Impact of Cumulative 6†mg/kg Antithymocyte Globulin on Early Posttransplant Outcomes in Kidney Transplant Recipients with Delayed Graft Function.

Introduction: Delayed graft function in kidney transplant is associated with an increased risk of rejection and graft loss. Use of rabbit antithymocyte globulin induction in delayed graft function has been correlated with less rejection compared to basiliximab, but optimal dosing remains unknown. Program Evaluation Aims: The purpose of this evaluation was to retrospectively assess the short-term effectiveness and tolerability of a clinical protocol that increased the net state of immunosuppression in delayed graft function kidney transplant recipients using cumulative 6 mg/kg rabbit antithymocyte globulin induction. Design: This retrospective cohort included 88 kidney transplant recipients with delayed graft function, transplanted between January 2017 and March 2021, who either received cumulative 4.5 mg/kg pre-protocol or 6 mg/kg post-protocol rabbit antithymocyte globulin. Outcomes evaluated were biopsy-proven acute rejection and incidence of graft loss, infection, and cytopenia at 6 months. Results: A significant reduction of biopsy-proven acute rejection incidence occurred post-protocol implementation (10/33, 30.3% vs 6/55, 10.9%; P = .04). Of those with rejection, significantly less post-protocol patients were classified as acute cellular rejection (9/10, 90.0% vs 2/6, 33.3%; P = .04). No death-censored graft loss was observed in either group. Rates of cytopenia and infection were similar pre- versus post-protocol implementation. Conclusion: Increasing the exposure to rabbit antithymocyte globulin and maintenance immunosuppression in delayed graft function kidney transplant recipients was tolerable and significantly reduced rejection occurrence at 6 months.

Safety and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Solid Organ Transplant Recipients.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may be effective in reducing body weight and hemoglobin A1c (HbA1c) post-kidney transplantation. Limited literature exists on use of these agents outside of kidney transplant. The purpose of this program evaluation was to evaluate the safety and efficacy of SGLT2i in kidney, liver, and lung transplant recipients. Methods: This was a retrospective program evaluation of adult kidney, liver, and lung transplant recipients between August 31, 2016 and July 31, 2021. Patients initiated on SGLT2i for diabetes for a minimum of 90 days with at least 1 follow-up appointment were screened for inclusion. Outcomes were compared between SGLT2i initiation to nadir values 3-12-months post-initiation. Outcomes included change in hemoglobin A1c, fasting blood glucose, actual body weight, and body mass index. Safety outcomes included adverse effects, cardiovascular events, death-censored graft loss, and all-cause mortality. Results: Forty-nine patients met inclusion criteria, (26 liver, 18 kidney, 4 lung, and 1 simultaneous liver-kidney recipient). The median time from transplant to SGLT2i initiation was 1216 days (IQR 524-2256). Glycemic and weight loss outcomes showed a statistically significant benefit from SGLT2i use. Total safety outcome incidence was minimal at 12 months. No patient experienced myocardial infarctions, graft loss, or mortality at 3-12 months. One incidence of urinary tract infection and stroke occurred each. The most common adverse effects included hypotension and hypoglycemia. Conclusion: This program evaluation demonstrated that SGLT2i can be used safely in solid organ transplant recipients. These agents can provide an additional non-insulin agent for post-transplant diabetes mellitus management in solid organ transplant.

Single-center Evaluation of Safety & Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Solid Organ Transplantation.

Introduction: Given the negative outcomes associated with uncontrolled diabetes mellitus, non-insulin therapies with glycemic, cardiovascular, and weight-loss benefits in the general population, such as the glucagonlike peptide-1 receptor agonists (GLP1-RA) have become a more alluring therapeutic option in transplant populations. However, limited evidence exists to demonstrate its safety and efficacy in solid organ transplant. Methods: This program evaluation included adult kidney, liver, lung transplant recipients initiated on a GLP1-RA for diabetes mellitus management for a minimum of 3 months, had at least one follow-up visit after starting therapy, and had at least one hemoglobin A1c (HbA1c) level drawn between 3-12 months after GLP1-RA initiation. Outcomes were assessed at time of initiation of GLP1-RA (baseline) and 3-12 months post-initiation. Nadir values between 3-12 months were utilized to assess outcomes. Results: One-hundred eighteen patients met study inclusion criteria. Seventy-percent of patients received a kidney transplant, 19.5% received a liver transplant, and 6.8% received a lung transplant. A statistically significant difference was observed in median fasting blood glucose and HbA1c at baseline to 3-12-month nadir (P < 0.0001). A significant weight loss benefit was also observed. The rate of adverse drug reactions was low. Seven-percent of patients experienced nausea, 4.2% developed pancreatitis, and 7.1% reported having had at least one hypoglycemic event. Discussion: This is the largest study evaluating GLP1-RA in organ transplantation and demonstrates GLP1-RA is both safe and effective. Further assessment on long-term use of these agents on cardiovascular and renal outcomes is still needed.

