Kidney Transplant Failure

Perl, Jeffrey

doi:10.2215/cjn.04670514

Cited by 14 publications

(8 citation statements)

References 25 publications

(30 reference statements)

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“…Despite the considerable advances in short term outcomes, kidney transplant recipients continue to experience late allograft failure, and little improvement has been made over the past 15 years 45. Although the failure of a kidney allograft represents an important cause of end stage renal disease, robust and widely validated prognostication systems for the risk of allograft failure in individual patients are lacking 6. Accurately predicting individual patients’ risk of allograft loss would help to stratify patients into clinically meaningful risk groups, which may help to guide monitoring of patients.…”

Section: Introductionmentioning

confidence: 99%

Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study

Loupy

Aubert

Orandi

et al. 2019

BMJ

224

271

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ObjectiveTo develop and validate an integrative system to predict long term kidney allograft failure.DesignInternational cohort study.SettingThree cohorts including kidney transplant recipients from 10 academic medical centres from Europe and the United States.ParticipantsDerivation cohort: 4000 consecutive kidney recipients prospectively recruited in four French centres between 2005 and 2014. Validation cohorts: 2129 kidney recipients from three centres in Europe and 1428 from three centres in North America, recruited between 2002 and 2014. Additional validation in three randomised controlled trials (NCT01079143, EudraCT 2007-003213-13, and NCT01873157).Main outcome measureAllograft failure (return to dialysis or pre-emptive retransplantation). 32 candidate prognostic factors for kidney allograft survival were assessed.ResultsAmong the 7557 kidney transplant recipients included, 1067 (14.1%) allografts failed after a median post-transplant follow-up time of 7.12 (interquartile range 3.51-8.77) years. In the derivation cohort, eight functional, histological, and immunological prognostic factors were independently associated with allograft failure and were then combined into a risk prediction score (iBox). This score showed accurate calibration and discrimination (C index 0.81, 95% confidence interval 0.79 to 0.83). The performance of the iBox was also confirmed in the validation cohorts from Europe (C index 0.81, 0.78 to 0.84) and the US (0.80, 0.76 to 0.84). The iBox system showed accuracy when assessed at different times of evaluation post-transplant, was validated in different clinical scenarios including type of immunosuppressive regimen used and response to rejection therapy, and outperformed previous risk prediction scores as well as a risk score based solely on functional parameters including estimated glomerular filtration rate and proteinuria. Finally, the accuracy of the iBox risk score in predicting long term allograft loss was confirmed in the three randomised controlled trials.ConclusionAn integrative, accurate, and readily implementable risk prediction score for kidney allograft failure has been developed, which shows generalisability across centres worldwide and common clinical scenarios. The iBox risk prediction score may help to guide monitoring of patients and further improve the design and development of a valid and early surrogate endpoint for clinical trials.Trial registrationClinicaltrials.gov NCT03474003.

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Section: Introductionmentioning

confidence: 99%

Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study

Loupy

Aubert

Orandi

et al. 2019

BMJ

224

271

View full text Add to dashboard Cite

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“…A large meta‐analysis also confirmed that the first year on dialysis shows significantly higher mortality in failed transplant recipients compared with subsequent years 17 . The mortality risk of patients with transplant failure is quite different in different countries 18 . Canadian Dialysis registry data from the early 1990s indicated similar mortality risk in transplant‐naïve and transplant failure patients 19 .…”

Section: Factors To Consider For the Management Of Immunosuppressive Medicationsmentioning

confidence: 83%

“…17 The mortality risk of patients with transplant failure is quite different in different countries. 18 Canadian Dialysis registry data from the early 1990s indicated similar mortality risk in transplant-naïve and transplant failure patients. 19 An analysis from the French Renal Epidemiology and Information Network similarly demonstrated equivalent survival between the two groups.…”

Section: Potential Complications From Overimmunosuppressed State: Mortality Infection Risk and Malignancymentioning

confidence: 97%

The failing kidney allograft: A review and recommendations for the care and management of a complex group of patients

Lubetzky

Tantisattamo

Molnar

et al. 2021

American Journal of Transplantation

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The return to dialysis after allograft failure is associated with increased morbidity and mortality. This transition is made more complex by the rising numbers of patients who seek repeat transplantation and therefore may have indications for remaining on low levels of immunosuppression, despite the potential increased morbidity. Management strategies vary across providers, driven by limited data on how to transition off How to cite this article: Lubetzky M, Tantisattamo E, Molnar MZ, et al. The failing kidney allograft: A review and recommendations for the care and management of a complex group of patients.

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“…The longterm survival after renal transplantation, however, has disappointingly remained almost unchanged over the years [3,4], with half of renal transplant recipients (RTR) experiencing graft failure (defined as return to dialysis or retransplantation) or death within a decade after transplantation [5]. This late graft failure is not only a personal disaster [6], but also a significant burden for the healthcare system, because, nowadays, return to dialysis as a consequence of a failing graft is one of the most common reasons for initiation of dialysis [7,8]. This stresses the importance of identifying potentially modifiable risk factors for premature graft failure.…”

Section: Introductionmentioning

confidence: 99%

Urinary sulfate excretion and risk of late graft failure in renal transplant recipients – a prospective cohort study

et al. 2020

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Hydrogen sulfide (H 2 S), produced from metabolism of dietary sulfur-containing amino acids, is allegedly a renoprotective compound. Twenty-fourhour urinary sulfate excretion (USE) may reflect H 2 S bioavailability. We aimed to investigate the association of USE with graft failure in a large prospective cohort of renal transplant recipients (RTR). We included 704 stable RTR, recruited at least 1 year after transplantation. We applied logrank testing and Cox regression analyses to study association of USE, measured from baseline 24 h urine samples, with graft failure. Median age was 55 [45-63] years (57% male, eGFR was 45 AE 19 ml/min/1.73 m 2). Median USE was 17.1 [13.1-21.1] mmol/24 h. Over median follow-up of 5.3 [4.5-6.0] years, 84 RTR experienced graft failure. RTR in the lowest sex-specific tertile of USE experienced a higher rate of graft failure during follow-up than RTR in the middle and highest sex-specific tertiles (18%, 13%, and 5%, respectively, log-rank P < 0.001). In Cox regression analyses, USE was inversely associated with graft failure [HR per 10 mmol/24 h: 0.37 (0.24-0.55), P < 0.001]. The association remained independent of adjustment for potential confounders, including age, sex, eGFR, proteinuria, time between transplantation and baseline, BMI, smoking, and high sensitivity C-reactive protein [HR per 10 mmol/24 h: 0.51 (0.31-0.82), P = 0.01]. In conclusion, this study demonstrates a significant inverse association of USE with graft failure in RTR, suggesting high H 2 S bioavailability as a novel, potentially modifiable factor for prevention of graft failure in RTR.

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Kidney Transplant Failure

Cited by 14 publications

References 25 publications

Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study

Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study

The failing kidney allograft: A review and recommendations for the care and management of a complex group of patients

Urinary sulfate excretion and risk of late graft failure in renal transplant recipients – a prospective cohort study

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