Adult Kidney Transplant Recipients Research Articles

Utilization Trends of Glucose-Lowering Medications Among Adult Kidney Transplant Recipients with Type 2 Diabetes in the United States.

Background: To date, there are limited studies describing the use of glucose-lowering medications (GLMs) in adult kidney transplant recipients (KTRs), and the uptake of sodium glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1RAs). Thus, we aimed to evaluate the use of GLMs, including SGLT2i and GLP1RA, among adult KTRs with type 2 diabetes (T2D). Methods: This is an ecologic study of adult KTR with T2D. Data were sourced from two large U.S. health insurance claim databases from 2014 to 2023. The proportions of any user and incident use of GLMs were reported in percentage. Any use of GLM was defined through prescription claims, and incident use was further defined as the absence of any prior dispensing within the preceding 365 days. Results: From 2014 to 2023, we identified 33,913 adult KTRs with T2D who were prescribed any GLMs. Any use of SGLT2i and GLP1RA increased throughout the study period (0.4% to 14.4% for SGLT2i, and 2.8% to 12.5% for GLP1RA). While insulin was the most frequently used GLM, ranging from 58% to 74%, the usage gradually declined over time. By 2023, SGLT2i and GLP1RA were initiated nearly as frequently as insulin (5.1% for SGLT2i, 5.7% for GLP1RA, and 5.7% for insulin). Compared with insulin initiators, SGLT2i initiators (n = 1009) had a higher prevalence of cardiovascular comorbidities and proteinuria, while GLP1RA initiators (n = 2149) had a higher prevalence of obesity. Conclusions: Any use of both SGLT2i and GLP1RA among KTRs with T2D increased over time with the incident use of SGLT2i and GLP1RA as high as insulin by 2023. Our findings emphasize the need for the effectiveness and safety analysis of SGLT2i and GLP1RA among KTRs with T2D.

Association analysis of T and B-cell epitopes with humoral alloimmunisation in kidney transplantation: A Tunisian cohort study.

HLA matching is critical for successful kidney transplantation. This study aimed to investigate the impact of eplet mismatches and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) scores on the development of de novo donor-specific antibodies (dnDSA) and graft survival in a Tunisian cohort, characterized by a high prevalence of living donors and significant genetic diversity in HLA profiles. This retrospective study included 112 adult kidney transplant recipients who underwent transplantation between 2012 and 2018. Donor and recipient HLA typing was performed using One Lambda Labtype PCR-SSO and PCR-SSP kits, with high-resolution typing inferred using validated tools and reference datasets. Luminex DSA screening (One Lambda) was conducted at transplantation, during follow-up for graft dysfunction or proteinuria, and at the study's conclusion. Eplet mismatches and PIRCHE-II scores were calculated using EpVix and PIRCHE-II software. Nineteen patients (17%) developed dnDSA, predominantly targeting HLA-DQ, with a median detection timeframe of 50months (range: 11-106months) post-transplantation. Male donor sex was negatively associated with dnDSA development, while prolonged cold ischemia time was a significant risk factor. Molecular HLA-DQ mismatches and high PIRCHE-II scores were significantly associated with dnDSA. Factors independently associated with reduced death-censored graft survival included history of transfusion after transplantation, allelic DRB1 mismatch, dnDSA development, and elevated PIRCHE-II score. Our findings highlight the critical role of HLA-DQ compatibility in kidney transplantation and suggest that molecular HLA-DQ matching should be considered in kidney allocation strategies to minimise alloimmune responses and improve long-term graft outcomes.

Outcomes of Adult Kidney Transplant Recipients with BMI Changes on the Waitlist

Outcomes of Adult Kidney Transplant Recipients with BMI Changes on the Waitlist

Tacrolimus to belatacept conversion in proteinuric kidney transplant recipients.

