Role of 1,25-Dihydroxy Vitamin D3and Parathyroid Hormone in Urinary Calcium Excretion in Calcium Stone Formers

Introduction Gain-of-function mutations in the CASR gene cause Autosomal Dominant Hypocalcemia Type 1 (ADH1), the most common genetic cause of isolated hypoparathyroidism. Subjects have increased calcium sensitivity in the renal tubule, leading to increased urinary calcium excretion, nephrocalcinosis and nephrolithiasis when compared with other causes of hypoparathyroidism. The traditional approach to treatment includes activated vitamin D but this further increases urinary calcium excretion. Methods In this case series, we describe the use of recombinant human parathyroid hormone (rhPTH)1–84 to treat subjects with ADH1, with improved control of serum and urinary calcium levels. Results We describe two children and one adult with ADH1 due to heterozygous CASR mutations who were treated with rhPTH(1–84). Case 1 was a 9.4-year-old female whose 24-h urinary calcium decreased from 7.5 to 3.9 mg/kg at 1 year. Calcitriol and calcium supplementation were discontinued after titration of rhPTH(1–84). Case 2 was a 9.5-year-old male whose 24-h urinary calcium decreased from 11.7 to 1.7 mg/kg at 1 year, and calcitriol was also discontinued. Case 3 was a 24-year-old female whose treatment was switched from multi-dose teriparatide to daily rhPTH(1–84). All three subjects achieved or maintained target serum levels of calcium and normal or improved urinary calcium levels with daily rhPTH(1–84) monotherapy. Conclusions We have described three subjects with ADH1 who were treated effectively with rhPTH(1–84). In all cases, hypercalciuria improved by comparison to treatment with conventional therapy consisting of calcium supplementation and calcitriol.

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Effects of calcium-modulating hormones on thiazide receptor density.

Journal of the American Society of Nephrology ◽

10.1681/asn.v771052 ◽

1996 ◽

Vol 7 (7) ◽

pp. 1052-1057 ◽

Cited By ~ 1

Author(s):

P Blakely ◽

D A Vaughn ◽

D D Fanestil

Keyword(s):

Parathyroid Hormone ◽

Calcium Ion ◽

Excretion Rate ◽

Urinary Calcium ◽

Plasma Calcium ◽

Urinary Calcium Excretion ◽

Ion Concentration ◽

Calcium Excretion ◽

Calcitropic Hormones ◽

Calcium Ion Concentration

Thiazide diuretic drugs act in the distal convoluted tubule (DCT) to inhibit a Na+Cl- cotransporter and enhance reabsorption of luminal calcium. The density of receptors for thiazides in the rat DCT is known to be increased by adrenocortical steroids, furosemide, and bendroflumethiazide, but decreased by ischemia. Because the DCT is a physiologic site of action by calcitonin and parathyroid hormone, this study examined the effects of these calcitropic hormones in thyroparathyroidectomized Sprague-Dawley rats on (1) the density of the rat thiazide receptor (TZR), as quantitated by binding of (3H)metolazone to renal membranes, and (2) urinary electrolyte excretion rate. Salmon calcitonin (sCT) (20 to 100 ng/h) (1) increased the density of the renal TZR twofold, an effect that is maximal by 6 h after sCT administration, and (2) decreased urinary calcium excretion rate. Adequate dietary calcium must be provided for the effects of sCT to be observed. Regression analysis demonstrated that renal TZR density correlated negatively with total urinary calcium excretion rate but not with plasma calcium ion concentration. In addition, neither rat calcitonin (rCT), at doses that cause hypocalcemia, nor parathyroid hormone, at doses that cause hypercalcemia, produce direct effects on TZR density in the DCT of the thyroparathyroidectomized rat. Our findings indicate that upregulation of TZR by sCT, which occurs independently of plasma calcium-ion concentration, is likely via a calcitonin-like receptor other than that for rat calcitonin itself.

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A bout of resistance exercise increases urinary calcium independently of osteoclastic activation in men

Journal of Applied Physiology ◽

10.1152/jappl.1997.83.4.1159 ◽

1997 ◽

Vol 83 (4) ◽

pp. 1159-1163 ◽

Cited By ~ 22

Author(s):

Noriko Ashizawa ◽

Rei Fujimura ◽

Kumpei Tokuyama ◽

Masashige Suzuki

Keyword(s):

