High pretransplant serum levels of CXCL9 are associated with increased risk of acute rejection and graft failure in kidney graft recipients

Background: The frequency and outcomes of starting maintenance dialysis in the hospital as an inpatient in kidney transplant recipients with graft failure are poorly understood. Objective: To determine the frequency of inpatient dialysis starts in patients with kidney graft failure and examine whether dialysis start status (hospital inpatient vs outpatient setting) is associated with all-cause mortality and kidney re-transplantation. Design: Population-based cohort study. Setting: We used linked administrative healthcare databases from Ontario, Canada. Patients: We included 1164 patients with kidney graft failure from 1994 to 2016. Measurements: All-cause mortality and kidney re-transplantation. Methods: The cumulative incidence function was used to calculate the cumulative incidence of all-cause mortality and kidney re-transplantation, accounting for competing risks. Subdistribution hazard ratios from the Fine and Gray model were used to examine the relationship between inpatient dialysis starts (vs outpatient dialysis start [reference]) and the dependent variables (ie, mortality or re-transplant). Results: We included 1164 patients with kidney graft failure. More than half (55.8%) of patients with kidney graft failure, initiated dialysis as an inpatient. Compared with outpatient dialysis starters, inpatient dialysis starters had a significantly higher cumulative incidence of mortality and a significantly lower incidence of kidney re-transplantation ( P < .001). The 10-year cumulative incidence of mortality was 51.9% (95% confidence interval [CI]: 47.4, 56.9%) (inpatient) and 35.3% (95% CI: 31.1, 40.1%) (outpatient). After adjusting for clinical characteristics, we found inpatient dialysis starters had a significantly increased hazard of mortality in the first year after graft failure (hazard ratio: 2.18 [95% CI: 1.43, 3.33]) but at 1+ years there was no significant difference between groups. Limitations: Possibility of residual confounding and unable to determine inpatient dialysis starts that were unavoidable. Conclusions: In this study we identified that most patients with kidney graft failure had inpatient dialysis starts, which was associated with an increased risk of mortality. Further research is needed to better understand the reasons for an inpatient dialysis start in this patient population.

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Outcomes of kidney transplantation over a 16-year period in Korea: An analysis of the National Health Information Database

PLoS ONE ◽

10.1371/journal.pone.0247449 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0247449

Author(s):

Hyung Soon Lee ◽

Minjin Kang ◽

Banseok Kim ◽

Yongjung Park

Keyword(s):

Risk Factors ◽

Kidney Transplantation ◽

Health Insurance ◽

Acute Rejection ◽

Health Information ◽

National Health ◽

Graft Failure ◽

Survival Rates ◽

Increased Risk ◽

Information Database

Background This study investigated the outcomes of kidney transplantation (KT) over a 16-year period in Korea and identified risk factors for graft failure using a nationwide population-based cohort. Methods We investigated the Korean National Health Insurance Service-National Health Information Database. Health insurance claims for patients who underwent KT between 2002 and 2017 were analyzed. Results The data from 18,331 patients who underwent their first KT were reviewed. The percentage of antithymocyte globulin (ATG) induction continuously increased from 2.0% in 2002 to 23.5% in 2017. Rituximab began to be used in 2008 and had increased to 141 patients (9.6%) in 2013. Acute rejection occurred in 17.3% of all patients in 2002 but decreased to 6.3% in 2017. The rejection-free survival rates were 78.8% at 6 months after KT, 76.1% after 1 year, 67.5% after 5 years, 61.7% after 10 years, and 56.7% after 15 years. The graft survival rates remained over 80% until 12 years after KT, and then rapidly decreased to 50.5% at 16 years after KT. In Cox’s multivariate analysis, risk factors for graft failure included being male, more recent KT, KT from deceased donor, use of ATG, basiliximab, or rituximab, tacrolimus use as an initial calcineurin inhibitor, acute rejection history, and cytomegalovirus infection. Conclusions ATG and rituximab use has gradually increased in Korea and more recent KT is associated with an increased risk of graft failure. Therefore, meticulous preoperative evaluation and postoperative management are necessary in the case of recent KT with high risk of graft failure.

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Degree of Glomerulosclerosis in Procurement Kidney Biopsies from Marginal Donor Kidneys and Their Implications in Predicting Graft Outcomes

Journal of Clinical Medicine ◽

10.3390/jcm9051469 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1469

Author(s):

Wisit Cheungpasitporn ◽

Charat Thongprayoon ◽

Pradeep K Vaitla ◽

Api Chewcharat ◽

Panupong Hansrivijit ◽

...

