We aimed to evaluate the effect of different immunosuppressive regimens on the risk of major adverse cardiovascular events (MACEs) in kidney transplant recipients (KTRs).

This retrospective cohort study used nationwide claims data from the Korean Health Insurance Review and Assessment Service from between 2010 and 2021. Immunosuppressive medications were analyzed as time-dependent variables, and the primary outcome was MACEs, defined as a composite of myocardial infarction, coronary revascularization, ischemic stroke, and all-cause mortality.

A total of 8,056 KTRs were included in the analysis, with significant risk factors for MACEs identified as male sex, older age, longer dialysis duration, lower economic status, and greater comorbidity. At the time of the kidney transplant, 86.7% of the KTRs were administered standard triple therapy, after which various immunosuppressive regimens, including sirolimus-inclusive regimens, were employed. The risk of MACE was lower or comparable in KTRs standard triple therapy than in those receiving most other immunosuppressive regimens. However, corticosteroid withdrawal was associated with a significant reduction in cardiovascular risk, particularly in KTRs with preexisting diabetes or dyslipidemia.

These findings suggest that early consideration should be given to minimizing steroid use in KTRs with dyslipidemia or diabetes to optimize cardiovascular outcomes.

Hydrogen sulfide (H2S) produced endogenously by the CTH gene-encoded cystathionine gamma-lyase protects from renal ischemia-reperfusion injury in preclinical models. Here, we hypothesized that CTH gene polymorphisms (single nucleotide polymorphism [SNP]) and recipient H2S serum levels influence kidney graft outcomes after transplantation.

We included all consecutive recipients of a first kidney transplant in the Swiss Transplant Cohort Study and with available genotyping. In addition, 192 deceased-donor kidney transplant recipients were randomly selected to measure baseline serum H2S levels. The primary endpoint was graft loss during follow-up.

CTH SNPs were identified in up to 50% of the patients. During median follow-up (6.4 y, interquartile range: 3.9-9.8), graft loss was observed in 247 (9.8%) of 2518 patients. The incidence of graft loss was associated with the presence or absence of CTH SNPs. Specifically, rs672203 and rs10458561, increased the risk of graft loss (hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.04-1.78, P = 0.02; and HR: 1.29, 95% CI: 1.0-1.66, P = 0.05; respectively), whereas rs113285275 was protective (HR: 0.78, 95% CI: 0.6-1.01, P = 0.05). Interestingly, rs672203 was associated with an increased risk of acute rejection (P = 0.05), whereas rs113285275 was associated with a lower risk of acute rejection (P = 0.01). Finally, in patients with delayed graft function, serum H2S levels correlated with lower graft dysfunction (defined as estimated glomerular filtration rate <30 mL/min/1.73 m2) (P = 0.05).

Graft outcome after kidney transplantation was associated with CTH genotype and, to some extent, H2S serum levels. Further research is needed to define the underlying protective mechanisms.

Late kidney allograft loss occurs through one of two mechanisms: ( 1 ) deterioration of kidney function leading to retransplantation or dialysis (death-censored graft loss) and ( 2 ) premature death with a normally functioning transplant (death with graft function)-each accounting for approximately 50% of late kidney graft losses. Late death-censored graft loss typically results from a combination of immune and nonimmune events leading to common nonspecific end points ( e.g ., tubular atrophy, interstitial fibrosis, and glomerulosclerosis). Conversely, leading causes of death with graft function typically include cardiovascular events, malignancy, and infection. With an improved understanding of the multiple mechanism by which late graft dysfunction develops, there is an opportunity to identify patients at greatest risk and institute novel strategies to quell the process. Newer cardiometabolic agents with proven benefit in the general population have not been well-studied in kidney transplant recipients. However, in addition to their potential benefits in reducing cardiovascular, infectious, and malignancy end points (thus minimizing death with graft function risk), many novel agents may have additional anti-inflammatory and/or antifibrotic benefit (minimizing death-censored graft loss risk) in the kidney transplant population. In this review, we summarize existing literature regarding major causes of death-censored graft loss and death with graft function and discuss the potential roles of new cardiorenal metabolic agents including sodium-glucose cotransport 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, glucagon-like peptide 1 receptor agonists, and dual endothelin and angiotensin receptor antagonists in the kidney transplant population, including potential mechanisms to improve death with graft function and death-censored graft loss outcomes.

Kidney transplantation is the optimal form of renal replacement therapy, but the long-term survival rate of kidney graft has not improved significantly. Currently, no well-validated model exists for predicting long-term kidney graft survival over an extended observation period.

Recipients undergoing allograft kidney transplantation at the Organ Transplantation Center of the First Affiliated Hospital of Kunming Medical University from 1 August 2003 to 31 July 2023 were selected as study subjects. A nomogram model was constructed based on least absolute selection and shrinkage operator (LASSO) regression, random survival forest, and Cox regression analysis. Model performance was assessed by the C-index, area under the curve of the time-dependent receiver operating characteristic curve, and calibration curve. Decision curve analysis (DCA) was utilized to estimate the net clinical benefit.

The machine learning-based nomogram included cardiovascular disease in recipients, delayed graft function in recipients, serum phosphorus in recipients, age of donors, serum creatinine in donors, and donation after cardiac death for kidney donation. It demonstrated excellent discrimination with a consistency index of 0.827. The calibration curves demonstrated that the model calibrated well. The DCA indicated a good clinical applicability of the model.