Proteinuria is associated with worse allograft outcomes in kidney transplant recipients (KTRs) and treatment strategies are limited. We examined the outcomes of calcineurin inhibitor (CNI) to belatacept conversion in proteinuric KTRs. In a pilot phase II single-arm multicenter prospective trial, we recruited adult KTRs >6 months post-kidney transplantation with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m2 and proteinuria >1 g/day. Patients were converted from CNI to belatacept. The primary outcome was a 25% reduction in proteinuria at 12 months. A total of 15 KTRs were recruited who had pre-conversion median (interquartile range) proteinuria of 1.8 (IQR 1.4 - 3.5) g/g and estimated glomerular filtration rate (eGFR) of 48 (IQR 32 - 52.5) ml/min/1.73m2. At 12 months post-conversion, median proteinuria was 1.4 (IQR 0.4 - 2.2) g/g (P = 0.068) and eGFR was maintained at 43 (34 - 54.5) ml/min/1.73m2. The primary outcome of at least a 25% reduction in proteinuria occurred in 53% (8/15) at 12 months. Abbreviated IBOX scores predicting 7-year graft survival were also stable at 1-year post-conversion compared to baseline. At extended follow-up at 5 years, both proteinuria and eGFR remained stable at 0.69 (0.24 - 2.15) g/g and 39 (31 - 57) ml/min/1.73m2, respectively. CNI to belatacept conversion was associated with preserved allograft function in KTRs with significant proteinuria. These findings need to be confirmed in a larger randomized clinical trial. https://clinicaltrials.gov/, identifier NCT0232740.

New Immunosuppressants in Pediatric Kidney Transplantation: What's in the Pipeline for Kids?

The 1- and 5-year patient and graft survival rates of pediatric kidney transplant recipients have improved considerably in recent years. Regardless of early success, kidney transplantation is challenged by suboptimal long-term allograft and patient survival. Many kidney transplants are lost due to immune (rejection) and nonimmune allograft injuries, and patient survival is limited from cardiovascular disease, infection, and malignancy. Many of these co-morbidities are due to side effects of the currently available immunosuppressive drugs, especially calcineurin inhibitors and glucocorticoids, which are associated with long-term toxicity. Hence, there is an urgent need to develop new, more specific and less toxic immunosuppressive drugs. Unfortunately, there have also been no new drug approvals for adult kidney transplant recipients since belatacept in 2012, leaving the immunosuppressive drug armamentarium unchanged for more than 20 years. As a consequence of the lack of innovation in adult kidney transplant recipients, the pipeline of novel immunosuppressive agents for pediatric solid organ transplant recipients is also limited. The most promising agent in the near future, at least for adolescent patients, appears to be belatacept, despite its many limitations. In this review article, we report on three areas that appear to be the most relevant topics at this time: (i) extended-release tacrolimus, (ii) costimulation blockade with belatacept, and (iii) treatment of antibody-mediated rejection. Improved synergies between the pharmaceutical industry and the transplant community are needed to achieve the ultimate goal of improving long-term outcomes in pediatric kidney transplantation.

Disparities in Access to Valganciclovir Cytomegalovirus Prophylaxis in High-Risk African American Kidney Transplant Patients.

While access and outcomes disparities for African American (AA) kidney transplant recipients are documented, there are limited studies assessing medication access disparities in transplantation. Cytomegalovirus (CMV) causes severe complications for transplant recipients, and we aimed to understand differences in access to CMV prophylaxis valganciclovir and its impact on CMV infection rates in AA transplant recipients. This single-center, retrospective longitudinal cohort study examined high-risk (CMV serostatus D+/R-) adult kidney transplant recipients between June 1, 2010, and May 31, 202, through EMR abstraction. Standard univariate comparative statistics were employed alongside binary logistic regression for multivariable modeling. During the 10 year period,418 kidney transplant recipients were included, with 179 (42.8%) identified as AA and 239 as non-AA. There were significant differences in mean age (p = 0.001) and private versus Medicaid insurance status (p < 0.001). AAs experienced higher death-censored graft loss rates (10.6% AA vs. 5.0% non-AA, p = 0.031). CMV infection rate, opportunistic infection rate, leukopenia incidence, and death did not differ significantly between AA and non-AA patients. AA patients were 42% less likely to receive valganciclovir out-of-pocket cost assistance compared to non-AA patients (OR 0.58, [0.379-0.892], p = 0.013). When incorporating age, Medicaid status, and donor marginality in a multivariable model, the impact of AA race on utilizing assistance programs became statistically non-significant (OR 0.70, [0.448-1.094], p = 0.118). AAs were significantly less likely to leverage assistance programs or utilize personal resources to access valganciclovir. This disparity was partially explained by age, insurance status, and donor type. Despite this, CMV infection rates were similar between AA and non-AA cohorts.

