidity and mortality of patients with CKD may result in large part from medial vascular calcification, a process promoted by hyperphosphatemia and involving osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Reduced serum zinc levels have frequently been observed in patients with CKD, but the functional relevance of this remains unclear.Methods We performed experiments in primary human aortic VSMCs; klotho-hypomorphic (kl/kl), subtotal nephrectomy, and cholecalciferol-overload mouse calcification models; and serum samples from patients with CKD.Results In cultured VSMCs, treatment with zinc sulfate (ZnSO4) blunted phosphate-induced calcification, osteo-/chondrogenic signaling, and NF-κB activation. ZnSO4 increased the abundance of zinc-finger protein TNF-α-induced protein 3 (TNFAIP3, also known as A20), a suppressor of the NF-κB pathway, by zinc-sensing receptor ZnR/GPR39-dependent upregulation of TNFAIP3 gene expression. Silencing of TNFAIP3 in VSMCs blunted the anticalcific effects of ZnSO4 under high phosphate conditions. kl/kl mice showed reduced plasma zinc levels, and ZnSO4 supplementation strongly blunted vascular calcification and aortic osteoinduction and upregulated aortic Tnfaip3 expression. ZnSO4 ameliorated vascular calcification in mice with chronic renal failure and mice with cholecalciferol overload. In patients with CKD, serum zinc concentrations inversely correlated with serum calcification propensity. Finally, ZnSO4 ameliorated the osteoinductive effects of uremic serum in VSMCs.Conclusions Zinc supplementation ameliorates phosphate-induced osteo-/chondrogenic transdifferentiation of VSMCs and vascular calcification through an active cellular mechanism resulting from GPR39-dependent induction of TNFAIP3 and subsequent suppression of the NF-κB pathway. Zinc supplementation may be a simple treatment to reduce the burden of vascular calcification in CKD.

MOnitored supplementation of VItamin D in preterm infants (MOSVID trial): study protocol for a randomised controlled trial.

BACKGROUND: The pivotal role of vitamin D (vit D) in skeletal health is well known. Neonatal vit D storage at birth is dependent on maternal levels, and newborns receive 50-70% of their mother's 25-hydroxyvitamin D [25(OH)D]. Deficiency of vit D can lead to prematurity bone disease, with an incidence of up to 55% in infants weighing < 1000 g. The aim of this study is to assess the effectiveness of monitored supplementation of vit D in a population of preterm infants. METHODS/DESIGN: Preterm infants born at 24-32 weeks of gestation will be recruited within the first 7 days of life. Depending on the type of feeding, and after reaching partial enteral feeding or at 7 days of life, vit D supplementation will consist of 500 IU and an additional 150-300 IU/kg included in human milk fortifiers (if fed exclusively with breast milk) or 190 IU/kg in milk formulas. Subjects will be randomised to either monitored (with an option of dose modification based on 25(OH)D levels as per protocol) or standard therapy up to 52 weeks of post-conceptional age (PCA). The primary outcome measure will be the number of neonates with deficiency or excess levels of 25(OH)D at 40 ±2 weeks of PCA. Additional 25(OH)D levels will be measured at birth, at 4 and 8 weeks of age, and/or at 35 and 52 ±2 weeks of PCA. Secondary objectives will include the incidence of osteopenia, nephrocalcinosis and nephrolithiasis. Serum parameters of calcium phosphorus metabolism will also be measured. DISCUSSION: Despite multiple years of research and numerous publications, there is still a lack of consensus in regard to how much vit D infants should receive and how long they should receive it. Because 80% of calcium and phosphorus placental transfer occurs between 24 and 40 weeks of gestation, preterm infants are especially prone to adverse effects of vit D insufficiency. However, both inadequate and excessive amounts of vit D may be unsafe and lead to serious health issues. The results of our study may shed new light on these concerns and contribute to optimising vit D supplementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03087149 . Registered on 15 March 2017.

