Transplantation of Renal Allograft After Removal of Renal Cell Carcinoma: Case Report and Review of the Literature.

With the rising incidence of end-stage renal disease in the United States, patients needing renal transplants are waiting longer for increasingly scarce grafts. Formerly, the general practice was to avoid organs with tumors for transplant because of the risk of malignancy transmission to the recipient. However, with comprehensive donor selection and a small-sized primary tumor, the positive outcomes of transplant outweigh the risks of transmission after a partial nephrectomy. In our case, a 31-year-old woman, the daughter of the recipient, underwent a laparoscopic nephrectomy with an existing 8-mm tumor later confirmed as renal cell carcinoma. An ex vivo tumor enucleation was performed before the allograft was transplanted into the 69-year-old patient with endstage renal disease. At last follow-up, graft function has remained excellent with no evidence of local recurrence or metastasis in both the donor and recipient. Here, we describe our case and perform a literature review on the incidence and management of renal allografts with incidentally detected renal cell carcinoma during transplant.

Impact of navigators on completion of steps in the kidney transplant process: a randomized, controlled trial.

BACKGROUND AND OBJECTIVES: Many patients with ESRD, particularly minorities and women, face barriers in completing the steps required to obtain a transplant. These eight sequential steps are as follows: medical suitability, interest in transplant, referral to a transplant center, first visit to center, transplant workup, successful candidate, waiting list or identify living donor, and receive transplant. This study sought to determine the effect of navigators on completion of steps. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cluster randomized, controlled trial at 23 Ohio hemodialysis facilities. One hundred sixty-seven patients were recruited between January 2009 and August 2009 and were followed for up to 24 months or until study end in February 2011. Trained kidney transplant recipients met monthly with intervention participants (n=92), determined their step in the transplant process, and provided tailored information and assistance in completing the step. Control participants (n=75) continued to receive usual care. The primary outcome was the number of transplant process steps completed. RESULTS: Starting step did not significantly differ between the two groups. By the end of the trial, intervention participants completed more than twice as many steps as control participants (3.5 versus 1.6 steps; difference, 1.9 steps; 95% confidence interval, 1.3-2.5 steps). The effect of the intervention on step completion was similar across race and sex subgroups. CONCLUSIONS: Use of trained transplant recipients as navigators resulted in increased completion of transplant process steps.

Donor phosphorus levels and recipient outcomes in living-donor kidney transplantation.

BACKGROUND AND OBJECTIVES: In living-donor kidney transplantation, various donor factors, including gender, age, and baseline kidney function, predict allograft function and recipient outcomes after transplantation. Because higher phosphorus is predictive of vascular injury in healthy adults, the effect of donor phosphorus levels on recipient renal function after transplantation was investigated. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Phosphorus levels in 241 living donors were analyzed from a 7-year period, and recipient renal function and acute rejection at 1 year posttransplantation were examined controlling for other influencing factors, including multiple donor variables, HLA matching, and acute rejection. RESULTS: Female and African-American donors had significantly higher phosphorus levels predonation. By multivariable analysis, higher donor phosphorus correlated with higher recipient serum creatinine (slope=0.087, 95% confidence interval [CI]: 0.004 to 0.169, P=0.041) and lower recipient estimated GFR (slope=-4.321, 95% CI: -8.165 to -0.476, P=0.028) at 12 months. Higher donor phosphorus also displayed an independent correlation with biopsy-proven acute rejection and delayed or slow graft function after transplantation. CONCLUSIONS: In a cohort of living kidney donors, higher donor phosphorus correlated with female gender and African-American ethnicity and was an independent risk factor for early allograft dysfunction after living-donor kidney transplantation.

New-onset diabetes mellitus after solid organ transplantation.

New-onset diabetes mellitus is a common complication of solid organ transplantation and is likely to become even more common with the current epidemic of obesity in some countries. It has become clear that both new-onset diabetes and prediabetic states (impaired fasting glucose and impaired glucose tolerance) negatively influence graft and patient survival after transplantation. This observation forms the basis for recommending meticulous screening for glucose intolerance before and after transplantation. Although a number of clinical factors including age, weight, ethnicity, family history, and infection with hepatitis C are closely associated with the new-onset diabetes mellitus, immunosuppression with corticosteroids, calcineurin inhibitors and possibly sirolimus plays a dominant role in its pathogenesis. Management of new-onset diabetes after transplantation generally conforms to the guidelines for treatment of type 2 diabetes mellitus in the general population. However, further studies are needed to determine the optimal immunosuppressive regimens for patients with this disorder.

