Evidence of antibody-mediated injury (DSA or C4d) is common (57%) in patients with new onset late kidney allograft dysfunction. The risk of subsequent graft failure is significantly worse in the presence of C4d+ staining.

Herpes zoster (HZ) infection is a frequent and serious complication of organ transplantation that has not been examined in the current era of immunosuppression.All solid organ transplants performed between 1994 and 1999 (n = = 869) at our center were analyzed to determine the incidence, complications and risk factors for developing HZ.The overall incidence of HZ was 8.6% (liver 5.7%, renal 7.4%, lung 15.1% and heart 16.8%). The median time of onset was 9.0 months. We observed high rates of cutaneous scarring (18.7%) and post-herpetic neuralgia (42.7%). Independent organ-specific risk factors included: female gender and mycophenolate mofetil therapy (liver), and antiviral treatment other than prolonged cytomegalovirus (CMV) prophylaxis (renal and heart). For all organs combined, induction therapy and antiviral treatment other than prolonged CMV prophylaxis were independent predictors for the development of HZ.Herpes zoster is common and results in significant morbidity for solid organ transplant recipients. Risk factors include induction therapy and antiviral drug therapy other than CMV prophylaxis. The latter variable identifies a subpopulation that is likely at increased risk of latent herpesvirus reactivation. The high first-year post-transplant incidence rate suggests immunization pretransplant, even in varicella zoster virus immunoglobulin seropositive individuals, may be preventative. Key words: Herpes zoster, infection, transplantationReceived 12 March, revised 22 July, re-revised 18 August and accepted for publication 19 August 2003Varicella zoster virus (VZV) is the most infectious of the human herpesviruses and infection is almost universal (95%) by adulthood in North American and European populations. Reactivation of latent VZV [herpes zoster (HZ) or shingles] is a painful, cutaneous eruption, dermatomal in distribution, associated with a risk of dissemination. Previously described risk factors for HZ include age, malignancy, HIV infection, organ transplantation, immunodeficiency and treatment with immunosuppressive medications (1).Herpes zoster leads to significant morbidity and its most frequent complication (2) is post-herpetic neuralgia (PHN), which is associated with persistent pain for 30 or more days after acute infection, lasting years in some cases (3). Unfortunately, immunocompromized patients tend to have the most severe complications of reactivation with a greater tendency for a prolonged course of disease (4). Severely immunocompromized patients with HZ have a risk of dissemination of up to 40%, which can result in mortality rates, despite antiviral therapy, of between 4 and 34% (5-7).Previously reported incidences vary widely (8-17) and, to our knowledge, no population-based studies have been performed that define the incidence of HZ in adult multiorgan transplant cohorts. However the following incidences have been suggested in this population: renal 3-10%, liver 5-10%, lung 8-12% and hearts 20-25% (7). Possible reasons for this variation include center effect, the immunosuppressive drug ...

Further, these results did not qualitatively change after additional adjustments for C4d staining or donor specific antibody. Stepwise regression identified the most significant markers of graft failure which include iatr score. We propose that a more global assessment of inflammation in kidney allograft biopsies to include inflammation in atrophic areas may provide better prognostic information. Phenotypic characterization of these inflammatory cells and appropriate treatment may ameliorate late allograft failure.

The onset of diabetes mellitus following kidney transplantation or post-transplant diabetes mellitus (PTDM) is now recognized as being an increasingly common complication that is associated with poor graft and patient survival. The incidence and clinical correlates of PTDM in a Canadian kidney transplant population has not been examined and may vary based on differences in demographics (i.e. race). Furthermore, little information exists on the association of variables such as cumulative dose of corticosteroids and trough calcineurin inhibitor levels and PTDM. We examined all recipients of a kidney transplant in our center between 1995 and 2001 and found an overall PTDM rate of 9.8%. Five clinical factors were independently associated with PTDM: older recipient age, deceased donor, hepatitis C antibody status, rejection episode and use of tacrolimus (vs. cyclosporine). Furthermore, cumulative corticosteroid dose and calcineurin inhibitor trough level were not associated with PTDM. This study demonstrates that in a Canadian kidney transplant population that there is a significant risk of PTDM following kidney transplantation, and it is therefore advisable to minimize this risk.

We are studying two cohorts of kidney transplant recipients, with the goal of defining specific clinicopathologic entities that cause late graft dysfunction: (1) prevalent patients with new onset late graft dysfunction (Cross-Sectional Cohort); and (2) newly transplanted patients (Prospective Cohort). For the cross-sectional cohort (n=440), mean time from transplant to biopsy was 7.5±6.1 years. Local pathology diagnoses included CAN (48%), CNI toxicity (30%), and, perhaps surprisingly, acute rejection (cellular- or Ab-mediated) (23%). Actuarial rate of death-censored graft loss at 1 year post-biopsy was 17.7%; at 2 years, 29.8%. There was no difference in post-biopsy graft survival for recipients with vs. without CAN (p=0.9). Prospective cohort patients (n=2427) developing graft dysfunction >3 months posttransplant undergo “index” biopsy. The rate of index biopsy was 8.8% between months 3 and 12, and 18.2% by 2 years. Mean time from transplant to index biopsy was 1.0 ± 0.6 years. Local pathology diagnoses included CAN (27%), and acute rejection (39%). Intervention to halt late graft deterioration cannot be developed in the absence of meaningful diagnostic entities. We found CAN in late posttransplant biopsies to be of no prognostic value. The DeKAF study will provide broadly applicable diagnostic information to serve as the basis for future trials.