Hypertension is a characteristic complication of X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is a group of rare disorders caused by defective proximal tubular reabsorption of phosphate. Mutations in the PHEX gene are responsible for the majority of cases. There are very few reports of long-term complications of XLH other than skeletal and dental diseases. The aim of this study was to identify the phenotypic presentation of XLH during adulthood including complications other than skeletal and dental diseases. The clinical and biochemical phenotype of 22 adult patients with a PHEX gene mutation were examined retrospectively from their medical records. 6 patients had hypertension. The average age of hypertension onset was 29.0 years. Secondary hyperparathyroidism preceded the development of hypertension in 5 patients. 1 patient developed tertiary hyperparathyroidism. 15 patients had nephrocalcinosis. 2 patients had chronic renal dysfunction. Patients with hypertension had a significantly lower eGFR (p=0.010) compared to patients without hypertension. No significant difference was found in any other parameters. To examine the genotype-phenotype correlation, 10 adult males were chosen for analysis. No significant genotype-phenotype correlation analysis was revealed in any of the complications. However, there was a possibility that the age at nephrocalcinosis onset was younger in the non-missense mutation group than in the missense mutation group (p=0.063). This study corroborated the view that early-onset hypertension could be one of the characteristic complications seen in XLH patients. Considering the limited number of our patients, further study is necessary to address a potential cause of hypertension. XLH patients require careful lifelong treatment.

Prophylactic effect of coconut water (Cocos nucifera L.) on ethylene glycol induced nephrocalcinosis in male wistar rat.

PURPOSE: Many medicinal plants have been employed during ages to treat urinary stones though the rationale behind their use is not well established. Thus, the present study was proposed to evaluate the effect of coconut water as a prophylactic agent in experimentally induced nephrolithiasis in a rat model. MATERIALS AND METHODS: The male Wistar rats were divided randomly into three groups. Animals of group I (control) were fed standard rat diet. In group II, the animals were administrated 0.75% ethylene glycol in drinking water for the induction of nephrolithiasis. Group III animals were administrated coconut water in addition to ethylene glycol. All the treatments were continued for a total duration of seven weeks. RESULTS AND CONCLUSION: Treatment with coconut water inhibited crystal deposition in renal tissue as well as reduced the number of crystals in urine. Furthermore, coconut water also protected against impaired renal function and development of oxidative stress in the kidneys. The results indicate that coconut water could be a potential candidate for phytotherapy against urolithiasis.

Prophylactic effect of coconut water (Cocos nucifera L.) on ethylene glycol induced nephrocalcinosis in male wistar rat

Purpose Many medicinal plants have been employed during ages to treat urinary stones though the rationale behind their use is not well established. Thus, the present study was proposed to evaluate the effect of coconut water as a prophylactic agent in experimentally induced nephrolithiasis in a rat model. Materials and Methods The male Wistar rats were divided randomly into three groups. Animals of group I (control) were fed standard rat diet. In group II, the animals were administrated 0.75% ethylene glycol in drinking water for the induction of nephrolithiasis. Group III animals were administrated coconut water in addition to ethylene glycol. All the treatments were continued for a total duration of seven weeks. Results and Conclusion Treatment with coconut water inhibited crystal deposition in renal tissue as well as reduced the number of crystals in urine. Furthermore, coconut water also protected against impaired renal function and development of oxidative stress in the kidneys. The results indicate that coconut water could be a potential candidate for phytotherapy against urolithiasis. .

Raquitismo hipofosfatémico hereditario con hipercalciuria: a propósito de un caso / Hereditary hypophosphatemic rickets with hypercalciuria: Case report