This study constructed a nomogram for predicting the 20-year survival rate of kidney graft after allograft kidney transplantation using six factors, which may help clinicians assess kidney transplant recipients individually and intervene.

Kidney transplantation remains the best treatment for chronic kidney failure, offering better outcomes and quality of life compared with dialysis. Cardiovascular disease (CVD) is a major cause of morbidity and mortality in kidney transplant recipients and is associated with decreased patient survival and worse graft outcomes. Post-transplant CVD results from a complex interaction between traditional cardiovascular risk factors, such as hypertension and diabetes, and risk factors specific to kidney transplant recipients including chronic kidney disease, immunosuppressive drugs, or vascular access. An accurate assessment of cardiovascular risk is now needed to optimize the management of cardiovascular comorbidities through the detection of risk factors and the screening of hidden pretransplant coronary artery disease. Promising new strategies are emerging, such as GLP-1 receptor agonists and SGLT2 inhibitors, with a high potential to mitigate cardiovascular complications, although further research is needed to determine their role in kidney transplant recipients. Despite this progress, a significant gap remains in understanding the optimal management of post-transplant CVD, especially coronary artery disease, stroke, and peripheral artery disease. Addressing these challenges is essential to improve the short- and long-term outcomes in kidney transplant recipients. This narrative review aims to provide a comprehensive overview of cardiovascular risk assessment and post-transplant CVD management.

Kidney transplant recipients (KTRs) are at high risk for cardiovascular disease due to the long-term use of immunosuppressive therapy. This study aims to evaluate the long-term impact of sirolimus on cardiovascular outcomes in Korean KTRs.

From a cohort of 7180 eligible KTRs identified from 2010 to 2021, 387 KTRs who received sirolimus were included. To control for confounding variables, propensity score matching was applied, and the landmark method was used to address immortal time bias. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of myocardial infarction, coronary revascularization, ischaemic stroke and all-cause mortality.

The analysis showed no significant difference in MACE between the sirolimus-treated and untreated groups (hazard ratio, 1.40; 95% confidence interval, .77-2.55), despite a higher incidence of dyslipidaemia in the sirolimus-treated group. However, subgroup analysis revealed an increased MACE risk in KTRs with pre-transplant congestive heart failure (CHF) who were treated with sirolimus (hazard ratio, 6.22; 95% confidence interval, 1.78-21.74), while no significant differences were found in other subgroups.

These findings suggest that while sirolimus can be a viable option for immunosuppression, it should be used cautiously in those with pre-existing CHF.

Belatacept is a selective T cell costimulation blocker used in maintenance immunosuppression for kidney transplant recipients (KTRs), but evidence on cancer risk and other outcomes is limited. This retrospective cohort study used linked US transplant and cancer registry data on KTRs treated with belatacept (N = 1514) or tacrolimus (N = 7570) as initial maintenance therapy. We used multivariable Cox regression models to compare the incidence of invasive cancer, cutaneous squamous cell carcinoma, posttransplant lymphoproliferative disorder (PTLD), death, and graft failure/retransplantation (GF/RT) between belatacept and tacrolimus users. Overall, cancer incidence was 10.1 and 12.6 per 1000 person-years in belatacept and tacrolimus users, respectively. We did not find increased risk with belatacept for cancer overall (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.53-1.30), individual cancer types, or cutaneous squamous cell carcinoma. Belatacept was associated with increased risk of death (adjusted HR, 1.22; 95% CI, 1.04-1.43) but lower risk of GF/RT >4 years after transplantation (adjusted HR, 0.54; 95% CI, 0.35-0.83). PTLD risk was increased among Epstein-Barr virus-seropositive KTRs (adjusted HR, 1.96; 95% CI, 1.03-3.73). This study provides reassurance that belatacept does not increase cancer risk among KTRs, and there was a long-term protective association for GF/RT. However, we found evidence suggesting a potentially increased risk of PTLD and death with belatacept use.

The incidence of dengue and its complications increases globally, mainly in areas where it is endemic; however, little literature evaluates outcomes in kidney transplant recipients (KTR). The present analysis aimed to determine the incidence, signs and symptoms, and allograft dysfunction in dengue-infected KTR.

Systematic review of the literature following PRISMA 2020 indications with studies included until November 24, 2023.

Of 309 articles found, seven full-text studies were identified for analysis. 4337 KTRs with 214 dengue cases were evaluated. The incidence of dengue was 4.93%, varying between geographic regions. The average age was 41.50 years, and 61.21% were men. A mortality of 7.01% was reported. The symptoms were fever 83.18%, arthralgia 19.46%, myalgia 43.24% and headache 34.18%. The proportions of febrile dengue, with warning signs and severe dengue, were 63.55%, 23.83% and 11.68%, respectively. Transplant dysfunction and loss occurred in 63.08% and 4.67%, respectively.

Although the global distribution of dengue in KTR is unknown, there is a variable incidence between geographical areas and study times in which the KTR are evaluated. There is a high incidence of febrile symptomatology and transplant dysfunction consistent with global cohorts for non-KTR and KTR patients, respectively. Dysfunction is a prevalent event in KTRs with dengue infection, so correct screening should be done for donors and transplant candidates.

The management and outcomes of kidney transplant recipients have evolved over the past 3 decades. This study of US patients whose first kidney allograft failed examined long-term trends in subsequent waitlisting, retransplantation, and all-cause mortality.

Retrospective cohort study.

Patients recorded in the US Renal Data System (USRDS) whose first kidney allograft failed between 1990 and 2019.