Parathyroid Hormone ◽

Metabolic Acidosis ◽

Bone Resorption ◽

Resistance Exercise ◽

Urinary Calcium ◽

Urinary Calcium Excretion ◽

Osteoclastic Bone Resorption ◽

Calcium Excretion ◽

Repetition Maximum ◽

Renal Tubular

Ashizawa, Noriko, Rei Fujimura, Kumpei Tokuyama, and Masashige Suzuki. A bout of resistance exercise increases urinary calcium independently of osteoclastic activation in men. J. Appl. Physiol. 83(4): 1159–1163, 1997.—Metabolic acidosis increases urinary calcium excretion in humans as a result of administration of ammonium chloride, an increase in dietary protein intake, and fasting-induced ketoacidosis. An intense bout of exercise, exceeding aerobic capacity, also causes significant decrease in blood pH as a result of increase in blood lactate concentration. In this study we investigated changes in renal calcium handling, plasma parathyroid hormone concentration, and osteoclastic bone resorption after a single bout of resistance exercise. Ten male subjects completed a bout of resistance exercise with an intensity of 60% of one repetition maximum for the first set and 80% of one repetition maximum for the second and third sets. After exercise, blood and urine pH shifted toward acidity and urinary calcium excretion increased. Hypercalciuria was observed in the presence of an increased fractional calcium excretion and an unchanged filtered load of calcium. Therefore, the observed increase in urinary calcium excretion was due primarily to decrease in renal tubular reabsorption of calcium. Likely causes of the increase in renal excretion of calcium are metabolic acidosis itself and decreased parathyroid hormone. When urinary calcium excretion increased, urinary deoxypyridinoline, a marker of osteoclastic bone resorption, decreased. These results suggest that 1) strenuous resistance exercise increased urinary calcium excretion by decreasing renal tubular calcium reabsorption, 2) urinary calcium excretion increased independently of osteoclast activation, and 3) the mechanism resulting in postexercise hypercalciuria might involve non-cell-mediated physicochemical bone dissolution.

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The relationship between blood pressure and serum parathyroid hormone with special reference to urinary calcium excretion: The Tromsø study

Journal of Endocrinological Investigation ◽

10.1007/bf03345542 ◽

2006 ◽

Vol 29 (3) ◽

pp. 214-220 ◽

Cited By ~ 10

Author(s):

F. Saleh ◽

R. Jorde ◽

J. Svartberg ◽

J. Sundsfjord

Keyword(s):

Blood Pressure ◽

Parathyroid Hormone ◽

Special Reference ◽

Urinary Calcium ◽

Urinary Calcium Excretion ◽

Calcium Excretion ◽

Serum Parathyroid Hormone ◽

The Relationship

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Evidence that postprandial reduction of renal calcium reabsorption mediates hypercalciuria of patients with calcium nephrolithiasis

AJP Renal Physiology ◽

10.1152/ajprenal.00115.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. F66-F75 ◽

Cited By ~ 57

Author(s):

Elaine M. Worcester ◽

Daniel L. Gillen ◽

Andrew P. Evan ◽

Joan H. Parks ◽

Katrina Wright ◽

...

Keyword(s):

Parathyroid Hormone ◽

Serum Magnesium ◽

Normal Subjects ◽

Urinary Calcium ◽

Idiopathic Hypercalciuria ◽

Calcium Excretion ◽

Stone Formers ◽

Calcium Reabsorption ◽

Renal Tubular ◽

Filtered Load

Idiopathic hypercalciuria (IH) is common among calcium stone formers (IHSF). The increased urinary calcium arises from increased intestinal absorption of calcium, but it is unclear whether increased filtered load or decreased renal tubular reabsorption of calcium is the main mechanism for the increased renal excretion. To explore this question, 10 IHSF and 7 normal subjects (N) were studied for 1 day. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, and calories. Fasting and fed, ultrafiltrable calcium levels, and filtered load of calcium did not differ between N and IHSF. Urine calcium rose with meals, and fractional reabsorption fell in all subjects, but the change was significantly higher in IHSF. The changes in calcium excretion were independent of sodium excretion. Serum parathyroid hormone levels did not differ between N and IHSF, and they could not account for the greater fall in calcium reabsorption in IHSF. Serum magnesium and phosphorus levels in IHSF were below N throughout the day, and tubule phosphate reabsorption was lower in IHSF than N after meals. The primary mechanism by which kidneys ferry absorbed calcium into the urine after meals is via reduced tubule calcium reabsorption, and IHSF differ from N in the magnitude of the response. Parathyroid hormone is not likely to be a sufficient explanation for this difference.

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CALCIUM

The Professional Medical Journal ◽

10.29309/tpmj/2010.17.04.3027 ◽

2010 ◽

Vol 17 (04) ◽

pp. 698-701

Author(s):

MUHAMMAD ISHAQ ◽

ISRAR AHMED AKHUND ◽

MOULA BUX LAGHARI ◽

Muhammad Sabir

Keyword(s):

Urinary Tract ◽

Serum Calcium ◽

Upper Urinary Tract ◽

Urinary Calcium ◽

Stone Disease ◽

Urinary Calcium Excretion ◽

Calcium Excretion ◽

Stone Formers ◽

Study Results ◽

Urinary Tract Stone

Aims & Objectives: To evaluate the effects of Serum Calcium and Urinary Calcium excretion on upper urinary tract stone diseases in the Peshawar (a high stone incidence belt). Subjects & Methods: One hundred patients (age 20-60years) who were suffering severely from upper urinary tract stone disease were selected from LRH and Hayatabad Medical Complex Hospitals of Peshawar, same numbers of healthy controls from the same region were also selected for the study. Results: When results were summed up and testParameters were compared, it was seen that mean Serum Calcium in stone formers was greater than that of non-stone formers (P<0.001). Same pattern was also observed (P< 0.001) in both groups regarding mean urinary calcium excretion. Conclusions: We concluded that calcium is a definitive risk factor in upper urinary tract stone disease. However we suggest further work and research on wide scale population inorder to evaluate this relation.

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