The use of semaglutide in patients with renal failure- a retrospective cohort study.

OBJECTIVE: Semaglutide, a glucagon-like peptide-1 receptor agonist is approved for weight loss and diabetes treatment, but limited literature exists regarding semaglutide use in patients with advanced chronic kidney disease (CKD). Therefore, this project assessed the safety and efficacy of semaglutide among patients with eGFR (estimated glomerular filtration rate) 15-29 mL/min/1.73m2 (CKD stage 4), eGFR<15 mL/min/1.73m2 (CKD stage 5) or on dialysis. METHODS: This is a retrospective Electronic Medical Record based analysis of consecutive patients with advanced CKD (defined as CKD 4 or greater) who were started on semaglutide (injectable or oral). Data was collected between Jan 2018 and Jan 2023. Investigators verified CKD diagnosis and manually extracted data. Data were analyzed using Fisher's exact test, paired T-test, linear mixed effects models and Wilcoxon signed rank test. RESULTS: Seventy-six patients with CKD 4 or greater who initiated semaglutide were included. Most patients had a history of T2DM (96.0%), and most were male (53.9%). The mean age was 66.8 y (SD 11.5) with the mean BMI was 36.2 (SD 7.5). The initial doses were 3 mg orally and 0.25 mg by injection. Maximum prescribed dose was 1mg (injectable) in 28 (45.2%) patients and 14 mg (orally) in 2 (14.2%) patients. Patients received semaglutide for a median duration of 17.4 (IQR 0.43, 48.8) months. Forty-eight (63.1%) patients reported no adverse effects associated with the therapy. Mean weight decreased from 106.2(SD 24.2) to 101.3 (SD 27.3) kg (p<0.001). Eight patients (16%) with type 2 diabetes (T2DM) discontinued insulin after starting semaglutide. Mean HbA1c decreased from 8.0 % (SD 1.7) to 7.1 % (SD 1.3) (p<0.001). Adverse effects were the primary reason for semaglutide discontinuation (37.0%), with nausea, vomiting, and abdominal pain being the most common complaints. CONCLUSIONS: Based on this retrospective study semaglutide appears to be tolerated by most individuals with CKD 4 or greater despite associated gastrointestinal side effects similar to those observed in patients with better kidney function and leads to an improvement of glycemic control and insulin discontinuation in patients with T2DM. Modest weight loss (approximately 4.6 % of the total body weight) was observed on the prescribed doses. Larger prospective randomized studies are needed to comprehensively assess the risks and benefits of semaglutide in patients with CKD 4 or greater and obesity.

Impact of Perioperative Prophylaxis With Enterococcus Activity on Risk of Surgical-Site Infection After Pancreas Transplantation.

Surgical-site infection (SSI) is the most common early infectious complication after pancreas transplantation (PT). Although SSI has been shown to worsen outcomes, little data exist to guide optimal choices in perioperative prophylaxis. Methods: We performed a retrospective cohort study of PT recipients from 2010-2020 to examine the effect of perioperative antibiotic prophylaxis with Enterococcus coverage. Enterococcus coverage included antibiotics that would be active for penicillin-susceptible Enterococcus isolates. The primary outcome was SSI within 30 d of transplantation, and secondary outcomes were Clostridioides difficile infection (CDI) and a composite of pancreas allograft failure or death. Outcomes were analyzed by multivariable Cox regression. Results: Of 477 PT recipients, 217 (45.5%) received perioperative prophylaxis with Enterococcus coverage. Eighty-seven recipients (18.2%) developed an SSI after a median of 15 d from transplantation. In multivariable Cox regression analysis, perioperative Enterococcus prophylaxis was associated with reduced risk of SSI (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.35-0.96; P = 0.034). Anastomotic leak was also significantly associated with elevated risk of SSI (HR 13.95; 95% CI, 8.72-22.32; P < 0.001). Overall, 90-d CDI was 7.4%, with no difference between prophylaxis groups (P = 0.680). SSI was associated with pancreas allograft failure or death, even after adjusting for clinical factors (HR 1.94; 95% CI, 1.16-3.23; P = 0.011). Conclusions: Perioperative prophylaxis with Enterococcus coverage was associated with reduced risk of 30-d SSI but did not seem to influence risk of 90-d CDI after PT. This difference may be because of the use of beta-lactam/beta-lactamase inhibitor combinations, which provide better activity against enteric organisms such as Enterococcus and anaerobes compared with cephalosporin. Risk of SSI was also related to anastomotic leak from surgery, and SSI itself was associated with subsequent risk of a poor outcome. Measures to mitigate or prevent early complications are warranted.