The 5-year period in which the allograft failure occurred: 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014, or 2015-2019.

(1) Waitlisting for retransplantation, (2) retransplantation, and (3) all-cause mortality following first allograft failure.

Competing risk survival analyses with the approach described by Fine and Gray used for the outcomes of waitlisting and retransplantation, and Cox proportional hazards models used for the outcome of all-cause mortality.

The absolute number of patients whose allograft failed and who started dialysis increased from 3,197 in 1990 to 5,821 in 2019. Compared with 1990-1994, the rate of waitlisting for a second transplant increased with each subsequent 5-year period, peaking between 2005 and 2009 before decreasing again subsequently. The rate of retransplantation following allograft failure decreased by 9%, 14%, 18%, 7%, and 11% in the sequential 5-year eras; and the mortality rate was 25% lower in 2015-2019 (HR, 0.75 [95% CI, 0.72-0.77]) compared with 1990-1994. Women had a reduced rate of waitlisting (HR, 0.93 [95% CI, 0.91-0.95]) and lower rate of retransplantation (HR, 0.93 [95% CI, 0.91-0.95]) compared with men. Compared with White patients, African American and Hispanic patients had significantly lower rates of waitlisting, retransplantation, and mortality.

Retrospective data that lacks granular clinical information.

During the past 3 decades, among patients whose first kidney allograft failed and subsequently initiated dialysis, the rates of waitlisting for retransplantation increased while the rates of retransplantation and mortality decreased. Disparities based on race, ethnicity, and sex in waitlisting and retransplantation were observed and warrant further investigation.

Kidney allograft failure constitutes the fourth most common cause of dialysis initiation in the United States, and it accounts for 4% to 10% of yearly new dialysis starts globally. Little is known about the trends in the outcomes of patients whose kidney allograft failed. We studied US patients whose first kidney allograft failed between 1990 and 2019 to understand trends in waitlisting for retransplantation, retransplantation, and all-cause mortality after kidney allograft failure. Among patients whose first kidney allograft failed and started dialysis, rates of waitlisting increased and rates of retransplantation and mortality decreased over the past 3 decades. We found racial, ethnic, and sex-based disparities in outcomes. Compared with White patients, African American and Hispanic patients had significantly lower rates of waitlisting, retransplantation, and mortality. Women also had lower rates of waitlisting and retransplantation compared with men.

Torque Teno Virus (TTV) is a highly prevalent non-pathogenic DNA virus whose plasma levels may be related to the host's immune status. TTV gained attention about 25 years ago, but its replication is not fully understood, nor is its relationship with the host's immune system. Despite this lack of knowledge, TTV is currently being investigated as a functional biomarker of the immune system in patients with immunological damage and inflammatory diseases. Monitoring TTV viral load over time may help clinicians in making therapeutic decisions regarding immunosuppression as well as the likelihood of infectious complications. This review summarizes what we do and do not know about this enigmatic virus.

Cardiovascular disease is a leading cause of post-transplant mortality in kidney transplant recipients (KTRs), especially those with diabetes. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and kidney benefits in the general population with type 2 diabetes mellitus (T2DM), evidence regarding their effects in diabetic KTRs is limited.

This retrospective cohort study utilized data from the Global Collaborative Network in TriNetX, spanning January 1, 2006, to June 1, 2023. Propensity score matching (PSM) with 1:1 ratio was employed to create balanced cohorts. Adult KTRs with T2DM who received GLP-1 RAs within 3 months post-transplant were compared to a matched cohort of KTRs who did not. The primary outcome was all-cause mortality, with secondary outcomes including major adverse cardiovascular events (MACEs) and major adverse kidney events (MAKEs).

A total of 35,488 adult KTRs with T2DM (mean [SD] age, 57.7 [12.2] years; 57.7% men) were identified and 9.8% patients used GLP-1 RAs among 3 months post-transplant. Following PSM, 3564 GLP-1 RAs users were matched with an equal number of nonusers. After a median follow-up of 2.5 years, GLP-1 RAs users had lower risks of mortality (adjusted hazard ratio (aHR), 0.39; 95% CI 0.31-0.50), MACEs (aHR 0.66; 95% CI 0.56-0.79), and MAKEs (aHR 0.66; 95% CI 0.58-0.75). Adverse effects included higher risks of nausea, vomiting and diarrhea, while risks of suicide, hypoglycemia, retinopathy, and pancreatitis were not increased.

In KTRs with T2DM, GLP-1 RAs use was associated with substantial reductions in all-cause mortality, MAKEs, and MACEs compared to nonuse without increasing complications. However, the underutilization of GLP-1 RAs represents a significant opportunity to improve post-transplant outcomes in this high-risk population.

Reduced dependence on antirejection agents, improved long-term allograft survival, and induction of operational tolerance remain major unmet needs in organ transplantation due to the limitations of current immunosuppressive therapies. To address this challenge, investigators are exploring the therapeutic potential of adoptively transferred host- or donor-derived regulatory immune cells. Extracellular vesicles of endosomal origin (exosomes) secreted by these cells seem to be important contributors to their immunoregulatory properties. Twenty years ago, it was first reported that donor-derived exosomes could extend the survival of transplanted organs in rodents. Recent studies have revealed that regulatory immune cells, such as regulatory myeloid cells (dendritic cells, macrophages, or myeloid-derived suppressor cells), regulatory T cells, or mesenchymal stem/stromal cells can suppress graft rejection via exosomes that express a cargo of immunosuppressive molecules. These include cell surface molecules that interact with adaptive immune cell receptors, immunoregulatory enzymes, and micro- and long noncoding RNAs that can regulate inflammatory gene expression via posttranscriptional changes and promote tolerance through promotion of regulatory T cells. This overview analyzes the diverse molecules and mechanisms that enable regulatory immune cell-derived exosomes to modulate alloimmunity and promote experimental transplant tolerance. We also discuss the potential benefits and limitations of their application as therapeutic entities in organ transplantation.

