Optimum tacrolimus trough levels for enhanced graft survival and safety in kidney transplantation: a retrospective multicenter real-world evidence study.

BACKGROUND: The current study aimed to determine the optimal tacrolimus trough levels for balancing graft survival and patient safety following kidney transplantation. MATERIALS AND METHODS: We conducted a retrospective cohort study involving 11,868 kidney transplant recipients from five medical centers. The association between tacrolimus exposures (periodic mean trough level, coefficient of variability, time in therapeutic range) and composite allograft outcome (de novo donor specific antibody, biopsy-proven rejection, kidney dysfunction, and graft failure), as well as safety outcomes (severe infection, cardiovascular events, malignancy, and mortality) were assessed. Data were sourced from Clinical Data Warehouses and analyzed using advanced statistical methods, including Cox marginal structural models with inverse probability treatment weighting. RESULTS: Tacrolimus levels of 5.0-7.9 ng/mL and 5.0-6.9 ng/mL during the 2-12 month and 12-72 month post-transplantation periods, respectively, were associated with reduced risks of composite allograft outcomes. During the first post-transplant year, the adjusted hazard ratios (aHR) for composite allograft outcomes were: 0.69 (95% CI 0.55-0.85, P<0.001) for 5.0-5.9 ng/mL; 0.81 (95% CI 0.67-0.98, P=0.033) for 6.0-6.9 ng/mL; and 0.73 (95% CI 0.60-0.89, P=0.002) for 7.0-7.9 ng/mL (compared to levels ≥8.0 ng/mL). For the 6-year composite outcomes, aHRs were 0.68 (95% CI 0.53-0.87, P=0.002) for 5.0-5.9 ng/mL and 0.65 (95% CI 0.50-0.85, P=0.001) for 6.0-6.9 ng/mL. These optimal ranges showed reduced rates of severe infection (6 y), malignancy (6 y), and mortality (1 y). CONCLUSION: This multicenter study provides robust evidence for optimal tacrolimus trough levels during the periods 2-12 and 12-72 months following kidney transplantation.

Donor fat-to-muscle ratio and kidney transplant outcomes: A proposition of metabolic memory.

AIMS: The impact of donor abdominal fat-to-muscle ratio (FMR) on kidney transplant (KT) outcomes was assessed. Given the transient nature of the donor's metabolic environment in transplant recipients, this study investigated the capacity of body composition to induce metabolic memory effects. MATERIALS AND METHODS: KT patients (n = 895) who received allografts from living donors (2003-2013) were included. Donor fat and muscle were quantified using pre-KT abdominal computed tomography scans. Patients were categorised into donor FMR tertiles and followed up for graft outcomes. Additionally, genome-wide DNA methylation analysis was performed on 28 kidney graft samples from KT patients in the low- and high-FMR groups. RESULTS: Mean recipient age was 42.9 ± 11.4 years and 60.9% were males. Donor FMR averaged 1.67 ± 0.79. Over a median of 120.9 ± 42.5 months, graft failure (n = 127) and death-censored graft failure (n = 109) were more frequent in the higher FMR tertiles. Adjusted hazard ratios for the highest versus lowest FMR tertile were 1.71 (95% CI, 1.06-2.75) for overall graft failure and 1.90 (95% CI, 1.13-3.20) for death-censored graft failure. Genome-wide DNA methylation analysis identified 58 differentially methylated regions (p < 0.05, |Δß| > 0.2) and 35 genes showed differential methylation between the high- (FMR >1.91) and low-FMR (FMR <1.27) groups. CONCLUSIONS: Donors with increased fat and reduced muscle composition may negatively impact kidney allograft survival in recipients, possibly through the transmission of epigenetic changes, implying a body-composition-related metabolic memory effect.

Association of Serum Osteoprotegerin With Vascular Calcification, and Cardiovascular and Graft Outcomes in Kidney Transplant Patients: Results From the KNOW-KT.

