Nagaraju Sarabu

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.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.

HLA-DQ Mismatching: Mounting Evidence for a Role in Kidney Transplant Rejection

The HLA system consists of a group of cell surface proteins encoded for by genes located on the short arm of chromosome 6. Since the discovery of this system in the 1950s, it has become clear that HLA molecules play an important role in controlling immune responses generated by the interaction of

Utility of Mammography for Chronic Kidney Disease Patients Undergoing Kidney Transplant Evaluation

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.

Racial disparity in kidney transplant survival relates to late rejection and is independent of steroid withdrawal

Black kidney transplant recipients have more acute rejection (AR) and inferior graft survival. We sought to determine whether early steroid withdrawal (ESW) had an impact on AR and death‐censored graft loss (DCGL) in blacks. From 2006 to 2012, AR and graft survival were analyzed in 483 kidney recipients (208 black and 275 non‐black). Rates of ESW were similar between blacks (65%) and non‐blacks (67%). AR was defined as early (≤3 months) or late (>3 months). The impact of black race, early AR, and late AR on death‐censored graft failure was analyzed using univariate and multivariate Cox models. Blacks had greater dialysis vintage, more deceased donor transplants, and less HLA matching, yet rates of early AR were comparable between blacks and non‐blacks. However, black race was a risk factor for late AR (HR: 3.48 (95% CI: 1.87‐6.47)) Blacks had a greater rate of DCGL, partially driven by late AR (HR with late AR: 5.6; 95% CI: 3.3‐9.3). ESW had no significant interaction with black race for risk of early AR, late AR, or DCGL. Independent of ESW, black kidney recipients had a higher rate of late AR after kidney transplantation. Late AR was highly predictive of DCGL and contributed to inferior graft survival in blacks.

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.

Introduction to Solid Organ Transplantation

This chapter reviews history of solid organ transplantation including the mechanisms of rejection with respect to T and B cells and provides a brief overview of medications used to prevent and treat rejection. It also reviews outcomes of renal, liver, heart, lung, pancreas, and small bowel transplantation.