Cancer is a major cause of morbidity and mortality in kidney transplant recipients. Health professionals have a critical role in promoting cancer screening participation. From March 2023 to February 2024, an online survey was distributed to kidney transplant health professionals globally to assess their screening practices. We compared their reported screening practices to recommended guidelines and analyzed factors associated with these practices. We received 97 responses, and most were nephrologists (70%), and around 80% recommended breast, colorectal, and cervical cancer screening for kidney transplant candidates and recipients. About 85% recommended lung cancer screening for higher-risk individuals. Skin cancer screening recommendations varied from 69% for transplant candidates and 84% for recipients. Self-reported cervical cancer screening practices were most concordant with recommended guidelines, followed by breast and skin cancers. Barriers reported included a lack of cancer screening awareness (28%), perceived financial constraints (35%), and deficient structured cancer screening systems (51%). Professionals from high-income countries were more likely to advise screening than those from lower-middle-income countries, with odds ratios ranging from 2.9 to 12.3. Most health professionals reported recommending cancer screening for kidney transplant candidates and recipients. However, recommendations were influenced by costs and service delivery gaps within health systems.

The rise in the mean age of the global population has led to an increase in older kidney transplant (KT) patients. This demographic shift, coupled with the ongoing organ shortage, requires a nuanced understanding of which older adults are most suitable for KT. Recognizing the increased heterogeneity among older adults and the limitations of solely relying on chronological age, there is a need to explore alternative aging metrics beyond chronological age. In this review, we discuss the impact of older age on access to KT and postoperative outcomes. Emphasizing the need for a comprehensive evaluation that extends beyond chronological age, we explore alternative aging metrics such as frailty, sarcopenia, and cognitive function, underscoring their potential role in enhancing the KT evaluation process. Most importantly, we aim to contribute to the ongoing discourse, fostering an optimized approach to KT for the rapidly growing population of older adults.

Complications following kidney transplantation elevate the risks of readmission and mortality. The aim of this study was to assess the association between the age-adjusted Charlson Comorbidity Index (ACCI) and postoperative complications among kidney transplant (KT) recipients.

Between January 2015 and March 2021, a study involving 886 kidney transplant recipients at the Third Affiliated Hospital of Sun Yat-sen University was conducted. Postoperative complications were defined by the Clavien-Dindo Classification of Surgical Complications. Target Maximum Likelihood Estimation (TMLE) was employed to assess the association between ACCI and postoperative complications. The odds ratio (OR) was computed to determine the relationship between ACCI and postoperative complications. Subsequent interaction and stratified analyses were performed to assess the robustness of the findings.

Out of 859 KT participants ultimately included in the study, 30.7% were documented to have encountered postoperative complications. Participants with an ACCI value exceeding 3 exhibited a notably increased risk of postoperative complications following multivariable adjustment [aOR = 1.64, 95% CI [1.21,2.21], p = 0.001]. Congestive heart failure (OR = 16.18, 95% CI [1.98-132.17], p < 0.001), peripheral vascular disease (OR = 2.32, 95% CI [1.48-3.78], p < 0.001), and chronic obstructive pulmonary disease (OR = 6.05, 95% CI [2.95-12.39], p < 0.001) emerged as the top three preoperative comorbidities significantly linked to postoperative complications in ACCI.

An ACCI value exceeding 3 preoperatively constituted a risk factor for postoperative complications among KT patients.

The gut microbiome has been shown to play a significant role in solid organ transplantation, potentially influencing graft function and patient outcomes. Dysbiosis, characterized by reduced microbial diversity and an increase in pathogenic taxa, has been linked to higher incidences of allograft rejection, graft dysfunction, and post-transplant mortality. Several studies suggest that the gut microbiome might be able to serve as both a biomarker and a therapeutic target, potentially guiding personalized immunosuppressive therapies and other interventions to improve outcomes after solid organ transplantation. As summarized in this review, clinical studies have shown that specific microbial shifts correlate with adverse outcomes, including acute rejection and chronic allograft dysfunction. As research surrounding the relationship between the gut microbiome and solid organ transplant progresses, the integration of microbial analysis into clinical practice has the potential to revolutionize post-transplant care, offering new avenues to improve graft survival and patient quality of life. This review aims to provide a comprehensive overview of the relationship between gut microbial dysbiosis and transplantation outcomes, emphasizing the impact on kidney, liver, lung, and heart transplant recipients.

The coronavirus disease (COVID-19) pandemic is a global health emergency, and SARS-CoV-2 pneumonia poses significant challenges to health systems worldwide. Renal transplant recipients (RTRs) are a special group and are more vulnerable to viral pneumonia. However, few studies have elucidated the risk factors of SARS-CoV-2 pneumonia in RTRs infected with COVID-19. This study aimed to build a risk prediction model for SARS-CoV-2 pneumonia among RTRs based on demographic and clinical information.