BACKGROUND: Vascular calcification and stiffness contribute to increased cardiovascular morbidity in patients with chronic kidney disease. This study investigated associations between serum osteoprotegerin (OPG) levels and vascular calcification or stiffness to assess cardiovascular and graft outcomes in kidney transplant patients. METHODS: The KoreaN cohort study for Outcome in patients With Kidney Transplantation was a prospective multicenter cohort study. Serum OPG levels were measured at baseline and 3 y after transplantation in 1018 patients. Patients were classified into high and low OPG groups according to median serum OPG levels. The median follow-up duration was 93.5 mo. RESULTS: The mean age was 45.8 ±â€…11.7 y and 62.9% were men. Patients with high OPG had significantly higher coronary artery calcium scores, abdominal aortic calcification scores, and brachial-ankle pulse wave velocities than those with lower OPG; these parameters remained significant for 5 y after transplantation. The 3-y OPG levels were lower than baseline values ( P < 0.001) and were positively correlated ( r = 0.42, P < 0.001). Multivariate Cox regression analysis showed that high OPG levels were significantly associated with posttransplant cardiovascular events ( P = 0.008) and death-censored graft loss ( P = 0.004). Similar findings regarding posttransplant cardiovascular events ( P = 0.012) and death-censored graft loss ( P = 0.037) were noted in patients with high OPG at the 3-y follow-up. Mediation analyses revealed that coronary artery calcium scores, abdominal aortic calcification scores, and brachial-ankle pulse wave velocities could act as mediators between serum OPG levels and posttransplant cardiovascular events. CONCLUSIONS: Serum OPG concentration is associated with vascular calcification and stiffness and could be a significant risk factor for cardiovascular outcomes and graft loss in patients undergoing kidney transplantation.

Association of Serum Activin Levels with Allograft Outcomes in Patients with Kidney Transplant: Results from the KNOW-KT.

INTRODUCTION: Serum activin A has been reported to contribute to vascular calcification and kidney fibrosis in chronic kidney disease. We aimed to investigate whether higher serum activin levels were associated with poor allograft outcomes in patients with kidney transplantation (KT). METHODS: A total of 860 KT patients from KNOW-KT (Korean Cohort Study for Outcome in Patients with Kidney Transplantation) were analyzed. We measured serum activin levels pre-KT and 1 year after KT. The primary outcome was the composite of a ≥50% decline in estimated glomerular filtration rate and graft failure. Multivariable cause-specific hazard model was used to analyze association of 1-year activin levels with the primary outcome. The secondary outcome was coronary artery calcification score (CACS) at 5 years after KT. RESULTS: During the median follow-up of 6.7 years, the primary outcome occurred in 109 (12.7%) patients. The serum activin levels at 1 year were significantly lower than those at pre-KT (488.2 ± 247.3 vs. 704.0 ± 349.6). When patients were grouped based on the median activin level at 1 year, the high-activin group had a 1.91-fold higher risk (95% CI, 1.25-2.91) for the primary outcome compared to the low-activin group. A one-standard deviation increase in activin levels as a continuous variable was associated with a 1.36-fold higher risk (95% CI, 1.16-1.60) for the primary outcome. Moreover, high activin levels were significantly associated with 1.56-fold higher CACS (95% CI, 1.12-2.18). CONCLUSION: Post-transplant activin levels were independently associated with allograft functions as well as coronary artery calcification in KT patients.

Benefits of statin therapy within a year after kidney transplantation.

Cardiovascular disease remains a leading cause of morbidity and mortality after kidney transplantation (KT). Although statins reduce cardiovascular risk and have renal benefits in the general population, their effects on KT recipients are not well-established. We studied the effects of early statin use (within 1-year post-transplantation) on long-term outcomes in 714 KT recipients from the Korean cohort study for outcome in patients with KT. Compared with the control group, statin group recipients were significantly older, had a higher body mass index, and had a higher prevalence of diabetes mellitus. During a median follow-up of 85 months, 74 graft losses occurred (54 death-censored graft losses and 20 deaths). Early statin use was independently associated with lower mortality (hazard ratio, 0.280; 95% confidence interval 0.111-0.703) and lower death-censored graft loss (hazard ratio, 0.350; 95% confidence interval 0.198-0.616). Statin therapy significantly reduced low-density lipoprotein cholesterol levels but did not decrease the risk of major adverse cardiovascular events. Biopsy-proven rejection and graft renal function were not significantly different between statin and control groups. Our findings suggest that early statin use is an effective strategy for reducing low-density lipoprotein cholesterol and improving patient and graft survival after KT.

Creatinine-cystatin C ratio and death with a functioning graft in kidney transplant recipients.