Keyword(s):

Acute Rejection ◽

Graft Survival ◽

Graft Failure ◽

Patient Survival ◽

Graft Function ◽

Deceased Donor ◽

Delayed Graft Function ◽

Organ Shortage ◽

Increased Risk ◽

Significant Difference

Background: This study aimed to assess the association between the percentage of glomerulosclerosis (GS) in procurement allograft biopsies from high-risk deceased donor and graft outcomes in kidney transplant recipients. Methods: The UNOS database was used to identify deceased-donor kidneys with a kidney donor profile index (KDPI) score > 85% from 2005 to 2014. Deceased donor kidneys were categorized based on the percentage of GS: 0–10%, 11–20%, >20% and no biopsy performed. The outcome included death-censored graft survival, patient survival, rate of delayed graft function, and 1-year acute rejection. Results: Of 22,006 kidneys, 91.2% were biopsied showing 0–10% GS (58.0%), 11–20% GS (13.5%), >20% GS (19.7%); 8.8% were not biopsied. The rate of kidney discard was 48.5%; 33.6% in 0–10% GS, 68.9% in 11–20% GS, and 77.4% in >20% GS. 49.8% of kidneys were discarded in those that were not biopsied. Death-censored graft survival at 5 years was 75.8% for 0–10% GS, 70.9% for >10% GS, and 74.8% for the no biopsy group. Among kidneys with >10% GS, there was no significant difference in death-censored graft survival between 11–20% GS and >20% GS. Recipients with >10% GS had an increased risk of graft failure (HR = 1.27, p < 0.001), compared with 0–10% GS. There was no significant difference in patient survival, acute rejection at 1-year, and delayed graft function between 0% and 10% GS and >10% GS. Conclusion: In >85% KDPI kidneys, our study suggested that discard rates increased with higher percentages of GS, and GS >10% is an independent prognostic factor for graft failure. Due to organ shortage, future studies are needed to identify strategies to use these marginal kidneys safely and improve outcomes.

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H-Y Antigen Incompatibility Not Associated with Adverse Immunologic Graft Outcomes: Deceased Donor Pair Analysis of the OPTN Database

Journal of Transplantation ◽

10.1155/2011/148457 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Douglas Scott Keith ◽

James T. Patrie

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Graft Survival ◽

Graft Failure ◽

Organ Procurement ◽

Deceased Donor ◽

Kidney Graft ◽

The Difference ◽

One Year ◽

Deceased Donor Kidney Transplant

Background. H-Y antigen incompatibility adversely impacts bone marrow transplants however, the relevance of these antigens in kidney transplantation is uncertain. Three previous retrospective studies of kidney transplant databases have produced conflicting results.Methods. This study analyzed the Organ Procurement and Transplantation Network database between 1997 and 2009 using male deceased donor kidney transplant pairs in which the recipient genders were discordant. Death censored graft survival at six months, five, and ten years, treated acute rejection at six months and one year, and rates of graft failure by cause were the primary endpoints analyzed.Results. Death censored graft survival at six months was significantly worse for female recipients. Analysis of the causes of graft failure at six months revealed that the difference in death censored graft survival was due primarily to nonimmunologic graft failures. The adjusted and unadjusted death censored graft survivals at five and ten years were similar between the two genders as were the rates of immunologic graft failure. No difference in the rates of treated acute rejection at six months and one year was seen between the two genders.Conclusions. Male donor to female recipient discordance had no discernable effect on immunologically mediated kidney graft outcomes in the era of modern immunosuppression.

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MO940ACUTE REJECTION IN KIDNEY RETRANSPLANTATION: RISK FACTORS AND IMPACT IN GRAFT SURVIVAL

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab110.0019 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Rita Leal ◽

Clara Pardinhas ◽

Luís Rodrigues ◽

Maria Guedes Marques ◽

Lidia Santos ◽

...