Reduction in erythropoietin resistance after conversion from sirolimus to enteric coated mycophenolate sodium.

BACKGROUND: Anemia is a known adverse effect of sirolimus (SRL) therapy. Sirolimus may contribute to anemia by a direct antiproliferative effect or by increasing inflammation, worsening kidney function, or decreasing iron utilization. After observing the need for high dose exogenous erythropoietin dosage in some patients on SRL, we hypothesized that SRL therapy may influence anemia by inducing a state of erythropoietin resistance. METHODS: Twenty-five stable renal transplant patients on maintenance tacrolimus and SRL therapy were enrolled in a prospective trial with conversion from SRL to enteric coated mycophenolate sodium. Measurement of plasma erythropoietin and red cell indices were performed pre- and postconversion. RESULTS: Renal function remained unchanged after conversion. Serum hemoglobin (Hb) increased in 18/21 (86%) of patients after conversion. Endogenous erythropoietin level decreased from a median of 28.3 (11.5-374) to 16.6 (3.1-78.8) mIU/mL, (P<0.001); and the erythropoietin:Hb ratio dropped from 2.7 (0.7-34.3) to 1.2 (0.2-6.7), (P<0.001); indicating less erythropoietin resistance after conversion. Mean corpuscular volume increased after conversion, but transferrin saturation and ferritin did not change. Conversion was complicated by posttransplant erythrocytosis in two patients. DISCUSSION: Conversion from SRL to enteric coated mycophenolate sodium led to an increase in Hb and a decrease in erythropoietin resistance in stable kidney transplant recipients. Increase in Hb seemed to be independent of renal functional changes or changes in iron sequestration.

Use of sirolimus in solid organ transplantation.

Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor that inhibits cell cycle progression and has proven to be a potent immunosuppressive agent for use in solid organ transplant recipients. The drug was initially studied as an adjunct to ciclosporin (cyclosporine) to prevent acute rejection in kidney transplant recipients. Subsequent studies have shown efficacy when combined with a variety of other immunosuppressive agents. The most common adverse effects of sirolimus are hyperlipidaemia and myelosuppression. The drug has unique antiatherogenic and antineoplastic properties, and may promote immunological tolerance and reduce the incidence of chronic allograft nephropathy. Although sirolimus is relatively non-nephrotoxic when administered as monotherapy, it pharmacodynamically enhances the toxicity of calcineurin inhibitors. Ironically, the drug has been used to facilitate calcineurin inhibitor-free protocols designed to preserve renal function after solid organ transplantation. Whether sirolimus can be used safely over the long term with low doses of calcineurin inhibitors requires further study. The use of sirolimus as a corticosteroid-sparing agent also remains to be proven in controlled trials. Postmarketing studies have revealed a number of unforeseen adverse effects including impaired wound healing and possibly proteinuria, oedema, pneumonitis and thrombotic microangiopathy. Overall, sirolimus is a powerful agent when used judiciously with other available immunosuppressants. As is true for all immunosuppressive drugs available for treatment of solid organ transplant recipients, the efficacy of the drug must be balanced against its considerable adverse effects.

Hemodialysis vintage, black ethnicity, and pretransplantation antidonor cellular immunity in kidney transplant recipients.

