Bone disease after renal transplantation

Abstract

Kidney transplantation largely restores defective exocrine and endocrine renal function in patients with end-stage renal disease (ESRD). This in turn is expected to lead to a progressive correction of established renal bone disease. This widely held assumption, however, lacks convincing evidence from experimental and clinical data published thus far. A major obstacle to the investigation of renal osteodystrophy in transplant recipients has been its unpredictable evolution under the multiple biochemical and hormonal influences that regulate mineral metabolism and bone turnover independently. The clinical and histological features of the pre-existing uraemic bone disease at the time of kidney transplantation are highly variable. Moreover, its course after transplantation depends on persisting abnormalities such as hypercalcaemia, hypophosphataemia and hypomagnesaemia as well as on the type, dose and duration of immunosuppressive medications that are needed to minimize allograft rejection. These factors operate additively and their effects are often difficult to dissociate from the already existing osteopathy. The existence and type of post-transplant bone disease may not be recognized correctly and appropriate therapy may not be started in time. Although glucocorticoid therapy represents a pathogenetic key factor other immunosuppressive drugs such as cyclosporine, tacrolimus, azathioprine and rapamycin clearly contribute to its prevalence and expression through their pleiotropic pharmacological effects. These drugs have been shown to increase overall bone turnover anduor to stimulate loss of bone mass independently. Based on currently available data, only mycophenolate mofetil appears to have a neutral effect in this regard [1]. Only a limited number of reports dealt with this problem in the past. There is an obvious need for welldesigned prospective studies with sufficient patient numbers to determine the relative importance of the numerous factors involved in the perturbed bone remodelling following kidney transplantation. Furthermore, a consensus-based classification of the various types of renal allograft-associated osteopathy, including clinical, radiological and histomorphological criteria, might lead to a more reliable basis for experimental research into this particular disease and facilitate the comparison between studies. When working up a patient for symptoms and signs of renal transplant-associated bone disease, clinical data for an effective evaluation and treatment of this condition are often lacking. A longitudinal analysis of the disease process would undoubtedly allow a more precise diagnosis and a more appropriate care of post-transplant bone disease. In many cases, follow-up data from the time of transplantation or before are unavailable or inaccessible. Radiographic examinations of the thoracic and lumbar spine with a bone densitometry of the femoral neck or other sites, and an iliac crest biopsy with a histomorphometric analysis in at last some patients should be ideally obtained before a diagnosis is made and a treatment is initiated. Several main osteological complications of kidney transplantation will be reviewed in the following, as summarized in Table 1.