Cohort Of Kidney Transplant Recipients Research Articles

Genetics in nephrology - any news?

While genetic kidney diseases were long regarded as a rare cause of kidney failure, it has been shown in recent years that they account for a relevant proportion of cases. In cohorts of kidney transplant recipients, a monogenic cause is found in up to 30% of cases. Identifying the genetic cause of kidney disease has become much easier thanks to technological advances in DNA sequencing. The focus has now shifted to understanding the significance of the findings and identifying diagnostic gaps. It is still not possible to clarify all CKD cases of unclear aetiology. Besides very effective generic treatments for monogenic kidney disease (e.g., ACE-inhibitor use in Alport Syndrome), increasing knowledge of the pathophysiology of genetic kidney diseases has led to a growing number of targeted therapies. These include the treatment of ADPKD with Tolvaptan, which has now been in use for 10 years. Recently, exciting, and completely new approaches have been added, such as the first siRNA therapies in nephrology for primary hyperoxaluria type 1, the targeted treatment of hyperphagia in Bardet-Biedl syndrome, the therapy of APOL1-associated kidney disease or the use of the HIF-2 antagonist Belzutifan for renal cell carcinoma associated with Von-Hippel-Lindau syndrome. The new possibilities in the treatment of patients with genetic kidney diseases have also clearly revealed deficits in current patient care. Centers of excellence with extensive experience in this area therefore play an important role in improving care. This also applies to the further training of colleagues in the field. In Germany, the National Action Alliance for People with Rare Diseases (NAMSE) and the nationwide establishment of - to date - 36 centers for rare diseases play an important role in this regard.

Derivation of Human Leukocyte Antigen Molecular Mismatch Risk Thresholds in a Diverse Cohort of Kidney Transplant Recipients

Derivation of Human Leukocyte Antigen Molecular Mismatch Risk Thresholds in a Diverse Cohort of Kidney Transplant Recipients

Management of Early Post-Transplant Hyperglycemia by Dedicated Endocrine Care Improves Glycemic Outcomes.

Early post-transplant hyperglycemia (EPTH) is an independent risk factor for hospital readmissions, acute rejection, infections and developing post-transplant diabetes mellitus (PTDM). Close glycemic control is prudent in the early post-transplant period. The management of EPTH was evaluated among a cohort of kidney transplant recipients, who either received routine care (RC) or dedicated endocrine care (DEC). A retrospective analysis was conducted on kidney transplant recipients from 2019 to 2023. The impact of DEC on post-transplant glycemic control was investigated. Hospitalized patients receiving post-transplant insulin therapy were included. DEC involved at least twice-daily blood glucose (BG) assessment by an endocrinologist, while the RC received usual care. A mixed-model analysis was employed to assess differences in BG trajectories between DEC and RC over an eight-day period. Additionally, various glycemic control metrics were compared, including glucose variability, time-in-range for target BG, rates of hypoglycemia and response to hyperglycemia. The cohort comprised 113 patients. In the DEC group, 91% had pre-transplant DM compared to 15% in the RC group (p < 0.001). Patients under DEC had higher baseline BG and glycated hemoglobin compared to those under RC (p < 0.001, for both). The DEC group displayed a lower trajectory of BG over time compared to the RC group (p = 0.002). Patients under DEC were more likely to receive insulin if BG measured above 200 mg/dL (66% vs. 46%) and displayed less below-range BG (<110 mg/dL) compared to those under RC (12.9% vs. 23.6%, p < 0.001). Management of EPTH by DEC improves glycemic outcomes in renal transplant recipients.

Radiofrequency Echographic Multi Spectrometry (REMS) Technology for Bone Health Status Evaluation in Kidney Transplant Recipients.

