Death With Function and Graft Failure After Kidney Transplantation: Risk Factors at Baseline Suggest New Approaches to Management

Background and objectivesIn preclinical studies, ischemia-reperfusion injury and older donor age are associated with graft inflammation in the early phase after transplantation. In human kidney transplantation, impaired allograft function in the first days after transplantation is often adjudicated to donor- and procedure-related characteristics, such as donor age, donor type, and ischemia times.Design, setting, participants, & measurementsIn a cohort of 984 kidney recipients, 329 indication biopsies were performed within the first 14 days after transplantation. The histologic picture of these biopsies and its relationship with alloimmune risk factors and donor- and procedure-related characteristics were studied, as well as the association with graft failure. Multivariable Cox models were applied to quantify the cause-specific hazard ratios for early rejection and early inflammatory scores, adjusted for potential confounders. For quantification of hazard ratios of early events for death-censored graft failure, landmark analyses starting from day 15 were used.ResultsEarly indication biopsy specimens displayed microvascular inflammation score ≥2 in 30% and tubulointerstitial inflammation score ≥2 in 49%. Rejection was diagnosed in 186 of 329 (57%) biopsies and associated with the presence of pretransplant donor-specific HLA antibodies and the number of HLA mismatches, but not nonimmune risk factors in multivariable Cox proportional hazards analysis. In multivariable Cox proportional hazards analysis, delayed graft function, the graft dysfunction that prompted an early indication biopsy, HLA mismatches, and pretransplant donor-specific HLA antibodies were significantly associated with a higher risk for death-censored graft failure, whereas early acute rejection was not.ConclusionsIndication biopsies performed early after kidney transplantation display inflammatory changes related to alloimmune risk factors. Nonimmune risk factors for ischemia-reperfusion injury, such as cold and warm ischemia time, older donor age, and donor type, were not identified as strong risk factors for early inflammation after human kidney transplantation.

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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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Lifestyle, Inflammation, and Vascular Calcification in Kidney Transplant Recipients: Perspectives on Long-Term Outcomes

Journal of Clinical Medicine ◽

10.3390/jcm9061911 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1911 ◽

Cited By ~ 2

Author(s):

Camilo G. Sotomayor ◽

Charlotte A. te Velde-Keyzer ◽

Martin H. de Borst ◽

Gerjan J. Navis ◽

Stephan J.L. Bakker

Keyword(s):

Risk Factors ◽

Kidney Transplantation ◽

Kidney Disease ◽

Kidney Transplant ◽

Vascular Calcification ◽

Graft Failure ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Long Term Outcomes

After decades of pioneering and improvement, kidney transplantation is now the renal replacement therapy of choice for most patients with end-stage kidney disease (ESKD). Where focus has traditionally been on surgical techniques and immunosuppressive treatment with prevention of rejection and infection in relation to short-term outcomes, nowadays, so many people are long-living with a transplanted kidney that lifestyle, including diet and exposure to toxic contaminants, also becomes of importance for the kidney transplantation field. Beyond hazards of immunological nature, a systematic assessment of potentially modifiable—yet rather overlooked—risk factors for late graft failure and excess cardiovascular risk may reveal novel targets for clinical intervention to optimize long-term health and downturn current rates of premature death of kidney transplant recipients (KTR). It should also be realized that while kidney transplantation aims to restore kidney function, it incompletely mitigates mechanisms of disease such as chronic low-grade inflammation with persistent redox imbalance and deregulated mineral and bone metabolism. While the vicious circle between inflammation and oxidative stress as common final pathway of a multitude of insults plays an established pathological role in native chronic kidney disease, its characterization post-kidney transplant remains less than satisfactory. Next to chronic inflammatory status, markedly accelerated vascular calcification persists after kidney transplantation and is likewise suggested a major independent mechanism, whose mitigation may counterbalance the excess risk of cardiovascular disease post-kidney transplant. Hereby, we first discuss modifiable dietary elements and toxic environmental contaminants that may explain increased risk of cardiovascular mortality and late graft failure in KTR. Next, we specify laboratory and clinical readouts, with a postulated role within persisting mechanisms of disease post-kidney transplantation (i.e., inflammation and redox imbalance and vascular calcification), as potential non-traditional risk factors for adverse long-term outcomes in KTR. Reflection on these current research opportunities is warranted among the research and clinical kidney transplantation community.

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Ureteral strictures post-kidney transplantation: Trends, impact on patient outcomes, and clinical management

Canadian Urological Association Journal ◽

10.5489/cuaj.7003 ◽

2021 ◽

Vol 15 (10) ◽

Author(s):

Michelle Minkovich ◽

Olusegun Famure ◽

Yanhong Li ◽

Anand Ghanekar ◽

Markus Selzner ◽

...