Impact of weight change on kidney transplantation outcomes: A systematic review and meta-analysis.

Kidney transplant recipients frequently experience a wide range of metabolic complications, including weight changes, which significantly impact patient outcomes and graft function, yet the relationship between weight gain and transplant outcomes remains poorly understood. This systematic review and meta-analysis aimed to synthesise existing evidence on the influence of weight gain on patient and graft outcomes following kidney transplantation to enhance clinical practice and optimise post-transplant care strategies. A literature search was conducted across databases such as PubMed and Scopus for peer-reviewed studies published up to 8 August 2024. We included adult kidney transplant recipients (ages 18 years and older) with substantial and clinically relevant post-transplant weight gain and a control group without such changes, focusing on outcomes including all-cause mortality, graft survival, cardiovascular events and acute rejection. The pooled analysis, which included data from 11 studies, indicated no significant association between post-transplant weight gain and the risk of all-cause mortality (hazard ratio [HR] 1.21, 95% confidence interval [CI] 0.69 to 2.10, p = 0.51; I2 = 28%), cardiovascular events (HR 0.93, 95% CI 0.43 to 2.01, p = 0.85; I2 = 32%) or acute rejection (HR 1.13, 95% CI 0.76 to 1.68, p = 0.55; I2 = 9%). However, weight gain was significantly associated with an increased risk of graft failure (HR 1.58, 95% CI 1.22 to 2.05, p < 0.001; I2 = 0%). Substantial and clinically relevant weight gain after kidney transplant was associated with a higher risk of graft failure. Within the timeframes of study observation, risks of all-cause mortality, cardiovascular events or acute rejection were not increased by weight gain in kidney transplant recipients.

Precision in Immune Management: Balancing Steroid Exposure, Rejection Risk, and Infectious Outcomes in Adult Kidney Transplant Recipients.

With kidney transplant immunosuppression, physicians must balance preventing rejection with minimizing infection and malignancy risks. Steroids have been a mainstay of these immunosuppression regimens since the early days of kidney transplantation, yet their risks remain debated. Our study looks at the clinical outcomes of patients undergoing early steroid withdrawal (ESW) vs. steroid continuous (SCI) maintenance immunosuppression in adult kidney transplant recipients. A retrospective case-control study, utilizing propensity score-matching, was performed using the US Collaborative Network Database within TriNetX to evaluate renal transplant outcomes at one year in first-time kidney transplant adult patients (>18 years old) who were prescribed an ESW regimen (no steroids after post-transplant day 7 with maintenance tacrolimus [tac] + mycophenolic acid [MMP]/mycophenolate mofetil [MMF]) vs. SCI (tac + MMF/MMP + prednisone). Cohorts were matched on demographics, comorbidities, previously described risk factors for rejection, and induction immunosuppression. Primary outcomes included viral infections, pyelonephritis, and sepsis. Secondary outcomes included renal transplant rejection, death-censored allograft failure (eGFR < 15 mL/min), patient mortality, delayed graft function, and diabetes mellitus. A total of 2056 patients were in each cohort after matching (mean age: 50.7-51 years, 17.9-20.0% African American, 60-60.6% male.) The SCI cohort had a significantly higher cumulative incidence of composite viremia (18 vs. 28.1%, ESW vs. SCI, p < 0.01) driven by CMV, EBV, and BK virus. Post-transplant diabetes mellitus was significantly higher in the SCI cohort (3.21% vs. 5.49%, ESW vs. SCI, p < 0.01). Delayed graft function was also higher in the SCI cohort (19.55% vs. 22.79%, ESW vs. SCI, p < 0.01). Pyelonephritis (2.3 vs. 4.91%, ESW vs. SCI, p < 0.01) and sepsis (2.15 vs. 5.95%, ESW vs. SCI, p < 0.01) were higher in the SCI cohort. Rejection rates were similar between ESW and SCI (29 vs. 31%, ESW vs. SCI, p = 0.41). There were significantly higher incidences of graft failure (4.9 vs. 9.9%, ESW vs. SCI, p < 0.01) and mortality (0.8 vs. 2.1%, ESW vs. SCI, p < 0.01) in the SCI cohort. This well-matched case-control study suggests that ESW is associated with lower infectious outcomes, mortality, and graft failure without increasing rejection risk, supporting the potential benefits of ESW in kidney transplant patients.