Presentamos el caso clínico de un varón de 50 años de edad que consulta por presentar una enfermedad renal litiásica recidivante y una nefrocalcinosis. En la exploración clínica destacó una talla baja y un genu varo bilateral importante. Entre los datos bioquímicos se apreciaba una pérdida renal de fosfatos intensa con hipofosfatemia, una 25 OH vitamina D3 normal, una 1,25 OH2 vitamina D3 elevada y una hipercalciuria. La hormona paratiroidea (PTHi) se encontraba disminuida y en la ecografía renal se confirmó la existencia de una nefrocalcinosis bilateral grave, localizada en la médula renal. Además, se constató una insuficiencia renal crónica incipiente y una acidosis tubular renal incompleta, ambas secundarias a la nefrocalcinosis y no directamente relacionadas con la enfermedad basal. En el estudio molecular se encontró un cambio en homocigosis en el intrón 5 del gen SLC34A3 (NM_080877.2:c[448+5G>A]+[448+ 5G>A]). Sus tres hijos eran portadores de esta misma variante en heterocigosis y, aunque clínicamente estaban asintomáticos, dos de ellos tenían una hipercalciuria. Todos estos datos parecían (..) (AU)

We report a case of a male aged 50 years who consulted for renal disease recurrent lithiasis and nephrocalcinosis. The clinical examination showed external signs of rickets/osteomalacia and biochemical data as well as a severe loss of renal phosphate with hypophosphatemia, normal 25 OH vitamin D, high 1,25 OH vitamin D and hypercalciuria. Parathyroid hormone was low and renal ultrasound confirmed the existence of severe bilateral medullary nephrocalcinosis. They also found incipient chronic renal failure and incomplete renal tubular acidosis, both secondary to nephrocalcinosis and unrelated to the underlying disease. The molecular study found a change in homozygosity in intron 5 of gene SLC34A3 (NM_080877.2:c[ 448 +5G>A] + [ 448 +5G>A] ). His three children were carriers of the same variant in heterozygosis and although they were clinically asymptomatic two of them had hypercalciuria. All these data suggest that the patient had hereditary hypophosphataemic rickets with hypercalciuria (HHRH) secondary to an alteration in the sodium dependent phosphate cotransporter located in proximal tubule (NaPi-IIc). The HHRH is transmitted by autosomal recessive inheritance and is an extremely rare form of hypophosphatemic rickets. The diagnosis and treatment are essential to prevent bone sequelae of rickets and nephrocalcinosis. A correct differential diagnosis with other forms of hypophosphatemic rickets has implications on the treatment, as the management based only on phosphorus supplementation usually corrects all clinical and biochemical abnormalities, except for the loss of phosphorus in the urine. The exogenous supply of calcitriol, as advised in other hypophosphatemic rickets, may induce renal calcium deposits and nephrocalcinosis and worsens the prognosis (AU)

Calcimimetics as an adjuvant treatment for familial hypophosphatemic rickets.

BACKGROUND AND OBJECTIVES: The treatment for X-linked hypophosphatemia (XLH) with phosphate and calcitriol can be complicated by secondary hyperparathyroidism and nephrocalcinosis. Furthermore, vitamin D and phosphate stimulate FGF23 production, the pathogenic factor causing XLH. We investigated in XLH patients: 1) whether treatment with the calcimimetic agent, cinacalcet, will block the rise in parathyroid hormone (PTH) caused by phosphate administration; and 2) whether treatment with oral phosphate and calcitriol increases FGF23 levels. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Eight subjects with XLH were given a single oral dose of phosphate, followed the next day by combined treatment with phosphate and cinacalcet. Serum measurements of ionized calcium (Ca), phosphate, creatinine, intact PTH, 1,25(OH)(2)D, FGF23, and tubular threshold for phosphate/glomerular filtration rate (TP/GFR) were assessed in response to short-term treatment with phosphate and cinacalcet and compared with long-term administration of phosphate and calcitriol. RESULTS: Oral phosphate load increased serum phosphate, decreased ionized calcium, and increased PTH. Twenty-four hours later, FGF23 significantly increased and 1,25(OH)(2)D decreased. The concomitant administration of phosphate and cinacalcet resulted in further decrease in serum Ca(2+) but suppression of PTH and greater increase in serum phosphate and TP/GFR. Chronic treatment with phosphate and calcitriol resulted in a smaller increment in serum phosphate and high serum FGF23. CONCLUSIONS: Traditional therapy of XLH with phosphate and calcitriol elevates FGF23 and has the potential to stimulate PTH. Short-term treatment with cinacalcet suppresses PTH, leading to increase in TP/GFR and serum phosphate. Thus, long-term clinical studies are needed to investigate whether cinacalcet may be a useful adjuvant in the treatment of XLH, allowing the use of lower doses of phosphate and calcitriol.

