The Utility of Screening Colonoscopy During Kidney Transplant Evaluation.

OBJECTIVES: Transplant centers often recommend, but not necessarily require, screening colonoscopies for people over 50 years of age in accordance with the US Preventative Services Task Force guidelines for the general population. We sought to identify risk factors affecting colonoscopy results in renal failure patients undergoing kidney transplant evaluation. MATERIALS AND METHODS: We retrospectively examined patients undergoing kidney transplant evaluation from 2009 to 2012 (n = 469 patients). Comparisons were made between colonoscopy reports categorized as normal (no finding or hyperplastic polyp) or abnormal (adenomatous polyp or carcinoma). RESULTS: Of 469 patients who met the study criteria, 303 (64.6%) had normal colonoscopies and 166 (35.4%) had abnormal colonoscopies. Logistic regression analysis showed that male sex (odds ratio = 2.09; 95% confidence interval, 1.37-3.20; P = .001) and increasing age (odds ratio = 1.04; 95% confidence interval, 1.01-1.08; P = .019) were more likely to correspond to abnormal findings. Those with dialysis vintage (length of time on dialysis) up to 3 years (odds ratio = 2.10; 95% confidence interval, 1.09-4.06; P = .027) and hypertension as the cause of renal failure (odds ratio = 1.79; 95% confidence interval, 1.05-2.87; P = .002) had more abnormal findings. No differences in length of evaluation, rate of being listed for transplant, and rate of transplant were shown. CONCLUSIONS: The overall rate of adenomatous findings on colonoscopy was higher among patients with pretransplant end-stage renal disease than in the general population, as shown in other studies. Age, sex, dialysis vintage up to 3 years, and hypertensive renal failure were associated with adenomatous polyps of the colon in this study population. Because adenomatous polyp rates are high in patients with chronic kidney disease who are undergoing transplant evaluation and colonoscopic findings do not appear to delay transplant evaluations or listing rates, screening colonoscopies should be encouraged.

Utility of mammography for chronic kidney disease patients undergoing kidney transplant evaluation.

UNLABELLED: Transplant centers typically require screening mammography (MMG) for women ≥40 during evaluation. American Cancer Society recommends starting annual MMG at 40, while USPSTF recommends biennial MMG at 50. We sought to determine the effect of age and other breast malignancy risk factors on screening MMG in the pre-transplant renal failure population undergoing transplant evaluation. METHODS: We retrospectively examined women ≥40 undergoing kidney transplant evaluation from 2006 to 2012 (n = 541). RESULTS: Patients aged 40.0-49.9 and ≥50 had similar rates of breast biopsy and breast malignancy. African Americans underwent a higher rate of biopsies (OR 2.391, 95%CI 1.111-5.019, p = 0.026), with a lower rate of biopsy in those already on dialysis at presentation (OR 0.434, 95%CI 0.212-0.888, p = 0.022). Higher breast density (>50% fibroglandular tissue) increased both rate of biopsy (OR 2.876, 95%CI 1.377-6.010, p = 0.005) and malignancy (OR 5.061, 95%CI 1.012-25.315, p = 0.048). CONCLUSIONS: As we found no independent differences in biopsy or malignancy between age groups, it is reasonable for transplant centers to use the same evaluation MMG screening policy for all women ≥40. However, as malignancy risk increased with higher breast density, a lower threshold for additional workup may be warranted in patients with dense breasts or an indeterminate lesion on MMG.

Enhancing kidney function with thrombolytic therapy following donation after cardiac death: a multicenter quasi-blinded prospective randomized trial.

