Calcium Absorption In Patients Research Articles

Evidence in Favor of a Severely Impaired Net Intestinal Calcium Absorption in Patients with (Early-Stage) Chronic Kidney Disease

Introduction: Calcium and phosphorus are essential to many vital physiological processes. Little is known about the net and fractional intestinal absorption of calcium and phosphorus in patients with chronic kidney disease (CKD) and their clinical and hormonal determinants. Methods: Blood and 24-hour urine samples were collected in 20 healthy volunteers (HV) and 72 stable CKD stage 1–4 patients and analyzed for parameters of mineral metabolism including calcidiol, calcitriol, and parathyroid hormone (PTH). Dietary intake was assessed by dietary history. Results: The 24-hour urinary calcium excretion, as opposed to the phosphorus excretion, showed a stepwise decrease across CKD stages (median of 219, 84, 40, and 22 mg/day in HV and patients with CKD stages 1–2, 3 and 4, respectively). Younger age, high serum calcitriol, and high estimated GFR were associated with a high 24-hour urinary calcium excretion. High serum calcitriol levels and dietary phosphorus intake were associated with a high 24-hour urinary phosphorus excretion. The fractional intestinal calcium absorption, as estimated by the urinary-to-ingested calcium ratio, decreased across CKD stages. Conclusions: The 24-hour urinary excretion of calcium, as opposed to phosphorus, is markedly decreased in CKD, even in early-stage disease. This is partly explained by low calcitriol levels and older age. Assuming a neutral calcium balance at the time of urine collection, we infer that net intestinal calcium absorption may be severely impaired in CKD.

Vitamin D‐mediated calcium absorption in patients with clinically stable Crohn's disease: A pilot study

Vitamin D is the critical hormone for intestinal absorption of calcium. Optimal calcium absorption is important for proper mineralization of bone in the prevention of osteoporosis and osteoporotic fractures, among other important functions. Diseases associated with gut inflammation, such as Crohn's disease (CD), may impair calcium absorption. This pilot study evaluated vitamin D- dependent calcium absorption in subjects with CD. Male subjects with CD (n=4) and healthy age-matched controls (n=5) were studied. All subjects had fractional calcium absorption (FCA; by the dual calcium isotope method), serum 25-hydroxyvitamin D, serum calcium and 24 h urinary calcium excretion measurements at baseline. The FCA in response to vitamin D therapy was re-assessed following administration of oral calcitriol 0.25 mcg twice daily for 1 wk, followed by oral calcitriol 0.50 mcg twice daily for 1 wk. Serum calcium and 24 h urinary calcium determinations were re-assessed after each increasing dose of calcitriol as safety measures. There was no significant difference in calcium FCA at baseline or after increasing doses of calcitriol between the CD and controls. FCA in the control and CD group was approximately 35% at baseline, which increased to 60% after calcitriol therapy. No subject developed hypercalcemia or hypercalciuria. Our results suggest that CD patients have a normal response to vitamin D in enhancing the efficacy of calcium absorption. This suggests that stable CD patients can follow calcium and vitamin D guidelines of non-CD adults. Other factors independent of vitamin D status may impair intestinal calcium absorption in CD, including the degree and location of inflammation, presence of surgical resection and/or use of glucocorticoids.

Choroidal calcifications in patients with Gitelman’s syndrome

Gitelman’s syndrome is a renal tubular disorder characterized by a sodium and chloride reabsorption defect in distal tubular cells that determines hypokalemia, metabolic alkalosis, hypomagnesemia, and low calcium excretion. The presence of choroidal calcifications was sought in five patients with Gitelman’s syndrome by ophthalmic examination, fluorescein angiography, indocyanine green angiography, and ocular ultrasonography. Calcifications observed in the choroid of two patients were shown by ultrasonography in both patients. Ophthalmic and fluorangiographic examinations detected this alteration in one of the two subjects. Chondrocalcinosis was found in one patient with choroidal calcifications. These findings suggest that precipitation of calcium salts can occur in the choroidal tissue of patients with Gitelman’s syndrome. Deposits appeared to be well seen by ultrasonography because of their depth in ocular tissues. Sclerochoroidal calcifications may be favored by the low calcium excretion, which is associated with normal intestinal calcium absorption in patients with Gitelman’s syndrome.

Evidence that factors other than 1,25 dihydroxyvitamin D may play a role in augmenting intestinal calcium absorption in patients with primary hyperparathyroidism.

