Liise K. Kayler

Renal transplantation in elderly patients older than 70 years of age: results from the Scientific Registry of Transplant Recipients.

Background. Elderly patients (ages 70 yr and older) are among the fastest-growing group starting renal-replacement therapy in the United States. The outcomes of elderly patients who receive a kidney transplant have not been well studied compared with those of their peers on the waiting list. Methods. Using the Scientific Registry of Transplant Recipients, we analyzed data from 5667 elderly renal transplant candidates who initially were wait-listed from January 1, 1990 to December 31, 2004. Of these candidates, 2078 received a deceased donor transplant, and 360 received a living donor transplant by 31 December 2005. Time-to-death was studied using Cox regression models with transplant as a time-dependent covariate. Mortality hazard ratios (RRs) of transplant versus waiting list were adjusted for recipient age, sex, race, ethnicity, blood type, panel reactive antibody, year of placement on the waiting list, dialysis modality, comorbidities, donation service area, and time from first dialysis to first placement on the waiting list. Results. Elderly transplant recipients had a 41% lower overall risk of death compared with wait-listed candidates (RR=0.59; P<0.0001). Recipients of nonstandard, that is, expanded criteria donor, kidneys also had a significantly lower mortality risk (RR=0.75; P<0.0001). Elderly patients with diabetes and those with hypertension as a cause of end-stage renal disease also experienced a large benefit. Conclusions. Transplantation offers a significant reduction in mortality compared with dialysis in the wait-listed elderly population with end-stage renal disease.

Treatment for BK virus: incidence, risk factors and outcomes for kidney transplant recipients in the United States

There has been a notable rise of BK virus among kidney transplant recipients. Single‐center reports have identified risk factors for development of BK virus. However, there has not been an assessment of risk factors and incidence of this complication at a national level. This study utilized newly collected follow‐up information from the national SRTR database to investigate incidence, risk factors and outcomes for solitary kidney transplant recipients associated with treatment for BK virus (TBKV) from 2004 to 2006. Logistic and Cox models were utilized to assess risk factors and evaluate graft survival associated with TBKV. Incidence of TBKV was 1.6% at 6 months and 2.6% at 1 year following transplantation. Patients with and without TBKV at 6 months had 79% and 90% 3‐year overall graft survival respectively. Risk factors included advanced donor age, pediatric, African American and male recipients, human leukocyte antigen‐mismatching and tacrolimus and thymoglobulin induction as baseline immunosuppression. Acute rejection episodes were more frequent prior to and following TBKV. TBKV is a common and rising incidence, varies based on transplant characteristics and should be included as a safety endpoint in studies investigating immunosuppressive protocols. Careful monitoring and further understanding of disease etiology and treatment strategies are needed.

Influence of CIT-Induced DGF on Kidney Transplant Outcomes

Increased cold ischemia time (CIT) predisposes to delayed graft function (DGF). DGF is considered a risk factor for graft failure after kidney transplantation, but DGF has multiple etiologies. To analyze the risk of CIT‐induced DGF on graft survival, we evaluated paired deceased‐donor kidneys (derived from the same donor transplanted to different recipients) in which one donor resulted in DGF and the other did not, using national Scientific Registry of Transplant Recipients data between 2000 and 2009. Of 54 565 kidney donors, 15 833 were excluded for mate kidney nontransplantation, 27 340 because both or neither kidney developed DGF and 2310 for same/unknown CIT. The remaining 9082 donors (18 164 recipients) were analyzed. The adjusted odds (aOR) of DGF were significantly higher when CIT was longer by ≥1 h (aOR 1.81, 95% CI 1.7–2.0), ≥5 h (aOR 2.5, 95% CI 2.3–2.9), ≥10 h (aOR 3.3, 95% CI 2.7–2.9) and ≥15 h (aOR 4.4, 95% CI 3.4–5.8) compared to shorter CIT transplants. In the multivariable models adjusted for recipient characteristics, graft survival between paired donor transplants, with and without DGF, were similar. These results suggest that DGF, specifically induced by prolonged CIT, has limited bearing on long‐term outcomes, which may have important implications for kidney utilization.

