Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] derivatives in a uremic patient is justified only in the treatment of hyperparathyroidism (i.e. when plasma intact parathyroid hormone - PTH - levels are above five or three times the upper limit of normal according to whether the patient is on continuous ambulatory peritoneal dialysis or on hemodialysis and between 0.5-1.5, 1-2 and 2-3 times the upper limit of normal for a creatinine clearance of, respectively, 30, between 30 and 10, or below 10 ml/min/1.73 m2). The following prerequisites have however to be satisfied: (1) a good vitamin D3 repletion should be secured by plasma 25(OH(D) levels of 20-30 ng/ml (if necessary by administration of native vitamin D or 25(OH)D3), and (2) phosphate retention (which is aggravated by the increased phosphate intestinal absorption induced by the 1 alpha (OH)D derivatives) and the consequent possible hyperphosphatemia should be prevented or corrected by the oral administration of alkaline salts of calcium given before the meals as phosphate binders without inducing hypercalcemia. These prerequisites explain the narrow therapeutical margin of 1 alpha (OH)D3 derivatives in uremic patients before dialysis (more so in the adult than in the child) and the possible broadening of this margin in the patients on dialysis by the use of low dialysate calcium concentrations (1.25-1.00 mmol/l) in order to prevent hypercalcemia by inducing a negative perdialytic calcium balance. Once hyperphosphatemia is prevented by oral calcium, 1 alpha (OH)D3 derivatives have the advantage to suppress the transcription of the prepro PTH gene by a mechanism independent of an increase in plasma calcium. Controlled randomized trials have not confirmed the claimed advantage in efficacy and safety of the parenteral versus the oral route nor of the intermittent versus the daily mode of their administration. The advantages of using the so called 'nonhypercalcemic hyperphosphatemic' vitamin D3 derivatives in combination with oral calcium over 1 alpha(OH)D3 derivatives in the treatment of uremic hyperparathyroidism are still waiting for clinical demonstration. Vitamin D derivatives have no place in the treatment of aluminic bone diseases which necessitate long term deferoxamine treatment and prevention of aluminum exposure by the dialysate and the phosphate binders. They are not indicated in the treatment of 'idiopathic' adynamic bone disease which is due to uremia per se combined with an excessive PTH suppression for the degree of renal failure. This low bone turnover pattern is associated with an increased risk of hypercalcemia and hyperphosphatemia and necessitates only a stimulation of PTH secretion by inducing a negative calcium balance with a lower dialysate calcium concentration or simply by discontinuing the oral calcium supplement in the uremic patient not yet dialyzed. In rare cases this pattern is due to a granulomatosis and is corrected by prednisone.
Nephron 1995
PMID:1-alpha-Hydroxyvitamin D3 derivatives in the treatment of renal bone diseases: justification and optimal modalities of administration. 856 75

The concurrent use of calcitriol (CAL) pulse therapy to reduce parathyroid hormone (PTH) secretion and of calcium (Ca) salts as the most appropriate phosphate binders was evaluated for over 1 year in a group of 14 patients with good divalent ion control on CaCO3 therapy but with increasing levels of serum intact PTH. CAL pulse therapy was effective and safe in only 2 patients; in the remaining subjects it resulted in hypercalcemia and/or hyperphosphatemia, not reversed by adjusting the dialysate Ca concentration and or CaCO3 dose, and had to be stopped. Therefore, CAL pulse therapy does not seem to be compatible with Ca salts which, in our opinion, deserve priority in the therapy of renal dialysis patients.
Nephron 1995
PMID:Calcitriol pulse therapy for severe hyperparathyroidism or calcium salts as phosphate binders in renal dialysis patients? 856 85

