Tacrolimus extended-release tablets have been Food and Drug Administration-approved for use in the de novo kidney transplant population. Dosing requi rements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression. Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus, but this has not been established for tacrolimus extended-release tablets in the de novo setting.

To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.

Single-arm, prospective, single-center, open-label, observational study (ClinicalTrials.gov: NCT037 13645). Life cycle pharma tacrolimus (LCPT) orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight. If weight is more than 120% of ideal body weight, an adjusted body weight was used. LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL. Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.

Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (6 d vs 13.5 d vs 4.5 d; P = 0.025). Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (16 mg vs 16 mg vs 12 mg; P = 0.010) (0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg; P = 0.018). CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers (7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL; P = 0 0.008). No differences were identified with regards to kidney graft function at 30-d post-transplant. Serious adverse events were reported for 13 (36%) patients.

Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacro limus to achieve target trough concentrations. We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.

Tacrolimus is known to exhibit significant inter- and intra-patient pharmacokinetic (PK) and pharmacodynamic (PD) variability regarding therapeutic response. LCP-tacrolimus (LCPT-Envarsus XR) was approved in 2018 for use as a de novo immunosuppressive agent in kidney transplants, but there is limited evidence to guide de novo dosing of LCPT in patients with obesity. The primary objective of this study was to evaluate the impact of different calculated weight-based de novo LCPT dosing on early transplant outcomes.

This was a retrospective study of patients with obesity (BMI ≥ 30 kg/m2 ) who received a kidney transplant at the University of Illinois Hospital and Health System (UIH), between March 2019 and March 2021. Subjects were included if were age 18 years or older and received de novo LCPT throughout index hospitalization. The primary endpoint of this study was to compare correlations between the first tacrolimus trough level and dosing weight strategy (e.g., TBW, AdjBW, IBW).

There was a statistically significant, though modest, correlation between all three dosing strategies and the first tacrolimus trough level (TBW correlation coefficient = .431, p < .001; AdjBW correlation coefficient = .455, p < .001; IBW correlation coefficient = .465; p < .001). In regression modeling for supratherapeutic levels each additional .01 mg/kg increase in dose by TBW, AdjBW, and IBW increased the odds of a supratherapeutic level by 1.46, 1.34, and 1.24, respectively (p < .001).

The use of LCPT in kidney transplant recipients with obesity dosed using TBW demonstrated the strongest correlation with initial supratherapeutic tacrolimus levels. Larger prospective studies are needed to investigate the further impact of body weight on dosing regimens in the obese population.

Obesity and chronic kidney disease (CKD) are highly prevalent worldwide and result in substantial health care costs. Obesity is a predictor of incident CKD and progression to kidney failure. Whether weight loss interventions are safe and effective to impact on disease progression and clinical outcomes, such as death remains unclear.

This review aimed to evaluate the safety and efficacy of intentional weight loss interventions in overweight and obese adults with CKD; including those with end-stage kidney disease (ESKD) being treated with dialysis, kidney transplantation, or supportive care.

We searched the Cochrane Kidney and Transplant Register of Studies up to 14 December 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Randomised controlled trials (RCTs) and quasi-RCTs of more than four weeks duration, reporting on intentional weight loss interventions, in individuals with any stage of CKD, designed to promote weight loss as one of their primary stated goals, in any health care setting.

Two authors independently assessed study eligibility and extracted data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess the certainty of evidence. We estimated treatment effects using random-effects meta-analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised mean difference (SMD) for continuous outcomes or in descriptive format when meta-analysis was not possible.

