K. K. Venkat

Complete replacement of methylprednisolone by azathioprine in cyclosporine-treated primary cadaveric renal transplant recipients

In cylosporine (CsA)-treated renal transplant recipients complete corticosteriod withdrawl followed by CsA monotherpy has been associted with severe rejection episodes in a significance proportion of patients. We report the results of replacements of steroids by azathioprine (AZA) in 25 primary cadaveric renal transplant recipients initially treated with CsA and methylprednisolone (MP). MP taper was started 8.85.6 months posttrasplant when the MP dose was either 10mg/day or 20 mg every other day. MP was tapered off over a 5-month period. At the initation of MP taper, AZA was added at 1 mg/kg/day and increased to 1.5 mg/kg/day after two months. The CsA dose was adjusted to maintain trough serum levels as measured by radioimmunoasay (RIA) of 50–75 ng/ml, during and after MP with drawl. Seventeen patients have remained continuously off MP for 14.65.0 months with stable renal function. Reinstitution of MP at 10 mg/day was required in 8 patients, 6 for rejection (1.80.7 months after MP with drawl), 1 for AZA-indiced leukopenia, and 1 for denovo glomerulopathy. Renal function returned to baseline in all 6 patients have again been successfully retapered off MP. In the patients withdrawn from MP, body weight and mean arterial blood pressure had decreased by 2.11.3 kg (P<.05) and 117 mmHg (P<.05), respectively, at the time of the most recent follow-up compared with values at the initiation of steroid withdrawal. The number of blood pressure medications per patient decresed by 38% (P<.05) and 6 patients were able to discontinue all antihyupertansive drugs after cessation of steroids. Discontinuation of MP also resulted in a decrease in serum cholesteorl concentration from 24850 to 21755 mg/dl (P<.05). We conclude that steroids can be replaced by AZA in the majority of CsA-treated primary cadaveric renal transplant recipients by the end of the first posttransplant year withour an adverse effect on graft survival. This protocol resulted in significant reductions in serum cholesterol, mean arterial blood pressure, and body weight, and may avoid the long-term siode effects of steroid therapy.

Removal Of Lymphocytotoxic Antibodies By Pretransplant Immunoadsorption Therapy In Highly Sensitized Renal Transplant Recipients

A high level of panel-reactive antibodies (PRA) in potential renal transplant recipients is associated with a long waiting time until transplantation and correlates inversely with graft outcome. We report our experience with the employment of immunoadsorption (IA) using a column composed to sepharose-bound staphylococcal protein A (which has a relatively selective affinity for binding IgG compared with other immunoglobulins) to decrease the PRA levels and expedite transplantation in 6 highly sensitized potential renal transplant recipients (1 primary and 5 awaiting second transplants). All patients had PRA levels of greater than or equal to 70% for a duration of 1 year prior to IA. Only patients with antibody specificity localized to 1 or 2 HLA A or B antigens were accepted for the study. IA procedures were performed on alternate days until a twofold decrease in antibody titer had occurred (maximum: 6 procedures). Repeat procedures were initiated if the HLA antibody titer returned to its baseline value. Intravenous cyclophosphamide (CY) (10 mg/kg/day every 3 weeks) and methylprednisolone (MP) (0.5 mg/kg/day) were provided as adjunctive immunosuppression until transplantation. A total of 44 immunoadsorption procedures were performed (27 primary and 17 repeat) with treatment of 2.49 +/- 0.02 plasma volumes per session. Serum IgG concentration decreased 95 +/- 3% and PRA activity decreased 75 +/- 16% after the primary treatment course. Four patients received cadaveric grafts within 3.7 +/- 1.2 months following the last IA procedure. Three grafts are functioning at 1 year, 8 months, and 8 weeks posttransplant. The remaining graft demonstrated primary nonfunction. All four patients had a past positive crossmatch using pre-IA sera with their respective donors. Patients not transplanted exhibited rapid resynthesis of IgG and a return of the PRA towards baseline levels within a few weeks after IA. We conclude that IA can effectively remove HLA antibodies and expedite graft availability in highly sensitized patients.

Cost-utility analysis of living-donor kidney transplantation followed by pancreas transplantation versus simultaneous pancreas-kidney transplantation

For a type I diabetic with end‐stage renal disease, the choice between a kidney‐alone transplant from a living‐donor (KA–LD) and a simultaneous pancreas–kidney (SPK) transplant remains a difficult one. The prevailing practice seems to favor KA–LD over SPK, presumably due to the superior long‐term renal graft survival in KA–LD and the elimination of the lengthy waiting time on the cadaver transplant list. In this study, two treatment options, KA–LD followed by pancreas‐after‐kidney (PAK) and SPK transplant, are compared using a cost–utility decision analysis model. The decision tree consisted of a choice between KA–LD+PAK and SPK. The analysis was based on a 5‐yr model and the measures of outcome used in the model were cost, utility and cost–utility. The expected 5‐yr cost was

Influence of the pretransplant hematocrit level on early graft function in primary cadaveric renal transplantation.

