The Influence of Antithymocyte Globulin Dose on the Incidence of CMV Infection in High-risk Kidney Transplant Recipients Without Pharmacological Prophylaxis.

BACKGROUND: Optimizing antithymocyte globulin (ATG) dosage is critical, particularly for high-risk kidney transplant (KT) recipients without cytomegalovirus (CMV) prophylaxis. METHODS: We studied 630 KT recipients with expanded criteria donors or panel reactive antibody ≥50% at Hospital do Rim, Brazil (January 1, 2013 to May 21, 2015) to determine whether a single ATG dose was safe and effective in patients without CMV prophylaxis. Patients received ≥4 doses (1-1.5 mg/kg/per dose) until June 17, 2014, when the induction protocol changed to a single ATG dose (3 mg/kg). We used Cox regression to compare the risk of CMV infection and acute rejection (AR) among KT recipients by ATG dose. RESULTS: Adjusting for clinical and transplant factors, a single ATG dose was associated with a lower risk of CMV infection (adjusted hazard ratio [aHR]: 0.63; 95% confidence interval [CI], 0.42-0.93; P = 0.02) and a similar risk of AR (aHR: 1.16; 95% CI, 0.47-2.83; P = 0.8), compared to multiple doses. We found no differences in death-censored graft loss (5.0% versus 4.8%, aHR: 1.06; 95% CI, 0.51-2.23; P = 0.9) or mortality (4.7% versus 3.4%; aHR: 1.42; 95% CI, 0.62-3.24; P = 0.4) at 1-year post-KT by ATG dose. CONCLUSIONS: In our study of high-risk KT recipients without CMV prophylaxis, a single ATG dose decreased the risk of CMV infection without increasing the risk of AR or compromising graft or patient survival.

Clinical features and outcomes of kidney transplant recipients with focal segmental glomerulosclerosis recurrence.

AIM: Focal segmental glomerulosclerosis recurs in up to 30% and up to 80% of adult and pediatric kidney transplant recipients, respectively. There is no standard of care treatment. The purpose of this study was to evaluate clinical characteristics, treatments and outcomes of patients with focal segmental glomerulosclerosis recurrence (FSGSr). METHODS: This was a retrospective single-center cohort study including FSGSr patients treated with plasmapheresis (PP) and combinations of high dose steroids, cyclosporine and rituximab. RESULTS: Among 61 patients included in this analysis the median time to diagnosis was 19 days. The incidence of first biopsy-confirmed FSGSr was 18% reaching 52.4% with follow-up biopsies. During PP treatment 54% of the patients developed infectious complications. PP was discontinued in 37% of patients due to treatment failure (no remission or graft loss) and in 26% due to an adverse event. All patients who discontinued PP due to adverse event did not show clinical response or lost the allograft. The incidence of acute rejection was 34.4%. The incidences of partial and complete remissions were 16.4% and 27.8%, respectively. Overall 6-years patient and graft survivals were 90.7% and 64.5%, respectively. CONCLUSION: This analysis confirms the low, variable and unpredictable rate of FSGSr remission, inconsistencies among available therapeutic options and its high rate of adverse events, and the negative impact on graft survival.

Limitations of the interpretation and extrapolation of clinical trial data in kidney transplant recipients.

OBJECTIVE: The risks and benefits of the participation of kidney transplant recipients in randomized clinical trials (RCTs) investigating new immunosuppressive therapies are unknown. DESIGN AND SETTING: We included patients from 12 prospective phase II/III RCTs randomized to the experimental (G1, n=319) or standard-of-care internal control group (G2, n=118). We constructed two additional external control groups with (G3, n=319) or without (G4, n=319) matching inclusion/exclusion criteria based on transplant date. The primary outcome analysis was the composite clinical efficacy failure, defined as biopsy-proven acute rejection (BPAR), graft loss, death, or loss to follow-up 12 months after kidney transplantation. RESULTS: Survival free of composite clinical efficacy failure was higher among participants in RCT, without difference between experimental or standard-of-care therapy (80∙3 vs 78∙0 vs 69∙9 vs 66∙1%, P<.001), respectively. Patient (98.1 vs 99.2 vs 96.9 vs 91.8 P<.001) and graft (94.0 vs 98.3 vs 90.9 vs 82.4) survivals were also higher in G1 compared to G4, but no differences in survival free of BPAR were observed (85.3 vs 78.8 vs 82.8 vs 81.2 P>.05), respectively. CONCLUSION: These findings suggested that new treatments investigated in kidney transplant recipients are not associated with detectable harm compared to standard of care.

Expanding the use of expanded criteria donors in kidney transplantation.

PURPOSE: Although the use of kidney allografts from expanded criteria donors (ECD) has increased in recent years, the reported discard rates are also growing. The influence of ECD characteristics on transplant outcomes is still underevaluated. METHODS: This retrospective study investigated the influence of preimplantation biopsy findings and delayed graft function (DGF) on patient and graft survivals and renal function at 36 months in a cohort of 372 ECD kidney transplant recipients. RESULTS: Patient and graft survivals were 91.6 and 68.9 %. The incidence of biopsy-proven acute rejection was 31 %. There were no differences in patient (88.6 vs. 91.1 vs. 94.7 vs. 78.6 %, p = 0.10) or graft (78.1 vs. 72.2 vs. 60.5 vs. 62.6 %, p = 0.14) survivals and renal function (41.7 ± 25.6 vs. 39.9 ± 29.9 vs. 38.1 ± 30.6 vs. 37.4 ± 29.2 mL/min, p = 0.79) comparing ECD kidneys with mild, moderate, and severe histological changes or with no preimplantation biopsy, respectively. However, severe scored transplants had the worst death-censored graft survival (OR 3.1, 95 % CI 1.4-6.9, p = 0.007). No significant differences in patient (86.2 vs. 83.4 %, p = 0.17) or graft (73.7 vs. 65.9 %, p = 0.06) survivals and renal function (38.9 ± 28.6 vs. 39.9 ± 28.4 mL/min, p = 0.72) were observed comparing patients with or without DGF. Multivariable analysis found diabetes history as the only independent risk factor for graft loss (OR 2.1, 95 % CI 1.3-3.3, p = 0.003) or patient death (OR 3.1, 95 % CI 1.5-5.8, p < 0.001). CONCLUSIONS: Within the limitations of sample size and short follow-up time, in this cohort of ECD kidney transplant recipients the severity of histological changes observed in preimplantation biopsies was independently associated with graft loss.