Death with a functioning graft is important cause of graft loss after kidney transplantation. However, little is known about factors predicting death with a functioning graft among kidney transplant recipients. In this study, we evaluated the association between post-transplant creatinine-cystatin C ratio and death with a functioning graft in 1592 kidney transplant recipients. We divided the patients into tertiles based on sex-specific creatinine-cystatin C ratio. Among the 1592 recipients, 39.5% were female, and 86.1% underwent living-donor kidney transplantation. The cut-off value for the lowest creatinine-cystatin C ratio tertile was 0.86 in males and 0.73 in females. The lowest tertile had a significantly lower 5-year patient survival rate and was independently associated with death with a functioning graft (adjusted hazard ratio 2.574, 95% confidence interval 1.339-4.950, P < 0.001). Infection was the most common cause of death in the lowest tertile group, accounting for 62% of deaths. A low creatinine-cystatin C ratio was significantly associated with an increased risk of death with a functioning graft after kidney transplantation.

Successful robotic kidney transplantation for surgeons with no experience in minimally invasive surgery: a single institution experience.

BACKGROUND: Robotic kidney transplantation (RKT) is a novel and welcomed innovation yielding good surgical outcomes. However, data on the feasibility and safety of performing RKT by surgeons with a lack of prior minimally invasive surgery (MIS) experience are limited. The authors aimed to evaluate the surgical and functional results of RKT and present the learning curves (LC) of RKT by a single surgeon with no prior experience in MIS. MATERIALS AND METHODS: This was a retrospective study of all RKT performed between November 2019 and April 2023 at Severance Hospital in Seoul, South Korea. The authors analyzed surgical and functional outcomes, as well as complication rates of RKT in comparison to open kidney transplantation (OKT). The authors evaluated LCs using the cumulative summation method to describe the number of cases associated with the competency of a single surgeon. RESULTS: A total of 50 patients who underwent RKT and 104 patients who underwent OKT were included in this study. In RKT group, the median surgical console time was 193 min (interquartile range, 172-222) and the median vascular anastomoses time was 38 min (35-44). Total operation time was 323 min (290-371) and rewarming time was 62.5 min (56.0-70.0) in RKT group compared to 210 min (190-239) and 25 min (21-30), respectively, in OKT group. Despite extended surgical durations with a robotic technique, both groups had comparable intraoperative and postoperative outcomes, as well as renal function. Estimated blood loss and post-transplant hospital stays were significantly lower in RKT group than in OKT group. LC analysis of RKT by the single surgeon revealed that surgical competence was achieved after 15 cases. CONCLUSION: Even if surgeons do not have prior experience with MIS, they can rapidly overcome the LC and safely perform RKT with adequate preparation and acquisition of basic robotic surgical techniques.

Clinical relevance of the living kidney donor profile index in Korean kidney transplant recipients.

BACKGROUND: The Living Kidney Donor Profile Index (LKDPI) was developed in the United States to predict graft outcomes based on donor characteristics. However, there are significant differences in donor demographics, access to transplantation, proportion of ABO incompatibility, and posttransplant mortality in Asian countries compared with the United States. METHODS: We evaluated the clinical relevance of the LKDPI score in a Korean kidney transplant cohort by analyzing 1860 patients who underwent kidney transplantation between 2000 and 2019. Patients were divided into three groups according to LKDPI score: <0, 1-19.9, and ≥20. RESULTS: During a median follow-up of 119 months, 232 recipients (12.5%) experienced death-censored graft loss, and 98 recipients (5.3%) died. High LKDPI scores were significantly associated with increased risk of death-censored graft loss independent of recipient characteristics (LKDPI 1-19.9: HR 1.389, 95% CI 1.036-1.863; LKDPI ≥20: HR 2.121, 95% CI 1.50-2.998). High LKDPI score was also significantly associated with increased risk of biopsy-proven acute rejection and impaired graft renal function. By contrast, overall patient survival rates were comparable among the LKDPI groups. CONCLUSION: High LKDPI scores were associated with an increased risk of death-censored graft loss, biopsy-proven acute rejection, and impaired graft renal function among a Korean kidney transplant cohort.

Outcomes of ABO-Incompatible Living Donor Kidney Transplantation Compared to Waiting or Deceased Donor Kidney Transplantation.