Prolonged exposure to dialysis before transplantation and black ethnicity are known risk factors for acute rejection and graft loss in kidney transplant recipients. Because the strength of the primed antidonor T cell repertoire before transplantation also is associated with rejection and graft dysfunction, this study sought to determine whether hemodialysis (HD) vintage and/or black ethnicity affected donor-directed T cell immunity. An enzyme-linked immunosorbent spot (ELISPOT) assay was used to measure the frequency of peripheral T cells that expressed IFN-gamma in response to donor stimulator cells before transplantation in 100 kidney recipients. Acute rejection occurred in 38% of ELISPOT (+) patients versus 14% of ELISPOT (-) patients (P = 0.008). The median (HD) vintage was 46 mo (0 to 125 mo) in ELISPOT (+) patients versus 24 mo (0 to 276 mo) in ELISPOT (-) patients (P = 0.009). Black recipients had a greater median HD vintage (55 versus 14 mo in nonblack recipients; P < 0.001). Black recipients with less HD exposure had a low incidence of an ELISPOT (+) test, similar to nonblack recipients. Among variables examined, only HD vintage remained a significant positive correlate with an ELISPOT (+) result (odds ratio per year of HD 1.3; P = 0.003). These data suggest that the risk for developing cross-reactive antidonor T cell immunity increases with longer HD vintage, providing an explanation for the previously observed relationship between increased dialysis exposure and worse posttransplantation outcome. Longer HD vintage may also explain the increased T cell alloreactivity that previously was observed in black kidney recipients.

Long-term graft outcomes after steroid withdrawal in African American kidney transplant recipients receiving sirolimus and tacrolimus.

BACKGROUND: We previously reported excellent short-term outcomes in African American kidney transplant patients receiving tacrolimus/sirolimus and withdrawn from corticosteroid therapy three months after transplantation. We now report the long-term outcomes of patients subjected to this protocol. METHODS: In all, 47 African American kidney transplant recipients were enrolled in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids, without antibody induction therapy. Eligible patients were withdrawn from prednisone between three and five months posttransplant, and followed for acute rejection and changes in renal function. Outcomes (group 1, n=32) were compared to those of patients deemed not to be candidates for steroid withdrawal (group 2, n=15). RESULTS: After a mean follow-up of 48.5 months, 13 of 32 patients (41%) in group 1 developed acute rejection; only 13 patients (41%) remain steroid-free. Nine of 13 rejection episodes were associated with noncompliance. Graft loss occurred in 8 of 32 patients (25%) in group 1 and in 5 of 15 patients (33%) in group 2 (P=NS). Serum creatinine rose from 1.4+/-0.41 to 2.45+/-1.7 mg/dL in group 1 (P=0.004) and from 2.1+/-0.45 to 2.62+/-1.2 mg/dL (P=NS) in group 2. Among 13 patients in group 1 who remain steroid-free, creatinine concentration has risen from 1.28+/-.0.37 prior to steroid withdrawal to 1.64+0.54 at last follow-up (P=0.027). CONCLUSIONS: Late noncompliance and/or rejection in African Americans withdrawn from steroids have a negative impact on long-term graft function and survival. Steroid withdrawal may be associated with long-term deterioration of renal function, even in the absence of overt acute rejection.

Improved renal function after conversion from tacrolimus/sirolimus to tacrolimus/mycophenolate mofetil in kidney transplant recipients.

BACKGROUND: There is limited data on the potential nephrotoxicity of sirolimus (SRL) and tacrolimus (TAC) in combination. METHODS: We reviewed the course of 97 kidney transplant patients treated with SRL and reduced-dose TAC. Conversion from SRL to mycophenolate mofetil (MMF) was prescribed in a minority (n = 19) for various nonrenal side effects. We compared outcomes of converted patients to those remaining on TAC/SRL (n = 78). RESULTS: TAC levels were increased in converters (P = 0.009). Rejection rates were similar between groups over 18 months (21% vs. 16%, p = ns). Serum creatinine (Cr) and MDRD glomerular filtration rate (GFR) were similar between groups at nadir and six-months, but at 18 months the percent change from six-month Cr was +17% in non-converters vs. -10% in converters (P = 0.004 for the difference). The difference in GFR between groups at 18 months was also significant (P = 0.01). By multivariate analysis, only conversion to MMF was associated with a greater percent change in Cr from 6 to 18 months (P = 0.015). Conversion to MMF also correlated with higher GFR at 18 months independent of rejection, delayed graft function, and ethnicity. CONCLUSIONS: Conversion from TAC/SRL to TAC/MMF led to improved renal function despite increased TAC exposure after conversion.

Comparative effects of sirolimus and mycophenolate mofetil on erythropoiesis in kidney transplant patients.