We examined 17 patients with primary hyperparathyroidism for their serum 1,25 dihydroxyvitamin D levels and for their fractional intestinal calcium absorption rates using a whole body counter and calcium-47. As controls, 10 normal volunteers were examined both before and after administration of 1 alpha-hydroxyvitamin D to increase serum 1,25 dihydroxyvitamin D. Values of serum 1,25 dihydroxyvitamin D were 71.6 +/- 37.6 pg/ml (mean +/- SD) in patients with primary hyperparathyroidism and 75.3 +/- 27.7 pg/ml (mean +/- SD) in normal volunteers after administration of 1 alpha-hydroxyvitamin D, while values of intestinal calcium absorption rate were 61.5 +/- 16.5% (mean +/- SD) in patients with primary hyperparathyroidism and 34.1 +/- 5.1% (mean +/- SD) in normal controls, respectively. There was a positive correlation between values of serum 1,25 dihydroxyvitamin D and intestinal calcium absorption in both groups. However, in patients with primary hyperparathyroidism, intestinal calcium absorption was more increased than that in normal volunteers when compared to their serum values of 1,25 dihydroxyvitamin D. This suggests that another factor than 1,25 dihydroxyvitamin D plays an important role in the intestinal calcium absorption in patients with primary hyperparathyroidism.

Enhancement of calcium absorption in rats by coadministration of glucose polymer

Glucose polymer derived from corn starch is widely used in infant formula and nutritional supplements as a readily digestible, low osmolarity source of calories. We have previously observed that glucose polymer causes a marked increase in intestinal calcium absorption in patients with intestinal malabsorption and in normal subjects. The present study investigates the effect of concurrently administered glucose polymer on intestinal 45calcium absorption in rats. The effect of glucose polymer on calcium absorption was compared to that of equivalent doses of dextrose or lactose. Femur radioactivity was determined as an index of calcium absorption. Carbohydrates were prepared at doses of 0.5, 2.0 and 4.0 mg/g body weight and administered with 45Ca by stomach gavage. Control rats received 45Ca in water alone. Coadministration of glucose polymer resulted in a dose-dependent increase in calcium absorption. At the highest dose of polymer studied calcium absorption was 75% greater than in control animals. Administration of lactose and dextrose also resulted in a dose-dependent increase in calcium absorption. Calcium absorption was 122 and 67% greater than controls when 4 mg/g BW lactose and dextrose were given with the 45Ca. We conclude that glucose polymer stimulates calcium absorption in rats similar to lactose and glucose. These results suggest that glucose polymer may be a useful therapeutic adjunct in patient groups in which there is a desire to increase intestinal calcium absorption.

Effect of 1,25-dihydroxyvitamin D3 on calcium absorption in the colon of healthy humans.

Calcium absorption in patients with short bowel syndrome is significantly higher when the colon is left intact. To study calcium transport in the large bowel, we investigated whether exogenous 1,25-dihydroxyvitamin D3 [1,25(OH2)D3] can induce or enhance colonic calcium absorption in healthy subjects ingesting a normal diet. Steady-state colon perfusion studies were performed before and after 1 wk of 1,25(OH)2D3 administration (2 micrograms/day, 10 subjects). Serum 1,25-dihydroxyvitamin D concentration rose from 23.0 +/- 2.2 to 39.5 +/- 4.3 pg/ml (mean +/- SE, P less than 0.01). In the basal state the mean net movement of calcium was not significantly different from zero when a 5 mM calcium gluconate solution was perfused (100 +/- 84 mumol X h-1 X entire colon secreted-1). Vitamin D administration resulted in a significant change toward calcium absorption (106 +/- 47 mumol X h-1 X entire colon absorbed-1, P less than 0.02). 1,25(OH)2D3 had no effect on colonic magnesium, phosphate, water, and electrolyte movement. This study demonstrates that in healthy humans exogenous 1,25(OH)2D3 can change colonic calcium movement toward absorption. We suspect that similar changes in colonic calcium transport are caused by endogenous 1,25(OH)2D3 when calcium deficiency has occurred in short bowel syndrome.