277 638 for KA–LD+PAK and

Histologic and immunophenotypic evaluation of pretreatment renal biopsies in OKT3-treated allograft rejections

288 466 for SPK. When adjusted for utilities, KA–LD+PAK at a cost of

Increasing Trend in Infection-Related Death-Censored Graft Failure in Renal Transplantation

153 911 was less cost‐effective than SPK at a cost of

Recurrence of Scedosporium Apiospermum Infection Following Renal Re-Transplantation

110 828 per quality‐adjusted year. One‐way sensitivity analyses were performed by varying patient and graft survival probabilities, utilities and cost. SPK remained the optimal strategy over KA–LD+PAK across all variations. Two‐way sensitivity analysis showed that in order for KA–LD+PAK to be at least as cost‐effective as SPK, 5‐yr pancreas and patient survival rates following PAK would need to surpass 86 and 80%. In conclusion, according to the 5‐yr cost–utility model presented in this study, KA–LD followed by PAK is less cost‐effective than SPK as a treatment strategy for a type I diabetic with end‐stage renal disease. For patients interested in the benefits of a pancreas transplant, it would be reasonable to offer SPK as the optimal treatment, even if a living kidney donor is available.

Utility of Estimated Glomerular Filtration Rate in Live Kidney Donation

Although use of human recombinant erythropoietin has alleviated symptoms of anemia in renal failure, effects of increased hematocrit (HCT) on early post-transplant renal function are unknown. Of 244 consecutive primary cadaveric kidney recipients transplanted over 74 months, 43% had HCT ≥ 30% and 57% had HCT < 30% at transplantation. The incidence of delayed graft function (DGF) was greater in recipients with HCT ≥ 30% (61%) than in recipients with HCT < 30% (33%; P=0.0001). Ten percent of recipients with HCT ≥ 30% experienced primary nonfunction (PNF) of the allograft (P=0.0001). No recipient with HCT < 30% had PNF. Absolute rises in HCT over the 3 months preceding transplantation were greatest in those with PNF (2.5± 2.4) followed by those with DGF (2.0±3.1) and immediate graft function (IGF) (0.215.2; P=0.0328). Logistic regression analysis identified HCT ≥ 30% (P=0.0014), cold storage ≥ 24 hr (P=0.0006) and rising HCT (P=0.0090) as independent predictors of DGF with relative risks of 3.1-, 3.3-, and 2.7-fold, respectively. Recipients with rising pretransplant HCTs who underwent dialytic fluid removal within 24 hr before transplantation had DGF with greater frequency (67%) than non-dialyzed recipients with rising HCTs (45%). Primary cadaveric kidney recipients with HCT ≥ 30% at transplantation have significantly greater risk for DGF and PNF. Rising pretransplant HCT levels may predispose recipients to DGF; this risk may be heightened in those undergoing hemodialysis shortly before transplantation.

Effective long-term immunosuppression maintained by low cyclosporine levels in primary cadaveric renal transplant recipients

The histologic features immunophenotype of intragraft mononuclear populations, and HLA-Dr expression in pretreatment formalin-fixed renal allograft biopsies were correlated with outcome of OKT3 therapy in 35 steroid resistant renal transplant rejections. Therapeuic response (63% overall) was better in pure acute cellular rejections (ACR) (13/15, 87%) than ACR with interstitial fibrosis (4/12, 33%) or with vascular injury (5/8, 62%). Intragraft T lymphocytes were more numerous in vascular rejection (mean 566/mm2) compared with pure ACR (mean 265/mm2, P=.049), and macrophages were greater in pure ACR (203/mm2) compared with ACR with interstitial fibrosis (83/mm2, P=.051). Distribution of T cells, B cells, plasma cells, and macrophages among various histologic categories was otherwise statistically similar. There was no correlation between therapeutic response to OKT3 and intragraft

The Utility of Serial Allograft Biopsies during Delayed Graft Function in Renal Transplantation under Current Immunosuppressive Regimens

Background. Advances in kidney transplantation have significantly improved early outcomes but failed to improve long-term graft survival. Despite many causes, the contribution of infection to death-censored graft failure (DCGF) is unknown. The aim of our study is to assess the impact of infections on DCGF using United Network for Organ Sharing data. Methods. We analyzed 38,286 DCGFs among 189,110 first kidney transplants performed between January 1, 1990 and December 31, 2006. Information on infection contributing to DCGF was available in 31,326 DCGF recipients. Students two-sample t test for normally distributed variables, Wilcoxon rank sum test for nonnormally distributed, and Chi-square test for categorical variables were used in univariable comparisons. Multivariable logistic regression analysis was performed to assess the independent contribution of variables to infection-related DCGF. Results. Overall, infection accounted for 7.7% (2397/31,326) of all DCGF. The rate of infection-related DCGF increased from 6.4% in 1990 to 10.1% in 2006 and was significantly higher during 1997 to 2006 when compared with 1990 to 1996 period (9.1% vs. 6.3%, P<0.001). Over these 17 years, the trends in infection-related DCGF and rejection rates showed an inverse relationship with the former exceeding the latter starting in 2005. The risk of infection-related DCGF was higher (14.1%) in recipients older than 65 years and exceeded the rejection rate in those older than 60 years. Urological complications and polyoma infection were the most significant risk factors with odds ratios of 8.77 (confidence interval: 5.15–14.93) and 2.55 (confidence interval: 1.41–4.61), respectively. Conclusion. Infection is increasingly contributing to DCGF in recent years and warrant reevaluation of current immunosuppression protocols, especially in older recipients.