Tacrolimus trough levels higher than 6 ng/mL might not be required after a year in stable kidney transplant recipients

Background: Little is known regarding optimal tacrolimus (TAC) trough levels after 1 year post-transplant in stable kidney transplant recipients (KTRs) who have not experienced renal or cardiovascular outcomes. This study aimed to investigate the effect of 1-year post-transplant TAC trough levels on long-term renal and cardiovascular outcomes and opportunistic infections in stable KTRs. Methods: KTRs receiving TAC with mycophenolate-based immunosuppression who did not experience renal or cardiovascular outcomes within 1 year post-transplant were enrolled from a multicenter observational cohort study. Renal outcome was defined as a composite of biopsy-proven acute rejection, interstitial fibrosis and tubular atrophy, and death-censored graft loss. Cardiovascular outcome was defined as a composite of de novo cardiomegaly, left ventricular hypertrophy, and cardiovascular events. Opportunistic infections were defined as the occurrence of BK virus or cytomegalovirus infections. Results: A total of 603 eligible KTRs were divided into the low-level TAC (LL-TAC) and high-level TAC (HL-TAC) groups based on a median TAC level of 5.9 ng/mL (range 1.3-14.3) at 1 year post-transplant. The HL-TAC group had significantly higher TAC trough levels at 2, 3, 4, and 5 years compared with the levels of the LL-TAC group. During the mean follow-up of 63.7 ± 13.0 months, there were 121 renal outcomes and 224 cardiovascular outcomes. In multivariate Cox regression analysis, LL-TAC and HL-TAC were not independent risk factors for renal and cardiovascular outcomes, respectively. No significant differences in the development of opportunistic infections and de novo donor-specific anti-human leukocyte antigen antibodies and renal allograft function were observed between the two groups. Conclusions: TAC trough levels after 1 year post-transplant remained at a similar level until the fifth year after kidney transplantation and were not directly associated with long-term outcomes in stable Korean KTRs who did not experience renal or cardiovascular outcomes. Therefore, in Asian KTRs with a stable clinical course, TAC trough levels higher than approximately 6 ng/mL might not be required after a year of kidney transplantation.ope

Impact of changes in waist-to-hip ratio after kidney transplantation on cardiovascular outcomes

Recently, waist to hip ratio (WHR) has been reported to be a better indicator of predicting cardiovascular outcomes than body mass index (BMI). We evaluated the effects of pre or post-transplant changes of WHR or BMI on the new onset cardiovascular diseases (CVD) in recipients of kidney transplantation (KT). A total of 572 patients were enrolled from a multicenter observational cohort (KNOW-KT). Measurement of WHR and BMI was done at pre-KT, first and last visit year after KT, and the changes of these parameters and their effect on the incident CVD were analyzed. During the median follow up period of 32.73 ± 15.26 months, the new onset CVD developed in 31 out of 572 patients. The older age, diabetes mellitus and increase of WHR from pre KT or previous follow up year were found to be independent factors predicting the new onset CVD in these patients. However, baseline BMI, WHR prior to KT did not predict the incident CVD. The new metabolic burden, presented as increase of WHR in KT patients has a critical impact on the development of new onset CVD. Strategies to prevent the metabolic burden after KT might improve cardiovascular outcomes and patient's survival.ope

Pregnancy outcomes after living kidney donation from a nationwide population-based cohort study from Korea

While most living kidney donors experience good outcomes and high rates of satisfaction, kidney donation can increase the risk of gestational hypertension or preeclampsia. However, pregnancy outcomes in non-white donors are limited. We conducted a nationwide cohort study of 112 living kidney donors and 672 matched healthy non-donors using the Korean National Health Insurance Claims Database. Donors and healthy non-donors were matched according to age, year of cohort entry, residency, income, number of pregnancies, and the time to the first pregnancy after cohort entry. We assessed pregnancy outcomes of live kidney donors compared with matched healthy non-donors using the nationwide database. Gestational hypertension or preeclampsia was more common in kidney donors than in non-donors (8.9% vs. 1.8%; adjusted odds ratio, 2.68; 95% confidence interval, 1.11-6.50). However, the incidence of severe gestational hypertension or preeclampsia that required antihypertensive medication was comparable (2.7% vs. 0.9%; P = 0.121). The time from donation to delivery within 5 years and primiparity were risk factors for preeclampsia in donors. Low birth weight, stillbirth, and ectopic pregnancy were not significantly different between the two groups. Maternal death occurred in two non-donor cases, but none occurred in donors compared to non-donors. Our findings indicate that kidney donors are associated with an increased risk of gestational hypertension or preeclampsia than matched healthy non-donors. However, the probabilities of serious maternal and fetal outcomes remained low and are not increased significantly after kidney donation.ope

