Prevention of renal osteodystrophy in peritoneal dialysis

Renal osteodystrophy (ROD) is still one of the major long-term complications in end-stage renal disease leading to considerable morbidity. Despite some progress in understanding the pathogenesis of secondary hyperparathyroidism (sHPT) during recent years, prevention and treatment of ROD is still suboptimal, requiring surgical parathyroidectomy in 6 to 10% of all patients on dialysis after 10 years. In addition, the spectrum of bone lesions has changed, with non-aluminum-related adynamic bone disease (ABD) found in up to 43% of peritoneal dialysis (PD) patients.

Current recommendations concerning prevention of ROD in PD based on the literature and personal recent data were reviewed. The focus is on (i) the importance of early prophylactic intervention to prevent parathyroid gland hyperplasia, (ii) the pathogenesis of ABD, and (iii) the role of metabolic acidosis in ROD.

There is ample evidence that sHPT starts early during the course of renal failure and results from both hypersecretion of PTH by parathyroid cells and glandular hyperplasia. As shown by experimental and clinical studies, established parathyroid cell hyperplasia is hardly reversible by pharmacological means, and therefore prevention of parathyroid cell proliferation needs to start early. Recent data from randomized trials document the efficacy and safety of low dose active vitamin D (0.125 to 0.25 microgram/day) and/or an oral calcium substitute to prevent progression of sHPT in patients with mild to moderate renal failure. Since little is known about the pathogenesis, natural course and clinical impact of ABD in PD, specific therapeutic concepts have not yet been generated. Diabetes and advanced age are established risk factors, whereas the role of calcium and vitamin D overtreatment or the type of dialysis (PD vs. HD) are still controversial. Currently no evidence for different functional behavior of the parathyroids in ABD and sHPT has been found. The role of circulating or local factors such as cytokines, growth factors or the presence of advanced glycation end-product (AGE)-modified matrix proteins for the pathogenesis of either type of ROD deserves further investigation. Avoiding oversuppression of parathyroid gland and the use of low calcium dialysate may help prevent ABD. There is growing evidence that a correction of metabolic acidosis will influence ROD by both direct effects on the bone and on parathyroid cell function. New dialysate composition for CAPD with a high HCO3 concentration will allow normalization of acid-based metabolism in PD patients. Their effects on ROD under long term conditions remain to be determined.

Therapeutic efforts should aim to prevent the development of parathyroid gland hyperplasia and sHPT early during the course of renal failure, and should include the use of low dose vitamin D therapy and oral calcium substitution as well as correction of metabolic acidosis. Concerning ABD, more information is needed regarding the causes and consequences of this type of bone lesion to develop a more specific therapy.