Outcomes of Deceased Donor Kidney Transplantation Using Expanded Criteria Donor Kidneys Following Pulsatile Preservation.

Aim We compared the outcomes of transplanting expanded criteria donor (ECD) kidneys undergoing machine perfusion (MP) versus cold storage (CS). Material and methods Data on all expanded criteria deceased donor kidney transplants performed at the University of Pittsburgh Medical Center from January 2003 through December 2012 were collected from an in-house electronic repository. There were 78 patients in the MP group and 101 patients in the CS group. The majority of the ECD kidneys were imported from other organ procurement organizations: 69 of 73 in the MP group (94.5%, 5 from unknown sources); and 90 of 99 in the CS group (91%), 2 from an unknown source). Most of the patients in the MP group (77 of 78) received a combination of MP and static CS. MP was performed just prior to transplantation in all MP patients. We used descriptive statistics to characterize our sample. We used logistic regression analysis to model the binary outcome of delayed graft function (DGF; i.e., "yes/no") and Cox (proportional hazard) regression to model time until graft failure. The Kaplan-Meier product-limit method was used to estimate survival curves for graft and patient survival. Results A total of 179 transplants were done from ECD donors (MP, 78; CS, 101). The mean static cold storage time was 14 ± 4.1 hours and the mean machine perfusion time was 11.2 ± 6.3 hours in the MP group. The donor creatinine was higher (1.3 ± 0.6 mg/dl vs. 1.2 ± 0.4 mg/dl, p = 0.01) and the cold ischemia time was longer (28.9 ± 10 hours vs. 24 ± 7.9 hours, p = 0.0003) in the MP patients. There were no differences between the two groups in DGF rate (20.8% [MP] vs. 25.8% [CS], p = 0.46), six-year patient survival (74% [MP] vs. 63.2% [CS], p = 0.11), graft survival (64.3% [MP] vs. 51.5% [CS], p = 0.22), and serum creatinine levels (1.5 mg/dl vs. 1.5 mg/dl) on univariate analysis. On unadjusted analysis, MP subjects without DGF had longer graft survival compared to CS subjects with DGF (p < 0.0032) and MP subjects with DGF (p < 0.0005). MP subjects without DGF had longer death-censored graft survival compared to CS subjects with DGF (p < 0.0077) and MP subjects with DGF (p < 0.0016). However, on regression analysis, MP subjects had longer graft survival than CS subjects when DGF was not present. MP subjects without DGF had longer patient survival compared to CS subjects with DGF (p < 0.0289), on unadjusted analysis. MP subjects had a reduced risk of graft failure (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.17, 0.68) and death-censored graft failure (HR, 0.44; 95% CI, 0.19, 1.00), compared to CS subjects when DGF was not present. Conclusions Reduction of DGF rates for imported ECD kidneys is vital to optimize outcomes and increase their utilization. One strategy to decrease DGF rates may be to reduce static CS time during transportation, by utilizing a portable kidney perfusion machine.

Outcomes in human immunodeficiency virus-infected recipients of heart transplants.

BACKGROUND: With the advent of combined antiretroviral therapy (cART), growing evidence has shown human immunodeficiency virus (HIV) may no longer be an absolute contraindication for solid organ transplantation. This study compares outcomes of heart transplantations between HIV-positive and HIV-negative recipients using SRTR transplant registry data. METHODS: Patient survival, overall graft survival and death-censored graft survival were compared between HIV-positive and HIV-negative recipients. Multivariate Cox regression and Cox regression with a disease risk score (DRS) methodology were used to estimate the adjusted hazard ratios among heart transplant recipients (HTRs). RESULTS: In total, 35 HTRs with HIV+ status were identified. No significant differences were found in patient survival (88% vs 77%; P = 0.1493), overall graft survival (85% vs 76%; P = 0.2758), and death-censored graft survival (91% vs 91%; P = 0.9871) between HIV-positive and HIV-negative HTRs in 5-year follow-up. No significant differences were found after adjusting for confounders. CONCLUSIONS: This study supports the use of heart transplant procedures in selected HIV-positive patients. This study suggests that HIV-positive status is not a contraindication for life-saving heart transplant as there were no differences in graft, patient survival.

HMG-CoA reductase inhibitors in kidney transplant recipients receiving tacrolimus: statins not associated with improved patient or graft survival.