Improvement of medication adherence with simplified once-daily immunosuppressive regimen in stable kidney transplant recipients: A prospective cohort study

Background: Many immunosuppressive drugs are prescribed as twice-daily dosing. A simplified once-daily dosing of immunosuppressive drug regimen may improve medication adherence. We investigated medication adherence of simplified once-daily immunosuppressive regimen consisting of extended-release tacrolimus, sirolimus, and corticosteroids along with the efficacy and safety of this regimen. Methods: This study was a prospective, multicenter, controlled and cohort trial. Stable kidney transplant recipients who had received transplantation at least 3 months before the study enrollment were eligible for the study. Participants were required to fill-out the self-reported immunosuppressant therapy barrier scale (ITBS) questionnaire before and after the conversion. Other clinical laboratory parameters and adverse events were evaluated until 6 months post-conversion. Results: A total of 160 kidney recipients comprised the intention-to-treat population. The mean total ITBS score was 19.5 +/- 14.0 at pre-conversion and 6 months after converting, the mean total ITBS score was 16.6 +/- 13.6 (p < 0.001). Particularly, the ITBS scores of 4 questions related to the frequency of medication dosing were significantly different between pre-conversion and post-conversion. Only 1 patient (0.62%) was diagnosed as biopsy-confirmed acute rejection in the study period. There was no significant change in the mean estimated glomerular filtration rate after the conversion. Overall 95 patients (59.4%) had an adverse event and 28 patients (17.5%) had a serious adverse event. No graft loss and 1 death were reported. Conclusion: Medication adherence after the conversion to the once-daily immunosuppressive regimen was significantly improved with no additional risks of efficacy failure or adverse events.ope

KNOW-KT (KoreaN cohort study for outcome in patients with kidney transplantation: a 9-year longitudinal cohort study): study rationale and methodology

Background : Asian patients undergoing kidney transplantation (KT) generally have better renal allograft survival and a lower burden of cardiovascular disease than those of other racial groups. The KNOW-KT aims to explore allograft survival rate, cardiovascular events, and metabolic profiles and to elucidate the risk factors in Korean KT patients. Methods : KNOW-KT is a multicenter, observational cohort study encompassing 8 transplant centers in the Republic of Korea. KNOW-KT will enroll 1,000 KT recipients between 2012 and 2015 and follow them up to 9 years. At the time of KT and at pre-specified intervals, clinical information, laboratory test results, and functional and imaging studies on cardiovascular disease and metabolic complications will be recorded. Comorbid status will be assessed by the age-adjusted Charlson co-morbidity index. Medication adherence and information on quality of life (QoL) will be monitored periodically. The QoL will be assessed by the Kidney Disease Quality of Life Short Form. Donors will include both living donors and deceased donors whose status will be assessed by the Kidney Donor Risk Index. Primary endpoints include graft loss and patient mortality. Secondary endpoints include renal functional deterioration (a decrease in eGFR to <30 mL/min/1.73 m2), acute rejection, cardiovascular event, albuminuria, new-onset diabetes after transplant, and QoL. Data on other adverse outcomes including episodes of infection, malignancy, recurrence of original renal disease, fracture, and hospitalization will also be collected. A bio-bank has been established for the acquisition of DNA, RNA, and protein from serum and urine samples of recipients at regular intervals. Bio-samples from donors will also be collected at the time of KT. KNOW-KT was registered in an international clinical trial registry (NCT02042963 at http://www.clinicaltrials.gov webcite) on January 20th, 2014. Conclusion : The KNOW-KT, the first large-scale cohort study in Asian KT patients, is expected to represent the Asian KT population and provide information on their natural course, complications, and risk factors for complications.ope

Safety and Efficacy of Conversion from Twice-Daily Tacrolimus to Once-Daily Tacrolimus One Month after Transplantation: Randomized Controlled Trial in Adult Renal Transplantation

PURPOSE: The purpose of this study was to compare once-daily tacrolimus with twice-daily tacrolimus in terms of safety, efficacy, and patient satisfaction. MATERIALS AND METHODS:This prospective, randomized, open-label, multicenter study was conducted at three institutes. Patients in the investigational group were converted from tacrolimus twice daily to the same dose of extended-release tacrolimus once daily at 1 month post-transplantation, while patients in the control group were maintained on tacrolimus twice daily. The efficacies, safeties, and patient satisfaction for the two drugs at 6 months post-transplantation were compared. RESULTS:Sixty patients were enrolled and randomized to the investigational group (28 of 29 patients completed the study) or the control group (26 of 31 patients completed the study). At 6 months post-transplantation, composite efficacy failure rates including the incidences of biopsy-confirmed acute rejection in the investigational and control groups were 0% and 10.7%, respectively; patient survival was 100% in each group. No difference in estimated glomerular filtration rate values were observed at 6 months post-transplantation (p=0.97). The safety and satisfaction profile (immunosuppressant therapy barrier scale) of once-daily tacrolimus was comparable with that of twice-daily tacrolimus (p=0.35). CONCLUSION:Conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation is safe and effective.ope

