Immunosenescence gradually deteriorates the function of the immune system, making elderly patients susceptible to infection, while reducing rejection of organ transplants. Therefore, age-adaptive immunosuppression is necessary in the elderly. We evaluated clinical outcomes such as rejection and infection rate when using basiliximab and rabbit anti-thymocyte globulin (r-ATG) as induction agents in elderly and young organ transplant recipients. Methods: We retrospectively reviewed patients who underwent kidney transplantation (KT) between June 2011 and April 2019. We enrolled 704 adult KT patients and classified the patients into groups according to patient age. We compared the outcomes of infection and biopsy-proven acute rejection (BPAR) according to the type of induction agent (basiliximab and r-ATG [4.5 mg/kg]). Results: The patient group included 520 recipients (74.6%) in the younger recipient group and 179 recipients (25.4%) in the older recipient group. When r-ATG was used as an induction agent, BPAR within 6 months occurred less (p = 0.03); however, infections within 6 months were higher in older recipients. Deaths due to infection were more common in older recipients (p = 0.003). Conclusion: It may be necessary to use less intensive induction therapy for older recipients, of which dose reduction of r-ATG is one option.

Background: Calcineurin inhibitor (CNI) toxicity is a significant cause of graft dysfunction in kidney transplant recipients, yet distinguishing it from acute rejection (AR) and acute tubular necrosis (ATN) remains challenging. This study investigated the use of urinary mRNA biomarkers as a noninvasive tool for identifying CNI toxicity. Methods: We retrospectively enrolled 110 kidney transplant recipients and classified them into four groups based on pathological findings: stable graft function (n=35), CNI toxicity (n=25), AR (n=30), and ATN (n=20). Candidate biomarkers were selected using the GEO database. Urinary mRNA was extracted from cell pellets, reverse-transcribed, and quantified by real-time polymerase chain reaction. Results: Estimated glomerular filtration rates were comparable among the CNI toxicity, AR, and ATN groups. Four transcripts (LTF, NNMT, WFDC2, and HIF1A) were identified as candidate biomarkers. Urinary mRNA levels of LTF, NNMT, and HIF1A were significantly lower in the CNI toxicity group than the AR group. NNMT and HIF1A levels were also significantly lower than those observed in the ATN group. In contrast, WFDC2 levels did not differ significantly across groups. A three-gene signature (LTF, NNMT, and HIF1A) effectively differentiated CNI toxicity from AR and ATN (area under the curve [AUC], 0.867;95% confidence interval [CI], 0.787–0.947) and significantly enhanced the diagnostic performance of the clinical variable-based model (AUC increased from 0.776; 95% CI, 0.660–0.892, to 0.934; 95% CI, 0.881–0.986). Conclusions Urinary mRNA levels of LTF, NNMT, and HIF1A may serve as useful biomarkers for identifying CNI toxicity in kidney transplant recipients with graft dysfunction.

Purpose: This study evaluated the role of donor kidney ultrasonography (US) for predicting functional kidney volume and identifying ideal kidney grafts in deceased donor kidney transplantation. Methods: In total, 272 patients who underwent deceased donor kidney transplantation from 2000 to 2020 at Samsung Medical Center were enrolled. Donor kidney information (i.e., right or left) was provided to the radiologist who performed US image re-analysis. To binarize each kidney’s ultrasound parameters, an optimal cutoff value for estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2 within 1 year after kidney transplantation was selected using the receiver operating characteristic curve with a specificity >60%. Cox regression analysis was performed for an eGFR less than 30 mL/min/1.73 m2 within 1 year after kidney transplantation and graft failure within 2 years after kidney transplantation. Results: The product of renal length and cortical thickness was a statistically significant predictor of graft function. The odds ratios of an eGFR less than 30 mL/min/1.73 m2 within a year after kidney transplantation and the hazard ratio of graft failure within 2 years after kidney transplantation were 5.91 (P=0.003) and 5.76 (P=0.022), respectively. Conclusion Preoperative US of the donor kidney can be used to evaluate donor kidney function and can predict short-term graft survival. An imaging modality such as US should be included in the donor selection criteria as an additional recommendation. However, the purpose of this study was not to narrow the expanded criteria but to avoid catastrophic consequences by identifying ideal donor kidneys using preoperative US.