BACKGROUND: The beneficial effects of early statin use in kidney transplant recipients, especially those on tacrolimus-based immunosuppression, are not well established. We evaluated the predictors of statin use following kidney transplantation and examined its association with patient and allograft survival. METHODS: We examined 615 consecutive patients who underwent kidney transplant at our institution between January 1998 and January 2002. Statin use was assessed at baseline and 3, 6, 9, and 12 months following kidney transplant. Patients were followed for allograft and patient survival. RESULTS: 36% of the 615 kidney transplant recipients were treated with statin treatment. Statin use increased over the course of the study period. Older age, elevated body mass index, higher triglyceride levels, hypercholesterolemia, diabetes, history of myocardial infarction were associated with higher rates of statin use; elevated alkaline phosphatase levels and CMV IgG seropositivity were associated with less statin use. Older age, elevated BMI and hypercholesterolemia remained significant predictors of increased statin use after accounting for covariates using multiple regression. The early use of statins was not associated with improvements in unadjusted patient survival [HR 0.99; 95%CI 0.72-1.37] or graft survival [HR 0.97; 95% CI 0.76-1.24]. The risks of death and graft survival were not consistently reduced with exposure to statin using either adjusted models or propensity scores in Cox Proportional Hazards models. CONCLUSIONS: In a kidney transplant population primarily receiving tacrolimus-based immunosuppression, early statin use was not associated with significantly improved graft or patient survival.

Kidney after nonrenal transplantation-the impact of alemtuzumab induction.

BACKGROUND: Calcineurin inhibitor nephrotoxicity in nonrenal allograft recipients can lead to end-stage renal disease and the need for kidney transplantation. We sought to evaluate the role of alemtuzumab induction in this population. PATIENTS AND METHODS: We evaluated 144 patients undergoing kidney transplantation after nonrenal transplantation between May 18, 1998, and October 8, 2007. Seventy-two patients transplanted between January 15, 2003, and October 8, 2007, received alemtuzumab induction and continued their pretransplant immunosuppression. Seventy-two patients transplanted between May 18, 1998, and July 21, 2007, did not receive alemtuzumab induction, but received additional steroids and maintenance immunosuppression. Donor and recipient demographics were comparable. RESULTS: Overall, 1- and 3-year patient survival and renal function were comparable between the two groups. One- and 3-year graft survival was 93.0% and 75.3% in the alemtuzumab group and 83.3% and 68.7% in the no alemtuzumab group, respectively (P=0.051). The incidence of acute rejection was lower in the alemtuzumab group, 15.3%, than in the no alemtuzumab group, 41.7% (P=0.0001). The incidence of delayed graft function was lower in the alemtuzumab group, 9.7%, than in the no alemtuzumab group, 25.0% (P=0.003). The incidence of viral complications was comparable. CONCLUSION: Alemtuzumab induction with simple resumption of baseline immunosuppression in patients undergoing kidney transplantation after nonrenal transplantation represents a reasonable immunosuppressive strategy.

Neutrophilic tubulitis as a marker for urinary tract infection in renal allograft biopsies with C4d deposition.

BACKGROUND: Neutrophilic tubulitis accompanied by intratubular neutrophil clusters in the renal allograft is a surrogate marker for urinary tract infection (UTI). Overlapping histologic findings can occur in antibody-mediated rejection, which is characterized by peritubular capillary (PTC) deposition of C4d. This study evaluated the incidence of UTI in biopsies with concurrent neutrophilic tubulitis and PTC C4d staining. METHODS: Thirty-three allograft biopsies from 27 patients selected for the presence of simultaneous C4d staining and neutrophilic tubulitis were correlated with urine culture (U/C) results. RESULTS: U/C obtained on the same day as the biopsy confirmed UTI in 13 of 33 (39%) biopsies. Among 20 patients with negative U/C; prior culture results within 10 days of the biopsy were available for nine patients, and 5 of 9 (55%) were positive. Thus, UTI was confirmed in 18 of 33 (54%) biopsies. Biopsy interpretation and clinical management was confounded by changes of concurrent acute cellular rejection and antibody-mediated rejection confirmed by demonstration of donor-specific antibodies. Combined therapy with antibiotics and antirejection medications (ART) was administered to 12 of 18 (67%) patients. CONCLUSIONS: Neutrophilic tubulitis accompanied by neutrophil clusters in the tubular lumen is a useful marker of UTI, even in the presence of PTC C4d deposition. Therapeutic response to antibiotics is limited by co-existent T-cell or antibody-mediated rejection and underlying chronic allograft nephropathy.