INTRODUCTION: ABO-incompatible (ABOi) living donor kidney transplantation (LDKT) is considered only for patients who do not have an ABO-compatible (ABOc) LD. Therefore, a clinically practical question is whether to proceed with ABOi LDKT or remain on dialysis while waiting for ABOc deceased donor kidney transplantation (DDKT). However, this issue has not been addressed in Asian countries, where ABOi LDKT programs are more active than DDKT programs. METHODS: A total of 426 patients underwent ABOi-LDKT between 2010 and 2020 at Seoul National University Hospital and Severance Hospital, Korea. We compared outcomes between the ABOi-LDKT and the propensity-matched control groups (waiting-list-only group, n = 1,278; waiting-list-or-ABOc-DDKT group, n = 1,278). RESULTS: The ABOi-LDKT group showed a significantly better patient survival rate than the waiting-list-only group (p = 0.001) and the waiting-list-or-ABOc-DDKT group (p = 0.048). When the ABOi-LDKT group was categorized into a high-titer group (peak anti-ABO titer ≥1:128) and a low-titer group (peak anti-ABO titer ≤1:64), the low-titer group showed better patient survival rates than those of the waiting-list-or-ABOc-DDKT group (p = 0.046) or the waiting-list-only group (p = 0.004). In contrast, the high-titer ABOi-LDKT group showed no significant benefit in patient survival compared to the waiting-list-or-ABOc-DDKT group. Death-censored graft survival in the ABOi-LDKT group was not significantly different from that in the ABOc-DDKT group (p = 0.563). CONCLUSION: The ABOi-LDKT group has better outcomes than the waiting-list-or-ABOc-DDKT group in a country with a long waiting time.

High pretransplant FGF23 level is associated with persistent vitamin D insufficiency and poor graft survival in kidney transplant patients.

Vitamin D3 (25[OH]D3) insufficiency and fibroblast growth factor 23 (FGF23) elevation are usually attenuated after kidney transplantation (KT). However, elevated FGF23 may be associated with poor graft outcomes and vitamin D insufficiency after KT. This study investigated the effect of pretransplant FGF23 levels on post-KT 25(OH)D3 status and graft outcomes. Serum FGF23 levels from 400 participants of the KoreaN Cohort Study for Outcome in Patients With Kidney Transplantation were measured. Annual serum 25(OH)D3 levels, all-cause mortality, cardiovascular event, and graft survival were assessed according to baseline FGF23 levels. Serum 25(OH)D3 levels were initially increased 1 year after KT (12.6 ± 7.4 vs. 22.6 ± 6.4 ng/mL). However, the prevalence of post-KT vitamin D deficiency increased again after post-KT 3 years (79.1% at baseline, 30.8% and 37.8% at 3 and 6 years, respectively). Serum FGF23 level was decreased 3 years post-KT. When participants were categorized into tertiles according to baseline FGF23 level (low, middle, high), 25(OH)D3 level in the low FGF23 group was persistently low at a median follow-up of 8.3 years. Furthermore, high baseline FGF23 level was a risk factor for poor graft survival (HR 5.882, 95% C.I.; 1.443-23.976, P = 0.013). Elevated FGF23 levels are associated with persistently low post-transplant vitamin D levels and poor graft survival.

Survival Benefit of Kidney Transplantation in Patients With End-Stage Kidney Disease and Prior Acute Myocardial Infarction.

Patients with end stage kidney disease (ESKD) and a previous acute myocardial infarction (AMI) have less access to KT. Data on ESKD patients with an AMI history who underwent first KT or dialysis between January 2007 and December 2018 were extracted from the Korean National Health Insurance Service. Patients who underwent KT (n = 423) were chronologically matched in a 1:3 ratio with those maintained on dialysis (n = 1,269) at the corresponding dates, based on time-conditional propensity scores. The 1, 5, and 10 years cumulative incidences for all-cause mortality were 12.6%, 39.1%, and 60.1% in the dialysis group and 3.1%, 7.2%, and 14.5% in the KT group. Adjusted hazard ratios (HRs) of KT versus dialysis were 0.17 (95% confidence interval [CI], 0.12-0.24; p < 0.001) for mortality and 0.38 (95% CI, 0.23-0.51; p < 0.001) for major adverse cardiovascular events (MACE). Of the MACE components, KT was most protective against cardiovascular death (HR, 0.23; 95% CI, 0.12-0.42; p < 0.001). Protective effects of KT for all-cause mortality and MACE were consistent across various subgroups, including patients at higher risk (e.g., age >65 years, recent AMI [<6 months], congestive heart failure). KT is associated with lower all-cause mortality and MACE than maintenance dialysis patients with a prior AMI.