Background: The use of organs from donors with infection is limited because of the possibility of transmission. We aimed to investigate the transmission after deceased donor transplantation with bloodstream infection (BSI). Methods: A retrospective study of patients undergoing kidney or pancreas transplantation at five tertiary centers in Korea from January 2009 and November 2019 was performed. We analyzed the outcomes after transplantation from deceased donors with BSI. Results: Eighty-six recipients received transplantation from 69 donors with BSI. The most common isolated pathogens from donors were Gram-positive bacteria (72.0%), followed by Gram-negative bacteria (22.7%), and fungi (5.3%). Appropriate antimicrobial agents were used in 47.8% of donors before transplantation. Transmission occurred only in 1 of 83 recipients (1.2%) from bacteremic donors and 1 of 6 recipients (16.7%) from fungemic donors. One-year patient and graft survival was 97.5%and 96.3%, respectively. There was no significant difference in graft and patient survival between patients who received organs from infected donors and noninfected donors. Conclusion Using organs from donors with bacteremia seems to be a safe option with low transmission risk. The overall prognosis of using organs from donors with BSI is favorable.

Basiliximab (BSX) and antithymocyte globulins (ATGs), are two major immunosuppressive agents commonly used as induction therapy for kidney transplant (KT) recipients. The superiority of ATG over BSX has not been well established, especially in elderly KT recipients with low immunological risk. Methods: A total of 847 elderly (≥60 years old), low-risk KT patients in the Korean Organ Transplantation Registry were propensity score-matched at a 1:2 ratio and compared according to ATG or BSX induction therapy. The primary outcome was patient and graft survival and biopsy-proven acute cellular rejection. The secondary outcome was graft function, BK virus nephropathy, infection, cancer, new-onset diabetes mellitus after transplantation (NODAT), and delayed graft function. Results: In total, 165 patients in the ATG group were matched with 298 patients in the BSX group with average ages of 64.3 and 64.2 years, respectively. During a follow-up of 28.5 ± 10.4 months, the cumulative probabilities of death-censored graft failure at 3 years posttransplantation were 1.3% and 1.4% in ATG and BSX groups, respectively, without a significant difference (p = 0.72). The cumulative probability of NODAT at 3 years posttransplantation was significantly higher in the BSX group (35.6% vs. 21.6%, p = 0.02). The median tacrolimus trough level was significantly lower at 6 months after KT in the ATG group (5.7 ng/mL vs. 6.4 ng/mL, p = 0.001). There were no differences in the other evaluated outcomes. Conclusion: Compared with BSX, in elderly, low-risk KT patients, ATG reduced tacrolimus and steroid requirements without differences in all-cause mortality, rejection, or infection, resulting in a reduced NODAT incidence.

Proteinuria is associated with poor allograft and patient survival in kidney transplant recipients. However, the clinical relevance of spot urine protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) as predictors of renal outcomes during the early postoperative period following kidney transplantation (KT) has not been determined. Methods: This single-center retrospective cohort study included 353 kidney transplant recipients who underwent KT between 2014 and 2017 and were followed up for more than 3 years. Among them, 186 and 167 recipients underwent living donor KT and deceased donor KT, respectively. The PCR and ACR were measured during the immediate postoperative period (within 7 days postoperatively), before discharge (2–3 weeks postoperatively), and 3–6 months postoperatively. Results: The median age of the patients was 51 years (interquartile range, 43–59 years), and 62.9% were male. An immediate postoperative PCR of ≥1 mg/mg was associated with old age, diabetes mellitus, high systolic blood pressure, delayed graft function, and donor factors (deceased donor KT, old age, and high serum creatinine concentrations). The PCR and ACR 3 to 6 months posttransplant were inversely associated with the estimated glomerular filtration rate at 1 year posttransplant. Deceased donor KT recipients with immediate postoperative PCR of ≥3 mg/mg showed a greater incidence of delayed graft function and lower estimated glomerular filtration rate before discharge than those with immediate postoperative PCR of <3 mg/mg. Conclusion: Early postoperative proteinuria is a useful biomarker to predict early renal outcomes after KT.

Purpose: Thromboelastography (TEG) was investigated for the diagnosis of coagulopathy compared with traditional coagulation tests, in association with disease severity in patients with severe sepsis or septic shock. Methods: Retrospective data was collected from a single center between January 25th to March 24th, 2016. There were 18 patients with severe sepsis or septic shock admitted to intensive care units included in this study. Laboratory tests including TEG were performed at admission. Disease severity was measured using the Simplified Acute Physiology Score III, Sequential Organ Failure Assessment score, and the level of lactate. Results: There were 18 patients (61% males; median age, 60.5 years) who were diagnosed with severe sepsis, or septic shock requiring a norepinephrine infusion (n = 10, 55.6%). Of these, 4 patients had traditional coagulation tests, and TEG profiles which confirmed hypercoagulability. Eight patients had follow-up tests 48 hours post-admission with a Sequential Organ Failure Assessment score of 6.5 (3-9.5) at admission, decreasing to 4 (2-11) after 48 hours (although not significantly lower), however, the lactate level decreased statistically significantly from 2.965 at admission, to 1.405 mmol/L after 48 hours (p < 0.05). The TEG profiles tended to normalize after 48 hours compared with admission, but there was no statistically significant difference. Conclusion Coagulopathy with severe sepsis or septic shock patients can be life-threatening, therefore it is important to diagnose coagulopathy early and precisely. TEG can be a feasible tool to confirm coagulopathy with traditional coagulation tests.

