Graft Function In Recipients Research Articles

Intraoperative Low-Dose Dexmedetomidine Administration Associated with Reduced Hepatic Ischemia-Reperfusion Injury in Pediatric Deceased Liver Transplantation: A Retrospective Cohort Study.

BackgroundDexmedetomidine (DEX) attenuates hepatic ischemia-reperfusion injury (HIRI) in adult liver transplantation (LT), but its effects on postoperative liver graft function in pediatric LT remain unclear. We sought to investigate whether intraoperative DEX administration was associated with improved liver graft function in pediatric LT recipients. It was hypothesized that DEX administration was associated with reduced HIRI and improved liver graft function.Material/MethodsFrom November 2015 to May 2020, 54 deceased pediatric LT recipients were categorized into a control group and a DEX group. Intraoperatively, the DEX group received an additional infusion of DEX at 0.4 μg/kg/h from incision to the end of the operation in comparison with the control group. Preoperative, intraoperative, and postoperative data were reviewed. Postoperative liver enzyme levels and HIRI severity were assessed and compared. Independent risk factors for HIRI were determined by multivariate logistic regression analysis using a stepwise forward conditional method.ResultsWe enrolled 28 and 26 patients in the DEX and control groups, respectively. Patients in the DEX group exhibited a reduced incidence of moderate-to-severe HIRI (88.5% vs 60.7%, P=0.020) and decreased level of serum alanine aminotransferase (median [interquartile range]: 407 [230–826] vs 714 [527–1492] IU/L, P=0.048) compared with the controls. Binary logistic analysis revealed that longer cold ischemia time (odds ratio [OR]=1.006; 95% confidence interval [CI]=1.000–1.013; P=0.044) and intraoperative DEX use (OR=0.198; 95% CI=0.045–0.878; P=0.033) were independent predictors for moderate-to-severe HIRI.ConclusionsIntraoperative low-dose DEX administration was associated with a lower incidence of moderate-to-severe HIRI in pediatric deceased LT. However, further studies are needed to confirm our results and elucidate the underlying mechanisms.

Killer cell immunoglobulin-like receptor (KIR) gene distribution and allograft kidney function.

The inhibition and activation cycles of the NK cells are mainly regulated by killer cell immunoglobulin-like receptors (KIRs). In this study, we examined KIR genes/genotypes in kidney transplant recipients and healthy subjects. We aimed to determine if there are relations between certain KIR genes and allograft kidney function. Renal transplantation patients (n=131) and healthy controls (n=183) from the same ethnic background were included. Transplant patients with an obvious cause of graft dysfunction (increase in serum creatinine and decrease in estimated glomerular filtration rate) were excluded. Recruited patients were classified as graft dysfunction (GD) (n=38) or functioning graft (FG) (n=93) based on rejection and allograft dysfunction. Isolated DNA of all participants were typed for 16 KIR genes with specific primers using PCR. Patient groups were compared for KIR genes/genotypes and clinical features. Significant differences were observed for KIR2DL3 and KIR3DL1 genes presented with higher frequencies in healthy controls than in kidney transplant recipients (p=0.001, p=0.006 respectively). Comparison between GD and FG groups revealed a protective association for the KIR2DL1 gene (p=0.003, OR=0.148). KIR2DL1 gene was significantly more frequent in renal transplantation patients with FG. We suggest that the presence of KIR2DL1, which is an inhibitor gene for NK cell functions, might be associated with favorable graft function in kidney transplant recipients.

Anatomical variations of the renal artery: a computerized tomographic angiogram study in living kidney donors at a Nigerian Kidney Transplant Center.

Understanding of the renal vascular anatomy is key to a safe and successful donor nephrectomy, which ultimately impacts on the renal graft function and survival in kidney transplant recipients. To report the various anatomical configurations of the renal artery identified in living kidney donors in a Nigerian kidney transplant institution. The computerized tomography angiograms of 100 consecutive living kidney donors were prospectively reviewed over an 18-month period. Anatomical variations of the renal arteries including accessory arteries and early divisions were noted. Duration of surgery and ischemic time were recorded intra-operatively. Data analysis was carried out using IBM SPSS version 20. There were variations in renal artery configuration in 50 (50%) cases, 32% were accessory renal arteries while 18% were early branches of the renal artery. The classical bilateral solitary renal arteries were found in 50 (50%) of potential donors. There was statistically significant longer operating and ischemic time in donors with multiple renal arteries as compared with solitary arteries (p<0.05). There are a wide variety of renal artery configurations seen in potential kidney donors. The classical solitary renal artery remains the commonest and most favourable configuration for donor nephrectomy and transplantation.