Methenamine for Recurrent Urinary Tract Infections in Solid Organ Transplantation.

INTRODUCTION: Recurrent urinary tract infections remain a challenge in solid organ transplant and have a negative impact on morbidity/mortality. PROJECT AIM: The purpose of this program evaluation was to determine the impact of methenamine on recurrent urinary tract infection in kidney and liver-kidney transplant recipients. DESIGN: This retrospective review included patients > 18 years of age who received a kidney or liver-kidney transplant. Patients were divided into the following groups: (1) Methenamine therapy initiation received methenamine for ≥ 180 days or (2) Non-methenamine therapy: did not receive recurrent urinary tract infection prophylaxis. A total of 60 patients were included. RESULTS: When comparing outcomes between methenamine therapy initiation and non-methenamine therapy group, a significant reduction in the rate of recurrent urinary tract infection was reported in the methenamine therapy initiation group (0.6 vs 1.3 per 180 patient days follow-up, P = 0.0005). A significant reduction was also noted with rate of asymptomatic bacteriuria, treatment failures, bacteremia, hospitalizations due to recurrent urinary tract infection, multi-drug resistant organism isolated, and the average duration of antibiotic use. A significant difference in the time to failure of methenamine therapy initiation versus non-methenamine therapy is noted up to 180 patient-days follow-up (RR 1.56, P = 0.0019). CONCLUSION: This evaluation supported methenamine therapy for recurrent urinary tract infection in kidney and liver-kidney transplant. The most significant impact of methenamine recurrent urinary tract infection was seen in the first 30 days after initiation.

Pediatric en bloc kidney transplantation to adult recipients: more than suboptimal?

BACKGROUND: To optimize available organs, kidneys from young donors traditionally believed to be suboptimal are transplanted to adults. The purpose of this study is to compare graft survival (GS) of en bloc kidney (EBK) from young pediatric donors to other deceased donor transplants in adult recipients. METHODS: We analyzed United Network of Organ Sharing/STAR data on primary deceased donor kidney transplants to adult recipients (1988-2006). EBK (age younger than 5 years, n=1696) was compared with solitary pediatric (SP; age younger than 5 years) kidneys (n=1502), and matched standard adult donors (age 18-59 years, n=9594) and expanded criteria donor (ECD; n=6396). The adjusted GS was obtained using Cox proportional hazard model and hazard ratios were calculated. RESULTS: EBK had lowest acute rejection rates (6.0%) but similar to standard adult transplants (6.3%), and lower than SP and ECD (9.0% and 8.2%; P<0.0001). Delayed graft function rates were lowest in EBK (17.9%), highest in ECD (34.8%; P<0.0001), and similar among SP and standard adult transplants (24.4% and 24.2%). The estimated glomerular filtration rate (eGFR) was best in EBK and worst in ECD (P<0.0001). The eGFR of EBK and SP transplants continuously improved but the eGFR of standard adult and ECD declined. Graft loss was higher in EBK and SP transplants than adult donor transplants during the first 6 months. Despite the highest thrombosis rates in EBK (5.0%) (SP, 3.3%; standard adult, 1.8%; ECD, 2.0%, P<0.0001), GS of EBK became similar to standard adult donor transplants by 5 years and best at 10 years posttransplant (64.0%) and worst in ECD (39.6%; P<0.0001). CONCLUSION: EBK had the best long-term outcomes among deceased donor transplants and offer unique options for adult kidney transplant recipients.

Lower gastrointestinal bleeding: association with Sevelamer use.

Stercoral ulceration results from impaction of hard fecal mass on the colonic wall and is a relatively unknown cause of lower gastrointestinal bleeding. In this report, we describe a case of lower gastrointestinal bleeding due to stercoral ulceration resulting from Sevelamer, a drug which is commonly associated with constipation.

Hans Gunther and his disease.

Congenital erythropoietic porphyria (Gunther's disease) is one of the least common porphyrias. This article describes the life and career of Hans Gunther (after whom the disease is named), his contributions to the field of porphyrias and the current understanding of Gunther's disease.