We conducted a prospective cohort study among 383 RTRs (age ≥ 18 years) diagnosed with COVID-19 from December 21, 2022, to March 26, 2023. Patients' demographic and clinical information was collected through a questionnaire survey combined with electronic medical records. A stepwise logistic regression model was established to test the predictors of SARS-CoV-2 pneumonia. We assessed the diagnostic performance of the model by calculating the area under the curve (AUC) of the receiver operating characteristic (ROC) and calibration using the Hosmer-Lemeshow (HL) goodness-of-fit test.

Our study showed that the incidence of SARS-CoV-2 pneumonia among RTRs was 31.1%. Older age (OR = 2.08-3.37,95%CI:1.05-7.23), shorter post-transplantation duration (OR = 0.92,95% CI: 0.87,0.99), higher post-transplant Charlson Comorbidity Index (CCI) (OR = 1.84, 95%CI: 1.14,2.98), pulmonary infection history (OR = 3.44, 95%CI: 1.459, 8.099, P = 0.005), fatigue (OR = 2.11, 95%CI: 1.14, 3.90), cough (OR = 2.03, 95%CI: 1.08, 3.81), and lower estimated glomerular filtration rate (eGFR) at COVID-19 diagnosis (OR = 0.98, 95%CI:0.97,0.99) predicted a higher risk for SARS-CoV-2 pneumonia. The model showed good diagnostic performance with Chi-Square = 10.832 (P > 0.05) and AUC = 0.839 (P < 0.001).

Our study showed a high incidence of SARS-CoV-2 pneumonia among RTRs, and we built a risk prediction model for SARS-CoV-2 pneumonia based on patients' demographic and clinical characteristics. The model can help identify RTRs infected with COVID-19 at high risk of SARS-CoV-2 pneumonia to inform timely, targeted, and effective prevention and intervention efforts.

BK polyomavirus (BKPyV)-DNAemia is a common complication in kidney transplant recipients (KTRs). The significance of achieving viral clearance at different time intervals is not well understood.

All adult KTRs transplanted between January 1, 2015 and December 31, 2017 who developed BKPyV-DNAemia were included. Outcomes were analyzed based on persistent clearance of BKPyV-DNAemia at 3-month intervals up to 2 years after initial detection, and for recipients with persistent BKPyV-DNAemia at last follow-up. Uncensored graft failure, death-censored graft failure (DCGF), and a composite outcome of DCGF or fall in estimated glomerular filtration rate (eGFR) by ≥50% from the time of initial BKPyV-DNAemia were outcomes of interest.

Of 224 KTRs with BKPyV-DNAemia, 58 recipients (26%) achieved viral clearance by 3 months after initial detection, 105 (47%) by 6 months, 120 (54%) by 9 months, 141 (63%) by 12 months, 155 (69%) by 15 months, 167 (75%) by 18 months, 180 (80%) by 21 months, and 193 (86%) by 24 months. Nine recipients (4%) had persistent BKPyV-DNAemia at last follow-up. Compared to recipients who achieved viral clearance by 3 months, those who achieved clearance by 6 months (adjusted odds ratio [aOR]: 3.15; 95% confidence interval [CI]: 1.22-8.12; p = .02) and 9 months (aOR: 3.69; 95% CI: 1.02-13.43; p = .04) had significantly increased risk for uncensored graft failure. There was no significant association between time to viral clearance and DCGF or composite outcomes.

We found a trend of increased risk for uncensored graft failure among those who cleared BKPyV-DNAemia more slowly. Aiming to clear viremia early, without risking rejection, may be beneficial for allograft function and patient morbidity and mortality.

Infection and rejection are major complications that impact transplant longevity and recipient survival. Balancing their risks is a significant challenge for clinicians. Current strategies aimed at interrogating the degree of immune deficiency or activation and their attendant risks of infection and rejection are imprecise. These include immune (cell counts, function and subsets, immunoglobulin levels) and non-immune (drug levels, viral loads) markers. The shared risk factors between infection and rejection and the bidirectional and intricate relationship between both entities further complicate transplant recipient care and decision-making. Understanding the dynamic changes in the underlying net state of immunity and the overall risk of both complications in parallel is key to optimizing outcomes. The allograft biopsy is the current gold standard for the diagnosis of rejection but is associated with inherent risks that warrant careful consideration. Several biomarkers, in particular, donor derived cell-free-DNA and urinary chemokines (CXCL9 and CXCL10), show significant promise in improving subclinical and clinical rejection risk prediction, which may reduce the need for allograft biopsies in some situations. Integrating conventional and emerging risk assessment tools can help stratify the individual's short- and longer-term infection and rejection risks in parallel. Individuals identified as having a low risk of rejection may tolerate immunosuppression wean to reduce medication-related toxicity. Serial monitoring following immunosuppression reduction or escalation with minimally invasive tools can help mitigate infection and rejection risks and allow for timely diagnosis and treatment of these complications, ultimately improving allograft and patient outcomes.

Torque teno virus load (TTVL) is gaining importance as a surrogate parameter to assess immunocompetence in kidney transplant recipients. Although the dynamics of TTVL have been investigated before, the impact of different induction agents and variations in immunosuppressive maintenance therapies on TTVL remain unknown.

In this retrospective study, TTVL was quantified in 537 plasma or serum samples from 134 patients transplanted between 2018 and 2021. TTVL was examined pre-transplantation and 30-, 90-, 180-, and 360-days post-transplant. To assess the influence of induction therapy on TTVL, 67 patients receiving anti-thymocyte globulin (ATG) induction were matched with 67 patients receiving an interleukin-2 receptor antagonist (IL2-RA) induction in terms of age, sex, and donor modality.