Diagnostic and therapeutic challenges in implementing hypertension management after kidney transplantation.

Evidence for blood pressure (BP) measurement and hypertension management in kidney transplant recipients (KTR) remains lacking. Accurate BP measurement technique is a critical component of hypertension management, and 24-h ambulatory BP monitoring remains the gold standard for diagnosis of hypertension in KTR. BP target at different periods posttransplant is uncertain, but likely higher than that in nontransplant patients given factors related to long-standing uremic milieu and kidney transplantation such as vascular calcification altering transplant renal hemodynamic and allograft perfusion and immunosuppression. Dividing BP target into immediate, early, and late posttransplant periods can guide differential diagnoses of hypertension and BP control with a target SBP less than 160 mmHg in general and BP 115-135/65-85 mmHg for adult KTR receiving pediatric kidneys during the immediate posttransplant period, 130/80 mmHg during early and late posttransplant periods. Calcium channel blockers were shown to have favorable graft outcomes. Novel antihypertensive medications for resistant and refractory hypertension and device-based therapies are limited due to KTR's ineligibility for participating in clinical trials. In KTR, BP measurement and monitoring practice should follow the standard clinical practice guideline for nontransplant patients by considering posttransplant factors and immunosuppressive state. Novel treatment options required further studies.

Hypothalamic-Pituitary-Adrenal Axis Activity and Metabolic Disorders in Kidney Transplant Recipients on Long-Term Glucocorticoid Therapy.

Background/Objectives: Glucocorticoids are commonly used for maintenance immunosuppressive therapy in kidney transplant recipients (KTRs). We aimed to investigate the prevalence of hypothalamic-pituitary-adrenal (HPA) axis suppression and its association with metabolic disorders in stable KTRs on low-dose glucocorticoids. Methods: This cross-sectional study included adult KTRs on low-dose glucocorticoids. HPA axis suppression was defined as baseline morning cortisol < 5 μg/dL. Adrenocorticotropic hormone (ACTH), dehydroepiandrosterone-sulphate (DHEAS) and 24 h urinary free cortisol (UFC) levels were also assessed. Examined metabolic disorders included hypertension, dyslipidemia, central obesity and post-transplant diabetes mellitus (PTDM). Results: Eighty adult KTRs with a median 57 months (IQR 24-102) since transplantation were included in the study. The mean prednisolone dose was 5.0 ± 1.3 mg/day. Baseline cortisol < 5.0 μg/dL was observed in 27.5% of the KTRs. Participants with baseline cortisol < 5.0 μg/dL were older (55.1 vs. 47.4 years, p = 0.023) and had had a transplant for a longer time (101.4 vs. 67.0 months, p = 0.043), compared with the rest of the cohort. Baseline cortisol correlated positively with ACTH (rho = 0.544, p < 0.001), DHEAS (rho:0.459, p < 0.001) and UFC (rho: 0.377, p = 0.002). The area under the receiver-operating characteristic curve for ACTH as a predictor of baseline cortisol > 5.0 μg/dL was 0.79 [95% confidence interval (CI): 0.68-0.89]. After adjustment for covariates, HPA axis suppression was not associated with the examined metabolic disorders. Conclusions: Our study showed that stable KTRs on chronic low-dose glucocorticoids exhibited an increased prevalence of HPA axis suppression. ACTH may serve as a surrogate biomarker for HPA axis activity in this population. Further research could evaluate the association of glucocorticoid-induced HPA axis inhibition with metabolic disorders.

Examining Whole Blood, Total and Free Plasma Tacrolimus in Elderly Kidney Transplant Recipients.