Risk factors and outcomes for delayed kidney graft function in simultaneous heart and kidney transplant recipients: A UNOS/OPTN database analysis

There are no prior studies assessing the risk factors and outcomes for kidney delayed graft function (K-DGF) in simultaneous heart and kidney (SHK) transplant recipients. Using the OPTN/UNOS database, we sought to identify risk factors associated with the development of K-DGF in this unique population, as well as outcomes associated with K-DGF. A total of 1161 SHK transplanted between 1998 and 2018 were included in the analysis, of which 311 (27%) were in the K-DGF (+) group and 850 in the K-DGF (-) group. In the multivariable analysis, history of pretransplant dialysis (OR: 3.95; 95% CI: 2.94 to 5.29; p<.001) was significantly associated with the development of K-DGF, as was donor death from cerebrovascular accident and longer cold ischemia time of either organ. SHK recipients with K-DGF had increased mortality (HR: 1.99; 95% CI: 1.52 to 2.60; p<.001) and death censored kidney graft failure (HR: 3.51; 95% CI: 2.29 to 5.36; p<.001) in the multivariable analysis. Similar outcomes were obtained when limiting our study to 2008-2018. Similar to kidney-only recipients, K-DGF in SHK recipients is associated with worse outcomes. Careful matching of recipients and donors, as well as peri-operative management, may help reduce the risk of K-DGF and the associated detrimental effects.

PD45-12 INTRAOPERATIVE MANNITOL ADMINISTRATION DURING LAPAROSCOPIC DONOR NEPHRECTOMY AND IMPACT ON LONG-TERM GRAFT FUNCTION

You have accessJournal of UrologyRenal Transplantation & Vascular Surgery II (PD45)1 Sep 2021PD45-12 INTRAOPERATIVE MANNITOL ADMINISTRATION DURING LAPAROSCOPIC DONOR NEPHRECTOMY AND IMPACT ON LONG-TERM GRAFT FUNCTION Gustavo Gryzinski, Jason Farrow, Clinton Bahler, and Chandru Sundaram Gustavo GryzinskiGustavo Gryzinski More articles by this author , Jason FarrowJason Farrow More articles by this author , Clinton BahlerClinton Bahler More articles by this author , and Chandru SundaramChandru Sundaram More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002059.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: End-stage renal disease frequently results in dialysis, and at best, transplantation. Laparoscopic donor nephrectomy was introduced in 1995 and has been a valuable source of high-quality organs. Improving long-term graft function of recipients through judicious intraoperative medical management remains an essential goal. Infusion of mannitol prior to hilar clamping during donor nephrectomy has been utilized based on its proposed cytoprotective properties – theoretically improving renal perfusion, free-radical scavenging, and diuresis. However, there is a paucity of large, long-term studies evaluating its use. In this study, we aimed to explore the long-term effects of intraoperative mannitol administration on graft function as measured by creatinine. METHODS: A single-center, retrospective analysis of a contemporary cohort of donor nephrectomies was performed. Eighty donors (sample determined using a power of 0.8 to detect a 20% difference in creatinine) were identified and then matched to recipients using Indiana University’s Organ Transplant Tracking Record database. Patients were balanced by sex and stratified by intraoperative administration of mannitol (yes vs no). Creatinine was recorded at fixed intervals per routine nephrology follow-up. Statistical analysis was performed using SPSS. RESULTS: Basic demographics are presented in Table 1. The only significant difference in baseline clinical factors was donor intraoperative diuretic administration, which was more frequently co-administered with mannitol. Creatinine means by time can be seen in Figure 1. Multiple means comparisons were made using ANOVA and did not reveal any differences in creatinine at three years post-transplant (p > 0.05). CONCLUSIONS: Mannitol administration did not statistically affect post-transplant creatinine up to the three-year follow-up. On post-hoc analysis, elimination of cases where diuretics were co-administered did not change these results. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e746-e747 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gustavo Gryzinski More articles by this author Jason Farrow More articles by this author Clinton Bahler More articles by this author Chandru Sundaram More articles by this author Expand All Advertisement Loading ...

