Hypercalcemia in Children with Disorders of Calcium and Phosphate Metabolism During Long-Term Treatment with 1,25-Dihydroxyvitamin-D3

PEDIATRICS ◽  
1983 ◽  
Vol 72 (2) ◽  
pp. 225-233
Author(s):  
James C. M. Chan ◽  
Reuben B. Young ◽  
Uri Alon ◽  
Peter Mamunes
Keyword(s):  
Renal Function ◽  
Calcium Phosphate ◽  
Renal Insufficiency ◽  
Hypophosphatemic Rickets ◽  
Phosphate Metabolism ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Renal Function Deterioration ◽  
Calcium And Phosphate Metabolism ◽  
1,25 Dihydroxy Vitamin D3

Forty-two children received 1,25-dihydroxy-vitamin-D3 for treatment of disorders in calcium and phosphate metabolism secondary to chronic renal insufficiency (n = 29), sex-linked dominant hypophosphatemic rickets (n = 9), hypoparathyroidism (n = 2), and pseudohypoparathyroidism (n = 2). Serum calcium, phosphate, and creatinine concentrations were measured monthly for a mean of 26 months and a total of 1,079.5 patient-months. Patients with renal osteodystrophy manifested hypercalcemia (>11 mg/dL) once in every 13 months of treatment on the average. Of three children with hypophosphatemic rickets who experienced hypercalcemia, two proved to have tertiary hyperparathyroidism. Among children with hypoparathyroidism and pseudohypoparathyroidism, three episodes of hypercalcemia were observed during 124.5 patient-months, an incidence of one hypercalcemic episode per 39 treatment months. Renal function, as represented by reciprocals of serum creatinine determined retrospectively for a mean of 22 months before and prospectively for a mean of 26 months after initiation of 1,25-dihydroxyvitamin-D3 treatment, underwent no significant changes except in seven of 29 children with chronic renal insufficiency, six of whose rate of renal function deterioration increased on the treatment and one whose rate decreased. With one exception, hypercalcemia was associated in all cases with accelerated renal function deterioration. Before and after initiation of treatment with 1,25-dihydroxyvitamin-D3 the mean calcium x phosphate solubility products were 42.9 and 47.2, respectively. Values less than 60 are accepted as normal. Hypercalcemia is an occasional concomitant of such treatment and a more rapid deterioration of renal function may occur in some of the patients treated with 1,25-dihydroxyvitamin-D3. Thus, careful monitoring of concentrations of serum calcium, phosphate, and creatinine must accompany 1,25-dihydroxy-vitamin-D3 therapy.

Effects of I ,25-Dihydroxyvitamin-D3 on Renal Function, Mineral Balance, and Growth in Children with Severe Chronic Renal Failure

PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 559-571
Author(s):  
James C. M. Chan ◽  
Michael B. Kodroff ◽  
Douglas M. Landwehr
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Renal Insufficiency ◽  
Filtration Rate ◽  
Height Velocity ◽  
Dihydroxyvitamin D3 ◽  
Mineral Balance ◽  
1,25 Dihydroxyvitamin D3 ◽  
Calcium Phosphorus

To confirm and extend previous observations of enhanced linear growth in children with chronic renal disease being treated with 1,25-dihydroxyvitamin- D3 and to characterize further the calcium, phosphorus, magnesium, and zinc disorders in renal failure, 11 children (mean age 8 ± 5 years) with chronic renal insufficiency (glomerular filtration rate 18% ± 13% of normal) were evaluated on the basis of their reciprocal serum creatinine concentrations, height-velocity curves, mineral balances, and radiologic findings. Reciprocal serum creatinine concentrations analyzed retrospectively and prospectively during 32 months of 1,25-dihydroxyvitamin-D3 therapy showed progression of renal failure at rates linearly identical with those before treatment, thus suggesting that the treatment did not accelerate the rate of deterioration of glomerular filtration rate in chronic renal insufficiency. Indeed, one patient manifested a lesser decline in renal function (P sjlt .05). The height velocity of six of the children (75%) less than 12 years of age improved markedly over that expected for chronologic and bone ages after one year of treatment with orally administered 1,25-dihydroxyvitamin-D3, 15 to 35 ng/kg/day. All other medications except vitamin D2 were continued at their pretreatment dosage levels throughout the study. Growth velocity was unimproved in two of three children older than 12 years at the initiation of 1,25-dihydroxyvitamin- D3 therapy. Mineral balance data showed significant retention of calcium, phosphorus, magnesium, and zinc (357 ± 32 mg/sq m/day, 250 ± 82 mg/sq m/day, 38 ± 32 mg/sq m/day, and 1,157 ± 283 µ/sq m/day, respectively), after treatment for 12 months. In addition, serum calcium, alkaline phosphatase, and parathyroid hormone concentrations returned toward normal. Finally, healing of renal osteodystrophy was radiologically evident after six months of therapy.