Keyword(s):

Risk Factors ◽

Acute Rejection ◽

Kidney Transplant ◽

Graft Survival ◽

Graft Failure ◽

Graft Loss ◽

First Year ◽

Post Transplant ◽

Increased Risk

Abstract Background and Aims Kidney retransplantation confers a robust survival benefit over dialysis in selected patients and recent data has shown second graft outcomes similar to those of a first graft. However, the management of these patients is challenging, particularly due to allosensitization and an increased risk of acute rejection, which are related with poorer graft survival. The recognition of risk factors to acute rejection, dependent on the first and second graft, might help us to personalize standard care and achieve similar graft survival rates to patients with a first transplant. Our aim was to identify risk factors to second graft acute rejection, and the impact of acute rejection in graft failure. Method We performed a retrospective, longitudinal study including all patients submitted to a second kidney transplant between January 2008 and December 2019, excluding patients with more than 2 grafts or multi-organ transplant. Demographic, clinical and histocompatibility data from the donor and receptor were collected from our unit database. Delayed graft function was defined as the need of dialysis in the first week post-transplant. All acute rejection episodes were biopsy proven, according to Banff 2017 criteria. Follow-up was defined at 1st June 2020 for functioning grafts or at graft failure, with a mean time of 94±42 months. Results We included 109 patients of which 70 males (64%), mostly Caucasian (97%), with a mean age of 43±12 years at second kidney transplant. The main causes of end stage renal disease were glomerular disease (37%), undetermined cause (34%), and urological pathology (15%). First kidney transplant was performed before the year 2010 in 95 patients (87%). The median time of first graft survival was 75 months (IQR 58.5-91.4) and the main causes of first graft loss were chronic allograft nephropathy (N=62, 70.5%) and 11 patients (12.5%) presented primary disfunction due to surgical/vascular complications. During follow-up, 20 patients (18%) presented biopsy proven acute rejection: 3 patients borderline changes, 10 patients T cell mediated and 7 patients antibody mediated, the majority during the first-year post-transplant (N=17, 85%). The risk factors for second graft rejection are summarized in table 1. First year graft survival of the second transplant was 90% and survival at follow up was 72.5% (N=79). Acute rejection was an important risk factor for graft loss (OR 6.548 (95%CI[2.292 - 18.703]), p<0.01). Conclusion Worst outcomes in first kidney transplant, such as acute rejection, primary dysfunction and lower graft survival were related with an increased risk of acute rejection in second graft outcomes, and consequently a higher risk of graft failure.

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MO926RAPID VS. LATE RE-TRANSPLANTATION FOR EARLY KIDNEY GRAFT LOSS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab110.005 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Diana Rodríguez Espinosa ◽

Jose Jesus Broseta Monzo ◽

Evelyn Hermida-Lama ◽

Elena Cuadrado ◽

Jimena Del Risco ◽

...

Keyword(s):

Graft Survival ◽

Graft Failure ◽

Patient Survival ◽

Statistical Significance ◽

Graft Loss ◽

Human Leukocyte ◽

Type I ◽

Kidney Graft ◽

Antibody Mediated Rejection ◽

Increased Risk

Abstract Background and Aims Early graft failure (EGL) is a devastating complication of kidney transplantation. Patients with EGL have an increased risk of mortality of up to twelve times compared to patients who received grafts that survive beyond 30 days. Moreover, they may have become sensitized to antigens from the failed graft and that human leukocyte antigen antibodies (anti-HLA), identified on single antigen bead assays, may not be reliable until several weeks after transplantation. Thus, if rapid re-transplantation occurs, there is no certainty regarding the recipient's immunological status. Hence, there could be an increased immunological risk with the consequent disturbance of the new graft's survival. Method We performed a retrospective single-center observational study in re-transplanted patients with EGL (defined as graft loss before 30 days from transplant) between January 1977 and November 2019 from our center to analyze the outcomes of rapid re-transplantation (occurred within 30 days of EGL) vs late re-transplantation (occurred beyond those 30 days). Results: T here were 82 re-transplants after EGL. The median overall patient survival after re-transplantation was 32 years. Eight patients died within the first year. Among the mortality causes, there were four septic shocks, one cardiogenic shock, one massive pulmonary thromboembolism, one myocardial infarction, and one unknown cause. When analyzed for periods, death censored graft survival was 89% at one and five years after re-transplantation. One graft was lost at eight days due to antibody-mediated rejection (AMR), while there was one death with a functioning graft three months after re-transplantation secondary to a pulmonary embolism. Seventy-three late re-transplants occurred. When analyzed for periods, death censored graft survival was 81% and 69% at one and five years after re-transplantation, respectively. The median patient survival after late re-transplantation was 32 years. There were fewer deaths after rapid re-transplantation than late re-transplantation, but given the small number of cases in the former, this difference did not reach statistical significance (p = 0.3). There was no association between the timing of re-transplantation and an increased risk of graft failure (HR 0.30 [0.04 – 2.2]). While four rapid re-transplants did not share any incompatibilities between donors, four did share at least one HLA type I incompatibility, and one shared an incompatibility of HLA class I and class II. There were no T-cell mediated rejections (TCMR), and there was only one AMR in the rapid rapid re-transplantation group, whereas there were six TCMRs and fifteen AMRs in the late re-transplantation group (p = 0.03 and p = 0.4, respectively). Conclusion Rapid re-transplantation appears to be safe and does not entail increased rejection risk, nor it diminishes long-term graft survival when compared to late re-transplantation.