The Association Between Delayed Graft Function and Renal Resistive Index in Kidney Transplant Recipients.

Background and objectivesDelayed graft function (DGF) may increase the risk for kidney graft dysfunction. Renal resistive index (RRI) in Doppler ultrasonography is useful in measuring blood flow changes in kidneys which is indicative of tubulointerstitial damage. Most of the diseases in DGF etiology are related to tubulointerstitium and arteries of the kidneys. In this study, we investigated whether there is a relationship between delayed graft function and renal resistive index in kidney transplant recipients (KTR).Materials and methodsPatients who underwent kidney transplantation were included in this retrospective study. KTR were divided into two groups as DGF (+) and DGF (−). Comparison of RRI values of DGF (+) and DGF (−) groups according to the measurements at different times.ResultsThe findings showed that both RRI measurements (post-transplant in the first week and the end of the first year) of the DGF (+) group were higher than DGF (−) group (p=0.001 and p=0.003, respectively). The interaction of measurements and DGF did not have an effect on RRI (p>0.05).ConclusionThe value of RRI in the DGF (−) group was lower than DGF (+) group in the first week after kidney transplantation.

Elevated plasma free thiols are associated with early and one-year graft function in renal transplant recipients.

Reduced free thiols in plasma are indicative of oxidative stress, which is an important contributor to ischaemia-reperfusion injury (IRI) in kidney transplantation leading to kidney damage and possibly delayed graft function (DGF). In a post-hoc, exploratory analysis of the randomised controlled CONTEXT trial, we investigated whether higher (i.e. less oxidised) plasma levels of free thiols as a biomarker of reduced oxidative stress are associated with a better initial graft function or a higher GFR. Free thiol levels were measured in plasma at baseline, 30 and 90 minutes after reperfusion of the kidney as well as at Day 1, Day 5 and twelve months after kidney transplantation in 217 patients from the CONTEXT study. Free thiol levels were compared to the kidney graft function measured as the estimated time to a 50% reduction in plasma creatinine (tCr50), the risk of DGF and measured GFR (mGFR) at Day 5 and twelve months after transplantation. Higher levels of free thiols at Day 1 and Day 5 are associated with higher mGFR at Day 5 (p<0.001, r2adj. = 0.16; p<0.001, r2adj. = 0.25), as well as with mGFR at twelve months (p<0.001, r2adj. = 0.20; p<0.001, r2adj. = 0.16). However, plasma levels of free thiols at 30 minutes and 90 minutes, but not Day 1, were significantly higher among patients experiencing DGF. Higher levels of plasma free thiols at Day 1 and Day 5, which are reflective of lower levels of oxidative stress, are associated with better early and late graft function in recipients of a kidney graft from deceased donors. ClinicalTrials.gov Identifier: NCT01395719.

Urine the Right Direction: The Consensus Statement From the Committee on Transplant Anesthesia of the American Society of Anesthesiologists on Fluid Management During Kidney Transplantation.

Urine the Right Direction: The Consensus Statement From the Committee on Transplant Anesthesia of the American Society of Anesthesiologists on Fluid Management During Kidney Transplantation.

Perioperative Normal Saline Administration and Delayed Graft Function in Patients Undergoing Kidney Transplantation: A Retrospective Cohort Study.