Following transplantation, there was a steep increase in TTVL post-transplant for all patients with peak viral loads at 90 days post-transplant (median TTVL [IQR] 7.97×106, [4.50×105-1.12×108]) followed by subsequently declining viral loads. Compared to patients receiving IL2-RA as induction therapy, patients receiving ATG had significantly higher peak viral loads 3 months post-transplant (median TTVL [IQR] 2.82×107 [3.93×106-1.30×108] vs. median TTVL [IQR] 2.40×106 [5.73×104-2.60×107]; P<0.001). Throughout all post-transplant time points, patients receiving additional rituximab for induction along with higher tacrolimus target levels exhibited the highest TTVL.Patients whose TTVL 3-months post-transplant exceeded the currently proposed cutoff to predict infections within the first year post-transplant [6.2 log10] showed a trend towards a higher risk of being hospitalized with an infection in the following 9 months, albeit without being statistically significant (HR=1.642, P=0.07).

Higher TTVL reflects the greater immunosuppressive burden in immunological high-risk patients receiving intensive immunosuppression. The choice of induction agent and intensified immunosuppressive maintenance therapy notably affects TTVL at 3 months post-transplant and beyond, necessitating careful consideration when interpreting and applying TTVL cutoffs to monitor immunocompetence post-transplant.

The safety and benefit of the anti-CD38 monoclonal antibody daratumumab, which induces lysis of antibody-producing plasma cells in sensitized patients prior to kidney transplantation, remain to be determined.

A 2-phase (1 and 2), monocentric open-label study was conducted to evaluate the month 6 (M6) safety and efficacy of daratumumab in kidney transplant candidates with calculated panel reactive antibody (cPRA) > 95%. In the first (safety) phase, we used 4-weekly escalating doses of daratumumab. Phase 2 tested desensitization with 8 weekly infusions of 16 mg/kg daratumumab. cPRA 10,000 was calculated considering only human leukocyte antigen (HLA) antibodies with mean fluorescence intensity (MFI) of > 10,000.

Nine patients were enrolled in phase 1 and 14 in phase 2. Safety analysis showed 4 serious non-treatment-emergent adverse events (non-TEAEs), 36 mild TEAEs, mostly infusion-related reactions, grade 1 and 2 (causing 2 temporary drug discontinuations), but no serious TEAEs. Significant reductions in anti-HLA antibodies were observed at month 3 (M3), with cPRA 10,000 (P = 0.003), number of anti-HLA (P < 0.001), maximum MFI (MFI max) (P = 0.053), and the sum of MFI (MFI sum) (P < 0.001), with complete return to baseline levels at month 12 (M12). At M6, 46.15% (19.22%-74.87%) and 76.92% (46.19%-94.96%) of patients showed sustained response (1% decrease in cPRA) for cPRA 2000 and 10,000, respectively. At month 1 (M1), immune cells (T-reg, CD8 + TEMRA, CD19 + CD138 + B cells, and NK cells) significantly decreased. At M3, other antibodies decreased significantly, but returned to baseline levels at M12, except for gamma globulins, without any infectious complications.

The first use of daratumumab in desensitization demonstrated infusion-related adverse (AEs) events and rapid, albeit transient, reductions in anti-HLA antibodies, with less than 40% of durable responders, limiting its potential clinical use.

Advances in organ procurement, surgical techniques, immunosuppression regimens, and prophylactic antibiotic therapies have dramatically improved kidney transplant graft failure. It is unclear how these interventions have affected longer-term graft failure. It is hypothesized that graft failure has improved over the last 20 years.

Data on all first kidney transplants from 1995 to 2014 were extracted from the Australia and New Zealand Dialysis and Transplant Registry with follow-up as of 31 December 2021. Primary exposure was transplant era, classified into 5-year intervals. Primary outcome was all-cause 5-year graft failure. Secondary outcomes included all-cause 10-year graft failure and cause-specific graft failure. Kaplan-Meier curves and multivariable Cox proportional hazards regression models were used to assess trends in all-cause graft failure. Fine-Gray subdistribution hazard models verified that changes in death rates were not biasing the Cox proportional hazards regression models. Cumulative incidence functions were used to assess temporal trends in cause-specific graft failure.

Across 10 871 kidney transplants, there was a shift towards transplanting more recipients aged >45 years old, with more comorbidities, longer dialysis vintage, body mass index >30 kg/m2, and greater human leukocyte antigen mismatches. Donor age has increased but no clear shift in donor source was observed. Compared to 1995-99 (reference), the adjusted hazard ratio for 5-year graft failure was 0.78 (95% CI 0.67-0.91), 0.70 (95% CI 0.59-0.83), and 0.60 (95% CI 0.50-0.73) for 2000-04, 2005-09, and 2010-14, respectively. Ten-year graft failure similarly reduced from 0.83 (95% CI 0.74-0.93) for 2000-04 to 0.78 (95% CI 0.68-0.89) for 2010-14, compared to 1995-99.

Medium- and long-term all-cause graft failure has improved steadily since 1995-99. Significant reductions in graft failure due to rejection and vascular causes were observed at 5 years, and due to rejection, vascular causes, death, and glomerular disease at 10 years.