Association between sclerostin levels and vascular outcomes in kidney transplantation patients.

BACKGROUND: The impact of circulating sclerostin levels on vascular calcification has shown conflicting results depending on the target population and vascular anatomy. This study investigated the associations of sclerostin levels with vascular outcomes in kidney transplant patients. METHODS: In a prospective observational study of the Korean Cohort Study for Outcome in Patients with Kidney Transplantation, 591 patients with serum sclerostin level data prior to transplantation were analyzed. The main predictor was the pre-transplant sclerostin level. Vascular outcomes were the abdominal aortic calcification score and brachial-ankle pulse wave velocity measured at pre-transplant screening and three and five years after kidney transplantation. RESULTS: In linear regression analysis, sclerostin level positively correlated with changes in abdominal aortic calcification score between baseline and five years after kidney transplantation (coefficient of 0.73 [95% CI, 0.11-1.35] and 0.74 [95% CI, 0.06-1.42] for second and third tertiles, respectively, vs the first tertile). In a longitudinal analysis over five years, using generalized estimating equations, the coefficient of the interaction (sclerostin × time) was significant with a positive value, indicating that higher sclerostin levels were associated with faster increase in post-transplant abdominal aortic calcification score. Linear regression analysis revealed a positive association between pre-transplant sclerostin levels and changes in brachial-ankle pulse wave velocity (coefficient of 126.7 [95% CI, 35.6-217.8], third vs first tertile). Moreover, a significant interaction was identified between sclerostin levels and brachial-ankle pulse wave velocity at five years. CONCLUSIONS: Elevated pre-transplant sclerostin levels are associated with the progression of post-transplant aortic calcifications and arterial stiffness.

Comparison of high-dose IVIG and rituximab versus rituximab as a preemptive therapy for de novo donor-specific antibodies in kidney transplant patients.

De novo donor-specific antibody (dnDSA) is associated with a higher risk of kidney graft failure. However, it is unknown whether preemptive treatment of subclinical dnDSA is beneficial. Here, we assessed the efficacy of high-dose intravenous immunoglobulin (IVIG) and rituximab combination therapy for subclinical dnDSA. An open-label randomized controlled clinical trial was conducted at two Korean institutions. Adult (aged ≥ 19 years) kidney transplant patients with subclinical class II dnDSA (mean fluorescence intensity ≥ 1000) were enrolled. Eligible participants were randomly assigned to receive rituximab or rituximab with IVIG at a 1:1 ratio. The primary endpoint was the change in dnDSA titer at 3 and 12 months after treatment. A total of 46 patients (24 for rituximab and 22 for rituximab with IVIG) were included in the analysis. The mean baseline estimated glomerular filtration rate was 66.7 ± 16.3 mL/min/1.73 m2. The titer decline of immune-dominant dnDSA at 12 months in both the preemptive groups was significant. However, there was no difference between the two groups at 12 months. Either kidney allograft function or proteinuria did not differ between the two groups. No antibody-mediated rejection occurred in either group. Preemptive treatment with high-dose IVIG combined with rituximab did not show a better dnDSA reduction compared with rituximab alone.Trial registration: IVIG/Rituximab versus Rituximab in Kidney Transplant With de Novo Donor-specific Antibodies (ClinicalTrials.gov Identifier: NCT04033276, first trial registration (26/07/2019).

The first successful eculizumab rescue therapy of a kidney transplant recipient with atypical hemolytic uremic syndrome in South Korea: a case report.

Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) that can result in end-stage renal disease. Patients with aHUS often have predisposing dysfunction in the complement pathway, and continuous activation of complement proteins can be triggered after transplantation. Here, we report the first successful case of aHUS treatment in a kidney transplant recipient with early use of a C5 inhibitor, eculizumab, in South Korea. The patient was a 32-year-old man, and the donor was his 60-year-old mother. The graft showed immediate good function. On postoperative day (POD) 3, the clinical diagnosis of TMA was made. Persistent renal dysfunction despite 10 plasma exchange (PE) sessions prompted eculizumab treatment on POD 18 under suspicion of aHUS. Next-generation sequencing reported gene mutations classified as variants of unknown significance in coagulation-associated genes. The patient was discharged after three doses of eculizumab with serum creatinine of 1.82 mg/dL. In total, 16 doses of eculizumab were administered. At the last follow-up, 21 months after eculizumab discontinuation, the graft was well functioning. De novo TMA after kidney transplantation can be caused by sustained activation of the complement pathway, and early eculizumab treatment appears important in the successful treatment of aHUS refractory to PE.