Perioperative normal saline administration remains common practice during kidney transplantation. The authors hypothesized that the proportion of balanced crystalloids versus normal saline administered during the perioperative period would be associated with the likelihood of delayed graft function. The authors linked outcome data from a national transplant registry with institutional anesthesia records from 2005 to 2015. The cohort included adult living and deceased donor transplants, and recipients with or without need for dialysis before transplant. The primary exposure was the percent normal saline of the total amount of crystalloids administered perioperatively, categorized into a low (less than or equal to 30%), intermediate (greater than 30% but less than 80%), and high normal saline group (greater than or equal to 80%). The primary outcome was the incidence of delayed graft function, defined as the need for dialysis within 1 week of transplant. The authors adjusted for the following potential confounders and covariates: transplant year, total crystalloid volume, surgical duration, vasopressor infusions, and erythrocyte transfusions; recipient sex, age, body mass index, race, number of human leukocyte antigen mismatches, and dialysis vintage; and donor type, age, and sex. The authors analyzed 2,515 records. The incidence of delayed graft function in the low, intermediate, and high normal saline group was 15.8% (61/385), 17.5% (113/646), and 21% (311/1,484), respectively. The adjusted odds ratio (95% CI) for delayed graft function was 1.24 (0.85 to 1.81) for the intermediate and 1.55 (1.09 to 2.19) for the high normal saline group compared with the low normal saline group. For deceased donor transplants, delayed graft function in the low, intermediate, and high normal saline group was 24% (54/225 [reference]), 28.6% (99/346; adjusted odds ratio, 1.28 [0.85 to 1.93]), and 30.8% (277/901; adjusted odds ratio, 1.52 [1.05 to 2.21]); and for living donor transplants, 4.4% (7/160 [reference]), 4.7% (14/300; adjusted odds ratio, 1.15 [0.42 to 3.10]), and 5.8% (34/583; adjusted odds ratio, 1.66 [0.65 to 4.25]), respectively. High percent normal saline administration is associated with delayed graft function in kidney transplant recipients.

SARS-CoV-2 and lung transplantation. What do we know?

Introduction: In 2019, new Coronavirus (SARS-CoV-2) has spread around the globe. The virus can replicate in the cells of the lower respiratory tract, causing pneumonia, oedema and hypoxia. In some patients, the disease will progress to acute respiratory distress syndrome (ARDS) which is a life-threatening condition. Lung transplantation (LuTx) might be the only rescue therapy for severe respiratory failure. Additionally, little is known about the impact of SARS-CoV-2 on lung transplant recipients. The purpose of this systematic review is to present current knowledge about lung transplantation as a treatment method for ARDS associated with COVID-19 infection and to summarize information regarding the management of COVID infection in lung transplant recipients. Materials and methods: Literature search through different databases was conducted. Only case report and case series were included. Results: Out of 525 initial results, 16 studies were included in this systematic review. 7 articles presented patients with LuTx as a treatment option for ARDS and 9 presented management of lung recipients infected with COVID-19. A total of 37 patients were included in this systematic review. Discussion: The course of reviewed patients with SARS-CoV-2 infection was similar and lung transplantation should be considered as a treatment of last chance when extracorporeal life support cannot be withdrawn. Further research is still required to assess the impact of new coronavirus on graft function in lung transplant recipients. Currently, the treatment strategy involves immunosuppression modification and supplemental oxygen therapy. However, some patients do not present clinical symptoms.

A Pilot Study of the Safety and Efficacy of Alkali Therapy on Vascular Function in Kidney Transplant Recipients

IntroductionMetabolic acidosis is associated with cardiovascular events, graft function, and mortality in kidney transplant recipients (KTRs). We examined the effect of alkali therapy on vascular endothelial function in KTRs.MethodsWe performed an 18-week, randomized, double-blind, placebo-controlled crossover pilot study examining the effect of sodium bicarbonate therapy versus placebo on vascular function in 20 adult KTRs at least 1 year from transplant with an estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m2 and a serum bicarbonate level of 20 to 26 mEq/L. Each treatment period was 8 weeks in duration with a 2-week washout period between treatments. The primary outcome was change in brachial artery flow-mediated dilation (FMD) between sodium bicarbonate treatment and placebo.ResultsTwenty patients completed the study and were included in the primary analysis. The mean (SD) baseline eGFR of participants was 75 (22) ml/min per 1.73 m2, respectively. Serum bicarbonate levels did not increase significantly with treatment (0.3 [1.5] mEq/L, P = 0.37). Sodium bicarbonate therapy was not associated with worsening blood pressure, weight gain, or hypokalemia. There was no significant increase in FMD after 8 weeks of sodium bicarbonate therapy compared to placebo (mean change in FMD 2.2%, 95% CI –0.1 to 4.6, P = 0.06). There were no significant changes in high-sensitivity C-reactive protein, interleukin-6, eGFR, or urinary albumin-to-creatinine ratio during treatment. Urinary ammonium excretion decreased by 9 mmol/d (P=0.003), with sodium bicarbonate.ConclusionsSodium bicarbonate therapy is safe and feasible in KTRs, and our results strengthen the need for a larger randomized controlled trial.