Since the first success of kidney transplantation in 1954, significant advances have been achieved in the field of organ transplantation. It was possible with the introduction of immunosuppressive drugs belonging to the class of calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus, the advances in surgical techniques and perioperative management, the monitoring and management infections, and the highly sensitive and specific antibody detection techniques. Despite recent progress, we currently encounter the limitation of better long-term transplant outcomes mainly because of paradoxical CNI toxicity and failure to control antibody or antibody-mediated rejections. The future direction of immunosuppression can be continued by optimizing immunosuppressive regimens with currently available immunosuppressants for better control of antibodies while avoiding CNI toxicity and by using biological therapeutics such as costimulation blockade agents that provide effective control of antibodies along with a reduction in usage or avoidance of CNIs and may develop as new immunosuppressants in the near future. Moreover, a tolerance induction through transplantation of donor hematopoietic stem cells or an infusion of regulatory cells using various sources of immune cells can also be a promising strategy as it can fundamentally escape from the complications of immunosuppressants. Over and above, it is important to note that the results of clinically applicable immunosuppressants from research in the non-human primate xenotransplantation model at the forefront of the future development of immunosuppressants can be a good opportunity to selectively apply to allo-transplants. No immunosuppressants can be risk-free, and therefore, all new immunosuppressants should be evaluated under the considerations for the risk/benefit ratio in various clinical conditions.

Purpose: Thromboelastography (TEG) was investigated for the diagnosis of coagulopathy compared with traditional coagulation tests, in association with disease severity in patients with severe sepsis or septic shock. Methods: Retrospective data was collected from a single center between January 25th to March 24th, 2016. There were 18 patients with severe sepsis or septic shock admitted to intensive care units included in this study. Laboratory tests including TEG were performed at admission. Disease severity was measured using the Simplified Acute Physiology Score III, Sequential Organ Failure Assessment score, and the level of lactate. Results: There were 18 patients (61% males; median age, 60.5 years) who were diagnosed with severe sepsis, or septic shock requiring a norepinephrine infusion (n = 10, 55.6%). Of these, 4 patients had traditional coagulation tests, and TEG profiles which confirmed hypercoagulability. Eight patients had follow-up tests 48 hours post-admission with a Sequential Organ Failure Assessment score of 6.5 (3-9.5) at admission, decreasing to 4 (2-11) after 48 hours (although not significantly lower), however, the lactate level decreased statistically significantly from 2.965 at admission, to 1.405 mmol/L after 48 hours (p < 0.05). The TEG profiles tended to normalize after 48 hours compared with admission, but there was no statistically significant difference. Conclusion Coagulopathy with severe sepsis or septic shock patients can be life-threatening, therefore it is important to diagnose coagulopathy early and precisely. TEG can be a feasible tool to confirm coagulopathy with traditional coagulation tests.

Background: Non-HLA antibodies, anti-angiotensin II type 1 receptor antibodies (anti-AT1R) and anti-endothelial cell antibodies (AECA), are known to play a role in allograft rejection. We evaluated the role of both antibodies in predicting post-transplant outcomes in low-risk living donor kidney transplantation (LDKT) recipients. Methods: In 94 consecutive LDKT recipients who were ABO compatible and negative for pre-transplant HLA donor-specific antibodies, we determined the levels of anti-AT1Rs using an enzyme-linked immunosorbent assay and the presence of AECAs using a flow cytometric endothelial cell crossmatch (ECXM) assay with pre-transplant sera. Hazard ratio (HR) was calculated to predict post-transplant outcomes. Results: Pre-transplant anti-AT1Rs (≥11.5 U/mL) and AECAs were observed in 36 (38.3%) and 22 recipients (23.4%), respectively; 11 recipients had both. Pre-transplant anti-AT1Rs were a significant risk factor for the development of acute rejection (AR) (HR 2.09; P=0.018), while a positive AECA status was associated with AR or microvascular inflammation only (HR 2.47; P=0.004) throughout the follow-up period. In particular, AECA (+) recipients with ≥11.5 U/mL anti-AT1Rs exhibited a significant effect on creatinine and estimated glomerular filtration rate (P<0.001; P=0.028), although the risk of AR was not significant. Conclusions Pre-transplant anti-AT1Rs and AECAs have independent negative effects on post-transplant outcomes in low-risk LDKT recipients. Assessment of both antibodies would be helpful in stratifying the pre-transplant immunological risk, even in low-risk LDKT recipients.