Keyword(s):

Risk Factors ◽

Kidney Transplantation ◽

Patient Outcomes ◽

Clinical Management ◽

Graft Failure ◽

Graft Function ◽

Cox Proportional Hazards ◽

Ureteral Stricture ◽

Kidney Transplant Recipients ◽

Increased Risk

Introduction: Ureteral strictures post-kidney transplantation (KT) can be a significant morbidity to the patient, often requiring surgical intervention and impacting graft function. We sought to investigate the incidence, clinical management, and outcomes of ureteral strictures among kidney transplant recipients (KTRs) at a large, multi-organ transplant center. Methods: We conducted a single-center cohort study looking at KTRs who had transplant surgery from January 1, 2005 to March 31, 2017 with at least one-year followup (n=1742). Any KTRs done outside of our center or simultaneous multiorgan transplants were excluded. The Kaplan-Meier product-limit method was used to determine the incidence of ureteral strictures. Risk factors for ureteric strictures and clinical outcomes among patients with vs. without ureteric strictures were analyzed using Cox proportional hazards models. Results: The incidence of ureteral strictures was 1.31 (95% confidence interval [CI] 0.85, 2.01) per 100 person-years or a cumulative incidence of 1.2%. We did not find any donor or recipient demographic variables that were independently associated with an increased risk of ureteral stricture development. A large proportion was managed successfully with radiologic intervention alone (47.6%). Ureteral strictures were associated with death-censored graft failure (hazard ratio [HR] 7.17, 95% CI 2.81, 18.30), total graft failure (HR 3.04, 95% CI 1.41, 6.59), and hospital re-admission (HR 2.52, 95% CI 1.58, 4.00). Conclusions: Although uncommon, ureteral strictures can significantly impact patient outcomes after KT. A better understanding of risk factors and clinical management will be important to ensure optimal graft outcomes.

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Risk Factors for Early Graft Failure and Death After Kidney Transplantation in Recipients Older Than 70 Years

Kidney International Reports ◽

10.1016/j.ekir.2019.01.014 ◽

2019 ◽

Vol 4 (5) ◽

pp. 656-666 ◽

Cited By ~ 12

Author(s):

Mathilde Lemoine ◽

Dimitri Titeca Beauport ◽

Thierry Lobbedez ◽

Gabriel Choukroun ◽

Bruno Hurault de Ligny ◽

...

Keyword(s):

Risk Factors ◽

Kidney Transplantation ◽

Graft Failure ◽

Early Graft ◽

Early Graft Failure

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1693. Risk Factors and Outcomes of Histologic Acute Graft Pyelonephritis following Kidney Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1871 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S830-S830

Author(s):

Harry Ross Powers ◽

Walter Hellinger ◽

Cherise Cortese ◽

Mohamed Elrefaei ◽

Samir Khouzam ◽

...

Keyword(s):

Risk Factors ◽

Kidney Transplantation ◽

Stent Placement ◽

Graft Failure ◽

Significant Risk ◽

Ureteral Stent ◽

Univariable Analysis ◽

Post Transplant ◽

Tract Infections ◽

Acute Graft

Abstract Background Histologic acute graft pyelonephritis (HAGPN) is a complication of kidney transplantation (KT) diagnosed serendipitously by renal biopsy. A retrospective review of 1391 patients who underwent KT at our institution between 2008 and 2017 identified 46 cases (cumulative incidence 5%). Rejection was present in 50% of biopsies demonstrating HAGPN, complicating management. The aims of this study were to identify risk factors and outcomes of HAGPN. Methods Recipient, donor, operative and post-transplant characteristics of 46 cases of HAGPN and 138 controls randomly selected from the 1345 patients who underwent KT between 2008 and 2017 were assessed in univariable and multivariable Cox regression models. Associations of HAGPN with death or graft failure were assessed in univariable models. Results In univariable analysis, characteristics associated with increased risk of HAGPN in order of decreasing hazard ratio (HR) were rejection (HR 10.82, 5.66-20.72), urinary tract infections (UTI) or asymptomatic bacteriuria (ASB) (HR 6.28, 3.43-11.50), urologic malfunction (UM) within 30 days of KT, (HR 5.34, 2.85-10.02), less than 4 matches at HLA A/B/DR loci (HR 3.74, 1.19-11.76), delayed graft function (DGF) (HR 2.1, 1.47-3.00), basiliximab induction (HR 1.59, 1.05-2.42), diabetes mellitus (DM) at KT (HR 1.52, 1.07-2.16), operative time (HR 1.11, 1.03-1.19) and cold ischemic time (CIT) (HR 1.05, 1.02-1.06). UM, rejection and UTI or ASB were the most significant risk factors based on clinical and statistical importance, and after adjusting for them, DM, transplant type, CIT, ureteral stent placement and DGF remained significant risk factors. In univariable analysis, ureteral stent placement at transplant (HR 0.60, 0.43-0.88) and living-related donor (HR 0.18, 0.04-0.78) were each associated with reduced risk of HAGPN which persisted after multivariable analysis. In univariable analysis, HAGPN was associated with death (HR 17.04, 7.93-39.31) and graft failure (HR 3.77, 1.73, 8.20). Conclusion HAGPN is an infrequent, unanticipated, clinically significant complication of renal transplantation. Post-transplant dysfunction of the allograft collection system may be a modifiable risk factor. Disclosures All Authors: No reported disclosures

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