T-cell Exhaustion in Organ Transplantation.

Exhaustion of T cells occurs in response to long-term exposure to self and foreign antigens. It limits T cell capacity to proliferate and produce cytokines, leading to an impaired ability to clear chronic infections or eradicate tumors. T-cell exhaustion is associated with a specific transcriptional, epigenetic, and metabolic program and characteristic cell surface markers' expression. Recent studies have begun to elucidate the role of T-cell exhaustion in transplant. Higher levels of exhausted T cells have been associated with better graft function in kidney transplant recipients. In contrast, reinvigorating exhausted T cells by immune checkpoint blockade therapies, while promoting tumor clearance, increases the risk of acute rejection. Lymphocyte depletion and high alloantigen load have been identified as major drivers of T-cell exhaustion. This could account, at least in part, for the reduced rates of acute rejection in organ transplant recipients induced with thymoglobulin and for the pro-tolerogenic effects of a large organ such as the liver. Among the drugs that are widely used for maintenance immunosuppression, calcineurin inhibitors have a contrasting inhibitory effect on exhaustion of T cells, while the influence of mTOR inhibitors is still unclear. Harnessing or encouraging the natural processes of exhaustion may provide a novel strategy to promote graft survival and transplantation tolerance.

Recovery of kidney function after AKI because of COVID-19 in kidney transplant recipients.

SummaryEvidence on the evolution of graft function in kidney transplant recipients recovering from coronavirus disease‐2019 (COVID‐19) is lacking. This multicenter observational study evaluated the short‐term clinical outcomes in recipients with acute kidney injury (AKI) secondary to COVID‐19. Out of 452 recipients following up at five centers, 50 had AKI secondary to COVID‐19. 42 recipients with at least 3‐month follow‐up were included. Median follow‐up was 5.23 months [IQR 4.09–6.99]. Severe COVID‐19 was seen in 21 (50%), and 12 (28.6%) had KDIGO stage 3 AKI. Complete recovery of graft function at 3 months was seen in 17 (40.5%) patients. Worsening of proteinuria was seen in 15 (37.5%) patients, and 4 (9.5%) patients had new onset proteinuria. Graft failure was seen in 6 (14.3%) patients. Kidney biopsy revealed acute tubular injury (9/11 patients), thrombotic microangiopathy (2/11), acute cellular rejection (2/11), and chronic active antibody‐mediated rejection (3/11). Patients with incomplete recovery were likely to have lower eGFR and proteinuria at baseline, historical allograft rejection, higher admission SOFA score, orthostatic hypotension, and KDIGO stage 3 AKI. Baseline proteinuria and the presence of orthostatic hypotension independently predicted incomplete graft recovery. This shows that graft recovery may remain incomplete after AKI secondary to COVID‐19.

Revisiting the former approach: Low-dose dopamine in kidney transplant recipients

Objective: We aim to evaluate the effects of low-dose dopamine (LDD) infusion (0.5 – 2.5 g/kg/min) on hemodynamic status and short-term graft function in kidney transplant recipients. Materials and Methods: Patients who underwent kidney transplantation surgery between January 2007 and December 2016 were included in the study. Demographic and laboratory data, presence of delayed graft function, and the rates of rejection, graft loss, and mortality were recorded. The data were compared between patients with and without LDD treatment. Results: A total of 126 patients were included in the study (M/F:50.8%/49.2%; mean age, 38.94 ± 11.8 years). Ninety-four patients (74.6%) received living-donor transplants. Fifty-seven patients underwent LDD infusion in the postoperative period (LDD group), while 69 patients did not receive LDD infusion. Demographic and laboratory data of the patients did not significantly differ between groups. Nineteen patients in the LDD group experienced delayed graft function (p=0.039). However, these patients tended to be older, have a longer dialysis period prior to transplantation, deceased and hypertensive donors. There was no significant difference in renal function at 6 months after transplantation between groups. Conclusion: Although, LDD infusion increases kidney blood flow,