Therapeutic monitoring is routinely performed to ensure tacrolimus whole-blood concentrations fall within a predefined target. Despite this, patients still experience inefficacy and toxicity that could be related to variability in free (unbound) tacrolimus exposure. Therefore, the aim of this study was to compare tacrolimus-free plasma (Cu), total plasma (Cp), and whole-blood (Cwb) concentrations in adult kidney transplant recipients and to characterize tacrolimus disposition across different matrices. Twelve-hour concentration-time profiling was performed in 15 recipients, allowing simultaneous measurement of Cu, Cp, and Cwb. Pharmacokinetic parameters were estimated using noncompartmental analysis. The relationship between Cwb and Cp were examined using a capacity-limited binding model, incorporating the hematocrit fraction (fHCT) to estimate maximum binding concentration (Bmax) and dissociation constant (Kd). The relationship between Cp and Cu was evaluated using a linear binding model to estimate the nonspecific binding parameter (Nplasma). Nonlinear regression analysis was used to obtain estimates of Bmax, Kd, and Nplasma. A total of 195 paired Cwb, Cp, and Cu values were collected. The median ratios of Cwb:Cp, Cp:Cu, and Cwb:Cu were 9:1, 20:1, and 138:1, respectively. Variability in free plasma exposure was large; free trough values ranged from 8 to 51 ng/L and free area-under-the-concentration-time-curve values ranged from 424 to 7160 ng·h/L. Median (range) estimates of Bmax, Kd, and Nplasma were 90.4 µg/L (22.4-752.5 µg/L), 2.36 µg/L (0-69.2 µg/L), and 0.05 (0.035-0.085), respectively. The interindividual variability (CV%) in binding parameters was considerable (Bmax 117.2%; Nplasma 32.5%). Large variability was observed in tacrolimus-free plasma exposure and binding parameters. Future research to characterize the relationship between tacrolimus Cu and patient outcomes may be of benefit.

Association of PIRCHE-II score with anti-donor T-cell response and risk of de novo donor-specific antibody production in kidney transplant recipients

BackgroundDe novo donor-specific antibodies (dnDSAs) affect long-term outcomes of kidney transplantation (KT). A higher Predicted Indirectly ReCognizable Human Leukocyte Antigen (HLA) Epitopes (PIRCHE-II) score correlates with various clinical outcomes, including dnDSA formation. However, a detailed analysis of the relationship between the PIRCHE-II score and anti-donor T-cell response is lacking. Therefore, this study investigated the relationship between PIRCHE-II scores associated with dnDSA formation and mixed lymphocyte reaction results of anti-donor T-cell response. MethodsData of 105 adult living-donor KT recipients were retrospectively assessed. ResultsOf the 105 patients, 13.3 % developed dnDSAs during the observation period. The PIRCHE-II score at the HLA-DQ locus (PIRCHE-DQ) was significantly higher in patients with dnDSA formation than in those without. The incidence of dnDSA formation was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group. The proportion of patients with increased anti-donor T-cell response was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group before KT and at 4 and 5 years after KT. ConclusionsPIRCHE-DQ may predict dnDSA formation and anti-donor T-cell response. Reducing the immunosuppressive drug dose in cases of high PIRCHE-DQ might not be prudent.

Prediction of Allograft Failure in Pediatric Kidney Transplant Recipients: A Validation Study of the Four-Variable Kidney Failure Risk Equation.

Recent findings suggest that the four-variable Kidney Failure Risk Equation (KFRE) may be useful in predicting the likelihood of allograft failure in adult kidney transplant (KT) recipients. However, research on its application in pediatric patients is lacking. This study aimed to assess the accuracy of the four-variable KFRE for prediction of the two-year and five-year risk of allograft failure in a cohort of pediatric KT recipients. A retrospective observational study of patients undergoing KT in a tertiary pediatric nephrology unit between 2007 and 2017 was conducted. The KFRE risk scores were determined using data collected one-year post-transplantation. Discrimination and calibration properties of the four-variable KFRE were assessed through the area under the receiver operating characteristic curves (AUC) and calibration plots. Fifty-nine patients with a median age of 12.4 (9.1-15.7) years at KT were included. Eleven (18.6%) were living donor recipients. The median estimated glomerular filtration rate one-year post-transplantation was 62.0 (49.0-75.0) mL/min/1.73 m2. One (1.7%) and three (5.1%) patients experienced allograft failure within two and five years following the one-year post-transplantation date, respectively. The four-variable KFRE showed excellent and very good discrimination for the two-year and five-year risks, respectively (AUC 0.966, 95% confidence interval (CI) 0.914-1.000; AUC 0.887, 95% CI 0.732-1.000). Calibration plots demonstrated imprecise calibration. The four-variable KFRE shows promise in predicting kidney failure progression in pediatric KT recipients with a functioning allograft one-year post-transplantation. Larger-scale studies are essential to confirm its predictive accuracy and establish more definitive conclusions.