Intensive training in a humid and warm environment can cause exertional heat stroke (ExHS) and rhabdomolysis (RBD) in military recruits. To investigate the role of vitamin D and monomeric calcitonin (CT) on the calcium metabolism in ExHS with RBD and acute renal failure (ARF), we studied 21 recruits with ExHS (mean age 21.4 years), 7 of which had ARF. Another 11 age-matched recruits with heat exhaustion (HE) and 11 healthy subjects were selected as controls. Our results showed that in 14 ExHS patients without ARF, mean serum creatinine (Cr) levels were significantly higher (151.16 vs. 106.08 mumol/l, p < 0.01), whereas serum osteocalcin (OC) levels were significantly lower (2.22 vs. 4.65 micrograms/l, p < 0.01) than in healthy controls. In 7 patients with ExHS and ARF, the mean serum Cr (774.38 vs. 105.20 mumol/l, p < 0.01), phosphorus (P) (2.26 vs. 1.26 mmol/l, p < 0.05), creatine phosphokinase (CPK) 274,143.97 vs. 85.78 IU/l, p < 0.05), intact parathyroid hormone (I-PTH) (299.81 vs. 18.66 ng/l, p < 0.05) and CT (13.58 vs. 6.63 ng/l, p < 0.01) levels on admission were significantly higher while the mean ionized calcium (iCa) levels were significantly lower than the healthy controls (0.9 vs. 1.18 mmol/l, p < 0.01). The mean serum 25-hydroxyvitamin D [25(OH)D] levels were not significantly different from healthy controls. However, mean serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels and the ratio of 1,25(OH)2D to 25(OH)D were significantly lower than healthy controls throughout the whole course of ARF. None of the 7 patients with ExHS and ARF developed hypercalcemia during the diuretic phase. Their mean serum I-PTH levels decreased significantly from 299 to 18 ng/l during the recovery phase (p < 0.05). Our study seems to suggest that the abnormal calcium metabolism in this unique patient group is in part caused by persistently decreased renal production of 1,25(OH)2D, although increased monomeric CT levels were associated with hypocalcemia. However, whether or not a causal relationship exists merits further investigation.
Nephron 1995
PMID:A prospective study of calcium metabolism in exertional heat stroke with rhabdomyolysis and acute renal failure. 858 23

We have used high-dose oral pulse therapy with 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3) to treat 40 hemodialysis patients suffering form secondary hyperparathyroidism. Forty patients with intact parathyroid hormone (PTH) levels of > 150 pg/ml were treated with 4 micrograms oral 1 alpha-OH-D3 twice weekly for 1 year. The mean PTH level was 515 +/- 50 pg/ml prior to treatment, which fell to 191 +/- 42 pg/ml after 6 months of treatment (p < 0.00001), and to 164 +/- 39 pg/ml after 12 months of treatment. Patients with very high PTH levels (> 800 pg/ml) suppressed less well than patients with lower levels (150-300 pg/ml). The therapeutic end point of PTH < 100 pg/ml was achieved in 23 patients (58%). The main side effect of the treatment was hypercalcemia, but this was symptomatic in only 3 patients, all above the age of 70 years. In summary, oral high-dose pulse therapy with 1 alpha-OH-D3 was highly effective in suppressing PTH levels in hyperparathyroid hemodialysis patients, and side effects were relatively few.
Nephron 1996
PMID:Successful treatment of secondary hyperparathyroidism in hemodialysis patients with oral pulse 1-alpha-hydroxy-cholecalciferol therapy. 868 18

It has been shown that calcium carbonate (CaCO3) is an effective phosphate binder which is less toxic than Al(OH)3. However, given that its use with standard calcium dialysate (CaD) levels may lead to hypercalcemia, a decrease in CaD levels has been proposed. The aim of the present study was to elevate the acute clinical and biochemical consequences of a lowering of CaD in HD patients. Dialysate composition was otherwise the same. (1) Blood pressure levels (BP) during short hemodialysis were measured in a group of 12 patients who underwent alternate hemodialyses with dialysate calcium of 1.75 and 1.25 mmol/l. (2) Ca2+ and PTH kinetics during short hemodialysis were studied in a group of 6 patients who were sequentially treated with 1.75 and 1.25 mmol/l CaD. The results show: (1) that cardiovascular stability in chronic HD patients during short HD sessions with low CaD (LCaD) may be good; (2) that a single treatment with standard CaD (SCaD) produces positive calcium balances (JCa2+) with Ca2+ plasma increase and PTHi inhibition at the end of HD sessions; during HD with LCaD there were neutral mean JCa2+ and no changes in post-dialysis mean Ca2+ and PTHi plasma levels; furthermore 2 patients showed a small PTHi increase during HD with LCaD and neutral JCa2+ because of a high positive bicarbonate balance during HD. In conclusion, as with several aspects of dialysis treatment, dialysate calcium levels should also be individualized to avoid hypercalcemic crises or PTHi stimulation.
Nephron 1996
PMID:Intradialytic calcium balances with different calcium dialysate levels. Effects on cardiovascular stability and parathyroid function. 945 16