Renal Hypophosphatemic Rickets: Growth Acceleration After Long-Term Treatment with 1,25-Dihydroxyvitamin-D3

PEDIATRICS ◽  
1980 ◽  
Vol 66 (3) ◽  
pp. 445-454 ◽  
Author(s):  
James C. M. Chan ◽  
Robert D. Lovinger ◽  
Peter Mamunes
Keyword(s):  
Serum Alkaline Phosphatase ◽  
Bone Age ◽  
Term Treatment ◽  
Hypophosphatemic Rickets ◽  
Phosphorus Concentration ◽  
Calcium Excretion ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Long Term Treatment

Treatment with 1,25-dihydroxyvitamin-D3 and phosphorus supplementation for as long as 48 months was evaluated in six patients with renal hypophosphatemic rickets. Previous phosphorus supplementation of 1,800 to 4,000 mg/sq m of body surface area per day was continued while 1,25-dihydroxyvitamin-D3 at 17 to 80 ng/kg of body weight per day was given orally in place of vitamin-D2. The serum calcium concentration stayed within the normal range in the majority of patients, while the serum phosphorus concentration rose from 2.5 ± 0.4 to 3.4 ± 1.2 mg/100 ml after one month (P < .01). With rare exceptions, serum alkaline phosphatase and parathyroid hormone concentrations stayed normal throughout the study. Healing of rickets was demonstrated by radiography. In five patients, growth velocity was evaluated for 12 months before and after therapy. Growth accelerations were 123% to 235% of that expected for changes in chronologic age and 114% to 200% expected for changes in bone age after therapy. Orally administered, 1,25-dihydroxyvitamin-D3 increased renal calcium excretion and calcium retention was achieved by virtue of the decreased fecal calcium loss. In contrast, 1,25-dihydroxyvitamin-D3, even at doses up to 4 µg/day (80 ng/kg/day) did not significantly alter renal phosphaturia. The phosphorus retention was therefore achieved as the result of the decreased fecal phosphate excretion. The absence of hypercalcemia even at high doses of 1,25-dihydroxyvitamin-D3 and the enhanced linear growth support the long-term therapeutic value of 1,25-dihydroxyvitamin-D3 in renal hypophosphatemic rickets.

scholarly journals FGF23, αKLOTHO AND VITAMIN D MEDIATED CALCIUM-PHOSPHATE METABOLISM IN HEMODIALYSIS PATIENTS

2020 ◽  
Author(s):  
Ozge Tugce Pasaoglu ◽  
Ayse Senelmis ◽  
Ozant Helvaci ◽  
Ulver Derici ◽  
Hatice Pasaoglu
Keyword(s):  
Calcium Phosphate ◽  
Kidney Diseases ◽  
Mineral Metabolism ◽  
Hemodialysis Patients ◽  
Dihydroxyvitamin D3 ◽  
Chronic Kidney Diseases ◽  
Hydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D3 ◽  
Significant Difference ◽  
25 Hydroxyvitamin D

Background: Klotho is a protein that acts as a co-receptor for FGF23. FGF23-Klotho axis has great importance regarding to the regulation of mineral metabolism by kidneys. In this study, we analyzed FGF23, αKlotho, 1,25-dihydroxyvitamin D3, 25-hydroxyvitamin D, parathormone, calcium and phosphate levels of hemodialysis patients in order to investigate the nature of the mineral metabolism disruption in chronic kidney diseases. Methods: Sixty hemodialysis patients and 34 healthy controls were included in the study. Serum iFGF, cFGF, soluble αKlotho were analyzed using ELISA kits. 1,25-dihydroxyvitamin D3 was determined using LC-MS/MS. Calcium, phosphate, iPTH and 25-hydroxyvitamin D were measured using autoanalyzers. Results: In hemodialysis patients, iFGF23, cFGF23, iPTH and P levels were significantly higher and 1,25-dihydroxyvitamin D3, αKlotho and Ca levels were significantly lower compared with the control group. There was no significant difference in 25-hydroxyvitamin D levels. Conclusion: Our study showed that lack of sufficient amounts of αKlotho is crucial for mineral metabolism disruptions seen as a complication of chronic kidney diseases. Despite the high levels of the hormone, FGF23 is unable to accomplish its function properly, likely due to deteriorated kidney function in hemodialysis patients.

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