Cryptosporidium spp. Infection in Adult Kidney Transplant Patients: A Systematic Review and Meta-Analysis.

Background: Diarrhea frequently occurs after vascular organ transplantation, including kidney transplants. This may result from non-infectious factors, adverse effects of immunosuppressive medications, or infections caused by various pathogens, including viruses, bacteria, fungi, or parasites, for example, intestinal protozoan parasites such as Cryptosporidium spp., which are particularly dangerous for immunocompromised patients. Methods: This review is based on scientific articles sourced from validated databases such as PubMed, the National Center for Biotechnology Information (NCBI), ScienceDirect, and Google Scholar. The primary search was conducted on 12-13 July 2024, using the keywords 'Cryptosporidium' AND 'cryptosporidiosis' AND 'kidney' AND 'transplant' AND 'adult'. Inclusion criteria encompassed human studies, case reports, peer-reviewed journal publications, review articles, and research articles in English. Exclusion criteria included studies not in English, gray literature (e.g., conference proceedings and abstracts), and data related to pediatric patients (under 18 years old) and HIV patients. Results: This systematic review and meta-analysis have highlighted an often-overlooked connection between Cryptosporidium spp. infections in adult kidney transplant recipients (KTR). Furthermore, it includes an analysis of the clinical presentation, diagnosis, and treatment of Cryptosporidium spp. infection in these patients, based on available case reports. Our study demonstrates that adult kidney transplant patients are at a significantly higher risk of acquiring Cryptosporidium spp. compared to healthy participants. Conclusions:Cryptosporidium spp. infections can be asymptomatic, making it essential to screen both symptomatic and asymptomatic kidney transplant recipients. The clinical presentation of cryptosporidiosis typically involves digestive symptoms and can be complicated by biliary tract involvement. In KTR patients presenting with diarrhea, it is crucial to not only test for Cryptosporidium spp. but also to rule out bacterial and viral etiologies, including infections such as C. difficile, C. colitis, Clostridium spp., and rotavirus. The diagnosis of Cryptosporidium spp. infections primarily relies on microscopic methods, which are known for their low sensitivity. Therefore, diagnostic approaches should include both direct methods and, where possible, molecular techniques. Based on the analyzed cases, the most effective treatment results were achieved with reduction in immunosuppression if possible (strong, very low) and nitazoxanide at a dose of 500 mg twice daily for 14 days. Considering the public health implications of our findings, the current epidemiological data underscore the need for further research to develop effective prevention and intervention strategies against cryptosporidiosis. Preventive measures, regular screening programs, and the treatment of Cryptosporidium spp. infections should be integrated into the clinical care of transplant patients. It is also important that patients are informed about environmental risk factors.

Preferences in treating polyomavirus infection in kidney transplant recipients: A discrete choice experiment with patients, caregivers, and clinicians.

Treatment strategies for BK polyomavirus (BKPyV) infection in kidney transplant recipients are heterogeneous among clinicians. We aimed to identify the treatment preferences of key stakeholders for BKPyV infection and measure the trade-offs between treatment outcomes. Adult kidney transplant recipients, caregivers, and clinicians were eligible to participate in a discrete choice experiment between February 2021 and June 2022. The five treatment-related attributes were achieving viral clearance and optimal graft function, as well as reducing the risk of graft loss, acute rejection, and complications. Results were analyzed using multinomial logistic models. In total, 109 participants (57 kidney transplant recipients, 10 caregivers, and 42 health professionals) were included. The most important attribute was the risk of graft loss, followed by side effects and acute rejection. As the risk of graft loss increased, all participants were less inclined to accept an assigned treatment strategy. For instance, if graft loss risk was increased from 1% to 50%, the probability of uptake of a treatment strategy for BKPyV infection was reduced from 87% to 3%. Graft loss is the predominant concern for patients, caregivers, and health professionals when deciding on the treatment for BKPyV infection, and should be included in intervention trials of BKPyV infection.