Kidneys from donors after cardiac death (DCD) are at risk for inferior outcomes, possibly due to microthrombi and additional warm ischemia. We describe an organ procurement organization-wide trial utilizing thrombolytic tissue plasminogen activator (tPA) during machine pulsatile perfusion (MPP). A kidney from each recovered kidney pair was prospectively randomized to receive tPA (50 mg Alteplase) or no tPA (control) in the MPP perfusate. From 2011 to 2013, 24 kidneys were placed with enrolled recipients from 19 DCD kidney donors. There were no significant differences for absolute values of flow or resistance while undergoing MPP between the groups, nor rates of achieving discrete flow and resistance targets. While there was a trend toward lower creatinine and higher glomerular filtration rates in the tPA group at 3, 6, 9, and 12 months, these differences were not significant. Delayed graft function (DGF) rates were 41.7% in the tPA group vs. 58.4% in the control group (OR 0.51, 95%CI 0.10-2.59, p = 0.68). Death-censored graft survival was similar between the groups. In this pilot study, encouraging trends are seen in kidney allograft function independent of MPP parameters following DCD kidney transplantation for those kidneys receiving thrombolytic tPA and MPP, compared with standard MPP.

Outcome differences between young children and adolescents undergoing kidney transplantation.

BACKGROUND/PURPOSE: Although graft loss remains the biggest challenge for all pediatric kidney transplant (KT) recipients, unique challenges exist within different age groups. We aim to evaluate the different characteristics and graft survival outcomes of young children and adolescents undergoing KT. METHODS: Children who underwent isolated KT between 2000 and 2013 at our institution were included in this retrospective analysis. Patient characteristics and outcomes were compared using student's t-test, chi-square test, Kaplan-Meier curve and Cox proportional hazards model. RESULTS: Of 73 children who underwent KT, 31 were <12 (young children), and 42 were ≥ 12 years old (adolescents). Overall patient survival was 100%. The younger group had superior 5-year (100% vs. 75.5%) and 10-year (94.4% vs. 43.8%) graft survival (p=0.008). Factors predictive of poor graft survival on multivariate analysis were older age at transplantation (HR 1.2, CI 1-1.4, p=0.047), female gender (HR 9.0, CI 1.9-43, p=0.006), and acute rejection episodes (HR 13, CI 2-90, p=0.008). The most common causes of graft loss were acute and chronic rejection episodes and immunosuppression nonadherence. CONCLUSION: Adolescents undergoing KT have inferior graft survival compared to younger children. In adjusted modeling, children with older age, female gender, and acute rejection episodes have inferior graft survival.

Arteriovenous grafts have higher secondary patency in the short term compared with autologous fistulae.

BACKGROUND: To estimate patency of arteriovenous fistulas (AVFs) and grafts (AVGs) for dialysis access. METHODS: Records of all adult patients who had a dialysis access placed from January 2008 to June 2011 were retrospectively reviewed. RESULTS: A total of 494 patients with 655 accesses (390 AVFs, 265 AVGs) were examined. We found that AVG fared worse in assisted primary patency. But AVG had superior secondary patency up to 1.2 years (hazard ratio [HR] .6, confidence interval [CI]: [.4 to .8]) and was no different than AVF after 1.2 years. (HR 1.6, CI: [.9 to 3.1]). On univariate analysis, dialysis catheters negatively impacted assisted primary patency (HR 1.4, CI: [1.09 to 1.77]). CONCLUSIONS: AVG can be maintained with higher rates of secondary patency in the short term and are no different in the long term. This result suggests that in patients with limited life expectancy an AVG may be an effective alternative to an AVF to reduce both catheter time and associated complications.

Fever, infection, and rejection after kidney transplant failure.