Impact of ABO incompatibility and early antibody-mediated rejection on chronic antibody-mediated rejection in kidney transplant patients.

INTRODUCTION: Early antibody-mediated rejection has been reported to increase chronic antibody-mediated rejection and decrease graft survival in kidney transplantation. However, the impact of early antibody-mediated rejection in ABO-incompatible kidney transplantation remains unclear. METHODS: We retrospectively analyzed living-donor kidney transplantation patients from two Korean centers. Patients were categorized based on ABO compatibility and early antibody-mediated rejection within 1 year. The primary outcome was chronic antibody-mediated rejection. The secondary outcomes were production of de novo donor-specific antibody and composite kidney outcome, defined as graft loss or a decline in estimated glomerular filtration rate to below 30 mL/min/1.73 m2. RESULTS: A total of 1639 patients were analyzed, including 1292 patients who underwent ABO-compatible kidney transplantation and 347 patients who underwent ABO-incompatible kidney transplantation. ABO-incompatible kidney transplantation had a lower risk of de novo donor-specific antibody production (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.48-0.95) and chronic antibody-mediated rejection (HR 0.33, 95% CI 0.12-0.92) with a comparable risk of the composite kidney outcome (HR 1.06, 95% CI 0.71-1.59) compared to ABO-compatible kidney transplantation. When outcomes of ABO-incompatible kidney transplantation were analyzed according to early antibody-mediated rejection, ABO-incompatible kidney transplantation without antibody-mediated rejection had a lower risk of de novo donor-specific antibody production (HR 0.60, 95% CI 0.41-0.88) and chronic antibody-mediated rejection (HR 0.28, 95% CI 0.09-0.91) than ABO-compatible kidney transplantation without antibody-mediated rejection. However, ABO-incompatible kidney transplantation with antibody-mediated rejection showed a higher risk of de novo donor-specific antibody production and similar risk of chronic antibody-mediated rejection compared to ABO-compatible kidney transplantation without antibody-mediated rejection. CONCLUSIONS: ABO-incompatible kidney transplantation showed a lower risk of de novo donor-specific antibody production and chronic antibody-mediated rejection compared to ABO-compatible kidney transplantation; however, early antibody-mediated rejection abrogated these beneficial effects of ABO-incompatible kidney transplantation.

Changes in Cardiac Structure and Function After Kidney Transplantation: A New Perspective Based on Strain Imaging.

BACKGROUND: We aimed to investigate left ventricular (LV) global longitudinal strain (GLS) in end-stage renal disease patients and its change after kidney transplantation (KT). METHODS: We retrospectively reviewed patients who underwent KT between 2007 and 2018 at two tertiary centers. We analyzed 488 patients (median age, 53 years; 58% male) who had obtained echocardiography both before and within 3 years after KT. Conventional echocardiography and LV GLS assessed by two-dimensional speckle-tracking echocardiography were comprehensively analyzed. Patients were classified into three groups according to the absolute value of pre-KT LV GLS (|LV GLS|). We compared longitudinal changes of cardiac structure and function according to pre-KT |LV GLS|. RESULTS: Correlation between pre-KT LV EF and |LV GLS| were statistically significant, but the constant was not high (r = 0.292, p < 0.001). |LV GLS| was widely distributed at corresponding LV EF, especially when the LV EF was > 50%. Patients with severely impaired pre-KT |LV GLS| had significantly larger LV dimension, LV mass index, left atrial volume index, and E/e' and lower LV EF, compared to mildly and moderately reduced pre-KT |LV GLS|. After KT, the LV EF, LV mass index, and |LV GLS| were significantly improved in three groups. Patients with severely impaired pre-KT |LV GLS| showed the most prominent improvement of LV EF and |LV GLS| after KT, compared to other groups. CONCLUSIONS: Improvements in LV structure and function after KT were observed in patients throughout the full spectrum of pre-KT |LV GLS|.

