Day Of Kidney Transplantation Research Articles

Albumin influences leucocyte FcRn expression in the early days of kidney transplantation.

FcRn, a receptor originally known for its involvement in IgG and albumin transcytosis and recycling, is also important in the establishment of the innate and adaptive immune response. Dysregulation of the immune response has been associated with variations in FcRn expression, as observed in cancer. Recently, a link between autophagy and FcRn expression has been demonstrated. Knowing that autophagy is strongly involved in the development of reperfusion injury in kidney transplantation and that albuminemia is transiently decreased in the first 2 weeks after transplantation, we investigated variations in FcRn expression after kidney transplantation. We monitored FcRn levels by flow cytometry in leukocytes from 25 renal transplant patients and considered parameters such as albumin concentrations, estimated glomerular filtration rate, serum creatinine, serum IgG levels, and ischaemia/reperfusion time. Two groups of patients could be distinguished according to their increased or non-increased FcRn expression levels between days 2 and 6 (d2-d6) post-transplantation. Leukocyte FcRn expression at d2-d6 was correlated with albumin concentrations at d0-d2. These results suggest that albumin concentrations at d0-d2 influence FcRn expression at d2-d6, raising new questions about the mechanisms underlying these original observations.

Effect of delayed graft function on immediate and long-term kidney transplant outcomes

Objective: to analyze the immediate and long-term outcomes of kidney transplantation (KT) depending on the duration of delayed graft function (DGF). Materials and methods. The study conducted a retrospective analysis of KT outcomes in 312 patients operated on at Botkin Hospital from June 2018 to December 2022. Exclusion criteria were primary non-function, severe surgical complications that required emergency transplantectomy in the first week after KT and cases where a comprehensive approach to DGF prevention was applied. DGF was defined as the need for dialysis within the first 7 days of KT. The severity of this complication was assessed by the time it took the transplanted kidney function to normalize from mild DGF to severe. We analyzed the immediate and long-term outcomes of KT depending on the presence of initial function and the severity of DGF. Results. DGF developed in 25.3% of cases. The mean time for graft function normalization was 16.5 ± 6.8 days. Mild DGF occurred in 68% of cases, severe DGF was determined in the remaining cases (32%). The incidence of complications was statistically significantly higher in the severe DGF group: 14/25 (56%) vs. 15/54 (27.8%) (p = 0.047). There were also no significant differences in the rate of complications between recipients with immediate and mild DGF: 43/233 (18.4%) vs. 15/54 (27.8%) (p > 0.05). Severe DGF lasting for more than 2 weeks had a statistically significant association with postoperative complications (p = 0.047) and with decreased long-term graft survival (log-rank p = 0.021). Conclusion. Development of severe DGF mainly depends on donor characteristics, timing and peculiarities of graft preservation. Nevertheless, other factors, such as acute calcineurin inhibitor nephrotoxicity, should not be ignored. Therefore, prevention of all potentially modifiable risk factors for DGF should go hand in hand with the expansion of the indications for donation.

#6257 PROGNOSTIC VALUE OF A POSITIVE CROSSMATCH BEFORE DESENSITIZATION IN A COHORT OF HIGHLY-SENSITIZED PATIENTS

Abstract Background and Aims Human Leukocyte antigen (HLA) sensitization in patients is a barrier for Kidney Transplantation (KT) access, and highly-sensitized patients remain on the waiting list longer than other patients which results in a higher morbidity and mortality. Desensitization may be an option to increase their access to KT. All patients transplanted in this context have a negative Complement-Dependent Cytotoxicity crossmatch (CDC-CM) the day of KT. However, the stratification of the long-term risk of graft loss according to flow cytometry crossmatch (FC-CM) and to CDC-CM during the desensitization period remains unknown. Method In this retrospective study, all highly-sensitized patients (Panel Reactive Antigen (PRA) ≥ 85) in our center were included. CDC-CM and FC-CM were performed on samples before and during the desensitization period and clinical follow-up data were retrieved. Pre-KT desensitization strategy consisted in two Rituximab infusions (375mg/m2) and a variable number of apheresis (mostly semi-specific immunoadsorption) associated with a classical immunosuppression-based regimen (tacrolimus, mycophenolate and steroids). Results A total of 183 highly-sensitized recipients received a KT between 2014 and 2022. Of these, 23 were desensitized prior to KT and among them 18 had a positive FC-CM before KT and 5 had no positive FC-CM on all assessed serums. Mean age was 52.9 ± 13 years. Mean follow-up was 5.2±4 and 3±2 years for non-desensitized and desensitized patients respectively. PRA before desensitization was higher in desensitized patients (98%) versus non-desensitized patients (95%) and the mean time on the waiting list was 5.8±4 versus 7.5±4 years respectively. Death-censored graft survival and patient's raw survival, using cox-survival analysis, were not statistically different between the desensitized kidney transplanted patients and the highly-sensitized patients without desensitization (p = 0.77 and p = 0.57 respectively). In sub-group analyses, the positivity of FC and/or CDC-CM did not add an additional risk of graft loss or patient mortality. Conclusion Desensitization allows highly-sensitized patients to access KT with an HLA-incompatible graft (with a positive CDC or FC-CM on the serum collected prior to desensitization), with the same graft survival as similarly sensitized patients transplanted with an HLA-compatible graft without desensitization.