BACKGROUND: Patients returning to dialysis therapy after renal transplant failure have high morbidity and retransplant rates. After observing frequent hospitalizations with fever after failure, it was hypothesized that maintaining immunosuppression for the failed allograft increases the risk of infection, while weaning immunosuppression can lead to symptomatic rejection mimicking infection. METHODS: One hundred eighty-six patients with failed kidney transplants were analyzed for rates of hospitalization with fever within 6 months of allograft failure. Patients were stratified by the presence of full immunosuppression versus minimal (low-dose prednisone) or no immunosuppression, before hospital admission. Subsequent rates of documented infection and nephrectomy, as well as patient survival, were ascertained. RESULTS: Hospitalization with fever within 6 months of allograft failure was common, occurring in 44% of patients overall. However, among febrile hospitalized patients who had been weaned off of immunosuppression before admission, only 38% had documented infection. In contrast, 88% of patients maintained on immunosuppression had documented infection (P<0.001). In both groups, dialysis catheter-related infections were the most common infection source. Allograft nephrectomy was performed in 81% of hospitalized patients with no infection, compared to 30% of patients with documented infection (P<0.001). Mortality risk was significantly higher in patients with concurrent pancreas transplants or who were hospitalized with documented infection. CONCLUSIONS: Maintenance immunosuppression after kidney allograft failure was associated with a greater incidence of infection, while weaning of immunosuppression commonly resulted in symptomatic rejection with fever mimicking infection on presentation. Management of the failed allograft should include planning to avoid both infection and sensitizing events.

Effects of cellular sensitization and donor age on acute rejection and graft function after deceased-donor kidney transplantation.

BACKGROUND: Allografts from older donors may be more immunogenic than those from younger donors. Pretransplantation cellular sensitization may interact with advanced donor age to increase the risk of immune injury after deceased-donor kidney transplantation. METHODS: The outcomes of 118 consecutive deceased-donor kidney transplant recipients with available pretransplantation donor-stimulated enzyme-linked immunosorbent spot (ELISPOT) assays for interferon gamma were analyzed retrospectively to determine the impact of cellular sensitization and other clinical variables, including donor age, on the incidence of acute rejection (AR) in the first year after deceased-donor transplantation and on estimated glomerular filtration rate 12 months after transplantation. RESULTS: The incidence of AR was higher in patients with positive pretransplantation ELISPOT assays versus those with negative assays (36% vs. 14%, P=0.009). Logistic regression indicated that the combination of donor age 50 years or older and a positive pretransplantation ELISPOT assay was more strongly associated with AR (odds ratio, 12.1; confidence interval, 1.1-133) than either variable alone. Estimated glomerular filtration 12 months after transplantation was highest in ELISPOT-negative patients receiving kidneys from donors younger than 50 years and lowest in ELISPOT-positive recipients with donors 50 years or older. CONCLUSION: The combination of advanced donor age and pretransplantation cellular sensitization increases the risk of AR and poor graft function after deceased-donor kidney transplantation beyond the risk associated with each factor alone.

Independent of nephrectomy, weaning immunosuppression leads to late sensitization after kidney transplant failure.

BACKGROUND: Patients returning to dialysis therapy after renal transplant failure have a high rate of human leukocyte antigen antibody sensitization, and sensitization has been linked to allograft nephrectomy. We hypothesized that nephrectomy for cause is a consequence of weaning immunosuppression and that weaning leads to sensitization even in the absence of nephrectomy. METHODS: We examined outcomes in 300 consecutive patients with kidney allograft failure and survival of more than 30 days after failure. We analyzed a subset of 119 patients with a low panel reactive antibody (PRA) before transplantation and follow-up PRA testing at 6 to 24 months after failure (late PRA). RESULTS: By late PRA testing, 56% of patients were highly sensitized (class I or II PRA ≥80%). On multivariate analysis controlling for human leukocyte antigen matching, allograft nephrectomy, and other variables, weaning of immunosuppression predicted high sensitization (odds ratio, 14.34; P=0.004). In a subset of patients, the percentage of those who were highly sensitized increased from 21% at the time of failure on immunosuppressive therapy to 68% by late PRA after weaning (P<0.001). Conversely, patients who maintained immunosuppression showed minimal sensitization after failure. Transplant nephrectomy was required in 41% of patients who weaned immunosuppression versus 0% of the 24 patients who maintained immunosuppression with calcineurin inhibitor therapy after failure (P<0.001). CONCLUSIONS: Weaning immunosuppression was a triggering event leading to late rejection and allograft nephrectomy and was an independent predictor of alloantibody sensitization after kidney allograft failure.

Pancreatic resection in octogenarians.