Anemia and erythrocytosis (PTE) are common after kidney transplantation. We sought to determine the influence of sirolimus compared to mycophenolate mofetil (MMF) on post-transplant erythropoiesis. A total of 214 patients with recent kidney or kidney-pancreas transplants were treated with either sirolimus-based (n = 87) or MMF-based (n = 127) therapy. At 12 months, the prevalence of anemia was 31% with MMF and 57% with sirolimus (p < 0.001). Linear regression was used to examine the independent influence of sirolimus on hemoglobin at 12 months, controlling for multiple factors including gender and renal function. Sirolimus remained a significant correlate of lower hemoglobin in all patients (slope =-1.060, 95% CI: -1.76 to -0.362, p = 0.003), and in patients without PTE (slope =-0.671, 95% CI: -1.32 to -0.028, p = 0.041). PTE, defined as a persistent hematocrit above 51%, occurred in 19% with MMF and 7% with sirolimus (p = 0.013). PTE was examined using logistic regression analysis. Sirolimus use correlated negatively with PTE (odds ratio with sirolimus = 0.33, 95% CI: 0.12 to 0.89, p = 0.028). Our results indicate that, compared to treatment with MMF, treatment of kidney or kidney-pancreas recipients with sirolimus is associated with a higher prevalence of anemia, lower hemoglobin levels and lower incidence of PTE.

Withdrawal of steroid therapy in African American kidney transplant recipients receiving sirolimus and tacrolimus.

BACKGROUND: Withdrawal of corticosteroids from the immunosuppressive regimens of kidney transplant recipients has been associated with an increased risk of acute and chronic allograft rejection. Previous studies indicate that the risk of rejection is particularly high in African Americans. METHODS: We prospectively enrolled 44 African American kidney transplant recipients to participate in an uncontrolled trial in which they were initially treated with sirolimus, tacrolimus, and corticosteroids. No patient received antibody induction therapy. Prednisone was withdrawn from eligible patients free of acute rejection beginning as early as 3 months posttransplant, and followed for a minimum of 9 months posttransplant. Patients were followed for acute rejection and for changes in blood pressure, body weight, and serum creatinine concentrations before and after withdrawal of steroids. RESULTS: Thirty of 44 patients (68%) were weaned off of prednisone. Follow-up after withdrawal of prednisone ranged from 3 to 26 months (mean, 14.3+/-7.7 months). Two of 30 patients (6.7%) developed acute rejection. At last follow-up, 27 of 30 patients (90%) remain steroid-free. Steroid withdrawal was associated with significant reductions in blood pressure. CONCLUSIONS: Use of sirolimus and tacrolimus, without the use of induction antibody therapy, allows withdrawal of prednisone as early as 3 months posttransplant with low rates of subsequent acute rejection in African American kidney transplant recipients. Withdrawal of prednisone was associated with lower blood pressures and the need for fewer antihypertensive medications.

Infectious disease prophylaxis in renal transplant patients: a survey of US transplant centers.

Definitive approaches to most infectious diseases following renal transplantation have not been established, leading to different approaches at different transplant centers. To study the extent of these differences, we conducted a survey of the practices surrounding specific infectious diseases at US renal transplant centers. A survey containing 103 questions covering viral, bacterial, mycobacterial and protozoal infections was developed. Surveys were sent to program directors at all U.S. renal transplant centers. Responses were received from 147 of 245 (60%) transplant centers and were proportionately represented all centers with respect to program size and geographical location. Pre-transplant donor and recipient screening for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cytomegalovirus (CMV) is uniform, but great discrepancy exists in the testing for other agents. HCV seropositive donors are used in 49% of centers. HIV seropositivity remains a contraindication to transplantation, although 13% of centers indicated they have experience with such patients. Post-transplant, there is wide variety in approach to CMV and Pneumocystis carinii (PCP) prophylaxis. Similarly divergent practices affect post-transplant vaccinations, with 54% of centers routinely vaccinating all patients according to customary guidelines in non-transplant populations. In contrast, 22% of centers indicated they do not recommend vaccination in any patients. We believe an appreciation of the differences in approaches to post-transplant infectious complications may encourage individual centers to analyse the results of their own practices. Such analysis may assist in the design of studies to answer widespread and important questions regarding the care of patients following renal transplantation.