The Role of Innate Immune Cells in the Prediction of Early Renal Allograft Injury Following Kidney Transplantation.

Background: Despite recent advances and refinements in perioperative management of kidney transplantation (KT), early renal graft injury (eRGI) remains a critical problem with serious impairment of graft function as well as short- and long-term outcome. Serial monitoring of peripheral blood innate immune cells might be a useful tool in predicting post-transplant eRGI and graft outcome after KT. Methods: In this prospective study, medical data of 50 consecutive patients undergoing KT at the University Hospital of Leipzig were analyzed starting at the day of KT until day 10 after the transplantation. The main outcome parameter was the occurrence of eRGI and other outcome parameters associated with graft function/outcome. eRGI was defined as graft-related complications and clinical signs of renal IRI (ischemia reperfusion injury), such as acute tubular necrosis (ATN), delayed graft function (DGF), initial nonfunction (INF) and graft rejection within 3 months following KT. Typical innate immune cells including neutrophils, natural killer (NK) cells, monocytes, basophils and dendritic cells (myeloid, plasmacytoid) were measured in all patients in peripheral blood at day 0, 1, 3, 7 and 10 after the transplantation. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for eRGI. Cutoff levels were calculated with the Youden index. Significant diagnostic immunological cutoffs and other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 50 included patients, 23 patients developed eRGI. Mean levels of neutrophils and monocytes were significantly higher on most days in the eRGI group compared to the non-eRGI group after transplantation, whereas a significant decrease in NK cell count, basophil levels and DC counts could be found between baseline and postoperative course. ROC analysis indicated that monocytes levels on POD 7 (AUC: 0.91) and NK cell levels on POD 7 (AUC: 0.92) were highly predictive for eRGI after KT. Multivariable analysis identified recipient age (OR 1.53 (95% CI: 1.003–2.350), p = 0.040), recipient body mass index > 25 kg/m2 (OR 5.6 (95% CI: 1.36–23.9), p = 0.015), recipient cardiovascular disease (OR 8.17 (95% CI: 1.28–52.16), p = 0.026), donor age (OR 1.068 (95% CI: 1.011–1.128), p = 0.027), <0.010), deceased-donor transplantation (OR 2.18 (95% CI: 1.091–4.112), p = 0.027) and cold ischemia time (CIT) of the renal graft (OR 1.005 (95% CI: 1.001–1.01), p = 0.019) as clinically relevant prognostic factors associated with increased eRGI following KT. Further, neutrophils > 9.4 × 103/μL on POD 7 (OR 16.1 (95% CI: 1.31–195.6), p = 0.031), monocytes > 1150 cells/ul on POD 7 (OR 7.81 (95% CI: 1.97–63.18), p = 0.048), NK cells < 125 cells/μL on POD 3 (OR 6.97 (95% CI: 3.81–12.7), p < 0.01), basophils < 18.1 cells/μL on POD 10 (OR 3.45 (95% CI: 1.37–12.3), p = 0.02) and mDC < 4.7 cells/μL on POD 7 (OR 11.68 (95% CI: 1.85–73.4), p < 0.01) were revealed as independent biochemical predictive variables for eRGI after KT. Conclusions: We show that the combined measurement of immunological innate variables (NK cells and monocytes on POD 7) and specific clinical factors such as prolonged CIT, increased donor and recipient age and morbidity together with deceased-donor transplantation were significant and specific predictors of eRGI following KT. We suggest that intensified monitoring of these parameters might be a helpful clinical tool in identifying patients at a higher risk of postoperative complication after KT and may therefore help to detect and—by diligent clinical management—even prevent deteriorated outcome due to IRI and eRGI after KT.