Living Donor Renal Transplantation Using Alemtuzumab Induction and Tacrolimus Monotherapy

Alemtuzumab was used as an induction agent in 205 renal transplant recipients undergoing 207 living donor renal transplants. All donor kidneys were recovered laparoscopically. Postoperatively, patients were treated with tacrolimus monotherapy, and immunosuppression was weaned when possible. Forty‐seven recipients of living donor renal transplants prior to the induction era who received conventional triple drug immunosuppression without antibody induction served as historic controls. The mean follow‐up was 493 days in the alemtuzumab group and 2101 days in the historic control group. Actuarial 1‐year patient and graft survival were 98.6% and 98.1% in the alemtuzumab group, compared to 93.6% and 91.5% in the control group, respectively. The incidence of acute cellular rejection (ACR) at 1 year was 6.8% in the alemtuzumab group and 17.0% (p < 0.05) in the historic control group. Most (81.3%) episodes of ACR in the alemtuzumab group were Banff 1 (a or b) and were sensitive to steroid pulses for the treatment of rejection. There was no cytomegalovirus disease or infection. The incidence of delayed graft function was 0%, and the incidence of posttransplant insulin‐dependent diabetes mellitus was 0.5%. This study represents the largest series to date of live donor renal transplant recipients undergoing alemtuzumab induction, and confirms the short‐term safety and efficacy of this approach.

Impact of Cold Ischemia Time on Graft Survival Among ECD Transplant Recipients: A Paired Kidney Analysis

Delays in expanded criteria donor (ECD) kidney placement increases cold ischemia times (CIT) potentially leading to discard. The effect of increased CIT on ECD kidney transplant outcomes is unknown. We evaluated paired ECD kidneys (derived from the same donor transplanted to different recipients) from the SRTR registry transplanted between 1995 and 2009 (n = 17 514). To test the effect of CIT, we excluded paired transplants with the same CIT (n = 3286). Of 14 230 recipients (7115 donors) the median difference in CIT was 5 h (Q1 = 3 h, Q3 = 9 h). Delayed graft function (DGF) was significantly more likely between pairs with greater CIT (35% vs. 31%, p < 0.001) including substantially higher rates for CIT differences ≥15 h (42%). Overall graft loss was not significantly different between recipients with higher CIT relative to paired donor recipients with lower CIT (p = 0.47) or for pairs with differences of 1–3 h (p = 0.90), 4–9 h (p = 0.41), 10–14 h (p = 0.36) or ≥15 h (p = 0.10). Results were consistent in multivariable models adjusted for recipient factors. Although increasing cold ischemia time is a risk factor for DGF among ECD kidney transplants, there is no effect on graft survival which may suggest an important utility for donor kidneys that may not currently be considered viable.

Outcomes and Utilization of Kidneys from Deceased Donors with Acute Kidney Injury

Utilization and long‐term outcomes of kidneys from donors with elevated terminal serum creatinine (sCr) levels have not been reported. Using data from the Scientific Registry of Transplant Recipients from 1995 to 2007, recipient outcomes of kidneys from adult donors were evaluated stratified by standard criteria (SCD; n = 82 262) and expanded criteria (ECD; n = 16 978) donor type and by sCr ≤1.5, 1.6–2.0 and >2.0 mg/dL. Discard rates for SCDs were ascertained. The relative risk of graft loss was similar for recipients of SCD kidneys with sCr of 1.6–2.0 and >2.0 mg/dL, compared to ≤1.5 mg/dL. For ECD recipients, the relative risk of graft failure significantly increased with increasing sCr. Of potential SCDs, the adjusted risk of discard was higher with sCr >2.0 mg/dL (adjusted odds ratio [AOR] 7.04, 95% confidence interval [CI] 6.5–7.6) and 1.6–2.0 mg/dL (AOR 2.7; CI 2.5–2.9) relative to sCr ≤1.5 mg/dL. Among potential SCDs, elevated terminal creatinine is a strong independent risk factor for kidney discard; yet, when kidney transplantation is performed elevated donor terminal creatinine is not a risk factor for graft loss. Further research is needed to identify safe practices for the optimal utilization of SCD kidneys from donors with acute kidney injury.

