Long Term Dialysis with Low-Calcium Solution (1.0 Mmol/L) in Capd: Effects on Bone Mineral Metabolism
Authors: Weinreich Thomas , Ritz Eberhard , Passlick-Deetjen Jutta ,   Collaborators of the Multicenter Study Group, Colombi A. , Echterhoff H.H. , Geberth S. , Mandelbaum A. , Kiefer T. , Mayer-Wehrstein R. , Hild P. , Leydig M. , Birkner I. Lubrich , Mielke G. , Schillinger-Pokorny C. , Nebel M. , Rieden K. 
Published: February 2020

Objective Peritoneal dialysate solutions with conventionally high-calcium (Ca) concentrations (1.75 mmol/L) are now widely replaced by solutions with a lower, more physiological calcium content to prevent hypercalcemia in patients treated with oral calcium-containing phosphate binders and/or calcitriol. While there is still debate on how far the dialysate calcium should be lowered (1.25 mmol/L or less), little information is available concerning the effects of a long-term treatment with low-calcium solutions on secondary hyperparathyroidism and bone mineral metabolism in general. Design A prospective, randomized, controlled multicenter study to compare the effects of low-calcium (LCa, dialysate calcium 1.0 mmol/L) versus standard calcium dialysate solution (SCa, dialysate calcium 1.75 mmol/L)on bone mineral metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients over 2 years of treatment. Setting Nephrology and dialysis units of primary and tertiary hospitals in Germany and Switzerland. Patients All CAPD patients in the participating centers between 18 and 80 years of age, stable on CAPD for at least 1 month, free of aluminum bone disease or prior parathyroidectomy were invited to enter the study. Sixty-four patients could be randomly allotted to LCa (n = 35) or SCa (n = 29) treatment in a 2-year protocol; 34 finished the study as planned. Interventions Calcium carbonate (CaCO3) was given as oral phosphate binder to maintain serum phosphate <2.0 mmol/L. If hypercalcemia supervened, CaCO3 was exchanged stepwise for aluminium hydroxide (AI(OH)3)’ until normocalcemia was obtained. Patients received calcitriol (0.25 μg/day per os) if parathyroid hormone (PTH) exceeded the upper limit of normal by a factor of 2 or more. Main Outcome Measures We assessed total and ionized serum calcium, phosphate, serum aluminum, alkaline phosphatase, osteocalcin, PTH (intact molecule), and phosphate binder intake at regular intervals. Measurements of bone mineral density and hand skeleton x-rays were obtained at the start and after 6 months and 2 years, respectively. Results With LCa, mean total and ionized serum calcium levels were within the normal range (total Ca: 2.0 2.6 mmol/L; ionized Ca: 1.19–1.32 mmol/L), but throughout the treatment period were significantly lower than with SCa. The incidence of hypercalcemia (>2.8 mmol/L) was three times higher in patients on SCa, despite the significantly higher amount of AI(OH)3 and less CaCO3 given in this group. In parallel, serum aluminum increased with SCa throughout the study, whereas it was slowly decreasing with LCa. Median PTH levels remained stable at about two times the upper limit of normal over the 2 years of study with LCa. However, 23% of the patients on LCa developed severe hyperparathyroidism, with PTH levels exceeding ten times the upper limit of normal compared to only 10.3% of the patients on SCa. With SCa, median PTH decreased towards near normal levels. Alkaline phosphatase and serum osteocalcin correlated positively with PTH levels. Bone mineral density was in the lower normal range in both groups a n d remained unchanged at the end of the study. Skeletal x-ray films showed only minor alterations in very few patients in both groups with no correlation to serum PTH or treatment modality. Conclusion In CAPD patients low-calcium dialysate solutions can be used successfully over prolonged periods of time with stable control of serum calcium. The risk of hypercalcemia resulting from calcium-containing phosphate binders and the need to use aluminum-containing phosphate binders is markedly diminished. However, there is a certain risk that severe secondary hyperparathyroidism with long-term LCa therapy will develop, even if normocalcemia is maintained. Thus, LCa dialysis requires closeand continuous monitoring of PTH and bone metabolism.