A traditional Chinese herbal antilithic formula, Wulingsan, effectively prevents the renal deposition of calcium oxalate crystal in ethylene glycol-fed rats.

We investigated the effects of a traditional Chinese herbal formula, Wulingsan (WLS), on renal stone prevention using an ethylene glycol-induced nephrocalcinosis rat model. Forty-one male Sprague-Dawley (SD) rats were divided into four groups. Group 1 (n=8) was the normal control; group 2 (n=11) served as the placebo group, and received a gastric gavage of starch and 0.75% ethylene glycol (EG) as a stone inducer; group 3 received EG and a low dose of WLS (375 mg/kg); and group 4 received EG and a high dose of WLS (1,125 mg/kg). Baseline and final 24 h urine samples were collected individually; biochemical data of urine and serum were also obtained at the beginning and at the end of the experiment. After 4 weeks, animals were killed and kidneys were harvested. The kidney specimens were examined by polarized light microscopy and the crystal deposits were evaluated by a semi-quantitative scoring method using computer software (ImageScoring). The results revealed that the rats of placebo group gained the least significant body weight; in contrast, the rats of WLS-fed groups could effectively reverse it. The placebo group exhibited lower levels of free calcium (p=0.059) and significantly lower serum phosphorus (p=0.015) in urine than WLS-fed rats. Histological findings of kidneys revealed tubular destruction, damage and inflammatory reactions in the EG-water rats. The crystal deposit scores dropped significantly in the WLS groups, from 1.40 to 0.46 in the low-dose group and from 1.40 to 0.45 in the high-dose group. Overall, WLS effectively inhibited the deposition of calcium oxalate (CaOx) crystal and lowered the incidence of stones in rats (p=0.035). In conclusion, WLS significantly reduced the severity of calcium oxalate crystal deposits in rat kidneys, indicating that Wulingsan may be an effective antilithic herbal formula.

Does citrate prevent nephrocalcinosis in preterm neonates?

Nephrocalcinosis (NC) occurs frequently in preterm neonates. A high U-calcium/citrate is one of the contributing factors to the development of NC. In stone-forming children and adults citrate supplementation is a successful preventive therapy. In this randomized controlled trial the effect of citrate therapy was studied on the development of NC in preterm neonates with a gestational age <32 weeks. Thirty-eight preterm neonates (mean gestational age 29.8 weeks (SD 1.6), mean birth weight 1,300 g (SD 351) were treated with sodium citrate (0.52 mmol/kg/day in four doses) from day 8 of life until at term and 36 preterm neonates (mean gestational age 29.6 weeks (SD 1.6), mean birth weight 1,282 g (SD 256) were not treated. U-calcium, U-creatinine, U-citrate and U-pH were measured at day 7, 14, 21, 28 of life and at term. Renal ultrasonography (US) was performed at term. U-citrate/creatinine and U-pH were significantly higher and U-calcium/citrate was significantly lower in the citrate group at day 14, 21 and 28 compared with the control group (P<0.05). Complications of citrate administration were not encountered, however the incidence of NC was not significantly different in the treated (34%) compared with the control group (44%), P=0.37. Preterm neonates treated with citrate in the first months of life have higher U-citrate/creatinine and lower U-calcium/citrate compared with controls. Sodium citrate therapy in a dosage of 0.52 mmol/kg/day is safe but does not prevent NC. Whether a higher dose or potassium citrate decreases the incidence of NC should be evaluated in further studies.

Reappraisal of the quantity and nature of renal calcifications and mineral metabolism in the magnesium-deficient rat. Effects of treatment with potassium citrate or the combination magnesium citrate and potassium citrate.

