Donor Gene Variant Associated with Higher Graft Failure Risk

Abstract Background There is emerging evidence that the 4-variable Kidney Failure Risk Equation (KFRE) can be used for risk prediction of graft failure in transplant recipients. However, geographical validation of the 4-variable KFRE in transplant patients is lacking, as is whether the more extensive 8-variable KFRE improves predictive accuracy. This study aimed to validate the 4- and 8-variable KFRE predictions of the 5-year death-censored risk of graft failure in patients in the United Kingdom. Methods A retrospective cohort study involved 415 transplant recipients who had their first renal transplant between 2003 and 2015 and were under follow-up at Salford Royal NHS Foundation Trust. The KFRE risk scores were calculated on variables taken 1-year post-transplant. The area under the receiver operating characteristic curves (AUC) and calibration plots were evaluated to determine discrimination and calibration of the 4- and 8-variable KFREs in the whole cohort as well as in a subgroup analysis of living and deceased donor recipients and in patients with an eGFR< 45 ml/min/1.73m2. Results There were 16 graft failure events (4%) in the whole cohort. The 4- and 8-variable KFREs showed good discrimination with AUC of 0.743 (95% confidence interval [CI] 0.610–0.876) and 0.751 (95% CI 0.629–0.872) respectively. In patients with an eGFR< 45 ml/min/1.73m2, the 8-variable KFRE had good discrimination with an AUC of 0.785 (95% CI 0.558–0.982) but the 4-variable provided excellent discrimination in this group with an AUC of 0.817 (0.646–0.988). Calibration plots however showed poor calibration with risk scores tending to underestimate risk of graft failure in low-risk patients and overestimate risk in high-risk patients, which was seen in the primary and subgroup analyses. Conclusions Despite adequate discrimination, the 4- and 8-variable KFREs are imprecise in predicting graft failure in transplant recipients using data 1-year post-transplant. Larger, international studies involving diverse patient populations should be considered to corroborate these findings.

Download Full-text

RAPID-F: A novel Primary Graft Failure risk score in Heart Transplantation

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(08)60543-3 ◽

2008 ◽

Vol 7 ◽

pp. 195-195

Author(s):

J SEGOVIA ◽

J BARCELO ◽

M GOMEZBUENO ◽

P GARCIAPAVIA ◽

S SERRANO ◽

...

Keyword(s):

Heart Transplantation ◽

Risk Score ◽

Graft Failure ◽

Failure Risk ◽

Primary Graft Failure

Download Full-text

The Ratio of Tibial Slope and Meniscal Bone Angle for the Prediction of ACL Reconstruction Failure Risk

The Surgery Journal ◽

10.1055/s-0038-1668111 ◽

2018 ◽

Vol 04 (03) ◽

pp. e152-e159 ◽

Cited By ~ 3

Author(s):

Steffen Sauer ◽

Robert English ◽

Mark Clatworthy

Keyword(s):

Anterior Cruciate Ligament ◽

High Risk ◽

Graft Failure ◽

Cruciate Ligament ◽

Tibial Slope ◽

Acl Graft ◽

Failure Risk ◽

Increased Risk ◽

Acl Failure ◽

Anterior Cruciate

Background A growing body of research is indicating that the tibial slope and the geometry of the tibiofemoral meniscal–cartilage interface may affect the risk of anterior cruciate ligament reconstruction (ACLR) failure. Increased lateral tibial posterior slope (LTPS) and reduced meniscal bone angle (MBA) are associated with increased risk of anterior cruciate ligament (ACL) injury. The significance of a LTPS–MBA ratio regarding the prediction of ACL failure risk remains unknown. As LTPS and MBA may eventually potentiate or neutralize each other, it is expected that a low LTPS–MBA ratio is associated with high chance of ACL graft survival while a high LTPS–MBA ratio is associated with high risk of ACL failure. Material and Methods Out of 1,487 consecutive patients who underwent hamstring ACLR between August 2000 and May 2013, 54 ACLR failures with intact lateral menisci were included in this study and matched one-to-one with 54 control participants by age, sex, graft, surgical technique, and graft fixation method. Control participants had undergone ACLR without signs of lateral meniscal injury, graft failure, or insufficiency. MBA and LTPS were assessed on magnetic resonance imaging. Logistic regression was used to identify LTPS/MBA key cut-off ratios. Results In this cohort, a LTPS–MBA ratio under 0.27 was associated with a 28% risk of ACLR failure (36% of patients), while a ratio exceeding 0.42 was associated with an 82% risk of ACLR failure (31% of patients). The odds of ACL failure increased by 22.3% per reduction of 1 degree in MBA (odds ratio [OR], 1.22; 95% limits, 1.1–1.34). No significant association was found between LTPS and the risk of ACL graft failure in transtibial ACLR, while the odds of ACL failure increased by 34.9% per degree of increasing LTPS in transportal ACLR (OR, 1.34; 95% limits, 1.01–1.79). No significant correlation was found between MBA and LTPS (p = 0.5). Conclusion Reduced MBA was associated with significantly increased risk of ACL graft failure. A ratio of LTPS and MBA was found to be useful for the prediction of ACLR failure risk and may preoperatively help to identify patients at high risk of ACLR failure. This may have implications for patient counseling and the indication of additional extra-articular stabilizing procedures.