Institutional protocol adherence in the incidence of recurrent urinary tract infection after kidney transplantation

ObjectivesRecurrent urinary tract infections (rUTIs) occur frequently after kidney transplantation (KT), however their optimal management remains undefined. This study aimed to identify risk factors for rUTI and to validate a protocol for UTI and rUTI treatment after KT. MethodsThis retrospective cohort study involved patients undergoing KT between January 2013 and July 2016. Patients were followed-up from day of KT until graft loss, death or end of follow-up (31 December 2018). We analysed all episodes of symptomatic UTI. The main outcome measure was rUTI after KT. Analysis was done per episode in a multilevel approach; patient features were considered in the distal level and UTI features in the proximal level. Univariate and multivariate analyses were performed by Cox regression. A propensity score was used to adjust the risk of patients with carbapenem-resistant Enterobacteriaceae. ResultsDuring the study period, 787 patients underwent KT, of whom 152 (19.3%) developed 356 UTI episodes. The most common micro-organisms wereEscherichia coli (165/356; 46.3%) and Klebsiella pneumoniae (101/356; 28.4%). Multidrug-resistant micro-organisms were isolated in 161 UTIs (45.2%). Risk factors for rUTI were diabetic nephropathy as the cause of end-stage renal disease (P = 0.02), UTI in first 180 days after KT (P = 0.04), anatomic alteration of the urinary tract at UTI diagnosis (P = 0.004) and length of time to effective therapy (P = 0.002); UTI treatment duration according to institutional protocol (P = 0.04) was the only protective factor identified. ConclusionAppropriate therapy duration has an impact on rUTI prevention after KT.

Significance of revised criteria for chronic active T cell-mediated rejection in the 2017 Banff classification: Surveillance by 1-year protocol biopsies for kidney transplantation.

Diagnostic criteria for chronic active T cell-mediated rejection (CA-TCMR) were revised in the Banff 2017 consensus, but it is unknown whether the new criteria predict graft prognosis of kidney transplantation. We enrolled 406 kidney allograft recipients who underwent a 1-year protocol biopsy (PB) and investigated the diagnostic significance of Banff 2017. Interobserver reproducibility of the 3 diagnosticians showed a substantial agreement rate of 0.68 in Fleiss's kappa coefficient. Thirty-three patients (8%) were classified as CA-TCMR according to Banff 2017, and 6 were previously diagnosed as normal, 12 as acute TCMR, 10 with borderline changes, and 5 as CA-TCMR according to Banff 2015 criteria. Determinant factors of CA-TCMR were cyclosporine use (vs tacrolimus), previous acute rejection, and BK polyomavirus-associated nephropathy. In survival analysis, the new diagnosis of CA-TCMR predicted a composite graft endpoint defined as doubling serum creatinine or death-censored graft loss (log-rank test, P<.001). In multivariate analysis, CA-TCMR was associated with the second highest risk of the composite endpoint (hazard ratio: 5.42; 95% confidence interval, 2.02-14.61; P<.001 vs normal) behind antibody-mediated rejection. In conclusion, diagnosis of CA-TCMR in Banff 2017 may facilitate detecting an unfavorable prognosis of kidney allograft recipients who undergo a 1-year PB.

The association of preoperative cardiac stress testing with 30-day death and myocardial infarction among patients undergoing kidney transplantation.

BackgroundAlthough periodic cardiac stress testing is commonly used to screen patients on the waiting list for kidney transplantation for ischemic heart disease, there is little evidence to support this practice. We hypothesized that cardiac stress testing in the 18 months prior to kidney transplantation would not reduce postoperative death, total myocardial infarction (MI) or fatal MI.MethodsUsing the United States Renal Data System, we identified ESRD patients ≥40 years old with primary Medicare insurance who received their first kidney transplant between 7/1/2006 and 11/31/2013. Propensity matching created a 1:1 matched sample of patients with and without stress testing in the 18 months prior to kidney transplantation. The outcomes of interest were death, total (fatal and nonfatal) MI or fatal MI within 30 days of kidney transplantation.ResultsIn the propensity-matched cohort of 17,304 patients, death within 30 days occurred in 72 of 8,652 (0.83%) patients who underwent stress testing and in 65 of 8,652 (0.75%) patients who did not (OR 1.07; 95% CI: 0.79–1.45; P = 0.66). MI within 30 days occurred in 339 (3.9%) patients who had a stress test and in 333 (3.8%) patients who did not (OR 1.03; 95% CI: 0.89–1.21; P = 0.68). Fatal MI occurred in 17 (0.20%) patients who underwent stress testing and 15 (0.17%) patients who did not (OR 0.97; 95% CI: 0.71–1.32; P = 0.84).ConclusionStress testing in the 18 months prior to kidney transplantation is not associated with a reduction in death, total MI or fatal MI within 30 days of kidney transplantation.