There is an urgent need for drugs capable of inhibiting renal calcifications, nephrocalcinosis and stones included, in humans. Current anticalcification medication is based mainly on alkalinization of the metabolism using potassium-containing citrate alone, despite the fact that calcium stone patients suffer marginally from both magnesium and potassium deficiency. We investigated the anticalcification efficacy of oral potassium citrate versus the combined administration of this drug and magnesium citrate in the magnesium-deficient rat developing corticomedullary nephrocalcinosis and luminal microliths in the long term. Among other things we employed specific stains for calcium and oxalate, light microscopy and element analysis for renal tissue and calcifications, respectively. In addition, minerals in renal tissue, urine and plasma were determined, as well as the state of extracellular calcium homeostasis. Magnesium deficiency caused pure calcium phosphate tissue deposits, containing no magnesium, but no deposition of calcium oxalate in the tubular lumen; tissue magnesium, calcium and phosphorus were increased, and there was marked potassium wastage via urine; despite mild hypercalcemia other signs of hyperparathyroidism were not found. Alkalinization with the two kinds of medication evoked an increase in urinary pH, citrate, and potassium; however, potassium citrate alone tended to aggravate renal concretions, whereas the combination of this drug with magnesium citrate completely prevented concretions. It was concluded that: (1) magnesium deficiency-induced calcifications are oxalate-free and are not sensitive to mobilization by alkalinization with potassium citrate, which might explain the failure of the drug to prevent stone recurrence in clinical stone patients, and (2) the combination of potassium citrate and magnesium citrate, which shows enormous anticalcification efficacy, deserves high priority in clinical trials aimed at evaluating strategies for the prevention of stones.

Dietary phosphorus restriction to half the minimum required amount slightly reduces weight gain and length of tibia, but sustains femur mineralization and prevents nephrocalcinosis in female kittens.

The effects of dietary P restriction to half the recommended minimum level on growth, bone and renal mineralization and urinary composition were studied in female kittens. In two separate experiments, 8-week-old weanling kittens were fed on purified diets containing either 4.6 or 9.2 mmol P/MJ (2.8 or 5.6 g P/kg diet). In the second experiment there was an additional low-P diet in which the Ca concentration was reduced from 9.5 to 4.8 mmol/MJ (7.5 v. 3.8 g Ca/kg diet). P restriction slightly but systematically reduced weight gain (to a maximum of 16%) and growth of the tibia (by 1-4%); the former effect was statistically significant (P < 0.05) between the ages of 15 and 20 weeks in Expt 1 only, and the latter did not reach statistical significance at any time point (P > or = 0.13). No adverse effect of P restriction was found on mineralization of femur at the age of 39 weeks. Kidney Ca concentrations were significantly lowered (Expt 1, 6 v. 20 mumol/g dry weight, P < 0.001; Expt 2, 7 v. 16 mumol/g dry weight, P < 0.01) in cats fed on the low-P diets, this effect not being affected by the dietary Ca:P ratio. Urinary P concentration was significantly depressed (by 50-96%) after feeding the low-P diets (P < 0.001). P intake did not influence P, Ca and Mg retention during the period of 15 to 39 weeks of age.

Guide-lines to the treatment of patients with X-linked hypophosphatemic rickets.

The causes of the development of nephrocalcinosis in familial hypophosphatemic rickets (FHR) are reviewed. The treatment combines vitamin D or 1,25 dihydroxyvitamin D and oral phosphate supplementation. Hypercalcaemia and hypercalciuria were thought to cause the renal calcification. On the basis of the data of eighteen patients with familiar hypophosphatemic rickets we have found that the main difference between the treatment of patients having nephrocalcinosis and those with normal renal morphology consisted in the dose of oral phosphate intake. Patients with nephrocalcinosis received significantly higher doses of oral phosphate (130 mg/kg/day versus 70 mg/kg/day, p < 0.01). Correspondingly, their urinary phosphate excretion was also significantly higher (p < 0.01). There was no difference between the two groups with respect of the doses of vitamin D and urinary calcium excretion. It can be concluded, that high concentrations of urinary phosphate can lead to nephrocalcinosis even if urinary calcium concentration is normal. In order to prevent nephrocalcinosis in patients with X-linked hypophosphatemia, the following guide-lines could be recommended: 1) urinary calcium excretion should be kept lower, than the usually allowed < 4 mg/kg/day; 2) oral phosphate supplementation should not exceed 100 mg/kg/day, 3) patients should be encouraged to drink large amounts of water, 4) regular ultrasound controls should be part of the routine follow-up.

