Hypercalcaemia of Malignancy: Evidence for a Non-Parathyroid Humoral Agent with An Effect on Renal Tubular Handling of Calcium

1984 ◽  
Vol 66 (2) ◽  
pp. 187-191 ◽  
Author(s):  
S. H. Ralston ◽  
I. Fogelman ◽  
M. D. Gardner ◽  
F. J. Dryburgh ◽  
R. A. Cowan ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Calcium Excretion ◽  
Renal Handling ◽  
Calcium Reabsorption ◽  
Humoral Agent ◽  
Calcium Infusion ◽  
Calcium Load ◽  
Renal Tubular

1. The renal handling of calcium was examined in 31 patients with hypercalcaemia of malignancy. Results were compared with those from patients with primary hyperparathyroidism, and normal controls rendered hypercalcaemic by calcium infusion. 2. On relating the urinary calcium excretion indices to serum calcium values, inappropriately low rates of urinary calcium excretion were generally found in patients with malignancy associated hypercalcaemia. Further, the pattern of urinary calcium excretion in these subjects was similar to that found in patients with primary hyperparathyroidism. 3. These observations suggest that, in many solid tumours, the development of hypercalcaemia may be attributable to a humoral mediator with a parathyroid hormone-like effect on renal tubular calcium reabsorption. 4. The relatively frequent occurrence of hypercalcaemia in malignant disease thus may be partially explained by the presence of this humoral agent, which may impair the renal excretion of an increase in filtered calcium load, whether due to bone metastases, or humorally mediated osteolysis.

Renal tubular calcium transport: effects of changes in filtered calcium load

1983 ◽  
Vol 245 (4) ◽  
pp. F515-F520
Author(s):  
R. A. Sutton ◽  
N. L. Wong ◽  
G. A. Quamme ◽  
J. H. Dirks
Keyword(s):  
Urinary Calcium ◽  
Calcium Excretion ◽  
Reciprocal Effect ◽  
Group I ◽  
Calcium Reabsorption ◽  
Calcium Infusion ◽  
Transport Effects ◽  
Calcium Load ◽  
Renal Tubular ◽  
Filtered Load

Micropuncture experiments were performed in thyroparathyroidectomized dogs to examine the influence of changes in filtered calcium load on segmental tubular calcium reabsorption. Filtered calcium load was changed either by reducing glomerular filtration rate (GFR) by aortic clamping (group I) or by progressive calcium infusion (group II) to increase plasma ultrafilterable calcium concentration (UFCa). The results suggest that fractional proximal calcium reabsorption responds similarly to altered filtered load, whether produced by changes in GFR or UFCa. In contrast, fractional reabsorption by the loop segment is progressively reduced as UFCa is increased but is relatively unchanged by alterations in filtered load secondary to altered GFR. These data indicate a specific parathyroid hormone-independent reciprocal effect of UFCa on calcium reabsorption in the loop segment, which may be an important determinant of urinary calcium excretion.

The comparative effects of feeding ammonium carbonate, ammonium sulfate, and ammonium chloride on urinary calcium excretion in the rat

1987 ◽  
Vol 65 (11) ◽  
pp. 2202-2204 ◽  
Author(s):  
Susan J. Whiting ◽  
David E. C. Cole
Keyword(s):  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Male Rats ◽  
Calcium Excretion ◽  
Acid Excretion ◽  
Calcium Reabsorption ◽  
Acid Load ◽  
Feeding Trials ◽  
Renal Tubular ◽  
Excretion Rates

When either sulfate or chloride is added to the diet, the resulting acid load causes a rise in urinary calcium excretion. There is, however, the possibility that sulfate, which has been shown to complex renal tubular calcium, will further decrease renal calcium reabsorption and thus produce a greater calciuria than chloride. Because addition of a fixed cation (e.g., sodium) to the diet may also stimulate calciuresis, experiments were conducted using metabolizable ammonium to minimize cation effects. Ammonium salts of sulfate, chloride, and carbonate (control) were added to the diets of male rats at 0.3 mequiv./g weight of diet. Twenty-four hour excretion rates of calcium, sulfate, chloride, and net acid were measured at various intervals up to 1 month. As expected, the chloride and sulfate diets were both associated with significantly elevated urine calcium and net acid excretion as compared with controls. However, those fed sulfate exhibited significantly less calcium and acid excretion and absorbed a smaller proportion of the anion load than those given chloride. In a second experiment, the amounts of supplemental sulfate and chloride were adjusted so that total absorptions were similar. At 2 weeks, both calcium and acid excretions in the fixed anion groups were no longer significantly different. Thus, in chronic feeding trials, there appears to be no measurable difference in the calciuretic properties of sulfate and chloride anions.

scholarly journals Primary Hyperparathyroidism in Homozygous Sickle Cell Patients: A Hemolysis-Mediated Hypocalciuric Hypercalcemia Phenotype?

