Longevity Matching for Living Donor Renal Transplantation.

INTRODUCTION: This study identifies the effect of individual donor and recipient characteristics on graft survival in living-donor kidney transplantation (LDKT) using a recently described novel measure, kidney life years (KLYs). MATERIALS AND METHODS: The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify first-time kidney-only LDKT recipients between 1987 and 2020 who did not experience death with a functioning graft (DWFG) and were not missing relevant information (n = 87,290). Patient characteristics were evaluated using Cox and multiple regression analyses, with the dependent variable being KLYs. An equation for expected KLYs based on patient characteristics was created using regression coefficients. The equation was validated using bootstrapped Pearson correlations and then applied to the DWFG group for comparison. RESULTS: Based on statistical significance from Cox and multiple linear regression analyses, 9 of the original 18 variables were selected for inclusion in the equation. Variables with notable impact included HLA match points (0.021 KLYs; 95% CI: [0.019,0.024]; P ≤ .001), Donor Age (-0.030 KLYs; 95% CI: [-0.035,-0.025]; P ≤ .001), and Donor African American Ethnicity (-2.356 KLYs; 95% CI: [-2.552,-2.159]; P ≤ .001). Equation validation was supported, given a negative correlation (r = -0.071; P ≤ .001) between expected KLY change and observed graft failure. Expected KLY change was found to be greater in those who eventually DWFG when compared with all other LDKTs (t = -5.735, P ≤ .001). CONCLUSIONS: Increasing HLA match points may be more beneficial for graft longevity than minimizing donor age in comparisons using realistic between-donor differences. Additionally, greater average expected KLYs in those who ultimately DWFG may illustrate an opportunity for improved donor-recipient matching.

Renal Cell Carcinoma in End-Stage Kidney Disease and the Role of Transplantation.

Kidney transplant patients have a higher risk of renal cell carcinoma (RCC) compared to non-transplanted end-stage kidney disease (ESKD) patients. This increased risk has largely been associated with the use of immunosuppression; however, recent genetic research highlights the significance of tissue specificity in cancer driver genes. The implication of tissue specificity becomes more obscure when addressing transplant patients, as two distinct metabolic environments are present within one individual. The oncogenic potential of donor renal tissue is largely unknown but assumed to pose minimal risk to the kidney transplant recipient (KTR). Our review challenges this notion by examining how donor and recipient microenvironments impact a transplant recipient's associated risk of renal cell carcinoma. In doing so, we attempt to encapsulate how ESKD-RCC and KTR-RCC differ in their incidence, pathogenesis, outcome, and approach to management.

Dosing strategies for de novo once-daily extended release tacrolimus in kidney transplant recipients based on CYP3A5 genotype.

BACKGROUND: 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. AIM: To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype. METHODS: 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. RESULTS: 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. CONCLUSION: 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.