Background: A significant loss in bone density and strength occurs during the post-renal-transplant period with higher susceptibility to fracture. The study aims to compare the performance of the Radiofrequency Echographic Multi Spectrometry (REMS) in the bone mineral density assessment with the conventional dual-energy X-ray absorptiometry (DXA) in a cohort of kidney transplant recipients (KTR). Methods: A cohort of 40 patients underwent both DXA and REMS examinations on the lumbar spine and/or proximal femur. The paired t-test was used to compare DXA and REMS measurements; the chi-square test was used to compare the prevalence of osteoporosis/osteopenia. The agreement between the two techniques was assessed through Spearman's correlation. Results: As expected, most KTR patients were osteopenic or osteoporotic with both REMS and DXA (86.5% and 81% for the femur; 88% and 65% for the lumbar spine p < 0.05). A modest correlation (r = 0.4, p < 0.01) was observed at the lumbar spine between the T-score measured by REMS and DXA. A strong correlation was defined between REMS and DXA in the femoral region (r = 0.7, p < 0.0001). Conclusions: The study demonstrates the exchangeability of the two techniques on the proximal femur in KTR and a higher diagnostic accuracy of REMS at the spine level than DXA.

HLA-DR/DQ eplet mismatch predicts risk of de novo donor-specific antibody development in a multi-ethnic Southeast Asian cohort of kidney transplant recipients

HLA-DR/DQ eplet mismatch predicts risk of de novo donor-specific antibody development in a multi-ethnic Southeast Asian cohort of kidney transplant recipients

The adaptive and innate immune systems coordinate for successful control of CMV infection

Previous studies of the immune control of cytomegalovirus infection have primarily focused on analysis of the traditional adaptive T-cell response. Donadeu etal. bring a new perspective through evaluation of multiple adaptive and innate immune subtypes in parallel with cytomegalovirus-specific cell-mediated immunity in a prospective cohort of kidney transplant recipients with findings validated in 2 independent studies. Identification of a natural killer T-cell subtype associated with cell-mediated immunity and freedom from cytomegalovirus infection demonstrates the importance of the coordinated innate and adaptive immune response for effective viral control.

P.127: Covid-19 infection in a large cohort of kidney transplant recipients from a single center.

P.127: Covid-19 infection in a large cohort of kidney transplant recipients from a single center.

Endobiogenic Biology of Function Indices in a Cohort of Kidney Transplant Recipients.

Background and Objectives: Endobiogeny is a global systems approach to human biology based on the concept that the endocrine system manages the metabolism. Biology of function (BoF) indices are diagnostic tools in endobiogenic medicine that reflect the action of the endocrine system on the cells and the metabolic activity of an organism. Kidney transplant recipients are a very specific patient population due to their constant use of immunosuppressive agents such as steroids and anamnesis of chronic kidney disease. The aim of this study was to assess the tendencies of endobiogenic BoF indices in a kidney transplant recipient population and to determine the relationship between BoF index values and histology-proven kidney transplant rejection. Materials and Methods: A total of 117 kidney transplant recipients undergoing surveillance or indication allograft biopsy were included in this study. Endobiogenic BoF indices were calculated from complete blood count tests taken before the kidney biopsy. Histology samples were evaluated by an experienced pathologist according to the Banff classification system. Clinical and follow-up data were collected from an electronic patient medical record system. Results: Overall, <35% of the patients had BoF index values assumed to be normal, according to the general population data. Additionally, >50% of the patients had lower-than-normal adaptation, leucocyte mobilization, genital, and adjusted genital ratio indices, while the Cata-Ana, genito-thyroid ratio, adrenal gland, and cortisol indices were increased in >50% of the transplant recipients. The adaptation index was significantly higher in patients with biopsy-proven transplant rejection and demonstrated an AUC value of 0.649 (95%CI 0.540-0.759) for discriminating rejectors from patients without transplant rejection. Conclusions: Most of the kidney transplant recipients had abnormal BoF index values, reflecting increased corticotropic effects on their cells. The adaptation index distinguished patients with biopsy-proven transplant rejection from those without it.

Molecular epidemiology and risk factors associated with BK and JC polyomavirus urinary shedding after kidney allograft.