Pharmacogenomics and beyond! Customized pharmacotherapy for solid organ transplant recipients.

Solid organ transplant recipients are reliant on immunosuppressive drugs, which have a narrow therapeutic index, and are concurrently vulnerable to adverse drug events due to comorbidity burden and the complexity of their medication regimens. Urgent management of post-transplant complications often falls to the generalist clinician or critical care specialist. The purpose of this narrative review is to discuss innovations and bedside applications of pharmacogenomics and therapeutic drug monitoring applied to immunosuppression and agents frequently encountered in transplant recipients. Medication formulations will be given specific attention, as interchange is frequently required in the acute care setting. Bioassays quantifying immune system activity will be described with practical applications. A structured approach to addressing drug-drug, drug-gene, and drug-drug-gene interactions will be modeled using a case-based approach synthesizing pharmacogenomics, therapeutic drug monitoring, pharmacokinetics, and pharmacodynamic principles.

Sodium-glucose cotransporter 2 inhibitors for treatment of diabetes mellitus after kidney transplantation.

INTRODUCTION: Diabetes mellitus in kidney transplant recipients is a risk factor for cardiovascular events and premature death. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly used in nontransplant populations to improve diabetes control and cardiovascular and renal benefits. Limited literature exists regarding the safety and efficacy of these agents in renal transplant recipients. METHODS: We retrospectively reviewed all kidney transplant recipients within our health system who were prescribed a SGLT2i after transplantation for diabetes. The safety, tolerability, and effectiveness of SGLT2i were analyzed. RESULTS: Thirty-nine kidney transplant recipients were initiated on SGLT2i therapy, twenty-seven of which remained on therapy for at least 1 year. Ten (25%) patients experienced an adverse event while on a SGLT2i, with urinary tract infections (UTI) being the most common. Seventeen patients (43%) discontinued the SGLT2i at the time of chart review, most commonly due to cost and kidney function decline. The median [IQR] hemoglobin A1c (HbA1c) at SGLT2i initiation of 8.4% [7.8-9.2] decreased to 7.5% [6.8-8.0%] after 3 months and 7.5% [6.5-7.9] after 12 months. No meaningful change in kidney function or tacrolimus exposure was observed. CONCLUSION: SGLT2i may be a safe and effective treatment for diabetes in kidney transplant recipients. Cost is a barrier to SGLT2i therapy, and UTIs were the most frequently encountered adverse events in this cohort. More studies are needed to understand the safety profile and determine the effect of SGLT2i on diabetes-related comorbidities among kidney transplant recipients.

Evaluating anticoagulation sensitivity among elderly patients managed with an institution's heparin protocol using initial anti-factor Xa levels.

PURPOSE: The purpose of this study was to assess an institution's heparin protocols in elderly and nonelderly adult populations to see if a response difference was observed. METHODS: This was a retrospective cohort study of hospitalized adults who were prescribed unfractionated heparin due to surgery, acute coronary syndrome (ACS), or deep vein thrombosis/pulmonary embolism (DVT/PE) from February 11, 2016, through August 1, 2017. Patients were divided into nonelderly adults 18 to 69 years of age and elderly patients 70 years of age or older. The anti-factor Xa (anti-Xa) level after protocol initiation was compared to the institution's goal range of 0.3 to 0.7 IU/mL. Outcomes of each protocol in the elderly population were compared to outcomes in their nonelderly counterparts to determine if there was a difference in heparin response. RESULTS: A total of 325 patients were included in the analysis, comprising 150 elderly and 175 nonelderly adults. Elderly patients had a higher initial anti-Xa levels than did their nonelderly adult counterparts in the ACS, DVT/PE, and surgery protocols, with P values of 0.02, <0.001, and 0.01, respectively. Only the ACS protocol demonstrated increased frequency of above-target-level anti-Xa levels in the elderly (P = 0.03). CONCLUSION: Elderly patients had significantly higher initial anti-Xa levels than did nonelderly adult patients across all protocols. This study identifies the need to further study elderly patients' increased heparin sensitivity to determine if a separate dosing protocol is needed.