Different causes of early and late-onset post transplant lymphoproliferative disorder in kidney transplantation patients after 2000

The purpose of this study was to analyze the link between PTLD incidence and its occurrence time in patients at a single center in comparable medical environments after 2000. Retrospectively, total 3305 kidney transplantation patients medical data were analyzed. Patients were divided into two groups based on the period from the day of kidney transplantation to the day of PTLD diagnosis. Early-onset was defined as PTLD development within two years after transplantation, whereas all other cases were categorized as late-onset PTLD. In the early-onset group, young age (0-19 years) was confirmed as a risk factor for PTLD incidence (HR 1.49, p=0.038). In the late-onset group, history of anti-rejection therapy was confirmed as a risk factor (HR 1.32, p=0.031). Overall survival rates were not significantly different between the two groups (p=0.556). Graft survival rates were also not different between the two groups (p=0.549). When patients with PTLD were classified into early-onset group and late-onset group at two years, overall survival and graft survival were comparable. And patients with early-onset PTLD are more likely to be associated with EBV, the late-onset patients are more likely to be immunosuppressed.

Impact of the pretransplant dialysis modality on kidney transplantation outcomes: a nationwide cohort study

ObjectiveMost patients with uraemia must undergo chronic dialysis while awaiting kidney transplantation; however, the role of the pretransplant dialysis modality on the outcomes of kidney transplantation remains obscure. The objective...

PREVALENCE OF NEW ONSET DIABETES IN PATIENTS AFTER KIDNEY TRANSPLANTATION – THE PROSPECTIVE STUDY

Objective While kidney transplantation is the best treatment of renal insufficiency and is recommended for patients with a glomerular filtration rate below 30 mL/min, new onset diabetes after transplantation (NODAT) reduces the benefits of this treatment, and present a significant, independent predictor of patient mortality and loss of graft function. The aim of the study was to determine the incidence of NODAT, as well as the risk factors for new onset diabetes mellitus (DM). The study included 84 patients older than 18 years, who underwent kidney transplantation in the Clinical Center Nis in the period from 2007 to 2016. Impaired glucose tolerance was found in all of these patients in the first three post-transplantation months. In addition to physical examination and basic laboratory analyses, in all of kidney transplant patinents the levels of tacrolimus and glycosylated hemoglobin HbA1c were determined. NODAT was registered in 7 (8.3%) patients after average 17.2+10.8 days of kidney transplantation. The patients with NODAT had significantly higher levels of serum creatinine 210.72±120.29 μmol/L and decreased creatinine clearance 43.31±17.57 ml/min/1.73m2 compared with a group of patients with diabetes prior to kidney trans-plantation 180.16±82.78 μmol/L and 52.12±18.45 ml/min/1.73m2, respectively (p <0.01), and a statistically significantly shorter follow-up period after kidney transplantation (p <0.05). The results showed a significantly higher level of body mass index (BMI) 30.6 ± 6.4% compared to patients with already present diabetes before transplantation 28.5±6.8%, as well as the level of triglycerides 2.87±0.79 mmol/L vs. 1.73±0.82 mmol/L (p <0.05). The level of tacrolimus was adequate for the given post-transplantation period. NODAT is a significant complication of kidney transplantation and is associated with risk factors, primarily with older recipient age and hereditary burden, but also with variable factors such as obesity and hypertriglyceridemia. We believe that the prevalence of NODAT can be changed if oral glucose tolerance test (OGTT) is done prior to transplantation in the potential kidney graft recipients.

Urinary Tissue Inhibitor of Metalloproteinase and Insulin-like Growth Factor–7 as Early Biomarkers of Delayed Graft Function After Kidney Transplantation

BackgroundRecently, urinary tissue inhibitor of metalloproteinase–2 (TIMP-2) and insulin-like growth factor–7 (IGFBP-7), markers for G1 cell cycle arrest, have been identified and validated in predicting the development of acute kidney injury in critically ill patients. It is unknown, however, whether these two biomarkers could predict the development of delayed graft function (DGF) after kidney transplantation (KT). MethodsThis is a single-center, prospective, observational study. We enrolled 74 patients who underwent KT between August 2013 and December 2016. Urine sample were collected immediately after the operation. The primary outcome was development of DGF as defined by need for dialysis of more than 1 session within 7 days of KT. ResultsTwenty-three patients (31%) were diagnosed with DGF. In univariate analysis, kidneys from expanded criteria donors, higher donor serum creatinine, lower donor estimated glomerular filtration rate, antithymoglobulin exposure, neutrophil gelatinase associated lipocalin, and urinary [TIMP-2]·[IGFBP7] were significantly different between early graft function and DGF. However, in multivariate analysis adjusting other factors, deceased donor and urinary [TIMP-2]·[IGFBP7] at 0 hours post-transplantation could predict the development of DGF. The receiver operating characteristic curve for prediction of DGF showed an area under the curve of 0.867 (sensitivity 0.86, specificity 0.71) for a cutoff value of 1.39. ConclusionsOur results indicate that urine [TIMP-2]·[IGFBP7] immediately after transplantation could be an early, predictive biomarker of DGF in kidney transplantation.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