Polyomaviruses BK (BKPyV) and JC (JCPyV), belonging to the Polyomaviridae, are responsible for human pathologies. In kidney transplant recipients, BKPyV replication can lead to irreversible nephron damage whereas JCPyV replication remains asymptomatic. Concomitant replication is rare and potential competition between the infections has been described. The aim of this retrospective case-control study was to describe the molecular epidemiology and risk factors associated with BKPyV and JCPyV replication in a cohort of kidney transplant recipients. In total, 655 urine samples from 460 patients were tested for BKPyV and JCPyV DNA. Positive samples were submitted to strain genotyping. Demographic and clinical characteristics were also compared. Isolated JCPyV and BKPyV was found in 16.5% and 23.3% of patients, respectively; co-replication was rare (3.9%). BKPyV strains Ib-2, Ib-1, and IVc-2 were the most prevalent. JCPyV strains mostly belonged to genotypes 4 and 1B. During follow-up, JCPyV shedding significantly reduced the risk of BKPyV DNAuria, with an odds ratio of 0.57 (95% confidence interval: 0.35-0.99), and was associated with better prognosis than BKPyV replication, based on the estimated glomerular filtration rate. Molecular epidemiology of BKPyV and JCPyV strains in our region was similar to previous studies. This study suggests that JCPyV is benign and appears to limit damaging BKPyV replication. JCPyV DNAuria screening could thus be a useful strategy to predict BKPyV-related outcomes.

#2403 Impact of pregnancy on kidney transplant recipients

Abstract Background and Aims Kidney transplantation (KT) provides an opportunity to increase fertility in women with chronic kidney disease and gestational desire. Lack of knowledge about obstetric complications and implications for the graft may lead to discourage pregnancy for these women. Although the incidence of pregnancy is rising in women receiving KT, the impact that it may have on the graft function is unknown. Method We conducted an observational, retrospective, single-centre study of a cohort of kidney transplant recipients (KTR) who became pregnant between 2007 and 2022. Clinical and analytical parameters were evaluated before, during and after pregnancy. The main aim was to assess the long-term impact of pregnancy on the graft by analysing renal function 3 years after pregnancy. Results We included 25 women receiving a KT between 1990 and 2018, among which 72% (n = 18) were transplanted from a deceased donor. 2 women (8%) received a combined liver-kidney transplant and 2 women (8%) a simultaneous pancreas-kidney transplant. Maintenance immunosuppression before conception included teratogenic drugs in 68% of cases [12 of them (48%) received mycophenolate mofetil and 5 of them (20%), mTOR inhibitors]. Planned withdrawal was only applied in 50.0% of pregnancies (n = 15). 30 pregnancies were identified (5 patients had 2 post-transplant pregnancies). Median age at gestation was 35 years [interquartile range (IQR) 33-39]. 5 conceptions required assisted reproductive technology. The main complications were gestational hypertension in 4 KTR (13.3%) and preeclampsia in 7 pregnancies (23.3%). 60% of neonates (n = 18) were preterm births (36 [IQR 34-37] weeks of pregnancy at birth) and 44% (n = 12) had low birth weight (2530 [IQR 2283-2950] grams). No foetal malformations were described. Due to physiological changes, a significant increase in estimated glomerular filtration rate (eGFR) was observed in the first and the second trimester of pregnancy (61 [IQR 50-91] ml/min and 70 [IQR 50-90] ml/min, respectively vs. baseline eGFR 59 [IQR 47-77] ml/min; p 0.001]. However, eGFR was equal to the previous one in the third trimester of pregnancy (60 [IQR 44-69] ml/min vs. 59 [IQR 47-77] ml/min; p 0.322). Median proteinuria remained below 0.5 g/day throughout pregnancy, without significant variation. Immunosuppression regimen during pregnancy was mainly based on a combined therapy of steroids, calcineurin inhibitors and azathioprine (21 KTR, 70%). Tacrolimus dose increase (median 63.6% [IQR 33.3-90.0%]) was necessary to maintain proper drug levels throughout gestation. Kidney graft function showed a decline in the first and second year after pregnancy compared to baseline function (54 [IQR 35-77] ml/min and 55 [IQR 36-75] ml/min vs. 59 [IQR 47-77] ml/min; p 0.018 and p 0.021, respectively]. Nevertheless, by the third year post-pregnancy, eGFR was similar to the baseline function (62 [IQR 43-73] ml/min vs. 59 [IQR 47-77] ml/min; p 0.365]. Likewise, annual eGFR variation was comparable during 3 years before (+1.0 ml/min/year) and 3 years after pregnancy (−0.9 ml/min/year), hence no worsening was observed after gestation (p 0.78). No differences were observed in proteinuria either (baseline proteinuria 0.17 [IQR 0.13-0.3] g/day vs. third-year proteinuria 0.21 [IQR 0.15-0.34] g/day; p 0.938). Only 5 women had a baseline serum creatinine above current recommendations for pregnancy (&amp;gt;1.5 mg/dl) and only 3 women presented baseline proteinuria &amp;gt; 0.5 g/day. In this group (n = 7), pregnancy occurred later after KT (96.0 [IQR 80.9-213.0] vs. 46.0 [IQR 16.0-67.5] months; p 0.024). The only 2 graft losses in the cohort were in this group. Both were attributed to transplant glomerulopathy, and they occurred at years 3 and 5 after pregnancy. On the other side, in this group there were no other baseline differences or obstetrical complications [Table 1]. Conclusion Pregnancy does not normally affect graft function and it stabilises within 3 years after gestation. It is important to increase data on women with suboptimal graft function to determine the direct implications that pregnancy may have on these KTRs.