We included 17 RCTs enrolling 988 overweight or obese adults with CKD. The weight loss interventions and comparators across studies varied. We categorised comparisons into three groups: any weight loss intervention versus usual care or control; any weight loss intervention versus dietary intervention; and surgical intervention versus non-surgical intervention. Methodological quality was varied, with many studies providing insufficient information to accurately judge the risk of bias. Death (any cause), cardiovascular events, successful kidney transplantation, nutritional status, cost effectiveness and economic analysis were not measured in any of the included studies. Across all 17 studies many clinical parameters, patient-centred outcomes, and adverse events were not measured limiting comparisons for these outcomes. In studies comparing any weight loss intervention to usual care or control, weight loss interventions may lead to weight loss or reduction in body weight post intervention (6 studies, 180 participants: MD -3.69 kg, 95% CI -5.82 to -1.57; follow-up: 5 weeks to 12 months, very low-certainty evidence). In very low certainty evidence any weight loss intervention had uncertain effects on body mass index (BMI) (4 studies, 100 participants: MD -2.18 kg/m², 95% CI -4.90 to 0.54), waist circumference (2 studies, 53 participants: MD 0.68 cm, 95% CI -7.6 to 6.24), proteinuria (4 studies, 84 participants: 0.29 g/day, 95% CI -0.76 to 0.18), systolic (4 studies, 139 participants: -3.45 mmHg, 95% CI -9.99 to 3.09) and diastolic blood pressure (4 studies, 139 participants: -2.02 mmHg, 95% CI -3.79 to 0.24). Any weight loss intervention made little or no difference to total cholesterol, high density lipoprotein cholesterol, and inflammation, but may lower low density lipoprotein cholesterol. There was little or no difference between any weight loss interventions (lifestyle or pharmacological) compared to dietary-only weight loss interventions for weight loss, BMI, waist circumference, proteinuria, and systolic blood pressure, however diastolic blood pressure was probably reduced. Furthermore, studies comparing the efficacy of different types of dietary interventions failed to find a specific dietary intervention to be superior for weight loss or a reduction in BMI. Surgical interventions probably reduced body weight (1 study, 11 participants: MD -29.50 kg, 95% CI -36.4 to -23.35), BMI (2 studies, 17 participants: MD -10.43 kg/m², 95% CI -13.58 to -7.29), and waist circumference (MD -30.00 cm, 95% CI -39.93 to -20.07) when compared to non-surgical weight loss interventions after 12 months of follow-up. Proteinuria and blood pressure were not reported. All results across all comparators should be interpreted with caution due to the small number of studies, very low quality of evidence and heterogeneity across interventions and comparators.

All types of weight loss interventions had uncertain effects on death and cardiovascular events among overweight and obese adults with CKD as no studies reported these outcome measures. Non-surgical weight loss interventions (predominately lifestyle) appear to be an effective treatment to reduce body weight, and LDL cholesterol. Surgical interventions probably reduce body weight, waist circumference, and fat mass. The current evidence is limited by the small number of included studies, as well as the significant heterogeneity and a high risk of bias in most studies.

Infectious complications can be a major cause of morbidity and mortality in solid organ transplant recipients. Preservation fluid is necessary to maintain organ viability but may serve as a vector or infection. The utility of screening preservation fluid routinely for microbial growth and the impact of culture-positive preservation fluid is controversial. Research Question: What is the clinical impact of a culture positive preservation fluid in a kidney transplant recipient?

This retrospective study was performed to define the incidence of post-operative infection related to PF and examine the negative sequelae of culture-positive PF. One hundred and fifty-two deceased donor renal transplant recipients from January 2015 to December 2017 were included for analysis.

Overall, 67% of patients (102/152) received an allograft from a culture-positive PF. Nearly 80% of microbial growth was consistent with skin flora, and coagulase-negative staphylococci was the most frequently isolated organism (56%). Sixty-seven percent of patients (68/102) with culture-positive PF received antimicrobial treatment for an average duration of 5 days. There was no difference in the incidence of infection between patients with culture positive PF compared to culture-negative PF. Furthermore, there were no cases of infection related to PF regardless of whether culture-positive PF was treated or untreated. The incidence of subsequent C. difficile infection and multidrug-resistant organisms was similar.

This study suggests antimicrobial treatment for culture positive PF may not be necessary with pathogens that are common contaminants and of low virulence. Interventional studies are needed to validate this strategy.