Intestinal calcium absorption in patients with active pulmonary tuberculosis

It has been reported recently that hypercalcemia might accompany active pulmonary tuberculosis. This change is more often encountered during the first weeks of antituberculous treatment, when hypercalcemia may be found in approximately 30–50% of the patients (Abbasi et al. 1979, Need et al. 1980, Kitrou et al. 1982). The mechanism(s) of this change remains as yet unknown. Measurements of immunoreactive serum parathyroid hormone in four patients showed low levels in three (Abbasi et al. 1979). On the basis of this finding Abbasi et al. (1979) suggested that hypercalcemia in pulmonary tuberculosis might be due to vitamin D overactivity, as is the case in sarcoidosis. This hypothesis would appear to be supported by the finding (Abbasi et al. 1979, Kitrou et al. 1982) that simultaneously to serum calcium increase during antituberculous treatment, there is an almost parallel increase in serum phosphorus. To test this hypothesis we decided to measure intestinal

An apparent 1,25-dihydroxyvitamin D-independent stimulation of intestinal calcium absorption in patients with paget disease of bone during a short-term diphosphonate therapy

Six patients with Paget disease of bone were treated with a 6-mo course of disodium-ethane-1-hydroxy-1, 1-diphosphate (EHDP) at a dosage of 5 mg/kg/day (one patient) or 20 mg/kg/day (five patients). In addition to symptomatic and biochemical improvement which persisted 3 mo after discontinuance of therapy, EHDP resulted in a significant increase in intestinal calcium absorption that was not correlated with a change in serum 1α,25-(OH) 2-vitamin D concentration. EHDP appears to stimulate intestinal calcium transport by either a vitamin D independent process or by an increased intestinal mucosal cell sensitivity to vitamin D.

Intestinal calcium absorption in patients with hyperthyroidism.

Intestinal 47Ca absorption was measured at 2 and 24 h after isotope ingestion in six patients with hyperthyroidism and seven normal subjects. Although 47Ca absorption was not different at 2 h, it was significantly lower (P < 0.01) after 24 h in the patients with hyperthyroidism. Factors related to the effects of thyroid hormone on intestinal function, in addition to abnormalities of vitamin D metabolism, are probably responsible for the defect.

A longitudinal study of bone-mineral content and intestinal calcium absorption in patients with chronic renal failure

In 14 nondialyzed patients with chronic renal failure (CRF) and at the start of treatment a glomerular filtration rate (GFR) of 14–47 ml/min changes in bone mineral mass (BMM), expressed in percentage of the initial value, showed a significant correlation with the mean GFR during an observation period of 16 ± 2 mo. During a predialysis period of 6 mo BMM decreased to 97.8 ± 3.2% of the original value in 9 patients, while after 6, 12, and 16 mo of dialysis treatment, BMM in the same patients fell to 94.5 ± 3.0%, 92.0 ± 3.2% and 91.8 ± 4.6% of the initial value. As after the onset of regular hemodialysis the fractional intestinal absorption of 47Ca does not decrease but even increases in most patients, the importance of the level of intestinal calcium absorption for the development of dialysis bone disease may be questioned.

Jejunal and ileal absorption in patients with chronic renal disease. Effect of 1alpha-hydroxycholecalciferol.

Calcium absorption in 30-cm segments of small intestine was measured by constant perfusion of test solutions containing different concentrations of calcium gluconate. In both the jejunum and ileum, calcium absorption rates increased progressively as luminal calcium concentration was increased stepwise between 1 and 20 mM. Although calcium transport was not saturable within these limits, unidirectional flux ratios of calcium (47Ca) suggest that calcium absorption is active in both the jejunum and ileum. Calcium absorption in patients with chronic renal disease was markedly depressed in both regions of the small intestine. This was due to decreased flux out of the lumen; flux in the reverse direction was normal. Flux ratios in the renal disease patients showed no evidence for active calcium transport. Treatment of these patients for 1 wk within 2 mug/day of 1alpha-hydroxycholecalciferol [1alpha-(OH)-D3] restored net calcium absorption and unidirectional calcium flux out of the lumen to normal values in the jejunum; in the ileum, 1alpha-(OH)-D3 increased calcium absorption 60-83% of normal at the various luminal calcium concentrations. 1alpha(OH)-D3 had no effect on unidirectional calcium flux into the lumen or on xylose and electrolyte absorption in either area of the small intestine.

Comparative effects of 1α-hydroxycholecalciferol in children and adults with renal glomerular osteodystrophy

Recent short-term studies have shown that microgram doses of both 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3), the hormonally active metabolite of vitamin D, and lα-hydroxycholecalciferol (lα-OH-D3), a synthetic analogue can increase intestinal absorption of calcium in patients with chronic renal failure in whom large (mg) doses of vitamin D are ineffective (1, 4, 5, 6). In patients with renal osteodystrophy, these compounds may reduce plasma parathyroid hormone concentration and osteoclastic bone resorption (2) and increase the calcium content of the bones of the hands (3). There is, however, little published work on the long-term effects of 1,25-(OH)2-D3 or lα-OH-D3 in patients with renal osteodystrophy. The present paper describes the effects of lα-OH-D3 in four children and three adults studied for up to 14 months.