#1207 Post transplant diabetes mellitus in kidney transplanted patients: factors related and impact on long-term outcome

Abstract Background Alterations in glucose metabolism are one of the most important complications of renal transplant recipients. The aim of this study was to analyze their prevalence and determinants and assess their influence on the main long-term clinical outcomes in a cohort of kidney transplant recipients. Methods we retrospectively analyzed the data of 832 kidney transplant recipients between 2004 and 2020 in our center. Patients were studied at 1 (T1), 6 (T6), and 12 (T12) months after transplantation and followed clinically for a follow-up time of 103 ± 60 months. At T6, an oral glucose tolerance test (OGTT) was performed in 484 patients. Results The mean age of the cohort studied was 49 ± 13 years, with a mean dialysis vintage of 54 ± 52 months. Hemodialysis was the therapy before KTx in 70.6% of patients, whereas 20.9% had been treated with peritoneal dialysis. The 8.5% of patients received a pre-emptive KTx. Fifty-seven percent of the patients were male and 83.5% had a KTx from a deceased donor. Both at T1 and T12, immunosuppressive therapy was mainly composed of steroids (average cumulative dose at T12: 2914 ± 962 mg), calcineurin inhibitors and mycophenolate. In our cohort at T12, diabetic patients were 237 (28.6%), of which 51 (6.2%) were already affected by diabetes before KTx. Of note, we diagnosed diabetes by OGTT in 23 KTxps, while in 90 KTxps, OGTT showed prediabetic alterations. Patients with glucose metabolism abnormalities were significantly older, had an altered lipid profile associated with higher BMI values and a significantly higher inflammatory index. Interestingly, our data showed that graft loss was not affected by any type of alteration of glucose metabolism. On the contrary, we found that mortality was significantly higher in patients with pre-transplant diabetes and in those with alterations in glucose metabolism detected with OGTT (both including diabetes and considering only IGT and IFG). Conclusions Our data showed that age at transplantation, lipid profile, and the inflammatory state were the variables that most influenced the development of PTDM. Interestingly, mortality was significantly associated with pre-transplant diabetes and alteration in glucose metabolism. This allowed us to highlight the impact of prediabetes status and the importance of OGTT as a screening test in post-transplant and potentially pre-transplant. Future randomized controlled trials will be able to resume the topic, including the analysis of the effects of new antidiabetic drugs.

Urinary Dickkopf 3 Is Not an Independent Risk Factor in a Cohort of Kidney Transplant Recipients and Living Donors.

Urinary dickkopf 3 (uDKK3) is a marker released by kidney tubular epithelial cells that is associated with the progression of chronic kidney disease (CKD) and may cause interstitial fibrosis and tubular atrophy. Recent evidence suggests that uDKK3 can also predict the loss of kidney function in CKD patients and kidney transplant recipients, regardless of their current renal function. We conducted a prospective study on 181 kidney transplant (KTx) recipients who underwent allograft biopsy to determine the cause, analyzing the relationship between uDKK3 levels in urine, histological findings, and future allograft function progression. Additionally, we studied 82 living kidney donors before unilateral nephrectomy (Nx), 1-3 days after surgery, and 1 year post-surgery to observe the effects of rapid kidney function loss. In living donors, the uDKK3/creatinine ratio significantly increased 5.3-fold 1-3 days after Nx. However, it decreased significantly to a median level of 620 pg/mg after one year, despite the absence of underlying primary kidney pathology. The estimated glomerular filtration rate (eGFR) decreased by an average of 29.3% to approximately 66.5 (±13.5) mL/min/1.73 m2 after one year, with no further decline in the subsequent years. uDKK3 levels increased in line with eGFR loss after Nx, followed by a decrease as the eGFR partially recovered within the following year. However, uDKK3 did not correlate with the eGFR at the single time points in living donors. In KTx recipients, the uDKK3/creatinine ratio was significantly elevated with a median of 1550 pg/mg compared to healthy individuals or donors after Nx. The mean eGFR in the recipient group was 35.5 mL/min/1.73 m2. The uDKK3/creatinine ratio was statistically associated with the eGFR at biopsy but was not independently associated with the eGFR one year after biopsy or allograft loss. In conclusion, uDKK3 correlates with recent and future kidney function and kidney allograft survival in the renal transplant cohort. Nevertheless, our findings indicate that the uDKK3/creatinine ratio has no prognostic influence on future renal outcome in living donors and kidney recipients beyond the eGFR, independent of the presence of acute renal graft pathology, as correlations are GFR-dependent.