Better health-related quality of life in kidney transplant patients compared to chronic kidney disease patients with similar renal function

Renal functional deterioration is associated with physical and mental burdens for kidney transplant (KT) and chronic kidney disease (CKD) patients. However, the change in health-related quality of life (HRQOL) over time in KT patients compared to that of native CKD patients has not been evaluated. We addressed this issue using KT patients registered in the KNOW-KT cohort study and patients at CKD stage 1-3 registered in the KNOW-CKD cohort study. HRQOL scores were assessed using the Kidney Disease Quality of Life Short Form at baseline, 2-, and 4-years follow-up in 842 KT patients and at baseline and 5-year follow-up in 1,355 CKD patients. SF-36 scores declined at the 4-year follow-up, whereas CKD-targeted scores showed no change in the KT group. In contrast, CKD-targeted scores as well as SF-36 scores were decreased at the 5-year follow-up in CKD patients. When prognostic factors were analyzed for longitudinal HRQOL data over time, renal functions, diabetes, cardiovascular and cerebrovascular diseases, hemoglobin level, marital status, income, employment, and health care were significant prognostic factors. Furthermore, KT was an independent prognostic factor for better HRQOL. These results highlight that KT can offer a better HRQOL than that of CKD patients, even when renal function is similar.ope

Clinical Significance of Revised Banff Criteria in the Diagnosis of Antibody-Mediated Rejection

BACKGROUND: The diagnostic criteria of antibody-mediated rejection (ABMR) has been significantly changed since Banff 2013. The most important revision was adopting microvascular inflammation (MVI) as immunopathologic evidence for ABMR even in C4d-negative cases. In this study, we retrospectively reviewed previous allograft biopsy results and evaluated the impact of this change. METHODS: We reviewed results of 536 renal allograft biopsies at Severance Hospital during 2011 to 2013, which were diagnosed according to the Banff 2009 criteria. All biopsy results were reassessed according to the Banff 2017 criteria. RESULTS: According to the Banff 2009 criteria, antibody-mediated changes were observed in 48 cases out of the 536 allograft biopsies (9.0%). According to the Banff 2017 criteria, 28 additional cases (5.2%) were reclassified as antibody-mediated changes. Twenty-six of these cases were C4d-negative ABMR. The most frequent diagnostic finding in these cases was MVI comprising glomerulitis and peritubular capillaritis. Donor-specific antibodies were investigated in 14 of these cases, which revealed positive results in 12 cases. CONCLUSION: The incidence rate of ABMR has increased after the recent revision of the Banff criteria. The MVI in C4d-negative ABMR cases is the major cause for this increase.ope

Pretransplant and Posttransplant Alcohol Consumption and Outcomes in Kidney Transplantation: A Prospective Multicenter Cohort Study

The impact of pretransplant and posttransplant alcohol consumption on outcomes in kidney transplant recipients (KTRs) is uncertain. Self-reported alcohol consumption was obtained at the time of transplant and 2 years after transplant in a prospective cohort study. Among 907 KTRs, 368 (40.6%) were drinkers at the time of transplant. Compared to non-drinkers, alcohol consumption did not affect the risk of death-censored graft failure (DCGF), biopsy-proven acute rejection (BPAR), cardiovascular events, or all-cause mortality. Compared to persistent non-drinkers, the development of DCGF, BPAR, cardiovascular events, all-cause mortality, or posttransplant diabetes mellitus was not affected by the alcohol consumption pattern (persistent, de novo, or stopped drinking) over time. However, de novo drinkers had a significantly higher total cholesterol (p < 0.001) and low-density lipoprotein cholesterol levels (p = 0.005) compared to persistent non-drinkers 5 years after transplant, and had significantly higher total cholesterol levels (p = 0.002) compared to the stopped drinking group 7 years after transplant, even after adjusting for the use of lipid-lowering agents, age, sex, and body mass index. Although pretransplant and posttransplant alcohol consumption were not associated with major outcomes in KTRs during the median follow-up of 6.0 years, a new start of alcohol use after KT results in a relatively poor lipid profile.ope