Kidney transplantation in elderly people: the influence of recipient comorbidity and living kidney donors.

OBJECTIVES: To examine the extent to which donor and recipient characteristics were associated with transplant outcomes in elderly kidney transplant recipients. DESIGN: Retrospective review. SETTING: Single university center. PARTICIPANTS: One thousand one hundred two patients, including 266 patients aged 60 and older. MEASUREMENTS: Recipient and donor characteristics and patient and graft outcomes. RESULTS: Of the 1,102 patients included in this study, 266 (25%) were aged 60 and older, and 117 (11%) were aged 67 and older. According to Cox proportional hazards analysis, patient survival was worse in elderly recipients, although the survival outcome in the oldest group (ages 68-86) was comparable with that in their slightly younger peers (ages 61-67). Graft function did not differ according to age. Comorbidity was a significant predictor of patient survival in elderly recipients (hazard ratio (HR)=1.17, 95% confidence interval (CI)=1.03-1.34, P=.02) but not in the subset of elderly recipients of living donor kidneys (HR=1.01, 95% CI=0.8-1.3, P=.9). CONCLUSION: Older adults can achieve good outcomes with kidney transplantation, although in recipients with significant comorbid illness, careful donor selection and selective use of living donors may be vital to achieving good outcomes.

Acute changes in renal function after laparoscopic gastric surgery for morbid obesity.

BACKGROUND: Acute renal failure (ARF) is a serious complication that contributes to patient morbidity and may result in death. To date, no data are available regarding the predictive risk of ARF or its effect on the outcome of patients who undergo laparoscopic gastric bypass. METHODS: The medical records of 1800 patients who underwent gastric bypass from July 1997 to July 2003 at a single institution were analyzed. The data collected included demographics, comorbid factors, operative details, and postoperative outcomes. Multivariant analysis was performed and the results were compared with those of 500 age-, gender-, and comorbidity-matched control patients who underwent similar operations. RESULTS: The mean age was 50 +/- 8 years; 23 were men and 19 were women. Of the 1800 patients, 42 (2.3%) developed ARF after surgery. Dialysis was required in 6 patients, 2 of whom became dialysis dependent. ARF completely resolved in the remaining patients. CONCLUSION: Primary ARF after laparoscopic gastric bypass is an uncommon complication, with an incidence of 2.3% in our institution. Patients with a body mass index >50, previous chronic renal failure, and long operating times and intraoperative hypotension are at the greatest risk of postoperative renal failure. All patients who had normal renal function preoperatively returned to normal renal function within 6 months.

Transplantation: polyomavirus nephropathy and the risk of specific immunosuppression regimens.

BK virus is ubiquitously present in the latent state in humans, and awareness of the importance of BK polyomavirus is emerging among the kidney transplant community. First discovered in 1971 in the urine of a renal transplant recipient, BK virus nephropathy (BKVN) has come to be recognized as a significant cause of genitourinary disease and potential graft loss in the kidney transplant patient. In this review, we discuss the risk factors, available methods of diagnosis and therapeutic monitoring, and current approaches to therapy of BKVN.

Comorbid conditions in kidney transplantation: association with graft and patient survival.

Although the impact of comorbidity on outcomes in ESRD has been evaluated extensively, its contribution after kidney transplantation has not been well studied. It is believed that comorbidity assessment is critical to the informed interpretation of kidney transplant outcomes. In this study, the Charlson Comorbidity Index was used to assess the comorbid conditions of 715 patients who underwent kidney transplantation at the Starzl Transplant Institute between January 1998 and January 2003. The impact of pretransplantation comorbidity on the development of acute cellular rejection after transplantation and on patient and graft survival was examined. The most common comorbid conditions among our patient population were diabetes (n = 217, 30.3%) and heart failure (n = 85, 11.9%). It was found the number of patients with high comorbidity at the Starzl Transplant Institute has increased significantly over time (P = 0.04). In multivariate adjusted models, high comorbidity was associated with an increased risk for patient death, both in the perioperative period (hazard ratio 3.20, 95% confidence interval 1.32 to 7.78; P = 0.01) and >3 mo after transplantation (hazard ratio 2.63; 95% confidence interval 1.62 to 4.28; P < 0.001). The Charlson Comorbidity Index is a practical tool for the evaluation of comorbidity in the transplant population, which has an increasing burden of comorbid disease. Increased comorbidity affects both perioperative and long-term patient outcomes and carries significant implications not only for the development of individual patient therapeutic strategies but also for the interpretation of patient trials and the development of policies that govern distribution of donor organs.