Design, cohort profile and comparison of the KTD-Innov study: a prospective multidimensional biomarker validation study in kidney allograft rejection.

There is an unmet need for robust and clinically validated biomarkers of kidney allograft rejection. Here we present the KTD-Innov study(ClinicalTrials.gov, NCT03582436), an unselected deeplyphenotyped cohort of kidney transplant recipients with a holistic approach to validate the clinical utility of precision diagnostic biomarkers. In 2018-2019, we prospectively enrolled consecutive adult patients who received a kidney allograft at seven French centers and followed them for a year. We performed multimodal phenotyping at follow-up visits, by collecting clinical, biological, immunological, and histological parameters, and analyzing a panel of 147 blood, urinary and kidney tissue biomarkers. The primary outcome was allograft rejection, assessed at each visit according to the internationalBanff 2019 classification. We evaluated the representativeness of participants by comparing them with patients from French, European, and American transplant programs transplanted during the same period. A total of 733 kidney transplant recipients (64.1% male and 35.9% female) were included during the study. The median follow-up after transplantation was 12.3months (interquartile range, 11.9-13.1months). The cumulative incidence of rejection was 9.7% at one year post-transplant. We developed a distributed and secured data repository in compliance with the general data protection regulation. We established a multimodal biomarker biobank of 16,736 samples, including 9331 blood, 4425 urinary and 2980 kidney tissue samples, managed and secured in a collaborative network involving 7 clinical centers, 4 analytical platforms and 2 industrial partners. Patients' characteristics, immune profiles and treatments closely resembled those of 41,238 French, European and American kidney transplant recipients. The KTD-Innov study is a unique holistic and multidimensional biomarker validation cohort of kidney transplant recipients representative of the real-world transplant population. Future findings from this cohort are likely to be robust and generalizable.

Memory B-cell derived donor-specific antibodies do not predict outcome in sensitized kidney transplant recipients: a retrospective single-center study.

Repeated exposure to sensitizing events can activate HLA-specific memory B cells, leading to the production of donor-specific memory B cell antibodies (DSAm) that pose a risk for antibody-mediated rejection (ABMR) in kidney transplant recipients (KTRs). This single-center retrospective study aimed to identify DSAm and assess their association with outcomes in a cohort of KTRs with pretransplant serum donor-specific antibodies (DSA). We polyclonally activated pretransplant peripheral blood mononuclear cells (PBMCs) from 60 KTRs in vitro, isolated and quantified IgG from the culture supernatant using ELISA, and analyzed the HLA antibodies of eluates with single antigen bead (SAB) assays, comparing them to the donor HLA typing for potential DSAm. Biopsies from 41 KTRs were evaluated for rejection based on BANFF 2019 criteria. At transplantation, a total of 37 DSAm were detected in 26 of 60 patients (43%), of which 13 (35%) were found to be undetectable in serum. No significant association was found between pretransplant DSAm and ABMR (P=0.53). Similar results were observed in a Kaplan-Meier analysis for ABMR within the first year posttransplant (P=0.29). Additionally, MFI levels of DSAm showed no significant association with ABMR (P=0.28). This study suggests no significant association between DSAm and biopsy-proven clinical ABMR. Further prospective research is needed to determine whether assessing DSAm could enhance existing immunological risk assessment methods for monitoring KTRs, particularly in non-sensitized KTRs.

