Purpose: Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs. Materials and Methods: We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 . Results: During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome. Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.

The usefulness of the living kidney donor profile index (LKDPI) has not been widely demonstrated; therefore, it requires verification before clinical application. We analyzed the LKDPI using data from the Korean Organ Transplantation Registry (KOTRY) to confirm whether the LKDPI can be used to predict the survival of allografts in living donor kidney transplantation (LDKT) patients in Korea. Methods: The study population was obtained from the KOTRY database. A total of 2,598 kidney recipients registered in the KOTRY database were enrolled between May 2014 and December 2020. Donor and recipient information was observed, and the LKDPI was measured. Results: Median LKDPI score was 15.5 with a follow-up duration of 33.7 ± 16.1 months. According to LKDPI scores (group 1, <0; group 2, 0–20; group 3, 20–40; and group 4, >40), LKDPI group 4 had significantly higher death-censored graft loss than LKDPI group 1 (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.06– 3.40; p = 0.03). When divided based on the cutoff value (LKDPI, 36.6), the high LKDPI group had higher graft loss than the low LKDPI group (HR, 2.14; 95% CI, 1.37–3.34; p < 0.001). When follow-up was repeated after transplantation, it was confirmed that the higher the LKDPI value was, the lower the average estimated glomerular filtration rate (p < 0.001). Conclusion: This study confirmed that LKDPI can serve as an independent predictor for assessing the risk of allograft failure and transplant outcomes in Korean LDKT patients.

Cardiovascular disease is an important risk factor for mortality among kidney transplant recipients. In this study, we aimed to investigate the association between cardiovascular risk score at kidney transplantation and long-term outcomes of patients. Methods: In this prospective, observational cohort study, we enrolled kidney transplant recipients who participated in the Korean Organ Transplantation Registry and underwent transplantation between April 2014 and December 2019. The cardiovascular risk status of kidney transplant recipients was assessed using the Framingham risk score. All-cause mortality, major adverse cardiovascular events, allograft failure, estimated glomerular filtration rates (eGFRs), and composite outcomes were evaluated after kidney transplantation. Results: Of the 4,682 kidney transplant recipients, 96 died during 30.7 ± 19.1 months of follow-up. The Kaplan-Meier survival analysis results showed that high Framingham risk scores were associated with all-cause mortality, major adverse cardiovascular events, and composite outcomes. According to the multivariable Cox analysis, high Framingham risk scores were associated with an increased risk of mortality (hazard ratio [HR], 3.20; 95% confidence interval [CI], 1.30–7.91), major adverse cardiovascular events (HR, 8.43; 95% CI, 2.41–29.52), and composite outcomes (HR, 2.05; 95% CI, 1.19–3.46). The eGFRs after transplantation were significantly higher among patients in the low Framingham risk score group (p < 0.001). However, Framingham risk scores were not associated with graft loss or rapid decline in eGFRs. Conclusion: The Framingham risk score is a useful indicator of cardiovascular events, mortality, and kidney function after kidney transplantation.

Living kidney donors with hypertension are potential candidates for solving the donor shortages in renal transplantation. However, the safety of donors with hypertension after nephrectomy has not been sufficiently confirmed. Methods: A total of 642 hypertensive and 4,848 normotensive living kidney donors who were enrolled in the Korean Organ Transplantation Registry between May 2014 and December 2020 were included in this study. The study endpoints were a decreased estimated glomerular filtration rate (eGFR) and proteinuria. Results: In the entire cohort, donors with hypertension had a lower eGFR before nephrectomy in comparison to normotensive donors which remained lower after kidney transplantation. The incidence of proteinuria in hypertensive donors increased during follow-up. In propensity score-matched analysis, the risk of eGFR being <60 mL/min/1.73 m2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.50–1.19) or <45 mL/min/1.73 m2 (HR, 0.50; 95% CI, 0.06–4.03) was not significantly increased in donors with hypertension. However, hypertensive donors were found to have a significantly higher risk of proteinuria than normotensive donors (HR, 2.28; 95% CI, 1.05–4.94). Similar findings were also observed in the analysis of the entire cohort, indicating that hypertensive donors had a significantly higher risk of proteinuria (adjusted HR, 1.77; 95% CI, 1.10–2.85), without a substantial increase in the risk of decreased renal function. Conclusion: The risk of proteinuria after donation was substantially increased in donors with hypertension. These findings underscore the need for careful monitoring of proteinuria in hypertensive donors following donation.

