Contradictions exist in the literature regarding the effect of gastric secretion inhibition on phosphate absorption. In healthy controls, omeprazole would decrease the hyperphosphatemia or the hyperphosphaturia induced by an acute phosphate load, suggesting an inhibition of phosphate absorption. In chronic hemodialysis patients, gastric hypersecretion is associated with hyperphosphatemia, but inhibition of gastric hypersecretion by ranitidine in those receiving calcium carbonate (CaCO3) as a phosphate binder would paradoxically exacerbate their hyperphosphatemia. Because of these conflicting observations, we performed an open crossover study on 16 chronic stable hemodialyzed patients with a daily mean intake of 9.4+/-4 g of CaCO3, and we compared the plasmatic predialysis levels of phosphate, calcium, protides, bicarbonates, intact parathyroid hormone (PTH), urea, and creatininemia during 2 successive periods of 2 months, the first one without omeprazole and the second one with 20 mg omeprazole intake in the morning. Phosphatemia increased with omeprazole but not significantly from 1.80+/-0.38 to 1.89+/-0.42 mM whereas corrected calcemia decreased significantly (p = 0.04) from 2.41+/-0.18 to 2.36+/-0.16 mM as did bicarbonatemia from 26.7+/-3.5 to 25.7+/-3.1 mM (p < 0.05). No change in creatininemia or in blood urea was observed, suggesting the stable efficiency of dialysis as well as the stable intakes of protein and therefore of phosphate during the two study periods. In conclusion, inhibition of gastric secretion by omeprazole increases the plasmatic phosphate predialytic level but in a nonsignificant way. This increase may be explained by a slight but significant concomitant decrease of calcemia and bicarbonatemia. These results do not support the phosphate binding efficiency of CaCO3 being decreased by the inhibition of gastric acid secretion.

In dialysis centers using reverse osmosis-treated water but not restricting Al(OH)₃ administration, a high prevalence of histological aluminum bone disease has been reported. To assess wether this is also the case in our center where Al(OH)₃ intake has always been restricted and even completely given up after 1980 thanks to high doses of CaCO₃, we reviewed 42 bone biopsies performed between 1975 and 1985 in patients dialyzed for a mean duration of 56 months. Seventeen of these patients had been dialyzed before 1978 with softened water moderately contamined by aluminum, 15 had always been dialyzed with reverse osmosis-treated water and 10 had been exclusively treated by hemofiltration. The prevalence of aluminum bone disease in the whole population was 9.5% (4 patients) and consisted only of adynamic bone disease, osteomalacia being totally absent. When the patients dialyzed with aluminum-contaminated water were excluded as well as 1 diabetic patient who had taken Al(OH)₃ for 1.5 years the prevalence of aluminum bone disease was null in this population. When the whole population is considered the prevalence of the other types of bone disease was 76% for osteitis fibrosa and 14.5% for a non-aluminic adynamic bone disease (6 cases). These latter cases differed from the osteitis fibrosa group only by a relative hypoparathyroidism not explained by higher plasma concentrations and higher oral cumulative doses of calcium, magnesium and aluminum or by lower plasma concentrations of phosphate and bicarbonate. None had previous parathyroidectomy, one had an unsuccessful transplantation and one was diabetic. Iron overload was excluded by negative Perls staining. Duration of dialysis was shorter for these patients than for those with osteitis fibrosa. Conclusions: (1) In the absence of parenteral aluminum contamination, exclusion of Al(OH)₃ allows to prevent completely aluminic bone disease. (2) A new uremic bone disease is described: the idiopathic adynamic bone disease associated with a relative hypoparathyroidism.

To control hyperphosphataemia without hyperaluminaemia, A1(OH)3, which was given in addition to high doses of oral calcium, was replaced by Mg(OH)2 for 6 months in 20 haemodialysed patients and for 20 months in 12. The treatment during the control period was 110 +/- 91 mmol/day of oral calcium element given as CaCO3 and/or Calcium Sorbisterit and 1.05 +/- 1.47 g/day of A1(OH)3. Haemodialysis treatment was 4 h, thrice weekly. To prevent hypermagnesaemia, dialysate magnesium was decreased from 0.75 mmol/l to 0.375 mmol/l. After a control period of 3 months, Mg(OH)2 was given at a mean dose of 2.6 +/- 2 g/day and oral calcium supplements were decreased to 76 mmol/day. Two subsequent bone histomorphometry studies were performed at 8 month intervals in four patients and at 20 month intervals in seven patients. The results show a good control of plasma calcium (mean +/- SD: 2.43 +/- 0.1 mumol/l); phosphate (1.76 +/- 0.4 to 1.66 +/- 0.3 mmol/l); aluminum (1.3 +/- 0.1 mumol/l to 0.6 +/- 0.1 mumol/l); alkaline phosphatase (135 +/- 65 to 125 +/- 40 IU); and PTH fragments (PTH C terminal decreased from 260 +/- 214 to 185 +/- 182 pg/ml, PTH medium from 4185 +/- 5113 to 2270 +/- 4880 pg/ml). Plasma magnesium increased from 0.96 +/- 0.2 to 1.54 +/- 0.2 mmol/l. Bone histomorphometry shows no change in mineralisation, and a borderline decrease of resorption parameters. The main side-effects are (1) diarrhoea, which was well controlled by transient treatment with karaya gum, and (2) an increased need for potassium binders.(ABSTRACT TRUNCATED AT 250 WORDS)

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The use of 1 α-hydroxyvitamin D3 [ 1 α(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/1.73m²). 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 1α(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 lα(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, 1α(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 ‘nonhy-percalcemic hyperphosphatemic’ vitamin D3 derivatives in combination with oral calcium over 1α(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.