BACKGROUND: Few studies exist that evaluate outcomes of pancreatectomy in patients > or =80 y of age, an age group increasing in size in the United States. This study analyzes the outcomes of pancreatectomy in patients > or =80 y of age. METHODS: The medical records of 32 patients > or =80 y of age undergoing pancreatectomy at our institution from April 1995 through October 2008 were reviewed, and outcomes were analyzed. RESULTS: The median patient age was 82 y, and 75% were ASA Class 3. Eighty-one percent of the resections were pancreaticoduodenectomies. There were no operative deaths. Sixty-six percent of patients suffered at least one complication. The median length of stay was 11 d. Eighty-one percent of the resections were performed for cancer. Median survival for all patients was 14.4 mo. Median survival for patients with cancer was 12 mo versus 103 mo for patients without cancer, P = 0.017. CONCLUSIONS: Pancreatectomy in patients > or =80 y of age can be performed with a low risk of mortality but with significant morbidity.

Effect of parathyroidectomy on anemia and erythropoietin dosing in end-stage renal disease patients with hyperparathyroidism.

BACKGROUND: It has been suggested that parathyroidectomy for hyperparathyroidism (HPT) in end-stage renal disease (ESRD) may result in improvement in anemia and the response to erythropoiesis-stimulating drugs. This study examines the effect parathyroidectomy had on erythropoietin (EPO) dosing requirements and anemia in ESRD. METHODS: A retrospective review was conducted. Patients were included if pre-operative and 12 month postoperative hemoglobin (Hg) and hematocrit (Hct) levels were available and they did not receive a kidney transplant or have failure of parathyroidectomy during the follow-up. Erythropoietin (EPO) dose and serum levels of calcium, phosphorus, alkaline phosphatase, albumin, and parathyroid hormone (PTH) were also obtained. Other data collections were at 1 and 2 mos. postoperatively. RESULTS: Thirty-seven patients met inclusion criteria. Parathyroidectomy resulted in decreased PTH from 1,871 +/- 236 (mean +/- SEM) to 172 +/- 29 pg/mL (P < .001) at 1 year. EPO dosing requirement showed a profound decrease from 10,086 +/- 1,721 to 3,514 +/- 620 units/week (P < .05). Hb and Hct levels followed an upward trend at 12 mos (11.4 +/- 0.3 to 12.1 +/- 0.2 g/dL and 35.7 +/- 1.0 to 37.1 +/- 0.6%, respectively). CONCLUSION: In ESRD, parathyroidectomy for HPT improves anemia and decreases requirements for exogenous erythropoietin suggesting either increased endogenous EPO production or improved response. As a result, we propose refractory ESRD-associated anemia as a secondary indication for parathyroidectomy resection in this population.

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.

Early experience with intraoperative radiotherapy in patients with resected pancreatic adenocarcinoma.

BACKGROUND: The use of intraoperative radiotherapy (IORT) in patients with resected pancreatic adenocarcinoma has not been clearly defined. METHODS: The medical records of our first 22 patients receiving IORT for resected pancreatic adenocarcinoma (2001 to 2006) were reviewed and compared with the records of 27 consecutive patients not receiving IORT for resected pancreatic adenocarcinoma (2004 to 2006). RESULTS: There were no 30-day mortalities in either group, and complication rates were similar. Local recurrence occurred in 18% in the IORT group (median 14 months) and 12% in the no-IORT group (median 7 months). Distant recurrence occurred in 47% in the IORT group (median 11 months) and 32% in the no-IORT group (median 6.5 months). Median overall, stage-specific, and location-specific survival did not differ between the groups. CONCLUSIONS: Although limited in size and follow-up, our experience showed that complications, recurrence, and survival were not affected by IORT, but time to recurrence may be longer with IORT.

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.

An aggressive surgical approach is warranted in the management of cystic pancreatic neoplasms.