High-dimensional mass cytometry identified circulating natural killer T-cell subsets associated with protection from cytomegalovirus infection in kidney transplant recipients

Cytomegalovirus (CMV) infection is associated with poor kidney transplant outcomes. While innate and adaptive immune cells have been implicated in its prevention, an in-depth characterization of the in vivo kinetics of multiple cell subsets and their role in protecting against CMV infection has not been achieved. Here, we performed high-dimensional immune phenotyping by mass cytometry, and functional assays, on 112 serially collected samples from CMV seropositive kidney transplant recipients. Advanced unsupervised deep learning analysis was used to assess immune cell populations that significantly correlated with prevention against CMV infection and anti-viral immune function. Prior to infection, kidney transplant recipients who developed CMV infection showed significantly lower CMV-specific cell-mediated immune (CMI) frequencies than those that did not. A broad diversity of circulating cell subsets within innate and adaptive immune compartments were associated with CMV infection or protective CMV-specific CMI. While percentages of CMV (tetramer-stained)-specific T cells associated with high CMI responses and clinical protection, circulating CD3+CD8midCD56+ NK-T cells overall strongly associated with low CMI and subsequent infection. However, three NK-T cell subsets sharing the CD11b surface marker associated with CMV protection and correlated with strong anti-viral CMI frequencies in vitro. These data were validated in two external independent cohorts of kidney transplant recipients. Thus, we newly describe the kinetics of a novel NK-T cell subset that may have a protective role in post-transplantation CMV infection. Our findings pave the way to more mechanistic studies aimed at understanding the function of these cells in protection against CMV infection.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients.

Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019 (COVID-19) but its full correlation with COVID-19 infection remains unknown. To identify acute pancreatitis' occurrence, clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19. A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19. Data were obtained from hospital electronic medical records. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab. Four hundred and eight out of 1432 (28.49%) patients who received a renal allograft developed COVID-19 disease. The analyzed cohort included 321 patients (57% males). One hundred and fifty patients (46.7%) received at least one dose of the anti-SARS-CoV-2 vaccine before the infection. One hundred twenty-five (39.1%) patients required hospitalization, 141 (44.1%) developed pneumonia and four patients (1.3%) required mechanical ventilation. Treatment included immunosuppression modification in 233 patients (77.1%) and remdesivir in 53 patients (16.6%), besides the other supportive measures. In the study cohort, only one transplant recipient (0.3%) developed acute pancreatitis during acute COVID-19, presenting with abdominal pain and significantly elevated pancreatic enzymes. She survived without complications with a stable kidney allograft function. Although rare, acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients. The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

Myosteatosis is associated with poor survival after kidney transplantation: a large retrospective cohort validation.

We aim to establish diagnostic thresholds of sarcopenia and myosteatosis based on CT measurements, and to validate their prognostic value in a large cohort of kidney transplant recipients. Local healthy population with abdominal CT between 2010 and 2022, and patients underwent kidney transplantation between 2015 and 2019 at our center were retrospectively included. The skeletal muscle index and muscle attenuation of abdominal muscles were calculated based on CT image at the middle of the third lumbar vertebra. Primary endpoints included all-cause mortality and death censored allograft survival. Age- and sex-specific thresholds for sarcopenia and myosteatosis were established based on 1598 healthy local population. The final patient cohort consisted of 992 kidney transplant recipients (median age 34years, interquartile range 28-44years; 694 males), including 33 (3.3%) with sarcopenia and 95 (9.5%) with myosteatosis. Multivariate analysis revealed myosteatosis (adjusted hazard ratio = 3.08, p = 0.022) was an independent baseline risk factor of mortality after adjusting for age, the history of cancer, and the history of cardiovascular event. Multivariate analysis found preemptive transplantation (adjusted hazard ratio = 0.36, p = 0.037) was an independent protective factor of allograft loss. No difference was found in the prognosis between kidney transplant recipients with and without sarcopenia. Myosteatosis was an independent risk factor of mortality after kidney transplantation, but sarcopenia was not. Neither sarcopenia nor myosteatosis was associated with graft loss.

Single-dose antithymocyte globulin in standard immunological risk kidney transplant recipients: efficacy and kinetics of peripheral blood CD3+ T lymphocyte modulation.