The effect of 5,6-trans vitamin D3 on calcium absorption in chronic renal disease.

Calcium absorption was determined in 6 patients with chronic renal disease (GFR values 4.8 to 37 ml/min) on a constant diet before and after administration of 5,6-trans vitamin D3. Administration of 0.5 to 1.0 mg of 5,6-trans D3 for 8 days did not improve calcium absorption. In two of these same patients (the most uremic) administration of 5 mg of 5,6-trans D3 for 8 day sincreased calcium absorption markedly. Two other uremic patients who were studied under the same conditions and received 5 mg of native vitamin D3 for 8 days had no significant in crease incalcium absorption. Since 5,6-trans D3 normalized calcium absorption in patients with far-advanced renal disease, it is suggested that this analogue of vitamin D may be a useful agent in the treatment of hypocalcemia in patients with renal failure.

Effect of long-term thiazide therapy on intestinal calcium absorption in patients with recurrent renal calculi

Recurrent calcium-containing renal calculi are a common and poorly understood problem. Thiazide diuretics decrease urinary calcium excretion but their effect on other parameters of calcium metabolism is not established. The purpose of this study was to determine the effect of chronic administration of thiazide diuretics on intestinal calcium absorption, skeletal calcium turnover, and urinary calcium excretion, and to use this information to attempt to clarify the pathogenesis of idiopathic hypercalciuria. Forty-one patients with recurrent calcium-containing renal calculi were studied; 73% had hypercalciuria, 44% had increased intestinal absorption, and 7% had increased bone turnover. Thiazide diuretics given to 22 patients for 3–16 mo resulted in a consistent reduction in urinary calcium excretion, while calcium absorption was unchanged (< 6%) in 12 patients and significantly decreased (by 20%) in ten patients. Decreased intestinal absorption appeared to be a secondary effect of thiazides, presumably due to reduced urinary calcium losses. Bone turnover was significantly decreased by thiazides in each case in which it had been elevated and was unchanged in patients with initially normal values. These results indicate that increased bone turnover is probably not the primary defect in idiopathic hypercalciuria. The effects of long-term thiazide diuretic therapy on intestinal calcium absorption suggest that there may be two different subpopulations of patients with hypercalciuria, one with primary intestinal hyperabsorption which persists despite correction of urinary losses, and one with primary renal loss of calcium.

Study of intestinal absorption of calcium in patients with renal failure

Study of intestinal absorption of calcium in patients with renal failure. Absorption of 47 Ca was measured with a method which assesses true absorption and shows good reproducibility in 256 subjects, including 47 normal, 16 with early renal failure (serum creatinines ≦2.5 mg/100 ml), 96 with advanced renal failure (serum creatinines >2.5 mg/100 ml), 58 undergoing regular hemodialysis, and 39 renal transplant recipients. In normal subjects 47 Ca absorption varied inversely with previous habitual dietary calcium intake, and absorption did not differ from normal in patients with early renal failure. In patients with advanced renal failure and in those treated with hemodialysis, 47 Ca absorption was below normal; deviation below normal was greater when dietary calcium intake was considered. In individual patients, calcium absorption often increased slightly with initiation of regular hemodialysis, but values generally remained subnormal. Renal transplantation restored absorption to normal, but absorption was reduced in those with serum creatinine >2.0 mg/100 ml and was inversely related to prednisone dosage. Thus true intestinal calcium absorption is clearly impaired with renal failure although the defect cannot be detected with mild renal failure. The diets of these patients contain low quantities of calcium, probably contributing to hypocalcemia in uremic patients. The impaired calcium absorption is discussed in relation to the kidney's role in producing 1,25-dihydroxycholecalciferol, the presumed active form of vitamin D. Etude de l'absorption intestinale de calcium chez des malades atteints d'insuffisance renale. L'absorption de 47 Ca a ete mesuree par une methode qui determine l'absorption vraie et possede une bonne reproductibilite chez 256 sujets, dont 47 sujets normaux, 16 au stade initial de l'insuffisance renale (creatinines plasmatiques 2.5 mg/100 ml), 58 soumis a l'hemodialyse periodique et 39 transplantes. Chez les normaux l'absorption de 47 Ca varie en fonction inverse des habitudes alimentaires anterieures, elle n'est pas differente de celle des sujets au stade initial de l'insuffisance renale. Chez les malades atteints d'insuffisance renale avancee et ceux traites par hemodialyse l'absorption de 47 Ca etait inferieure a la normale et l'ecart etait plus grand quand l'ingestion de calcium etait prise en consideration. Chez certains malades une augmentation moderee de l'absorption contemporaine du debut de l'hemodialyse periodique a ete observee, mais dans l'ensemble les valeurs sont demeurees subnormales. La transplantation a ramene l'absorption a la normale sauf chez les malades dont la creatinine etait superieure a 2.0 mg/100 ml et l'absorption etait inversement correlee a la posologie de la Prednisone. Ainsi l'absorption intestinale vraie de calcium est nettement diminuee par l'insuffisance renale quoique le deficit ne puisse etre detecte au cours de l'insuffisance renale moderee. La ration alimentaire de ces malades contient peu de calcium, ce qui contribue probablement a l'hypocalcemie des malades uremiques. Le deficit d'absorption de calcium est discute en tenant compte du role du rein dans la production du 1,25-dihydroxycholecalciferol, la forme active presumee de la vitamine D.