The QuantiFERON-Monitor assay (QTF-Monitor) is intended to assess innate and adaptive immune responses by quantifying interferon (IFN)-γ release upon whole blood stimulation with a TLR7/8 agonist and an anti-CD3 antibody. We performed the QTF-Monitor in 126 kidney transplant recipients (KTRs) at different points during the first 6 post-transplant months. The primary outcome was overall infection, whereas secondary outcomes included bacterial infection, opportunistic infection and de novo cancer. The association between IFN-γ production and outcomes was analyzed as "low" immune responses (<15 IU/mL) and as a continuous variable to explore alternative thresholds. There were no significant differences in the occurrence of overall infection according to the QTF-Monitor at any monitoring point. Regarding secondary outcomes, KTRs with a low response at week 2 experienced a higher incidence of bacterial infection (50.8% versus 24.4%; P-value = 0.006). Low response at month 1 was also associated with opportunistic infection (31.6% versus 14.3%; P-value = 0.033). The discriminative capacity of IFN-γ levels was poor (areas under the ROC curve: 0.677 and 0.659, respectively). No differences were observed for the remaining points or post-transplant cancer. In conclusion, the QTF-Monitor may have a role to predict bacterial and opportunistic infection in KTRs when performed early after transplantation.

Predicting long-term mortality postkidney transplantation (KT) using baseline clinical data presents significant challenges. This study aims to evaluate the predictive power of artificial intelligence (AI)-enabled analysis of preoperative electrocardiograms (ECGs) in forecasting long-term mortality following KT.

We analyzed preoperative ECGs from KT recipients at three Mayo Clinic sites (Minnesota, Florida, and Arizona) between January 1, 2006, and July 30, 2021. The study involved 6 validated AI algorithms, each trained to predict future development of atrial fibrillation, aortic stenosis, low ejection fraction, hypertrophic cardiomyopathy, amyloid heart disease, and biological age. These algorithms' outputs based on a single preoperative ECG were correlated with patient mortality data.

Among 6504 KT recipients included in the study, 1764 (27.1%) died within a median follow-up of 5.7 y (interquartile range: 3.00-9.29 y). All AI-ECG algorithms were independently associated with long-term all-cause mortality ( P < 0.001). Notably, few patients had a clinical cardiac diagnosis at the time of transplant, indicating that AI-ECG scores were predictive even in asymptomatic patients. When adjusted for multiple clinical factors such as recipient age, diabetes, and pretransplant dialysis, AI algorithms for atrial fibrillation and aortic stenosis remained independently associated with long-term mortality. These algorithms also improved the C-statistic for predicting overall (C = 0.74) and cardiac-related deaths (C = 0.751).

The findings suggest that AI-enabled preoperative ECG analysis can be a valuable tool in predicting long-term mortality following KT and could aid in identifying patients who may benefit from enhanced cardiac monitoring because of increased risk.

The management of noninfectious complications in kidney transplant recipients includes a broad spectrum of conditions, including metabolic issues, cardiovascular diseases, and malignancies, each presenting unique challenges for nephrologists managing these patients. Unlike infectious complications, these noninfectious issues require nuanced, multidisciplinary approaches for prevention, diagnosis, and management, emphasizing the need for personalized care plans. Cardiovascular disease is particularly significant, standing as the primary cause of death post-transplantation, with recent data indicating an overtaking of cancer death rates over infections among kidney transplant recipients. The intricacies of managing these patients, influenced by the burden of kidney disease and immunosuppression, highlight the importance of a collaborative care model. Although nephrologists may not directly treat all these conditions, their understanding of the unique aspects of transplant recipients is crucial. They play a pivotal role in coordinating care with specialists such as cardiologists, endocrinologists, hematologists, and oncologists, ensuring comprehensive management that addresses these specific post-transplant complications. This review discusses the epidemiology, underlying mechanisms, clinical manifestations, and management strategies of various noninfectious complications post-kidney transplant, with a focus on cardiovascular, metabolic, oncologic, and hematologic complications.

Post-transplantation cancer is a significant cause of mortality among kidney transplant recipients (KTR). The incidence of post-transplantation cancer varies based on geographic region and ethnicity. However, data on KTR from South East Asia, where characteristics differ from other parts of Asia, is lacking. We conducted a retrospective cohort study at a transplant center in Thailand to investigate the incidence of post-transplantation cancer and mortality rates. Factors associated with post-transplantation cancer and patient outcomes were analyzed using competing-risks regression. The study included 1156 KTR with a post-transplant follow-up duration of 5.1 (2.7-9.4) years. The age- and sex-adjusted incidence rate of post-transplant cancer was highest for urothelial cancer (6.9 per 1000 person-years), which also resulted in the highest standardized incidence ratio (SIR) of 42.5 when compared to the general population. Kidney cancer had the second-highest SIR of 24.4. Increasing age was the factor associated with an increased risk of post-transplant cancer (SHR 1.03; 95% CI 1.01-1.05). Human leukocyte antigen (HLA) DR mismatch was associated with a decreased risk of post-transplant cancer (SHR 0.72; 95% CI 0.52-0.98). Post-transplantation cancer was significantly associated with patient mortality (HR 3.16; 95% CI 2.21-4.52). Cancer significantly contributes to KTR mortality, and the risk profile for cancer development in Thai KTRs differs from that of Western and most Asian counterparts. Further research is essential to explore appropriate screening protocols for countries with high rates of urothelial and kidney cancer, including Thailand.

Ischemic-reperfusion injury resulting from kidney transplantation declines the post-transplant graft function. Remote ischemic conditioning (RIC) is known to be able to reduce the criticality of ischemic reperfusion injury. This study aimed to meta-analyze whether the application of remote ischemic conditioning to kidney transplantation patients improves clinical outcomes.