Polyclonal anti-T cell antibodies (ATG or thymoglobulin®) are used as induction therapy in kidney transplant recipients. This study evaluates the safety, efficacy, and CD3+T lymphocyte modulation of two ATG regimens. The trial included two cohorts of kidney transplant recipients that were followed for one year. The study group, including standard immunological risk recipients, received one 3mg/kg dose of ATG. The comparator group, including standard and high immunological risk kidney transplant recipients, received a fractionated dose regimen (up to four 1.5mg/kg doses). Patient and graft outcomes and the kinetics of CD3+T lymphocyte modulation in the peripheral blood were evaluated. One hundred kidney transplant recipients were included in each group. The one-year incidence of treated acute rejection, and patient and graft survival did not differ between groups. Bacterial infections were significantly more frequent in fractionated-dose group patients (66%versus 5%; P = 0.0001). At one-year follow-up, there was no difference in the incidence of cytomegalovirus infection (P = 0.152) or malignancies (P = 0.312). CD3+T lymphocyte immunomodulation in the single-dose group was more effective in the first two days after transplantation. After the third post-transplant day, CD3+T lymphocyte modulation was more efficient in the fractionated dose group. Both regimens resulted in low rejection rates and equivalent survival. The single and reduced dose regimen protects from the occurrence of bacterial infections. CD3+T lymphocyte modulation occurred with different kinetics, although it did not result in distinct outcomes.

Belatacept with time-limited tacrolimus coimmunosuppression modifies the 3-year risk of eplet mismatch in kidney transplantation

Solid organ transplant donor-recipient eplet mismatch has been correlated with donor-specific antibody (DSA) formation, antibody-mediated rejection, and overall rejection rates. However, studies have been predominantly in patients on tacrolimus-based immunosuppression regimens and have not fully explored differences in ethnically and racially diverse populations. Evidence indicates that patients on belatacept have lower rates of DSA formation, suggesting mediation of the immunogenicity of mismatched human leukocyte antigen polymorphisms. We performed a retrospective, single-center analysis of class II eplet disparity in a cohort of kidney transplant recipients treated using belatacept with tacrolimus induction (Bela/TacTL) or tacrolimus regimens between 2016 and 2019. Bela/TacTL (n = 294) and tacrolimus (n = 294) cohorts were propensity score-matched with standardized difference <0.15. Single-molecule eplet risk level was associated with immune event rates for both groups. In Cox regression analysis stratified by eplet risk level, Bela/TacTL immunosuppression was associated with a decreased rate of DSA (hazard ratio [HR] = 0.4), antibody-mediated rejection (HR = 0.2), and rejection (HR = 0.45). In the low-risk group, cumulative graft failure was lower for patients on Bela/TacTL (P < .02). Analysis of eplet mismatch burden may be a useful adjunct in identifying high-risk populations with increased immunosuppression requirements and should encourage the design of allocation rules to incentivize lower-risk pairings without negatively impacting equity in access.

A Multi-Step Precision Pathway for Predicting Allograft Survival in Heterogeneous Cohorts of Kidney Transplant Recipients.

Accurate prediction of allograft survival after kidney transplantation allows early identification of at-risk recipients for adverse outcomes and initiation of preventive interventions to optimize post-transplant care. Many prediction algorithms do not model cohort heterogeneity and may lead to inaccurate assessment of longer-term graft outcomes among minority groups. Using data from a national Australian kidney transplant cohort (2008-2017) as the derivation set, we developed P-Cube, a multi-step precision prediction pathway model for predicting overall graft survival in three ethnic subgroups: European Australians, Asian Australians and Aboriginal and Torres Strait Islander Peoples. The concordance index for the European Australians, Asian Australians, and Aboriginal and Torres Strait Islander Peoples subpopulations were 0.99 (0.98-0.99), 0.93 (0.92-0.94) and 0.92 (0.91-0.93), respectively. Similar findings were observed when validating P-cube using an external dataset [Scientific Registry of Transplant Recipient Registry (2006-2020)]. Six sub-categories of recipients with distinct risk factor profiles were identified. Some factors such as blood group compatibility were considered important across the entire transplant population. Other factors such as human leukocyte antigen (HLA)-DR mismatches were unique to older recipients. The P-cube model identifies allograft survival specific risk factors within a heterogenous population and offers personalized survival predictions in a diverse cohort.