Comparison of humoral immunogenicity in solid organ transplant recipients after third-dose mRNA vaccine with homologous or heterologous schedules: An observational study.

BACKGROUND: Solid organ transplant recipients (SOTRs) are susceptible to severe coronavirus disease 2019 (COVID-19); however, immunogenicity studies of the Omicron variants per vaccination schedules are still lacking. We examined humoral immunogenicity following third-dose mRNA vaccine administration in Korean SOTRs who received primary COVID-19 vaccine series on homologous or heterologous schedules. METHODS: We recruited SOTRs at Severance Hospital from October 27, 2021, to March 31, 2022. Blood samples were collected between 14 days and 5 months after the second and third mRNA vaccine (BNT162b2 or mRNA-1273) doses. SARS-CoV-2 anti-spike IgG titer was analyzed. The neutralization inhibition rate was analyzed using the surrogate neutralization assay for the wild-type, Delta, and Omicron variants. RESULTS: No significant differences existed in the SARS-CoV-2 anti-spike IgG positivity rate between the homologous BNT162b2/BNT162b2/BNT162b2 (85%) and other heterologous groups (83% of ChAdOx1/ChAdOx1/BNT162b2, 90% of ChAdOx1/ChAdOx1/mRNA-1273, and 78% of ChAdOx1/BNT162b2/BNT162b2). No significant difference existed in the neutralization inhibition rates between the four groups for wild-type, Delta, and Omicron variants. Median neutralization inhibition rates against the Omicron variant (2-5%) were significantly lower than those against the wild-type (87-97%) and Delta (55-89%) variants (P < 0.001). CONCLUSIONS: Regardless of the schedule, the neutralization inhibition rate against the Omicron variant was poor; therefore, additional preventive measures are required in such high-risk populations.

Impact of iron status on kidney outcomes in kidney transplant recipients.

Iron plays an important role in hemodynamics and the immunity, independent of anemia. Since dynamic changes occur in iron storage after kidney transplantation (KT), we investigated the association between iron status and kidney outcomes in KT patients. We analyzed data from the KoreaN cohort study for Outcome in patients With KT (KNOW-KT). The iron status was classified into three groups based on ferritin or transferrin saturation (TSAT) levels one year after KT, with reference ranges of 20‒35% and 100‒300 ng/mL for TSAT and ferritin, respectively. The primary outcome was the composite outcome, which consisted of death, graft failure, and an estimated glomerular filtration rate decline ≥ 50%. In total, 895 patients were included in the final analysis. During a median follow-up of 5.8 years, the primary outcome occurred in 94 patients (19.8/1000 person-years). TSAT levels decreased one year after KT and thereafter gradually increased, whereas ferritin levels were maintained at decreased levels. The adjusted hazard ratios (95% confidence intervals) for the composite outcome were 1.67 (1.00-2.77) and 1.20 (0.60-2.40) in the TSAT > 35% and ferritin > 300 ng/mL groups, respectively. High iron status with high TSAT levels increases the risk of graft failure or kidney functional deterioration after KT.

Low skeletal muscle mass is associated with mortality in kidney transplant recipients.

Muscle wasting in chronic kidney disease is associated with increased cardiovascular events, morbidity, and mortality. However, whether pretransplantation skeletal muscle mass affects kidney transplantation (KT) outcomes has not been established. We analyzed 623 patients who underwent KT between 2004 and 2019. We measured the cross-sectional area of total skeletal muscle at the third lumbar vertebra level on pretransplantation computed tomography scan. The patients were grouped into low and normal skeletal muscle mass groups based on the sex-specific skeletal muscle mass index lowest quartile. During the entire follow-up period, 45 patients (7.2%) died and 56 patients (9.0%) experienced death-censored graft loss. Pretransplantation low skeletal muscle mass was independently associated with all-cause mortality (adjusted hazard ratio, 2.269; 95% confidence interval, 1.232-4.182). Low muscle mass was also associated with an increased risk of hospital readmission within 1 year after transplantation. Death-censored graft survival rates were comparable between the 2 groups. The low muscle group showed higher creatinine-based estimated glomerular filtration rates (eGFRs) than the normal muscle group. Although cystatin C-based eGFRs were measured in only one-third of patients, cystatin C-based eGFRs were comparable between the 2 groups. Pretransplantation low skeletal muscle mass index is associated with an increased risk of mortality and hospital readmission after KT.