Net intestinal absorption of calcium in patients with chronic renal failure

Net intestinal absorption of calcium in patients with chronic renal failure. Most patients with chronic renal failure consume a smaller amount of calcium than normal. Net calcium absorption in such patients is negative, whereas in normal subjects on a similar calcium intake net calcium absorption is positive. The absorption of calcium in the remaining patients whose intake is by choice within or above the normal range may be normal. There is a statistically significant correlation between the calcium content of the self-chosen diet of patients with chronic renal failure and net calcium absorption. The absorption of calcium in patients with chronic renal failure and in normal subjects when ingesting large amounts of supplemental calcium is the same. L'absorption intestinale nette de calcium chez des patients en insuffisance renale. La plupart des malades atteints d'insuffisance renale chronique ingere moins de calcium que les sujets normaux. L'absorption nette du calcium chez ces malades est negative alors que chez les sujets normaux l'absorption est positive pour un apport de calcium egal. L'absorption du calcium est normale chez les autres malades dont l'ingestion est dans ou au-dessus de l'eventail des valeurs habituelles. II existe une correlation statistiquement significative entre le contenu en calcium de l'alimentation librement choisie par un malade atteint d'insuffisance renale chronique et l'absorption nette de calcium. L'absorption de calcium chez les malades atteints d'insuffisance renale chronique est la meme que les sujets normaux quand tous deux ingerent de grandes quantites de calcium supplementaires.

Usefulness of 45Ca intestinal absorption tests in the clinical situation

Radioactive isotopes of calcium were used to measure calcium absorption in patients with various diseases. In most clinical groups there was great variation in plasma concentration after oral administration with overlap with the normal group. Patients with uraemia and pancreatectomy showed significantly low values. A method for calculating absorption and removal constants of radioactive calcium is described, and methods of calculating absorption and removal constants are discussed. It was concluded that these calculations do not add information to that obtained from plasma concentrations. Plasma concentrations after oral ingestion of radioactive calcium are of value mainly in following the course of disease in individual patients

The Nature of Vitamin D Resistance of Patients With Chronic Renal Disease

Chronic renal disease is characteristically attended by derangements in calcium homeostasis and bone metabolism. 1-3 Many investigators have documented an impaired intestinal absorption of calcium in patients with chronic renal failure using either classical metabolic balance or isotopic marking techniques. 3-5 This defect has also been noted in patients without manifest azotemia or acidosis 3,6 and has been confirmed in chronic experimental renal insufficiency by Kessner and Epstein. 7 Liu and Chu initially considered a "resistance" to vitamin D action in the uremic individual as a cause for defective intestinal calcium absorption. 8 Stanbury and Lumb 3 and Dent and co-workers 9 have also suggested that the "acquired vitamin D resistance" results primarily in the defective absorption of calcium from the gastrointestinal tract. The subsequent studies of Fletcher et al made during the therapeutic trials of alkali, aluminum hydroxide, vitamin D, and calcium supplements in uremic osteodystrophic patients appear confirmatory

Oral calcium absorption in patients with renal failure treated by chronic hemodialysis

Oral calcium absorption, measured by a simplified isotopic method, has been assessed in patients undergoing chronic hemodialysis. By comparison with normal subjects, these patients had markedly impaired absorption irrespective of the duration of treatment or the number of dialyses. Responses to vitamin D administration were nil at 25,000 units but the pattern of absorption was successively increased into the low normal range by 50,000 and 100,000 units. It is concluded that dialysis successful by conventional criteria may fail to correct the defect in calcium absorption which accompanies renal failure. The resultant calcium deficiency may be important in the pathogenesis of renal osteodystrophy during dialysis.