Long-term phosphorus restriction prevents corticomedullary nephrocalcinosis and sustains reproductive performance but delays bone mineralization in rats.

In a long-term experiment with three successive generations of rats, the influence of dietary phosphorus restriction (2 instead of 4 g phosphorus/kg diet) on nephrocalcinosis, reproduction and bone mineralization was studied. Nephrocalcinosis in female rats, as based on kidney calcium concentration and histological examination, was prevented by phosphorus restriction. The low phosphorus diet caused reduced femur concentrations of magnesium, calcium and phosphorus in rats of the first and second generation aged 4 to 12 wk. The low phosphorus diet resulted in lower plasma phosphorus concentrations. In the kidneys of female rats, immediately after lactation, a higher degree of tubular hyperplasia was seen after the low phosphorus diet was fed. Reproductive performance was not affected by phosphorus restriction. We conclude that 0.2% phosphorus in the diet prevents nephrocalcinosis in female rats while it sustains reproduction but delays bone mineralization.

Dietary fluoride prevents phosphorus-induced nephrocalcinosis in female rats.

The effect of dietary fluoride (F) on nephrocalcinosis was studied in young, female rats. Nephrocalcinosis was induced by a diet rich in phosphorus (P). F in the diet effectively counteracted P-induced nephrocalcinosis in a dose-dependent fashion. The feeding of increasing amounts of F caused decreasing calcium (Ca) and F concentrations in kidney. This suggests that the amount of Ca in kidney determines F accumulation in this organ, rather than F intake. Increasing amounts of F in the diet caused increasing rates of urinary and fecal excretion and whole-body retention of F. Dietary F did not influence urinary and fecal excretion and plasma concentrations of Ca, magnesium (Mg), and P. The metabolic basis for the protective effect of F against the development of nephrocalcinosis remains to be established.

Influence of dietary phosphorus restriction on calcium and phosphorus metabolism in rats.

The effect of dietary phosphorus (P) on calcium (Ca) and phosphorus metabolism was studied in young female rats. P levels in the semipurified diets ranged from 0.1 to 0.4% (w/w). A level of 0.4% P in the diet is recommended for rats. Kidney calcification was observed in rats fed the 0.4%-P diet whereas P restriction prevented this condition. Rats fed the diet containing 0.1% P, showed severe hypercalciuria, hypercalcemia, reduced growth and impaired bone mineralization. These effects did not occur when the diet contained 0.2 or 0.3% of P. This study suggests that in short-term studies P in the diet of female rats can be restricted to 0.2% so as to prevent nephrocalcinosis without affecting their development.

Kidney function in rats with corticomedullary nephrocalcinosis: effects of alterations in dietary calcium and magnesium.

Single-nephron and whole-kidney function were studied in female rats with corticomedullary nephrocalcinosis, and in animals where the lesion had been prevented either by a dietary magnesium supplement or by using a diet with a calcium:phosphorus ratio in excess of 1. At the single-nephron level, rats with nephrocalcinosis had prolonged tubular fluid transit times. Proximal transit time was 19.42 +/- 1.98 (mean +/- S.E. of mean) vs. 11.58 +/- 0.19 s for controls; distal transit time was 62.64 +/- 9.16 vs. 31.50 +/- 1.03 s for controls. Although single-nephron function is altered in nephrocalcinosis, data obtained from rats in metabolism cages indicate that whole-kidney function is largely unaffected by the lesion.