Background: Although insulin resistance is common, its significance in kidney transplant recipients remains unclear. We explored clinical implications of the triglyceride-glucose (TyG) index as a marker for unfavorable allograft outcomes in kidney transplant recipients. Methods: A total of 6,354 kidney transplant recipients were enrolled in a multicenter prospective cohort study between May 2014 and December 2022. The TyG index was assessed between 6 and 12 months after transplantation. We evaluated the association between the TyG index and the risk of adverse kidney outcomes. Results: The cumulative rates of ≥50% decline in estimated glomerular filtration rate (eGFR), death-censored graft survival, and major adverse kidney events differed across TyG index quartiles, with the highest rate observed in quartile 4 (p < 0.001). TyG index quartile 4 was associated with the highest risk of death-censored graft loss after multivariable adjustment (adjusted hazard ratio, 2.13; 95% confidence interval [CI], 1.28–3.55). The risk of ≥30% decline in eGFR was 1.46 times higher (95% CI, 1.17–1.82) in quartile 4 compared with quartile 1, and the risk of ≥50% decline was 1.78 times higher (95% CI, 1.30–2.44). Quartile 4 also showed a significantly steeper decline in renal function, with an adjusted mean difference in eGFR slope of –4.72 mL/min/1.73 m2 (95% CI, –7.39 to –2.04). Conclusion Kidney transplant recipients with high TyG index were at increased risk of eGFR decline and graft loss, and also exhibited a more rapid deterioration in renal function. The TyG index is a useful marker for identifying individuals at high risk for adverse graft outcomes.

Background: Posttransplant diabetes mellitus (PTDM) complicates kidney transplant recipients (KTRs) in morbidity and mortality. This study aimed to predict PTDM risk in KTRs using machine learning and deep learning models. Methods: Data were obtained from the Korea Organ Transplantation Registry, a nationwide cohort study of KTRs. Four machine learning algorithms, including eXtreme Gradient Boosting (XGBoost), CatBoost, light gradient boosting machine and logistic regression, and deep learning were implemented on 41 pretransplant and 31 posttransplant variables to predict PTDM. Model performance was assessed using the area under the curve (AUC) of the receiver operating characteristic curve, accuracy, precision, recall, and F1 score. Results: Among 3,213 KTRs, 497 patients (15.5%) developed PTDM within 1 year. The PTDM group had higher age, body mass index (BMI), triglyceride level, and prevalence of hypertension and cardiovascular disease, and lower total cholesterol level at baseline than the No-PTDM group. The XGBoost model showed the highest AUC (0.738) and F1 score (0.42), and modest accuracy (0.86), while the CatBoost model exhibited the highest accuracy (0.87) and precision (0.79). Feature importance in XGBoost was highest for recipient age, followed by baseline BMI, triglyceride level at posttransplant 6 months, baseline glycated hemoglobin and high-density lipoprotein cholesterol level, white blood cell (WBC) count and serum uric acid level at 6 months, baseline WBC count, and tacrolimus trough level at discharge. Conclusion The XGBoost model demonstrated the best performance for predicting PTDM within 1 year, offering an accurate tool for early identification and personalized care of high-risk KTRs for PTDM.

