OBJECTIVE -To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS -We searched databases (MEDLINE, EM-BASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence.RESULTS -Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (Ͻ10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P ϭ 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted.CONCLUSIONS -Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs. Diabetes Care 25:583-592, 2002P osttransplantation diabetes (PTD) is a complication of solid-organ transplantation. Beyond the description of PTD as the development of diabetes after transplantation, there is no consensus regarding the definition of this condition. Estimates of the frequency of PTD range from 2 to 50%. Some factors, such as age of the transplant recipient, are consistently described as increasing the risk of PTD. Under dispute is the importance of other factors, such as the recipients ethnicity, body weight, immunosuppressive regimen, and family history of diabetes, as well as the vital status of the organ donor. The prognostic implications of PTD and its optimal treatment are similarly unclear.The goals of this systematic review were to estimate the incidence of PTD, identify the risk factors for its development, determine its implications for prognosis, and discover treatment strategies that lead to improved patient outcomes. RESEARCH DESIGN AND METHODS Questions askedOur review was designed to answer four questions: 1) For patients with no history of diabetes before transplantation, what is the risk that PTD will develop? 2) What are the risk factors for the development of PTD? 3) What is the prognosis for patients with PTD? 4) Which therapies improve glycemic control and prognosis in patients with PTD? Identification and retrieval of primary studiesWe searched MEDLINE (O...

Posttransplantation lymphoproliferative disorder (PTLD) is an uncommon but often fatal complication of solid organ transplantation that occurs in approximately 3% of patients. To determine the relative importance and relationship of potential risk factors for PTLD before transplantation (i.e., Epstein-Barr virus [EBV] serostatus of the recipient and the cytomegalovirus [CMV] sero-status of the recipient and the potential donor) and the principal risk factor after transplantation (immunosuppression with antilymphocyte antibody), we analyzed the findings for the first 381 consecutive adult nonrenal transplant recipients seen at Mayo Clinic. In the absence of the other risk factors, the incidence rate of PTLD for EBV-seronegative recipients was 24 times higher (95% confidence interval [CI]: 6.2, 89) than that for EBV-seropositive recipients. The additional risk factors of therapy with OKT3 for rejection and CMV seromismatch (i.e., a negative recipient and a positive donor) each further amplified this risk four- to sixfold. Together, all three risk factors acted synergistically to increase the incidence rate of fatal and/or CNS PTLD by a factor of 654 (CI: 368, 1,162) compared with the low incidence rate (.458 cases per 100 person years) when none of these risk factors were present. Pretransplantation determination of recipient EBV and CMV serostatus can identify a subgroup of patients whose risk for severe PTLD may preclude transplantation.

Many patients who have an otherwise acceptable living-kidney donor do not undergo transplantation because of the presence of antibodies against the donor cells resulting in a positive crossmatch. In the current study, 14 patients with a positive cytotoxic crossmatch (titer £1 : 16) against their living donor underwent a regimen including pretransplant plasmapheresis, intravenous immunoglobulin, rituximab and splenectomy. Eleven of 14 grafts (79%) are functioning well 30-600 days after transplantation. Two grafts were lost to accelerated vasculopathy and one was lost to death with good function. No hyperacute or cellular rejections occurred. Antibody-mediated rejection occurred in six patients [two clinical (14%) and four subclinical (29%)] and was reversible with plasmapheresis and steroids. Our results suggest that selected crossmatch-positive patients can be transplanted successfully with living-donor kidney allografts, using a protocol of pretransplant plasmapheresis, intravenous immunoglobulin, rituximab and splenectomy. Longer follow-up will be needed, but the absence of anti-donor antibody and good early outcomes are encouraging.

Calcineurin inhibitors have decreased acute rejection and improved early renal allograft survival, but their use has been implicated in the development of chronic nephrotoxicity. We performed a prospective, randomized trial in kidney transplantation comparing sirolimus-MMF-prednisone to tacrolimus-MMFprednisone. Eighty-one patients in the sirolimus group and 84 patients in the tacrolimus group were enrolled (mean follow-up = 33 months; range 13-47 months). At 1 year, patient survival was similar in the groups (98% with sirolimus, 96% with tacrolimus; p = 0.42) as was graft survival (94% sirolimus vs. 92% tacrolimus, p = 0.95). The incidence of clinical acute rejection was 10% in the tacrolimus group and 13% in the sirolimus group (p = 0.58). There was no difference in mean GFR measured by iothalamate clearance between the tacrolimus and sirolimus groups at 1 year (61 ± 19 mL/min vs. 63 ± 18 mL/min, p = 0.57) or 2 years (61 ± 17 mL/min vs. 61 ± 19 mL/min, p = 0.84). At 1 year, chronicity using the Banff schema showed no difference in interstitial, tubular or glomerular changes, but fewer chronic vascular changes in the sirolimus group. This study shows that a CNI-free regimen using sirolimus-MMF-prednisone produces similar acute rejection rates, graft survival and renal function 1-2 years after transplantation compared to tacrolimus-MMF-prednisone.