MO947KILLER CELL IMMUNOGLOBULIN LIKE RECEPTOR (KIR) GENE DISTRIBUTION AND ALLOGRAFT KIDNEY FUNCTION

Abstract Background and Aims There is increasing evidence about the alloreactivity of natural killer (NK) cells after kidney transplantation. The inhibition and activation cycles of the NK cells are mainly regulated by killer cell immunoglobulin-like receptors (KIRs) which may have extensive allelic polymorphisms within the population. In this study, we examined KIR genes/genotypes in kidney transplant recipients and healthy subjects. We aimed to determine if there are relations between certain KIR genes and graft function in kidney transplant patients. Method Renal transplant patients (n=131) and healthy controls (n=183) from the same ethnic background with similar demographics were included. Transplant patients with an obvious cause of graft dysfunction and presensitized patients were excluded. Recruited patients were classified as graft dysfunction (GD) (n=38) or functioning graft (FG) (n=93) on the basis of allograft rejection and dysfunction. Isolated DNA of all participants were typed for 16 KIR genes with specific primers using PCR. Patient groups were compared for KIR genes/genotypes and clinical features. Results Significant differences were observed for KIR2DL3 and KIR3DL1 genes that were presented with higher frequencies in healthy controls than in kidney transplant recipients (p=0.001 &amp; p=0.006). Comparison between GD and FG groups revealed a protective association for the inhibitor gene KIR2DL1 (p=0.003, OR=0.148). Distribution of the remaining 15 KIR genes and the rates of KIR genotype patterns were not different among these patient groups. Conclusion KIR2DL3 and KIR3DL1 genes were more common in healthy subjects. KIR2DL1 gene was significantly more frequent in patients with FG. We suggest that the presence of KIR2DL1, which is an inhibitor gene for NK cell functions, might be associated with favorable graft function in kidney transplant recipients.

Course of renal allograft function after diagnosis and treatment of post-transplant lymphoproliferative disorders in pediatric kidney transplant recipients.

Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication in renal transplant recipients. Immunomodulatory and chemotherapeutic treatment potentially affect allograft function. The aim of this study was to evaluate graft function of pediatric kidney transplant recipients following diagnosis and standardized treatment of PTLD. Patients were identified from the German Ped-PTLD registry, and data on renal function were retrospectively retrieved from patient charts. For PTLD treatment, immunosuppressive therapy was reduced and all children received rituximab (375mg/m2 ) for up to six doses. Two patients required additional low-dose chemotherapy. Renal allograft function was monitored by consecutive measurements of estimated glomerular filtration rate (eGFR) at defined time points. Follow-up was up to 60months after PTLD. Twenty patients were included in this cohort analysis. Median time from transplantation to PTLD was 2.4years. Histopathology showed monomorphic lesions in 16 and polymorphic in 4 patients. Two patients experienced PTLD relapse after 2 and 14months. Range-based analysis of variance showed stable allograft function in 17 of 20 patients (85%). Mean eGFR increased during early treatment phase. One patient experienced graft rejection 5.3years after diagnosis of PTLD. Another patient developed recurrence of primary renal disease (focal-segmental glomerulosclerosis) and lost his renal allograft 3.8years post-transplant (2.0years after PTLD diagnosis). Treatment of PTLD with rituximab with or without low-dose chemotherapy in combination with reduced immunosuppression, mostly comprising of an mTOR inhibitor-based, calcineurin inhibitor-free regimen, is associated with stable graft function and favorable graft survival in pediatric renal transplant patients.

Higher CD19+CD25+ Bregs are independently associated with better graft function in renal transplant recipients

BackgroundThe Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups.MethodThirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ.ResultsESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/μl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015).ConclusionsOur findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.

Long Hemodialysis Duration Predicts Delayed Graft Function in Renal Transplant Recipients From Living Donor: A Single-Center Study

This study aims to determine the ratio of delayed graft function in renal transplant recipients from living donors and the predictive value of hemodialysis time before transplant for delayed graft function. We conducted a study on 116 adult patients who were diagnosed with end-stage kidney disease and were treated with hemodialysis and transplanted kidneys from living donors for 2 years (from June 2018 to June 2020). Delayed graft function event was collected for each patient. The recipients had a median age of 36.5 years old, in which 55.2% of them were men, 4.3% of them had the diabetic mellitus, and the median hemodialysis duration was 6 months. The ratio of positive panel-reactive antibody was 33.6% and vascular reconstruction of the donor's kidney was 16.4%. The ratio of delayed graft function was 12.2% (14 of 116 patients). Delayed graft function significantly related to positive panel-reactive antibody, long duration of hemodialysis before transplant, and vascular reconstruction of donor's kidney with P < .001. Duration of hemodialysis before kidney transplant had a predictive value for delayed graft function (area under the curve, 0.83; P < .001). Delayed graft function was not rare in renal transplant recipients from living donors. Duration of hemodialysis before kidney transplant was a good predictor for delayed graft function.