The drug therapies for hypercalcemia of malignancy have been known to be associated with either limited efficacy or cumulative toxicity in patients with advanced renal failure. To establish the guidelines for the use of dialysis and to determine its optimal prescription for hypercalcemia, calcium-free hemodialysis was performed in 6 hypercalcemic patients with renal failure not responding enough to forced saline diuresis. Calcium-free dialysate contained sodium 135, potassium 2.5, chloride 108, magnesium 0.75, bicarbonate 30 mmol/l. Mean hemodialysis time was 160 +/- 27 min and mean Kt/V urea was 0.75 +/- 0.2. Plasma calcium concentrations fell from a mean value of 2.92 +/- 0.21 mmol/l (range 2.55-3.25) to 2.58 +/- 0.16 mmol/l at 1 h of hemodialysis and to 2.16 +/- 0.33 mmol/l (range 1.63-2.53) following 2-3 h of hemodialysis. The ionized calcium (n = 4) decreased from 1.44 +/- 0.14 mmol/l to 0.99 +/- 0.2 mmol/l. No patient showed any hypocalcemic symptoms and signs during hemodialysis. The rate of decrease in plasma calcium did not appear to produce adverse effects in any of the patients. There was a significant positive correlation between the decrease in plasma calcium concentration and the Kt/V urea (y = 1.4x - 0.29, r = 0.92, p < 0.01). We conclude that calcium-free hemodialysis is indicated when the presence of severe renal failure prevents the administration of large volumes of intravenous fluids to hypercalcemic patients. The amount of dialysis (Kt/V urea) can be used to predict the decrease in plasma calcium concentration during calcium-free hemodialysis.
Nephron 1996
PMID:Calcium-free hemodialysis for the management of hypercalcemia. 885 91

The effects of intravenous administration of 1 alpha-hydroxycholecalciferol [1 alpha (OH)D3] in combination with CaCO3 and 'low-calcium dialysis' (1.25 mmol/l) on plasma (p) parathyroid hormone (PTH) and biochemical bone markers (osteocalcin, alkaline phosphatase, procollagen type 1 c-terminal extension peptide) were examined in 54 patients on chronic hemodialysis with either normal or elevated PTH. Increasing doses of 1 alpha (OH)D3 were administered intravenously under careful control of p-Ca2+ and inorganic phosphate. Blood samples were obtained 1 week before the start of treatment and then every 2nd week. 20 patients with initially normal PTH levels (23.5 +/- 4.17 pg/ml) and 34 patients with initially elevated PTH levels (301 +/- 45 pg/ml) were followed for up to 88 weeks. The present investigation: demonstrated: (1) 'Low-calcium hemodialysis' (1.25 mmol/l) made it possible to use larger doses of CaCO3 and to reduce the doses of an aluminium-containing oral phosphate binder. A decrease in p-Ca2+ during dialysis was induced, and special care had to focus on the compliance to CaCO3, in order not to aggravate the secondary hyperparathyroidism. (2) The combination of 'low-calcium hemodialysis', CaCO3, and pulse intravenous 1 alpha (OH)D3 prevented the development of secondary hyperparathyroidism in patients with normal PTH levels and induced a long-term suppression of p-PTH (106 +/- 25 pg/ml, 88 weeks) in the patients with secondary hyperparathyroidism. By careful monitoring, severe hypercalcemia and hyperphosphatemia were avoided. There were no indications, clinically or biochemically, of development of adynamic bone disease. (3) Bone lesions were healed and a decrease of the bone mineral content in lumbar spine and femoral neck of patients with both normal and elevated PTH levels prevented. (4) The present results may suggest that PTH might be of influence on that regulation of procollagen type 1 c-terminal extension peptide.
Nephron 1996
PMID:Long-term effects of intravenous 1 alpha (OH)D3 combined with CaCO3 and low-calcium dialysis on secondary hyperparathyroidism and biochemical bone markers in patients on chronic hemodialysis. 888 25

