Protocol biopsy of a transplanted kidney as a tool for monitoring adequacy of immunosuppressive therapy: 10 years of experience from a single transplant center.

BACKGROUND: The aims of this prospective study were to determine the prevalence of clinically silent rejection changes and of nephrotoxicity of calcineurin inhibitors among repeated protocol biopsies of transplanted kidneys and to assess their impacts on chronic graft function and damage at the end of 1 year. METHODS: We performed 424 protocol biopsies among 158 patients over the first year after transplantation. We monitored parameters of graft function and progression of chronic changes among subjects with clinically silent rejection or toxicity for comparison with a control cohort showing normal histological findings. The results of statistical tests were considered to be significant at a level of P < .05. RESULTS: At 3 weeks, 3 months, and 12 months, there were normal histological findings among 30 (19%), 21 (14.8%), and 14 (11.3%) patients, respectively; subclinical rejection changes occurred in 49 (31%), 36 (25.4%), and 20 (16.2%) grafts, respectively. At the third week, histological signs of toxicity occurred in 33 (20.9%) patients with significant persistence despite reductions in calcineurin inhibitor doses. At the end of 1 year of follow-up, both subclinical and toxic changes produced similar increases in chronic changes as quantified by the Banff score and were significantly different from the control group (P < .05). Serum creatinine concentrations and glomerular filtration rates did not accurately reflect the degree of graft damage in the early posttransplantation period. CONCLUSIONS: Subclinical rejection and toxic changes among a significant proportion of grafts are associated with progression of chronic changes already over the first year following transplantation. Hence they represent independent risk factors for the development of irreversible graft damage. Protocol biopsy seems to be an important method to monitor immunosuppressive therapy.

Changes in bone mineral density and selected metabolic parameters over 24 months following renal transplantation.

Our aim was to evaluate changes in serum levels of selected bone metabolism indicators and bone density over 24 months following renal transplant. A partial objective was assessment of the effectiveness of prophylactic administration of vitamin D and calcium preparations to prevent progression of osteopathy after kidney transplantation. Forty patients after kidney transplantation were prophylactically given vitamins A and D (800 IU) and calcium (1000 mg) a day. During monitoring, the serum creatinine in all recipients was <200 micromol/L (subgroup A with creatinine concentration < 120 micromol/L versus subgroup B with creatinine 120 to 200 micromol/L). The concentration of serum parathormone, serum level of bone fraction of alkaline phosphatase, serum concentrations of phosphorus and calcium urinary 24-hour excretion of phosphorus and calcium were examined at 2 weeks and 2 years after transplantation. In the same time period, radiographs of thoracic, lumbar spine, and hip joints were obtained. Bone density (BMD) of the lumbar (L) spine and the hip was determined by dual-energy X ray (Lunar Prodigy). Two years after transplantation in subgroup A, the BMD showed decrease in 80% of recipients in the L spine area but hip showed a 15% BMD increase. In subgroup B, the BMD decreased in 95% recipients in L and hip and only 25% showed a BMD increase. No clinical or radiographic sign of fracture was detected in this group. We conclude that prophylactic administration of vitamin D and calcium is not sufficient to prevent the progression of osteopathy after renal transplantation. Changes in bone density evaluated after the kidney transplantation are affected by graft function.