Kidney graft function and arterial stiffness in renal transplant recipients.

In renal transplant recipients (RTRs), cardiovascular (CV) complications are associated with non-traditional risk factors, such as a decline in graft function, immunosuppressive therapy, time of dialysis before transplantation, inflammation and anemia. Higher value of arterial stiffness is the consequence of risk factors and it can lead to CV events. The aim of this study was the assessment of the arterial stiffness in RTRs with different value of estimated glomerular filtration rate (eGFR) and its correlation with classical and non-classical CV risk factors. 344 stable RTRs were enrolled in this study. The arterial stiffness was measured in all participants. The study population was divided in two groups based on the value of eGFR: 201 (≥45 ml/min/1,73 m2) and 143 (<45 ml/min/1,73 m2). Demographic, immunosuppression status, clinical and biochemical information were referred to a single assessment obtained from medical records in the patients' medical files. Vascular stiffness was determined by an automated oscillometric device. In the group with eGFR<45 ml/min/1.73 m2 there were more patients with cardiovascular diseases (CVD) and the participants were older, in comparison to those with eGFR≥45 ml/min/1.73 m2. Arterial stiffness was significantly higher in the group with worse graft function. The analysis showed a significant correlation between age, cardiovascular disease and all arterial stiffness parameters. In addition, a significant correlation was found between all PWV variables and pulse pressure (PP) and pulsatile stress (PS), in the total population and in groups with eGFR <45 ml/min/1.73 m2 and eGFR≥45 ml/min/1.73 m2. The multivariate analysis showed a significant correlation between age, CVD and baPWV left, baPWV right and cf PWV in the total population. Arterial stiffness did not differ depending on eGFR. Significant influence of age and CVD on arterial stiffness in RTRs was confirmed and PWV did not differ depending on eGFR. Our findings suggest that PS, as a marker for arterial stiffness, represents an easy and cost-effective tool.

Association of non-HLA antibodies against endothelial targets and donor-specific HLA antibodies with antibody-mediated rejection and graft function in pediatric kidney transplant recipients

BackgroundNon-HLA antibodies against endothelial targets have been implicated in the pathogenesis of antibody-mediated rejection (ABMR), but data in pediatric patients are scarce.MethodsWe retrospectively analyzed a carefully phenotyped single-center (University Children’s Hospital Heidelberg, Germany) cohort of 62 pediatric kidney transplant recipients (mean age at transplantation, 8.6 ± 5.0 years) at increased risk of graft function deterioration. Patients had received their transplant between January 1, 1999, and January 31, 2010. We examined at time of late index biopsies (more than 1-year post-transplant, occurring after January 2004) the association of antibodies against the angiotensin II type 1 receptor (AT1R), the endothelin type A receptor (ETAR), the MHC class I chain-like gene A (MICA), and vimentin in conjunction with overall and complement-binding donor-specific HLA antibodies (HLA-DSA) with graft histology and function.ResultsWe observed a high prevalence (62.9%) of non-HLA antibody positivity. Seventy-two percent of HLA-DSA positive patients showed additional positivity for at least one non-HLA antibody. Antibodies against AT1R, ETAR, and MICA were associated with the histological phenotype of ABMR. The cumulative load of HLA-DSA and non-HLA antibodies in circulation was related to the degree of microinflammation in peritubular capillaries. Non-HLA antibody positivity was an independent non-invasive risk factor for graft function deterioration (adjusted hazard ratio 6.38, 95% CI, 2.11–19.3).ConclusionsOur data indicate that the combined detection of antibodies to HLA and non-HLA targets may allow a more comprehensive assessment of the patients’ immune responses against the kidney allograft and facilitates immunological risk stratification.