Identifying risk factors for graft loss within 90 days of kidney transplantation in the modern era: A review of single center and UNOS databases

Identifying risk factors for graft loss within 90 days of kidney transplantation in the modern era: A review of single center and UNOS databases

Pre‐transplant pharmacokinetic profiling and tacrolimus requirements post‐transplant

To determine the proportion of patients achieving tacrolimus whole-blood concentrations of ≥10 ng/mL within 3 days of kidney transplantation, after randomization either to standard dosing (control group) or post-transplantation dosing guided by a 2-hour (C(2) ) level following a preoperative tacrolimus dose (T2 group). The first postoperative tacrolimus dose was given either according to standard care (control group) or 0.15 mg/kg b.d. if the pre-transplant C(2) level was ≤20 ng/mL, 0.1 mg/kg b.d. if the C(2) level was 21-59 ng/mL or 0.05 mg/kg b.d. if the C(2) level was ≥60 ng/mL (T2 group). Subsequent dosing in both groups was based upon tacrolimus trough level monitoring. Participants received concomitant mycophenolate mofetil and steroids. Ninety patients were recruited, of which 84 were included in the analysis (control group n=43; T2 group n=41). There was no difference in the proportion of subjects achieving tacrolimus trough levels ≥10 ng/mL (82.9% Control vs 93.0% T2; P=0.19) or between 10 and 15 ng/mL (41.5% Control vs 41.9% T2; P=0.97) at day 3 post transplant. The T2 group achieved tacrolimus trough levels of ≥10 ng/mL significantly faster than the control group (100% achievement in 14 days (Control) versus 4 days (T2); P=0.01). Performing a pre-transplant tacrolimus C(2) does not significantly increase the high proportion of subjects achieving 10 ng/mL tacrolimus concentrations by day 3 using routine protocols. However, compared with standard care, performing a pre-transplant tacrolimus C(2) does lead to patients achieving a whole-blood concentration of ≥10 ng/mL sooner.

Impact of pretransplant dialysis on early graft function in pediatric kidney recipients*

Delayed graft function (DGF) is a frequent complication of kidney transplantation (KT) that may affect both short- and long-term graft outcome. It has been reported that pretransplantation peritoneal dialysis was correlated with a better recovery of graft function than hemodialysis in adult kidney recipients. However, the effect of pretransplantation dialysis mode (PDM) seemed to be unclear on the early outcome of KT in pediatric recipients. In this study, the potential impact of PDM on early graft function was evaluated in 174 pediatric patients who underwent KT by using cadaveric donors. The primary outcome parameter was the time to reach a serum creatinine (SCr) level 50% of the pretransplantation value [T(1/2(SCr))], while DGF was defined as a T(1/2(SCr)) >3 days after KT (n = 40). By stratifying kidney recipients for normal function graft or DGF, this latter group showed a significantly higher body weight (BW) on the day of KT (P = 0.014), body surface area (BSA) (P = 0.005), warm ischemia time (WIT) (P = 0.022), early SCr on the day 1 after KT (P < 0.001), and T(1/2(SCr)) (P < 0.001), whereas lower urine volume (UV) collected in the first 24 h after KT (P < 0.001) and fluid load (P < 0.001) occurred. Univariate exponential correlation that was carried out between T(1/2(SCr)) and all the other variables had shown a better value than the linear correlation for BW (R(2) = 0.28 vs. R(2) = 0.04), BSA (R(2) = 0.29 vs. R(2) = 0.03), and SCr (R(2) = 0.51 vs. R(2) = 0.28). In a multivariate regression analysis performed by entering T(1/2(SCr)) as dependent variable and following a forward stepwise method, cold ischemia time (CIT) (P = 0.027) but not PDM (P = 0.195) reached significance. In a Cox regression analysis carried out with T(1/2(SCr)) as dependent variable, neither CIT nor PDM gained significance. This study suggests that PDM does not affect early graft function in pediatric kidney recipients.