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Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure

Journal of the American Society of Nephrology ◽

10.1681/asn.2018020205 ◽

2018 ◽

Vol 29 (9) ◽

pp. 2279-2285 ◽

Cited By ~ 10

Author(s):

Elena G. Kamburova ◽

Bram W. Wisse ◽

Irma Joosten ◽

Wil A. Allebes ◽

Arnold van der Meer ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Survival ◽

Graft Failure ◽

Kidney Graft ◽

Kidney Transplant Recipients ◽

Serum Samples ◽

Hla Antibodies ◽

Transplant Patients ◽

Increased Risk ◽

Positive Serum

Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients.Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay.Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non–C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non–C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non–C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%.Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.

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Association of Circulating Trimethylamine N-Oxide and Its Dietary Determinants with the Risk of Kidney Graft Failure: Results of the TransplantLines Cohort Study

Nutrients ◽

10.3390/nu13010262 ◽

2021 ◽

Vol 13 (1) ◽

pp. 262

Author(s):

Jose L. Flores-Guerrero ◽

Maryse C. J. Osté ◽

Paula B. Baraldi ◽

Margery A. Connelly ◽

Erwin Garcia ◽

...

Keyword(s):

Cohort Study ◽

Prediction Model ◽

Graft Failure ◽

Clinical Utility ◽

The Body ◽

Renal Transplant Recipients ◽

Kidney Graft ◽

Net Benefit ◽

Increased Risk ◽

Modifiable Factors

Background. Due to the critical shortage of kidneys for transplantation, the identification of modifiable factors related to graft failure is highly desirable. The role of trimethylamine-N-oxide (TMAO) in graft failure remains undetermined. Here, we investigated the clinical utility of TMAO and its dietary determinants for graft failure prediction in renal transplant recipients (RTRs). Methods. We included 448 RTRs who participated in the TransplantLines Cohort Study. Cox proportional-hazards regression analyses were performed to study the association of plasma TMAO with graft failure. Net Benefit, which is a decision analysis method, was performed to evaluate the clinical utility of TMAO and dietary information in the prediction of graft failure. Results. Among RTRs (age 52.7 ± 13.1 years; 53% males), the baseline median TMAO was 5.6 (3.0–10.2) µmol/L. In multivariable regression analysis, the most important dietary determinants of TMAO were egg intake (Std. β = 0.09 [95%CI, 0.01; 0.18]; p = 0.03), fiber intake (Std. β = −0.14 [95%CI, −0.22, −0.05]; p = 0.002), and fish and seafood intake (Std. β = 0.12 [95%CI, 0.03,0.21]; p = 0.01). After a median follow-up of 5.3 (4.5–6.0) years, graft failure was observed in 58 subjects. TMAO was associated with an increased risk of graft failure, independent of age, sex, the body mass index (BMI), blood pressure, lipids, albuminuria, and the Estimated Glomerular Filtration Rate (eGFR) (Hazard Ratio per 1-SD increase of TMAO, 1.62 (95% confidence interval (CI): 1.22; 2.14, p < 0.001)). A TMAO and dietary enhanced prediction model offered approximately double the Net Benefit compared to a previously reported, validated prediction model for future graft failure, allowing the detection of 21 RTRs per 100 RTRs tested, with no false positives versus 10 RTRs, respectively. Conclusions. A predictive model for graft failure, enriched with TMAO and its dietary determinants, yielded a higher Net Benefit compared with an already validated model. This study suggests that TMAO and its dietary determinants are associated with an increased risk of graft failure and that it is clinically meaningful.

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