Researchers included randomized controlled studies of the application of RIC to either kidney donors or recipients. Articles were retrieved from PubMed, Embase, Web of Science, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. The primary outcome was mortality after transplantation. Secondary outcomes were the incidence of delayed graft function, graft rejection, and post-transplant laboratory results. All outcomes were integrated by RevMan 5.4.1.

Out of 90 papers, 10 articles (8 studies, 1977 patients) were suitable for inclusion criteria. Mortality collected at all time points did not show a significant difference between the groups. Three-month mortality (RR, 3.11; 95% CI, 0.13-75.51, P = 0.49) tended to increase in the RIC group, but 12-month (RR, 0.70; 95% CI, 0.14-3.45, P = 0.67) or final-reported mortality (RR, 0.49; 95% CI, 0.23-1.06, P = 0.07) was higher in the sham group than the RIC group. There was no significant difference between the RIC and sham group in delayed graft function (RR, 0.64; 95% CI, 0.30-1.35, P = 0.24), graft rejection (RR, 1.13; 95% CI, 0.73-1.73, P = 0.59), and the rate of time required for a 50% reduction in baseline serum creatinine concentration of less than 24 h (RR, 0.98; 95% CI, 0.61-1.56, P = 0.93).

It could not be concluded that the application of RIC is beneficial to kidney transplantation patients. However, it is noteworthy that long-term mortality tended to decrease in the RIC group. Since there were many limitations due to the small number of included articles, researchers hope that large-scale randomized controlled trials will be included in the future.

PROSPERO CRD42022336565.

Renal transplant recipients confront a substantially elevated susceptibility to renal cell carcinoma (RCC), particularly in their native kidneys as opposed to allografts.

In this systematic scoping review, exhaustive searches were conducted of the MEDLINE and EMBASE databases. Information was gathered on clinical manifestations, donor demographics, diagnostic intervals, tumor dimensions, histopathological characteristics, and therapeutic outcomes associated with RCC arising in allograft kidneys.

The searches yielded a corpus of 42 case reports and 11 retrospective cohorts, encompassing a cohort of 274 patients. The majority of cases (75.4%) were clinically latent, discerned primarily through imaging modalities. Symptomatic presentations encompassed manifestations such as hematuria, elevated serum creatinine levels, abdominal discomfort, and graft-related pain. The mean temporal interval between renal transplantation and RCC diagnosis was calculated at 11.6 years, albeit displaying considerable variance. Notably, papillary and clear cell RCC emerged as the prevailing histopathological subtypes. However, the paucity of longitudinal follow-up data represents a notable caveat.

This investigation underscores the imperative of rigorous posttransplant surveillance regimes owing to the substantial prevalence of asymptomatic RCC instances. Future research should focus on clinical outcomes and cost-effectiveness of screening practices to develop preventive strategies.

Torque Teno Virus (TTV) is a ubiquitous component of the human virome, not associated with any disease. As its load increases when the immune system is compromised, such as in kidney transplant (KT) recipients, TTV load monitoring has been proposed as a method to assess immunosuppression. In this prospective study, TTV load was measured in plasma and urine samples from 42 KT recipients, immediately before KT and in the first 150 days after it. Data obtained suggest that TTV could be a relevant marker for evaluating immune status and could be used as a guide to predict the onset of infectious complications in the follow-up of KT recipients. Since we observed no differences considering distance from transplantation, while we found a changing trend in days before viral infections, we suggest to consider changes over time in the same subjects, irrespective of time distance from transplantation.

Cardiovascular disease, infection, malignancy, and thromboembolism are major causes of morbidity and mortality in kidney transplant recipients (KTR). Prospectively identifying monogenic conditions associated with post-transplant complications may enable personalized management. Therefore, we developed a transplant morbidity panel (355 genes) associated with major post-transplant complications including cardiometabolic disorders, immunodeficiency, malignancy, and thrombophilia. This gene panel was then evaluated using exome sequencing data from 1590 KTR. Additionally, genes associated with monogenic kidney and genitourinary disorders along with American College of Medical Genetics (ACMG) secondary findings v3.2 were annotated. Altogether, diagnostic variants in 37 genes associated with Mendelian kidney and genitourinary disorders were detected in 9.9% (158/1590) of KTR; 25.9% (41/158) had not been clinically diagnosed. Moreover, the transplant morbidity gene panel detected diagnostic variants for 56 monogenic disorders in 9.1% KTRs (144/1590). Cardiovascular disease, malignancy, immunodeficiency, and thrombophilia variants were detected in 5.1% (81), 2.1% (34), 1.8% (29) and 0.2% (3) among 1590 KTRs, respectively. Concordant phenotypes were present in half of these cases. Reviewing implications for transplant care, these genetic findings would have allowed physicians to set specific risk factor targets in 6.3% (9/144), arrange intensive surveillance in 97.2% (140/144), utilize preventive measures in 13.2% (19/144), guide disease-specific therapy in 63.9% (92/144), initiate specialty referral in 90.3% (130/144) and alter immunosuppression in 56.9% (82/144). Thus, beyond diagnostic testing for kidney disorders, sequence annotation identified monogenic disorders associated with common post-transplant complications in 9.1% of KTR, with important clinical implications. Incorporating genetic diagnostics for transplant morbidities would enable personalized management in pre- and post-transplant care.