Transmission of Cryptococcus neoformans by Organ Transplantation

BACKGROUND This article describes transmission of Cryptococcus neoformans by solid organ transplantation. METHODS We reviewed medical records and performed molecular genotyping of isolates to determine potential for donor transmission of Cryptococcus. RESULTS Cryptococcosis was diagnosed in 3 recipients of organs from a common donor with an undifferentiated neurologic condition at the time of death. Cryptococcal meningoencephalitis was later diagnosed in the donor at autopsy. The liver and 1 kidney recipient developed cryptococcemia and pneumonia and the other kidney recipient developed cryptococcemia and meningitis; 2 patients recovered with prolonged antifungal therapy. We tested 4 recipient isolates with multilocus sequence typing and found they had identical alleles. CONCLUSIONS Our investigation documents the transmission of Cryptococcus neoformans by organ transplantation. Evaluation for cryptococcosis in donors with unexplained neurologic symptoms should be strongly considered.

Kidney Transplant Ureteroneocystostomy Techniques and Complications: Review of the Literature

Despite a variety of urinary tract reconstructive techniques, urinary complications are the most frequent technical adverse event following renal transplantation. These complications can be associated with substantial morbidity and generate excess cost. In this review we comprehensively discuss 4 techniques of ureteroneocystostomy, compare complications, and evaluate the strengths and weaknesses of each technique focusing on 4 specific urologic complications: urine leak, ureteric obstruction, hematuria, and symptomatic vesicoureteral reflux.

Acute Cellular Rejection with CD20-Positive Lymphoid Clusters in Kidney Transplant Patients Following Lymphocyte Depletion

Lymphoid clusters (LC) containing CD20‐positive B cells in kidney allografts undergoing acute cellular rejection (ACR) have been identified in small studies as a prognostic factor for glucocorticoid resistance and graft loss. Allograft biopsies obtained during the first episode of ACR in 120 recipients were evaluated for LC, immunostained with CD20 antibody, and correlated with conventional histopathologic criteria, response to treatment and outcome. LC were found in 71 (59%) of the 120 biopsies. All contained CD20 positive B cells that accounted for 5–90% of the LC leukocyte content. The incidence of LC was highest in the patients who had no lymphoid depletion or had been treated with Thymoglobulin preconditioning (79% vs. 75%, respectively) compared to 37% in patients pretreated with Campath (p = 0.0001). Banff 1a/1b ACR were more frequent in the LC‐positive than the LC‐negative group (96% vs. 80%, respectively; p = 0.0051). With a posttransplant follow‐up of 953 ± 430 days, no significant differences were detected between LC‐postitive and LC‐negative groups in time to ACR, steroid resistance, serum creatinine and graft loss. CD20+LC did not portend glucocorticoid resistance or worse short to medium term outcomes. CD20+LC may represent a heterogenous collection in which there may be a small still to be fully defined unfavorable subgroup.

Correlation of histologic findings on preimplant biopsy with kidney graft survival

Kidney biopsies are being used to evaluate marginal deceased donor organs, but, the literature on the utility of this practice remains conflicting. We re‐examined this issue by performing a multivariate analysis of 597 kidney transplant recipients. The presence of moderate arteriosclerosis and/or moderate arteriolosclerosis (MA), defined as ≥25% luminal compromise, was a significant predictor of graft outcome in standard criteria donors (multivariate, P = 0.01) and in expanded criteria donors (ECD) as defined by UNOS criteria (univariate P = 0.02). One‐, 3‐, and 5‐year overall allograft survival with MA was 71%, 58%, and 40%, respectively. Increasing degrees of glomerulosclerosis (GS) were associated with earlier graft failure on univariate (P = 0.03) but not multivariate analysis (P = 0.36). GS > 20% and interstitial fibrosis >25% had a low frequency in the material reviewed, likely reflecting our organ utilization practices, and did not have a demonstrable effect on graft outcome. Clinical parameters independently associated with worse graft function were ECD status (P < 0.05), retransplantation (P = 0.004), recipient age (P < 0.05), and delayed graft function (P < 0.0001). Donor vascular disease is an independent risk factor for suboptimal graft survival. Great caution should be exercised in the decision to transplant kidneys with moderate arterial and/or arteriolar luminal narrowing.