Steroid-free lymphocyte depletion protocols. The potential for partial tolerance?

Induction of tolerance has been a longstanding goal in transplantation. Recent preliminary studies using a steroid-free lymphocyte depletion strategy have been met with great excitement and an equal degree of skepticism. Current studies in this area suggest that immunosuppression can be reduced substantially but acute rejection develops at a rate approximately twice that of standard triple drug protocols. None of the lymphocyte-depleting protocols has resulted in full tolerance as evidenced by patients attaining a maintenance drug-free state. Workers in the field have suggested that a degree of tolerance is achieved and they have coined a growing number of terms to describe this state: prope tolerance, metastable tolerance, and partial tolerance. To date, patient follow-up has been relatively short leaving many unanswered questions about graft survival, chronic allograft nephropathy, and the minimally effective maintenance immunosuppression. Despite these limitations, steroid-free lymphocyte depletion may offer an exciting new treatment paradigm.

Living-related donor renal transplantation in HIV+ recipients using alemtuzumab preconditioning and steroid-free tacrolimus monotherapy: a single center preliminary experience.

BACKGROUND: End-stage renal disease (ESRD) is an increasing problem in patients infected with the human immunodeficiency virus (HIV). The use of highly active antiretroviral therapy (HAART) has decreased the morbidity associated with HIV and has prompted renewed interest in renal transplantation. METHODS: We performed four cases of deceased donor renal transplantation in HIV+ recipients and three cases where laparoscopic live donor nephrectomy (LLDN) was utilized to obtain the kidney for transplantation into living-related HIV+ recipients. In the four deceased donor cases, conventional tacrolimus-based immunosuppression, without antibody induction was used. In the three living-related cases, the immunosuppressive regimen was based on two principles: recipient pretreatment and minimal posttransplant immunosuppression. Alemtuzumab 30 mg (Campath 1-H) was used for preconditioning followed by low-dose tacrolimus monotherapy. RESULTS: Of the four deceased donor cases, one patient continues to have good graft function, and another is not yet on dialysis but has significant graft dysfunction. Rejection was observed in three patients (75%). Infectious complications occurred in one patient (25%), all non-acquired immunodeficiency syndrome (AIDs) defining. In the three living-related cases, all had good graft function, and none have experienced acute rejection. HIV viral loads remain undetectable. CD4 counts are slowly recovering. No infectious or surgical complications occurred. There were no deaths in either group. CONCLUSIONS: These data suggest that living-related donor renal transplantation with steroid-free tacrolimus monotherapy in a "tolerogenic" regimen can be efficacious. However, long-term follow-up is needed to confirm this observation.

Drug therapy in transplant recipients: special considerations in the elderly with comorbid conditions.

Elderly patients with end-stage organ failure are now more frequently undergoing transplantation. Medication management in this population is challenging because of the combination of multiple comorbidities, polypharmacy, and immunological, pharmacokinetic and pharmacodynamic changes attributable to the aging process. Immunosuppressive medications can exacerbate pre-existing medical conditions and promote the development of disease processes. Cardiovascular disorders, such as hypertension, coronary artery disease, congestive heart failure and arrhythmias are common in elderly transplant recipients, and account for most of the deaths in this population. Blood pressure, blood glucose and cholesterol control is of particular concern because elderly transplant recipients frequently have or develop these complications. Elderly transplant recipients are commonly receiving anticoagulation therapy with warfarin and are at a higher risk of bleeding, especially if they have renal dysfunction. Infectious complications occur frequently in the transplanted population, with pneumonia being the most common infection seen in hospitalised patients. Attention to vaccination for the prevention of influenza and pneumococcal infections is important because of the increased risk of these diseases in this population. Depression itself has been associated with decreased survival in older individuals, and depression in elderly transplant recipients may be reversible with the administration of pharmacological agents. Effective long-term care of transplant recipients demands an understanding of how particular medications affect clinical evaluation and treatment. This article addresses some of the practical issues surrounding medication management and prevention of these particular problems in elderly transplant recipients.