Phosphate binders are necessary to control hyperphosphataemia in the majority of dialysis patients. Whilst aluminium salts are efficient phosphate binders, their use is associated with toxic side effects. Calcium salts are a widely used alternative, but hypercalcaemia is a common side effect, limiting their use and raising concern about metastatic calcification. Reduction of the dialysis fluid calcium concentration has been shown to reduce hypercalcaemia in haemodialysis patients, with an associated decrease in serum PTH. We analysed the effect of reduced calcium/magnesium (1.25/0.25 mmol/l), 40 mmol/l lactate, PD fluid (PD4) on 11 CAPD patients with uncontrollable hypercalcaemia (> 2.65 mmol/l) and hyperphosphataemia (> 1.80 mmol/l). Only 1 patient remained hypercalcaemic, while phosphate fell in 6 patients (2.23 +/- 0.16 on no binder, to 1.68 +/- 0.08 mmol/l at 6 months (p < 0.05), but was unchanged in 5 (2.10 +/- 0.15 to 2.48 +/- 0.14 mmol/l [p = NS]). Overall mean calcium x phosphate product changed little. However, in a subgroup it fell significantly (p < 0.05). Geometric mean iPTH rose, but not significantly. The subgroup of patients whose calcium x phosphate product fell, exhibited a much smaller rise in iPTH than the others (57.3-73.2 vs. 52.8-167.1 pg/ml). 1.25-Dihydroxyvitamin D3 was subnormal in all patients. Mean serum magnesium fell from 1.24 +/- 0.06 to 0.89 +/- 0.04 mmol/l (p < 0.001), whilst mean serum bicarbonate rose significantly (25.2 +/- 0.4 to 28.9 +/- 1.2 mmol/l; p < 0.01). Withdrawal of aluminium-containing phosphate binders resulted in mean serum aluminium falling significantly from 31.1 +/- 5.7 at start of PD4 to 15.4 +/- 2.7 mu g/l at 6 months (p < 0.05). In summary, in around 50% of CAPD patients with persistent hypercalcaemia and hyperphosphataemia, reduction in PD fluid calcium can produce significant improvement in phosphate, reduction of calcium x phosphate product, and enable avoidance of aluminium-containing phosphate binders. Patients whose calcium and phosphate control remains poor, still benefit from the reduction, or cessation, of oral aluminium intake.
Nephron 1996
PMID:Hypercalcaemia, hypermagnesaemia, hyperphosphataemia and hyperaluminaemia in CAPD: improvement in serum biochemistry by reduction in dialysate calcium and magnesium concentrations. 890 61

Two dialysis patients with markedly elevated plasma silicon (Si) levels (3,849 and 2,350 micrograms/l, respectively) and a presumed Si-related syndrome are described in this report. One patient presented with transient hypercalcemia in the face of low PTH, vitamin D and plasma A1 levels. Both patients had painful, nodular skin eruptions and aberrant hair growth, characterized as perforating folliculitis on skin biopsy, compatible with known effects of organosilicon compounds in man and animals. Plasma Si was found to be moderately elevated in 30 dialysis patients studied at random (710 +/- 53 micrograms/l, dialysis, vs. 152 +/- 9 micrograms/l, normal control), but there was no significant difference between the arterial values before and after dialysis, implying that the source of Si was ingested foods and fluids rather than dialysate. In these patients, plasma Si was weakly correlated with serum calcium as well as with serum calcium corrected for serum albumen, indicating that Si, like aluminum, may affect calcium metabolism.
Nephron 1997
PMID:Silicon-related syndrome in dialysis patients. 938 Feb 38

Pamidronate constitutes a major advance in the treatment of tumor-associated hypercalcemia. However, transient electrolyte abnormalities have been reported after pamidronate administration. We describe here a patient with multiple myeloma and severe hypercalcemia who developed transient but significant electrolyte disturbances (mainly hypophosphatemia and hypomagnesemia) after a single dose of 90 mg of pamidronate, focusing on the underlying pathophysiological mechanisms.
Nephron 1998
PMID:Multiple electrolyte abnormalities after pamidronate administration. 967 36


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