Exploring the Complexity of Death-Censored Kidney Allograft Failure.
Ontology highlight
ABSTRACT: Background
Few studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance.Methods
A novel approach assigns each persistent and relevant decline in renal function over the lifetime of a renal allograft to a standardized category, hypothesizing that singular or multiple events finally lead to GL. An adjudication committee of three physicians retrospectively evaluated indication biopsies, laboratory testing, and medical history of all 303 GLs among all 1642 recipients of transplants between January 1, 1997 and December 31, 2017 at a large university hospital to assign primary and/or secondary causes of GL.Results
In 51.2% of the patients, more than one cause contributed to GL. The most frequent primary or secondary causes leading to graft failure were intercurrent medical events in 36.3% of graft failures followed by T cell-mediated rejection (TCMR) in 34% and antibody-mediated rejection (ABMR) in 30.7%. In 77.9%, a primary cause could be attributed to GL, of which ABMR was most frequent (21.5%). Many causes for GL were identified, and predominant causes for GL varied over time.Conclusions
GL is often multifactorial and more complex than previously thought.
SUBMITTER: Mayrdorfer M
PROVIDER: S-EPMC8259637 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
Publications
Exploring the Complexity of Death-Censored Kidney Allograft Failure.
Mayrdorfer Manuel M Liefeldt Lutz L Wu Kaiyin K Rudolph Birgit B Zhang Qiang Q Friedersdorff Frank F Lachmann Nils N Schmidt Danilo D Osmanodja Bilgin B Naik Marcel G MG Duettmann Wiebke W Halleck Fabian F Merkel Marina M Schrezenmeier Eva E Waiser Johannes J Duerr Michael M Budde Klemens K
Journal of the American Society of Nephrology : JASN 20210421 6
<h4>Background</h4>Few studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance.<h4>Methods</h4>A novel approach assigns each persistent and relevant decline in renal function over the lifetime of a renal allograft to a standardized category, hypothesizing that singular or multiple events finally lead to GL. An adjudication committee of three physicians retrospectively evaluated indication biopsies, laboratory testing, and medical history of all 303 GLs a ...[more]
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Project description:Background and objectivesHypophosphatemia is common in the first year after kidney transplantation, but its clinical implications are unclear. We investigated the relationship between the severity of post-transplant hypophosphatemia and mortality or death-censored graft failure in a large cohort of renal transplant recipients with long-term follow-up.Design, setting, participants, & measurementsWe performed a longitudinal cohort study in 957 renal transplant recipients who were transplanted between 1993 and 2008 at a single center. We used a large real-life dataset containing 28,178 phosphate measurements (median of 27; first to third quartiles, 23-34) serial measurements per patient) and selected the lowest intraindividual phosphate level during the first year after transplantation. The primary outcomes were all-cause mortality, cardiovascular mortality, and death-censored graft failure.ResultsThe median (interquartile range) intraindividual lowest phosphate level was 1.58 (1.30-1.95) mg/dl, and it was reached at 33 (21-51) days post-transplant. eGFR was the main correlate of the lowest serum phosphate level (model R2 =0.32). During 9 (5-12) years of follow-up, 181 (19%) patients developed graft failure, and 295 (35%) patients died, of which 94 (32%) deaths were due to cardiovascular disease. In multivariable Cox regression analysis, more severe hypophosphatemia was associated with a lower risk of death-censored graft failure (fully adjusted hazard ratio, 0.61; 95% confidence interval, 0.43 to 0.88 per 1 mg/dl lower serum phosphate) and cardiovascular mortality (fully adjusted hazard ratio, 0.37; 95% confidence interval, 0.22 to 0.62) but not noncardiovascular mortality (fully adjusted hazard ratio, 1.33; 95% confidence interval, 0.9 to 1.96) or all-cause mortality (fully adjusted hazard ratio, 1.15; 95% confidence interval, 0.81 to 1.61).ConclusionsPost-transplant hypophosphatemia develops early after transplantation. These data connect post-transplant hypophosphatemia with favorable long-term graft and patient outcomes.
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Project description:Rationale & objectiveThe Kidney Failure Risk Equation (KFRE) is a simple widely validated prediction model using age, sex, estimated glomerular filtration rate, and urinary albumin-creatinine ratio to predict the risk for end-stage kidney disease. Data are limited for its applicability to kidney transplant recipients.Study designValidation study of the KFRE as a post hoc analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial.Setting & participantsAdult kidney transplant recipients with functioning kidney allografts at least 6 months posttransplantation from 30 centers in the United States, Canada, and Brazil. Participants with estimated glomerular filtration rates < 60 mL/min/1.73 m2 at study entry were included.Predictor2- and 5-year kidney failure risk predicted by the KFRE using variables at study entry.OutcomeGraft loss, defined by initiation of dialysis.Analytical approachDiscrimination of the KFRE was assessed using C statistics; calibration was assessed by plotting predicted risk against observed cumulative incidence of graft loss.Results2,889 participants were included. Within 2 years, 98 participants developed graft loss, 107 participants died with a functioning graft, and 129 participants were lost to follow-up, and by 5 years, 252 had developed graft loss, 265 died with a functioning graft, and 1,543 were lost to follow-up. The KFRE demonstrated accurate calibration and discrimination (C statistic, 0.85 [95% CI, 0.81-0.88] at 2 years and 0.81 [95% CI, 0.78-0.84] at 5 years); performance was similar regardless of donor type (living vs deceased) and graft vintage, with the noted exception of poorer calibration for graft vintage less than 2 years.LimitationsUnavailable cause of graft loss.ConclusionsThe KFRE accurately predicted the risk for graft loss among adult kidney transplant recipients with graft vintage longer than 2 years and may be a useful prognostic tool for nephrologists caring for kidney transplant recipients.
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Project description:In this proof-of-concept study, spatial transcriptomics combined with public single-cell RNA sequencing data were used to explore the potential of this technology to study kidney allograft rejection. We aimed to map gene expression patterns within diverse pathological states by examining biopsies classified across non-rejection, T cell-mediated acute rejection, and interstitial fibrosis and tubular atrophy (IFTA). Our results revealed distinct immune cell signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and their spatial organization within the renal interstitium. We also mapped chemokine receptors and ligands to study immune-cell migration and recruitment. Finally, our analysis demonstrated differential spatial enrichment of transcription signatures associated with kidney allograft rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores for rejection-associated gene expression patterns than did tubular areas, which had negative scores. This implies that these signatures are primarily driven by processes unfolding in the renal interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing cellular heterogeneity and immune signatures in renal transplant biopsies, and demonstrates its potential for studying the molecular and cellular mechanisms associated with rejection. However, certain limitations must be borne in mind regarding the development and future applications of this technology.
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