Graft Loss in Pediatric and Young Adult Kidney Transplantation in New Zealand: Who Is at Greatest Risk and When?

Much is reported regarding the detrimental effect of transfer to adult services for adolescent and young adult (AYA) kidney transplant (KT) recipients. However, AYA recipient age independent of time post-KT, and not relating to transfer of care, is also a strong predictor of graft loss. We assessed KT graft survival if experiencing solely pediatric (PO) or adult services (AO) versus transfer from pediatric to adult services (PTA). A retrospective cohort analysis of all first kidney transplant recipients between birth-24 years of age, from 2000 to 2019 in New Zealand. Participant identification and data were obtained via the Australia and New Zealand Dialysis and Transplantation registry. Primary outcome was graft survival stratified by service type. Cox proportional hazard modeling assessed independent risk factors of graft loss. Two hundred forty-four children and AYA with a median follow-up of 7.3 years were included. Graft survival stratified by service provision group was not different. The incidence rate of graft loss was 37, 34, and 45 per 1000 persons per year for PO, PTA, and AO respectively. Crude age-specific graft failure rates were highest for 22-24-year-olds with inferior outcomes starting from age 16, peaking at 24 years. Older adolescence and young adulthood reflect a high-risk period for KT loss. Transfer to adult services was not associated with worse graft survival compared to those experiencing either AO or PO alone. Improved models of care are needed to improve graft survival in this vulnerable population within New Zealand.

Renal Allograft Function and the Tacrolimus C/D Ratio: Insights from a Prospective Study on MeltDose Tacrolimus

Background: The tacrolimus concentration-to-dose (C/D) ratio is valuable for optimizing nephrotoxicity-related renal outcomes. Prospective data on the C/D ratio in kidney transplant recipients newly treated with MeltDose tacrolimus are limited. We analyzed the C/D ratio pattern of MeltDose tacrolimus and its effect on posttransplant renal function, comparing it with the literature data on immediate-release tacrolimus (IR-Tac). Methods: In total, 101 adult kidney transplant recipients on a standard immunosuppressive regimen including MeltDose tacrolimus were enrolled in this prospective, multicenter cohort study and followed for 12 months. The C/D ratio classified patients as fast, intermediate, or slow metabolizers. Renal function was assessed via the estimated glomerular filtration rate (eGFR). MeltDose tacrolimus data were compared with previous IR-Tac data by bootstrapping. Results: The cohort exhibited a right-skewed C/D ratio distribution with a mean of 2.12 ng/mL × 1/mg, which was significantly greater than the 1.29 mean for IR-Tac (p &lt; 0.001). Compared with fast metabolizers, slow metabolizers of MeltDose tacrolimus experienced greater eGFR gains at 6 months post-transplantation (median +7.9 vs. −3.6 mL/min; p = 0.005). A Bayesian linear mixed-effects model predicting the eGFR at month 12 identified the baseline eGFR, time from transplant, body mass index, and log-transformed C/D ratio as significant variables. A one-unit increase in the log-transformed C/D ratio corresponded to an approximate increase of 4.5 mL/min in the eGFR at month 12. Conclusions: Slow metabolizers of MeltDose tacrolimus had significantly better renal function outcomes than fast metabolizers. MeltDose tacrolimus is associated with slower metabolism than is IR-Tac, as evidenced by its higher C/D ratios.

Dynamic prediction of kidney allograft and patient survival using post-transplant estimated glomerular filtration rate trajectory.

