Immunosuppressive agents and bone disease in renal transplant patients with hypercalcemia

Renal transplantation is the definitive treatment for many metabolic abnormalities of uremic patients, although it is only partially effective for renal osteodystrophy, which may interact with posttransplant renal osteopathy. Osteopenic-osteoporotic syndrome represents, together with fractures secondary to osteoporosis and osteonecrosis, the bone complication most related to renal transplantation. Several factors contribute to the pathogenesis of posttransplantation osteoporosis, particularly immunosuppressive treatment. In this study, we evaluated the prevalence of factors related to posttransplant renal osteopathy and the clinical impact of immunosuppressive protocols. We studied 24 renal transplant recipients with hypercalcemia. Glomerular filtration rate was >50 mL/min. Mean age, time on dialysis, and time from transplantation were 49.6, 5.4, and 6.9 years, respectively. We evaluated serum and urine calcium and phosphorus, calcitonin, parathormone, bone-specific alkaline phosphatase, osteocalcin, urine deoxypyridinoline, telopeptide of type 1 procollagen, 1,25-(OH)(2) and 25-OH vitamin D, parathyroid ultrasound, and computerized bone mineralometry. The combination of sirolimus and steroids resulted in the most disadvantageous outcomes regarding alkaline phosphatase and mineralometry. Calcineurin inhibitors did not significantly influence bone metabolism markers; mycophenolate mofetil evidenced no effect on bone. According to the literature, steroids account for the abnormalities found in our patients and in severe osteopenia. Several factors may contribute to the development of osteoporosis and fractures in transplantation patients, although they are overcome by the prominent effect of steroids. In patients at high risk of osteoporosis, steroid-free therapy should be considered. Everolimus is indicated for diseases with bone loss. Combined therapy with everolimus and mycophenolic acid without cyclosporine and steroids, seemed to be particularly indicated. Prophylactic treatments should be commenced early. No single marker was useful to diagnose posttransplant renal osteopathy. The definitive diagnosis should be made by bone biopsy during transplantation, and noninvasive procedures, such as densitometry and evaluation of biologic markers, may be useful during follow-up.