Cyclosporin A-induced transient rise in plasma alkaline phosphatase in kidney transplant patients

Abstract

In 1981 cyclosporin A (CyA) became available and replaced azathioprine (Aza) as the immunosuppressive agent in kidney transplantation at the University Hospitals in Basel, Switzerland. Patients on CyA and prednisone (CyA/p) therapy frequently demonstrated an isolated rise in bone-derived serum alkaline phosphatase (aP) concentration, but patients on Aza and prednisone (Aza/p) therapy did not. On the basis of long-term aP concentration and using noninvasive means, the present retrospective study was designed to investigate biochemical markers and radiographic signs of bone disease after successful kidney transplantation in patients on Cya/p treatment. Similar investigations were performed in patients on Aza/p and the results were compared. Follow-up examinations included clinical examination, radiography of the hand, and biochemical analysis of serum and urine. In 139 renal transplant patients on CyA/p, aP increased transiently after successful grafting (at transplantation 84±43 U/l; on day 90, 112±82 U/l). In 50 patients aP levels were higher at the time of transplantation (120±80 U/l) and aP peaked after 8±6 months, at a mean concentration of 242±103 U/l. In these patients aP concentrations exceeded the normal range for 16±10 months. None of the patients on CyA/p showed symptoms of bone disease when aP was increased. Radiological surveys revealed more pronouced osteodystrophy in patients at the time of transplantation, which increased aP to above the normal range after transplantation. Despite this rise in aP, over the long term bone lesions improved radiographically while bone mass remained stable. In constrast, patients treated with Aza/p demonstrated a significant decrease in aP level after transplantation from 75±33 U/l to 54±29 U/l on day 90. In addition, radiographic bone changes persisted and bone mass decreased significantly. After a 2-year follow-up, serum parathyroid hormone, 1,25-(OH)₂-vitamin D₃, calcium, and phosphorus concentrations, urinary excretion of hydroxyproline, and tubular reabsorption of phosphate did not differ between patients on CyA/p and controls on Aza/p. We conclude that after successful kidney transplantation and initiation of CyA/p therapy, a transient increase in bone-derived aP frequently occurred. These patients more often demonstrated radiographic signs of pre-existing osteodystrophy. However, over the long term, these changes improved.