Labetalol-induced hyperkalemia in renal transplant recipients.

BACKGROUND: Labetalol is a commonly used agent for perioperative hypertension in renal transplant recipients. A previous report suggested that labetalol may cause life-threatening hyperkalemia after renal transplantation. METHODS: We performed a retrospective review of 103 consecutive renal transplants to determine whether labetalol was an independent predictor of hyperkalemia treatment. Thirty-eight patients (36.9%) received labetalol, and 65 patients (63.1%) had no labetalol medication. RESULTS: Of the 103 patients, 24 (23.3%) required treatment for hyperkalemia. Thirteen (34.2%) of the patients who had labetolol medication and 11 (16.9%) of the patients who did not receive labetalol were treated for hyperkalemia (p = 0.045). Factors considered for a logistic regression model included: the use of labetalol, cold ischemia time, diabetes, and dialysis method; intake of tacrolimus, beta blockers, angiotensin-converting enzyme inhibitors, or other antihypertensives prior to admission; the mannitol dose given intraoperatively, and the 24-hour urine output postoperatively. Intravenous labetalol (odds ratio OR = 4.52, confidence interval CI = 1.33-15.28; p = 0.02), 24- hour urine output (OR = 4.4, CI = 0.97-20.1: p = 0.47), increasing cold ischemia time (OR = 1.09, CI = 1.01-1.17; p = 0.02), and continuous ambulatory peritoneal dialysis (OR = 0.17, CI = 0.29-0.98; p = 0.036) were independent predictors. CONCLUSION: Labetalol appears to increase the risk of hyperkalemia in patients after renal transplantation.

Evaluation of renal function in transplant patients on tacrolimus therapy.

Glomerular filtration rate (GFR), as measured by 24-hour creatinine clearance and clearance of iothalamate, and effective renal plasma flow (ERPF), as measured by the clearance of para-aminohippuric acid (PAH), were evaluated at 2 weeks, 1 month, and 3 months after transplantation in 8 renal transplant patients and at 1 month and 1 year after transplantation in 9 liver transplant patients receiving tacrolimus (Prograf) therapy. In renal transplant patients, there was a significant increase in GFR after transplantation. There was no change in GFR at 1 and 3 months as compared to 2 weeks after transplantation, while ERPF (ml/min/1.73 m2) was lower (p < 0.05) at 3 months (212+/-42) compared to 1 month (306+/-118) after transplantation. In liver transplant patients, GFR and ERPF were below normal despite normal serum creatinine concentrations, but there was no difference in GFR or ERPF at 1 month and 1 year after transplantation. Although below normal, renal function was well preserved in transplant patients while receiving chronic tacrolimus therapy over the study period. Dosage alterations ofrenally eliminated drugs may be required for drugs with a narrow therapeutic index.

Hemorrhagic complications of enoxaparin and aspirin in patients with kidney transplants.

STUDY OBJECTIVE: To evaluate the frequency of early posttransplant hemorrhagic complications in patients with kidney and kidney-pancreas transplants who received thromboprophylaxis with enoxaparin and aspirin. DESIGN: Retrospective chart review. SETTING: University-based tertiary care center. PATIENTS: Thirteen patients who had received enoxaparin within 10 days of kidney or kidney-pancreas transplantation. INTERVENTION: Medical records were reviewed, and data from patients who had received low-dose aspirin 81 mg once/day and enoxaparin within 10 days of transplantation were collected. MEASUREMENTS AND MAIN RESULTS: Major bleeding events were defined as intracranial or retroperitoneal bleeding, or a decrease in hemoglobin of greater than 2 g/dl that was confirmed on repeat evaluation. Nine (69%) of the 13 patients had confirmed major bleeding events and required blood transfusions. Six of the nine patients had elevated serum creatinine levels. CONCLUSION: The combination of enoxaparin and low-dose aspirin early after kidney or kidney-pancreas transplantation was associated with a high frequency of hemorrhagic events. Further evaluation is needed to determine the safety of enoxaparin in combination with aspirin after transplantation.