2021 ◽  
Vol 10 (21) ◽  
pp. 5179
Author(s):  
Edmat Akhtar Khan ◽  
Lynda Cheddani ◽  
Camille Saint-Jacques ◽  
Rosa Vargas-Poussou ◽  
Vincent Frochot ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Sickle Cell ◽  
Fractional Excretion ◽  
Urinary Calcium ◽  
High Rate ◽  
Calcium Handling ◽  
Control Group ◽  
Calcium Excretion ◽  
Calcium Reabsorption ◽  
Chronic Hemolysis

Primary hyperparathyroidism (pHPT) has been reported to have a higher prevalence in sickle cell disease (SCD) patients, including a high rate of recurrence following surgery. However, most patients are asymptomatic at the time of diagnosis, with surprisingly infrequent hypercalciuria, raising the issue of renal calcium handling in SCD patients. We conducted a retrospective study including (1) 64 hypercalcemic pHPT non-SCD patients; (2) 177 SCD patients, divided into two groups of 12 hypercalcemic pHPT and 165 non-pHPT; (3) eight patients with a diagnosis of familial hypocalciuric hypercalcemia (FHH). Demographic and biological parameters at the time of diagnosis were collected and compared between the different groups. Determinants of fasting fractional excretion of calcium (FeCa2+) were also analyzed in non-pHPT SCD patients. Compared to non-SCD pHPT patients, our data show a similar ionized calcium and PTH concentration, with a lower plasmatic calcitriol concentration and a lower daily urinary calcium excretion in pHPT SCD patients (p < 0.0001 in both cases). Fasting FeCa2+ is also surprisingly low in pHPT SCD patients, and thus inadequate to be considered hypercalcemia, recalling the FHH phenotype. FeCa2+ is also low in the non-pHPT SCD control group, and negatively associated with PTH and hemolytic biomarkers such as LDH and low hemoglobin. Our data suggest that the pHPT biochemical phenotype in SCD patients resembles the FHH phenotype, and the fasting FeCa2+ association with chronic hemolysis biomarkers strengthens the view of a potential pharmacological link between hemolytic by-products and calcium reabsorption, potentially through a decreased calcium-sensing receptor (CaSR) activity.

scholarly journals Influence of renal function on clinico-pathological features of primary hyperparathyroidism

2003 ◽  
pp. 597-602 ◽  
Author(s):  
H Yamashita ◽  
S Noguchi ◽  
S Uchino ◽  
S Watanabe ◽  
T Murakami ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Insufficiency ◽  
Primary Hyperparathyroidism ◽  
Normal Renal Function ◽  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Calcium Excretion ◽  
Pathological Features ◽  
Function Group ◽  
Renal Function Group

OBJECTIVE: Disturbed renal function may play an important role in the clinico-pathological presentation of primary hyperparathyroidism (pHPT). We studied the influence of renal function on the clinico-pathological characteristics of 141 patients (123 women and 18 men) with surgically proven pHPT. METHODS: The 141 patients were assigned to one of two groups based on creatinine clearance (C(cr)) level: a renal insufficiency group (n=37) in which C(cr) of patients was <70 ml/min and a normal renal function group (n=104) in which C(cr) was > or =70 ml/min. Clinical presentation and biochemical indices were evaluated and compared between the two groups. RESULTS: Age, and frequency of hypertension and of diabetes mellitus were significantly (P<0.001, P<0.05 and P<0.05 respectively) higher in the renal insufficiency group than in the normal renal function group. Serum levels of calcium, intact parathyroid hormone and bone Gla protein were significantly (P<0.05) higher and the excised parathyroid weighed significantly more (P<0.05) in the renal insufficiency group than in the normal renal function group; however, serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and 24 h urinary calcium excretion were significantly (P<0.001 and P<0.05 respectively) lower in the former than in the latter group. There was a significant inverse correlation between C(cr) level and serum calcium (r=0.315, P<0.001) and a significant positive correlation between C(cr) level, 1,25(OH)(2)D (r=0.315, P<0.001), and 24 h calcium excretion (r=0.458, P<0.0001). CONCLUSIONS: Clinico-pathological features of pHPT were notably influenced by even moderate renal insufficiency. Urinary calcium excretion decreased according to the decrease in glomerular filtration rate. Therefore, endocrinologists need to appraise urinary calcium excretion and renal function of pHPT patients when considering surgery or in discriminating familial hypocalciuric hypercalcemia.

scholarly journals Vitamin D Repletion in Patients with Primary Hyperparathyroidism and Coexistent Vitamin D Insufficiency

2005 ◽  
Vol 90 (4) ◽  
pp. 2122-2126 ◽  
Author(s):  
Andrew Grey ◽  
Jenny Lucas ◽  
Anne Horne ◽  
Greg Gamble ◽  
James S. Davidson ◽  
...  
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Serum Calcium ◽  
Serum Alkaline Phosphatase ◽  
Vitamin D Insufficiency ◽  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Total Serum ◽  
Calcium Excretion ◽  
Intact Pth