Allograft loss is the most feared outcome of kidney transplant recipients. We aimed to develop a dynamic Bayesian model using estimated glomerular filtration rate (eGFR) trajectories to predict long-term allograft and patient survivals. We used data from the Australian and New Zealand Dialysis and Transplant registry and included all adult kidney transplant recipients (1980-2017) in Australia (derivation cohort) and New Zealand (NZ, validation cohort). Using a joint model, the temporal changes of eGFR trajectories were used to predict patient and allograft survivals. The cohort composed of 14 915 kidney transplant recipients [12 777 (86%) from Australia and 2138 (14%) from NZ] who were followed for a median of 8.9 years. In the derivation cohort, eGFR trajectory was inversely associated with allograft loss [every 10ml/min/1.73 m2 reduction in eGFR, adjusted hazard ratio [HR, 95% credible intervals (95%CI) 1.31 (1.23-1.39)] and death [1.12 (1.10-1.14)]. Similar estimates were observed in the validation cohort. The respective dynamic area under curve (AUC) (95%CI) estimates for predicting allograft loss at 5-years post-transplantation were 0.83 (0.75-0.91) and 0.81 (0.68-0.93) for the derivation and validation cohorts. This straightforward model, using a single metric of eGFR trajectory, shows good model performance, and effectively distinguish transplant recipients who are at risk of death and allograft loss from those who are not. This simple bedside tool may facilitate early identification of individuals at risk of allograft loss and death.

Tacrolimus Dose Requirement in De Novo Adult Kidney Transplant Patients Treated With Adoport® Can Be Anticipated.

All the factors potentially influencing tacrolimus dose requirement and combinations thereof have never been thoroughly investigated, precluding accurate prediction of tacrolimus starting dose. This prospective, non-interventional, multicenter study in de novo adult kidney transplant recipients over the first year after transplantation aimed to investigate the factors influencing tacrolimus dose-standardized trough blood concentration (C0/D) over the first week post-transplant (D4-D7, primary objective), D8-M3 and M3-M12 (secondary objectives). Statistical analysis employed mixed linear models with repeated measures. Eighteen sites enrolled 440 patients and followed them up for 9.5 ± 4.1months. Age at baseline (p = 0.0144), end-stage renal disease (p = 0.0092), CYP3A phenotype (p < 0.0001), dyslipidemia at baseline (p = 0.0031), hematocrit (p = 0.0026), total bilirubin (p = 0.0261) and plasma creatinine (p = 0.0484) independently increased with log(C0/D) over D4-D7, explaining together 72.3% of the interindividual variability, and representing a robust model to estimate tacrolimus initial dose. Donor age and CYP3A phenotype were also influential over D8-M3 and M3-12, in addition to recipient age. Corticosteroids, diabetes at baseline, and ASAT yielded inconstant results between D8-M3 and M3-M12. We found no ethnicity effect when CYP3A phenotype was accounted for, and no food effect. Intra-individual variability over M3-M12 was moderate, and significantly lower in patients with chronic hepatic disorder (p = 0.0196) or cancer (p = 0.0132).

Analysis of the Correlation between Hypercholesterolemia and Increased Cardiovascular Morbidity and Mortality among Adult Kidney Transplant Recipients

Introduction: The correlation between hypercholesterolemia and cardiovascular disease in kidney transplant recipients (KTRs) remains uncertain. We sought to characterize the association between abnormal cholesterol profiles and cardiovascular morbidity and mortality in this unique population. Methods: This retrospective cohort study was conducted at a single center and included all adult KTR, transplanted between January 2005 and April 2014. The primary outcome was major adverse cardiovascular events (MACE) while the secondary outcome was the composite outcome of MACE and all-cause mortality. Exposure to abnormal cholesterol levels was calculated using a time-weighted average calculation. MACE and mortality risk were analyzed using a multivariate time-varying Cox model. Results: The final cohort comprised 737 KTR, with a median follow-up of 2,920 days. A total of 126 patients (17.1%) experienced MACE. High LDL-C levels and MACE risk were correlated by multivariate analysis (HR 1.008 per mg/dL, 95% CI: 1.001–1.016), while low HDL-C levels were not significantly associated with MACE (HR 0.992 per mg/dL, 95% CI: 0.976–1.009). A higher LDL-C/HDL-C ratio was significantly associated with an increased risk of MACE in multivariate analyses (HR 1.502 per unit, 95% CI: 1.147–1.968), and also correlated with the composite outcome (HR 1.35 per unit, 95% CI: 1.06–1.71). Conclusions: A high LDL-C/HDL-C ratio is predictive of an increased risk of cardiovascular morbidity and mortality in KTRs. These findings emphasize the significance of the LDL-C/HDL-C ratio as a valuable marker of cardiovascular risk and support current recommendations to improve hypercholesterolemia in this high-risk group.