BACKGROUND: Cystic pancreatic neoplasms encompass a range of benign to malignant disease. Recommendations for surgical management vary. METHODS: Records of patients with cystic pancreatic neoplasms from January 1996 through December 2005 were retrospectively reviewed. RESULTS: Sixty resections were performed for 16 serous cystic neoplasms, 7 mucinous cystic neoplasms (MCNs), and 37 intraductal papillary mucinous neoplasms (IPMNs). Twenty-five percent (15/60) of neoplasms contained invasive cancer. Patients with MCN or IPMN invasive neoplasms experienced significantly diminished overall 5-year survival compared to patients with IPMN carcinoma in situ neoplasms and to patients with MCN or IPMN adenoma/borderline neoplasms (22% vs. 73% vs. 94%, P = .004). CONCLUSIONS: Given the poor long-term survival of patients with cystic pancreatic neoplasms containing invasive cancer and the current difficulty to preoperatively distinguish among the various types of lesions in a reliable manner, our data support an aggressive surgical approach to the management of cystic pancreatic neoplasms.

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.

Inhibition of nitric oxide synthase reduces renal ischemia/reperfusion injury.

BACKGROUND: The role of nitric oxide (NO) production because of inducible nitric oxide synthase (iNOS) in the pathogenesis of renal ischemia/reperfusion (I/R) injury is unclear. In this study the roles of both iNOS and NO were characterized in a rat model of renal I/R injury. In addition, the effect of iNOS inhibition on renal function was evaluated. METHODS: Sprague-Dawley rats underwent 45 min of left renal ischemia and contralateral nephrectomy followed by various periods of reperfusion and renal function analysis [plasma creatinine, fractional excretion of sodium (FENa), creatinine clearance (CrCl), and measurement of plasma and urine NO levels]. In addition, the effect of treatment with 1400W, a highly selective iNOS inhibitor, was evaluated. RESULTS: Renal dysfunction peaked at 48 h after reperfusion and immunohistochemistry studies revealed iNOS expression in the vasculature (3 h) and renal tubules (48 h) after reperfusion. Renal function improved significantly in treated animals compared to controls [creatinine of 1.1 v. 1.9 mg/dl (P < 0.05) and CrCl of 0.54 v. 0.31 ml/min (P < 0.05), respectively]. In addition, FENa was decreased by 50%, plasma NO levels were significantly lower (32.7 v. 45.7 micromol/L, P < 0.01), and deposition of nitrotyosine in the tubules of treated rats was less than in control animals. CONCLUSIONS: These data support the hypothesis that iNOS and NO are involved in the pathogenesis of renal I/R injury and suggests that use of iNOS inhibitors may be a valuable therapeutic strategy clinical situations where renal I/R may be prevalent.

Pre-transplant IFN-gamma ELISPOTs are associated with post-transplant renal function in African American renal transplant recipients.

Final crossmatch testing is routinely used to assess the risk of antibody-mediated graft injury/rejection post-transplant. Analogously, we postulated that quantitative measurements of anti-donor effector/memory T cells pre-transplant would independently assess post-transplant risk. To address this hypothesis, we determined the frequencies of pre-transplant, donor-specific interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spots (ELISPOTs) and correlated the results with post-transplant outcomes in 37 African American recipients of deceased donor kidney transplants treated with tacrolimus- and sirolimus-based immunosuppression. A positive ELISPOT test (>25 spots/300,000 cells) was detected in 14 (38%) of 37 patients. The incidence of biopsy-proven acute rejection was 50% (7/14) in ELISPOT-positive versus 17% (4/23) in ELISPOT-negative patients (p=0.036). Calculated glomerular filtration rate (MDRD) at 12 months was 37+/-16 mL/min in ELISPOT-positive versus 55+/-20 mL/min in ELISPOT-negative patients (p=0.01). ELISPOT status remained a correlate of allograft function at 12 months by linear regression analysis (p=0.001), independent of rejection and other contributing variables. Pre-transplant donor-directed IFN-gamma ELISPOT assessment of anti-donor cellular immunity may function as a 'cellular crossmatch' and independently correlates with renal allograft function in African Americans receiving tacrolimus- and sirolimus-based immunosuppression.

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.