Abstract Vitamin D insufficiency is common in patients with primary hyperparathyroidism (PHPT) and may be associated with more severe and progressive disease. Uncertainty exists, however, as to whether repletion of vitamin D should be undertaken in patients with PHPT. Here we report the effects of vitamin D repletion on biochemical outcomes over 1 yr in a group of 21 patients with mild PHPT [serum calcium &lt;12 mg/dl (3 mmol/liter)] and coexistent vitamin D insufficiency [serum 25 hydroxyvitamin D [25(OH)D] &lt;20 μg/liter (50 nmol/liter)]. In response to vitamin D repletion to a serum 25(OH)D level greater than 20 μg/liter (50 nmol/liter), mean levels of serum calcium and phosphate did not change, and serum calcium did not exceed 12 mg/dl (3 mmol/liter) in any patient. Levels of intact PTH fell by 24% at 6 months (P &lt; 0.01) and 26% at 12 months (P &lt; 0.01). There was an inverse relationship between the change in serum 25(OH)D and that in intact PTH (r = −0.43, P = 0.056). At 12 months, total serum alkaline phosphatase was significantly lower, and urine N-telopeptides tended to be lower than baseline values (P = 0.02 and 0.13, respectively). In two patients, 24-h urinary calcium excretion rose to exceed 400 mg/d, but the group mean 24-h urinary calcium excretion did not change. These preliminary data suggest that vitamin D repletion in patients with PHPT does not exacerbate hypercalcemia and may decrease levels of PTH and bone turnover. Some patients with PHPT may experience an increase in urinary calcium excretion after vitamin D repletion.

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

1997 ◽  
Vol 83 (4) ◽  
pp. 1159-1163 ◽  
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.

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

2007 ◽  
Vol 292 (1) ◽  
pp. F66-F75 ◽  
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.

scholarly journals Renal Tubular Impairment in Children with Idiopathic Hypercalciuria

2006 ◽  
Vol 49 (2) ◽  
pp. 109-111 ◽  
Author(s):  
Sylva Skálová ◽  
Štěpán Kutílek
Keyword(s):  
Reference Data ◽  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Idiopathic Hypercalciuria ◽  
Tubular Damage ◽  
Calcium Excretion ◽  
Spot Urine ◽  
Z Scores ◽  
Proximal Tubular ◽  
Renal Tubular

Idiopathic hypercalciuria (IH) is defined as hypercalciuria that persists after correction of dietary inbalances and has no detectable cause. The excretion of urinary N-acetyl-beta-D-glucosaminidase (U-NAG), a marker of proximal tubular damage, has been previously reported as either increased or normal in children with IH. We evaluated U-NAG in 20 children (13 boys and 7 girls, mean age 10.3 years ± 5.7 SD) with IH (urinary calcium excretion above 0.1 mmol/kg/24 hours, with no detectable cause) and with otherwise normal renal function tests. Ultrasound examination revealed urolithiasis (n = 4) and nephrocalcinosis (n = 1). The U-NAG values were evaluated in the spot urine collected from the second morning void and calculated as the urinary NAG/creatinine ratio (U-NAG/Cr) and expressed in nkat/mmol. The 24-hour urinary calcium excretion (U-Ca/24h) was assessed in a urinary sample from 24-hour collected urine and calculated in mmol/kg. The obtained results of U-Ca/24h and U-NAG/Cr were expressed as Z-scores. When compared to the reference data, the U-Ca/24h and U-NAG/Cr were significantly higher (p=0.0004 and p=0.006, respectively). There was no correlation between the U-NAG/Cr and U-Ca/24h (r = 0.18, p = 0.20). The U-NAG/Cr values were significantly higher in the 5 patients with urolithiasis/nephrocalcinosis, whether compared to the rest of the group (p=0.02), or to the reference data (p=0.01). The U-NAG/Cr activity was higher in 15 children without urolithiasis/nephrocalcinosis when compared to reference data (p < 0.01). There was no difference in U-Ca/24h between the children with and without urolithiasis/nephrocalcinosis (p = 0.58). These findings suggest that tubular impairment, as reflected by U-NAG/Cr, might occur in children with IH, especially in patients with urolithiasis/nephrocalcinosis. There doesn’t seem to be a direct relationship between the U-NAG/Cr activity and the degree of calcium leakage.

Factors influencing pre-operative urinary calcium excretion in primary hyperparathyroidism

2017 ◽  
Vol 87 (1) ◽  
pp. 97-102 ◽  
Author(s):  
Reto M. Kaderli ◽  
Philipp Riss ◽  
Angelika Geroldinger ◽  
Andreas Selberherr ◽  
Christian Scheuba ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Calcium Excretion ◽  
Factors Influencing
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