Download Full-text

Propensity score-based comparison of the graft failure risk between kidney transplant recipients of standard and expanded criteria donor grafts: Toward increasing the pool of marginal donors

American Journal of Transplantation ◽

10.1111/ajt.14651 ◽

2018 ◽

Vol 18 (5) ◽

pp. 1151-1157 ◽

Cited By ~ 9

Author(s):

A. H. Querard ◽

F. Le Borgne ◽

A. Dion ◽

M. Giral ◽

G. Mourad ◽

...

Keyword(s):

Propensity Score ◽

Kidney Transplant ◽

Graft Failure ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Failure Risk ◽

Expanded Criteria Donor ◽

Expanded Criteria ◽

Marginal Donors

Download Full-text

Joint association of vitamins D and K status with long-term outcomes in stable kidney transplant recipients

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfy399 ◽

2019 ◽

Vol 35 (4) ◽

pp. 706-714 ◽

Cited By ~ 8

Author(s):

Adriana J van Ballegooijen ◽

Joline W J Beulens ◽

Charlotte A Keyzer ◽

Gerjan J Navis ◽

Stefan P Berger ◽

...

Keyword(s):

Vitamin D ◽

Kidney Transplant ◽

Graft Failure ◽

Premature Mortality ◽

Matrix Gla Protein ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Hydroxyvitamin D ◽

Failure Risk ◽

Increased Risk

Abstract Background Kidney transplant recipients (KTRs) experience substantial survival benefit compared with dialysis patients. However, their mortality and graft failure risk remain high. KTRs are often low in micronutrient status, including vitamins D and K. We investigated the association of both vitamins D and K status, and vitamin D treatment with all-cause mortality and death-censored graft failure. Methods We studied 461 KTRs from a single-centre study at median 6.1 years after transplantation. At baseline, vitamins D and K concentrations were measured by 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix gla protein (dp-ucMGP) and patients were categorized into: 25(OH)D <50/≥50 nmol/L and median dp-ucMGP <1057/≥1057 pmol/L. Results Mean age was 52 ± 12 years, and 122 KTRs (26%) had low vitamins D and K status. During median 9.8 years follow-up, 128 patients (28%) died and 48 (10%) developed death-censored graft failure. Low vitamins D and K status was associated with 2.33 (1.26–4.30) [hazard ratio (95% confidence interval)] increased mortality risk and 3.25 (1.17–9.08) increased graft failure risk compared with KTR with 25(OH)D ≥50 nmol/L and dp-ucMGP <1057 pmol/L. Dp-ucMGP was strongly associated with mortality (per 500 pmol/L increase): 1.41 (1.08–1.41) for vitamin D treatment versus no treatment 1.07 (0.97–1.18), and graft failure 1.71 (1.17–2.49) for vitamin D treatment versus 1.19 (1.05–1.36) no treatment, P-interaction <0.07 for vitamin D treatment (n = 44). Conclusions Combined vitamins D and K deficiency are highly prevalent and are associated with increased mortality and graft failure risk compared with high vitamins D and K status. Low vitamin K status was strongly associated with an increased risk of premature mortality and graft failure for patients treated with vitamin D versus no vitamin D treatment.

Download Full-text

A Prognostic Tool for Individualized Prediction of Graft Failure Risk within Ten Years after Kidney Transplantation

Journal of Transplantation ◽

10.1155/2019/7245142 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Danko Stamenic ◽

Annick Rousseau ◽

Marie Essig ◽

Philippe Gatault ◽

Mathias Buchler ◽

...

Keyword(s):

Graft Failure ◽

Latent Class ◽

Latent Class Model ◽

Graft Loss ◽

Validation Dataset ◽

Individual Risk ◽

Kidney Graft ◽

Failure Risk ◽

One Year ◽

The Impact

Identification of patients at risk of kidney graft loss relies on early individual prediction of graft failure. Data from 616 kidney transplant recipients with a follow-up of at least one year were retrospectively studied. A joint latent class model investigating the impact of serum creatinine (Scr) time-trajectories and onset of de novo donor-specific anti-HLA antibody (dnDSA) on graft survival was developed. The capacity of the model to calculate individual predicted probabilities of graft failure over time was evaluated in 80 independent patients. The model classified the patients in three latent classes with significantly different Scr time profiles and different graft survivals. Donor age contributed to explaining latent class membership. In addition to the SCr classes, the other variables retained in the survival model were proteinuria measured one-year after transplantation (HR=2.4, p=0.01), pretransplant non-donor-specific antibodies (HR=3.3, p<0.001), and dnDSA in patient who experienced acute rejection (HR=15.9, p=0.02). In the validation dataset, individual predictions of graft failure risk provided good predictive performances (sensitivity, specificity, and overall accuracy of graft failure prediction at ten years were 77.7%, 95.8%, and 85%, resp.) for the 60 patients who had not developed dnDSA. For patients with dnDSA individual risk of graft failure was not predicted with a so good performance.

Download Full-text