Patients with sensitization and blood type O experience increased waiting times for deceased-donor kidney transplantation (DDKT). While allocation benefits are needed to resolve inequity in DDKT opportunity, whether DDKT has comparable outcomes in this disadvantaged population requires further study. This study assessed these outcomes and developed a new allocation system that balances equity and utility. Methods: Patients from national and hospital cohorts from two centers in Korea were categorized as B1 to B4 (according to panel reactive antibody [PRA] positivity and ABO blood type) and A1 to A4 (based on the maximal PRA% and blood type), respectively. Competing risk and Cox regression analyses were performed to assess the effects of PRA and blood type on graft failure and mortality, respectively. Based on DDKT opportunities and posttransplant outcomes, a new scoring system for kidney allocation was developed. Results: The national and hospital cohorts included 3,311 and 819 patients, respectively, who underwent DDKT. Despite the disparities in DDKT opportunities, the graft failure rates and mortality did not differ among the different PRA and blood type groups. Furthermore, posttransplantation outcomes did not differ according to the categories with different DDKT opportunities. A new scoring system to provide additional points to disadvantaged populations was developed based on the hazard ratios for DDKT. Conclusion: A new allocation approach based on PRA and ABO blood types offers benefits to disadvantaged patients with fewer DDKT opportunities and could enhance equity without sacrificing utility in Korea, which has a long waiting time for DDKT.

Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways.B cells also significantly contribute to the indirect presentation of antigens to T cells.Innate immune cells, such as dendritic cells, identify pathogen- or danger-associated molecular patterns through pattern recognition receptors, thereby facilitating effective antigen presentation to T cells. Recent studies have shown that innate immune cells, including macrophages and NK cells, can recognize allogeneic or xenogeneic antigens using immune receptors like CD47 or activating NK receptors, instead of pattern recognition receptors. Additionally, macrophages and NK cells are capable of exhibiting memory responses to alloantigens, although these responses are shorter than those of adaptive memory. T cells also recognize xenoantigens through either direct or indirect presentation. Notably, macrophages and NK cells can directly recognize xenoantigens via surface immune receptors in an antibody-independent manner, or they can be activated in an antibody-dependent manner. Advances in our understanding of the recognition mechanisms of adaptive and innate immunity against allogeneic and xenogeneic antigens may improve our understanding of graft rejection.

Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways.B cells also significantly contribute to the indirect presentation of antigens to T cells.Innate immune cells, such as dendritic cells, identify pathogen- or danger-associated molecular patterns through pattern recognition receptors, thereby facilitating effective antigen presentation to T cells. Recent studies have shown that innate immune cells, including macrophages and NK cells, can recognize allogeneic or xenogeneic antigens using immune receptors like CD47 or activating NK receptors, instead of pattern recognition receptors. Additionally, macrophages and NK cells are capable of exhibiting memory responses to alloantigens, although these responses are shorter than those of adaptive memory. T cells also recognize xenoantigens through either direct or indirect presentation. Notably, macrophages and NK cells can directly recognize xenoantigens via surface immune receptors in an antibody-independent manner, or they can be activated in an antibody-dependent manner. Advances in our understanding of the recognition mechanisms of adaptive and innate immunity against allogeneic and xenogeneic antigens may improve our understanding of graft rejection.

Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways.B cells also significantly contribute to the indirect presentation of antigens to T cells.Innate immune cells, such as dendritic cells, identify pathogen- or danger-associated molecular patterns through pattern recognition receptors, thereby facilitating effective antigen presentation to T cells. Recent studies have shown that innate immune cells, including macrophages and NK cells, can recognize allogeneic or xenogeneic antigens using immune receptors like CD47 or activating NK receptors, instead of pattern recognition receptors. Additionally, macrophages and NK cells are capable of exhibiting memory responses to alloantigens, although these responses are shorter than those of adaptive memory. T cells also recognize xenoantigens through either direct or indirect presentation. Notably, macrophages and NK cells can directly recognize xenoantigens via surface immune receptors in an antibody-independent manner, or they can be activated in an antibody-dependent manner. Advances in our understanding of the recognition mechanisms of adaptive and innate immunity against allogeneic and xenogeneic antigens may improve our understanding of graft rejection.