Competing and Noncompeting Risk Models for Predicting Kidney Allograft Failure.

BACKGROUND: Prognostic models are becoming increasingly relevant in clinical trials as potential surrogate endpoints, and for patient management as clinical decision support tools. However, the impact of competing risks on model performance remains poorly investigated. We aimed to carefully assess the performance of competing risk and noncompeting risk models in the context of kidney transplantation, where allograft failure and death with a functioning graft are two competing outcomes. METHODS: We included 11,046 kidney transplant recipients enrolled in 10 countries. We developed prediction models for long-term kidney graft failure prediction, without accounting (i.e., censoring) and accounting for the competing risk of death with a functioning graft, using Cox, Fine-Gray, and cause-specific Cox regression models. To this aim, we followed a detailed and transparent analytical framework for competing and noncompeting risk modelling, and carefully assessed the models' development, stability, discrimination, calibration, overall fit, clinical utility, and generalizability in external validation cohorts and subpopulations. More than 15 metrics were used to provide an exhaustive assessment of model performance. RESULTS: Among 11,046 recipients in the derivation and validation cohorts, 1,497 (14%) lost their graft and 1,003 (9%) died with a functioning graft after a median follow-up post-risk evaluation of 4.7 years (IQR 2.7-7.0). The cumulative incidence of graft loss was similarly estimated by Kaplan-Meier and Aalen-Johansen methods (17% versus 16% in the derivation cohort). Cox and competing risk models showed similar and stable risk estimates for predicting long-term graft failure (average mean absolute prediction error of 0.0140, 0.0138 and 0.0135 for Cox, Fine-Gray, and cause-specific Cox models, respectively). Discrimination and overall fit were comparable in the validation cohorts, with concordance index ranging from 0.76 to 0.87. Across various subpopulations and clinical scenarios, the models performed well and similarly, although in some high-risk groups (such as donors over 65 years old), the findings suggest a trend towards moderately improved calibration when using a competing risk approach. CONCLUSIONS: Competing and noncompeting risk models performed similarly in predicting long-term kidney graft failure.

Early start hemodialysis with a catheter may be associated with greater mortality: A propensity score analysis.

INTRODUCTION: Deciding when and how to initiate hemodialysis (HD) is still controversial. An early start (ES) seems to show a lack of benefit. "Lead time bias" and comorbidities have been associated with different outcomes in ES groups. On the other hand, it is well accepted that the impact the type of vascular access (VA) has on patient survival. Our aim was to evaluate survival with early start (ES) versus late start (LS) on HD, taking into account the vascular access (VA) used. METHODS: Between 01/1995 and 06/2018, 503 incidental patients initiated HD at our Dialysis Unit. eGFR was estimated by the CKD-EPI equation. Diabetes mellitus (DM), coronary disease (CD), and peripheral vascular disease (PVD) were considered comorbid conditions. According to eGFR and VA, patients were divided into four groups: G1: ES (eGFR > 7 mL/min) with catheter (ES + C), G2: ES with fistula or graft (F/G) (ES + F/G), G3: LS (eGFR< 7 mL/min) with catheter (LS + C), and G4: LS with F/G (LS + F/G). The cut-off value to define ES or LS was based on median eGFR for these 503 patients. We compared patient's survival rates by Kaplan-Meier and log-rank test. The four groups were compared before and after matching with propensity scores (PS). Cox analysis was performed to determine the impact of predictors of mortality. RESULTS: Median eGFR was 7 (5.3-9.5) mL/min/1.73 m2 , median follow-up time was 30.9 (13-50) months, 52.1% had F/G access at entry, and 46.9% died during the observation period. Among the four groups, the ES + C were significantly older, and there were more diabetics and comorbid conditions, while phosphatemia, iPTH, albumin, and hemoglobin were significantly higher in the LS groups. Before propensity score (PS) matching, the ES + C group had a poor survival rate (p < 0.0001), while LS + F/G access had the best survival. After PS, a total of 180 patients were selected in the same four groups and ES + C kept showing a statistically significant poorer survival. Multivariate analysis revealed that ES + C was an independent predictor of mortality. CONCLUSION: In this retrospective study, ES + C on HD was associated with a higher mortality rate than LS. This association persisted after PS matching.

Renal Transplantation in Patients Older Than 60 Years With High Comorbidity. Is There a Survival Benefit? A Multicenter Study in Argentina.

BACKGROUND: The impact of renal transplantation (RT) in the elderly with many comorbid conditions is a matter of concern. The aim of our study was to assess the impact of RT on the survival of patients older than 60 years compared with those remaining on the waiting list (WL) according to their comorbidities. METHODS: In this multicentric observational retrospective cohort study, we included all patients older than 60 years old admitted on the WL from 01 January 2006 to 31 December 2016. The Charlson comorbidity index (CCI) score was calculated for each patient at inclusion on the WL. Kidney donor risk index was used to assess donor characteristics. RESULTS: One thousand and thirty-six patients were included on the WL of which 371 (36%) received an RT during a median follow-up period of 2.5 (1.4-4.1) years. Patient survival was higher after RT compared to patients remaining on the WL, 87%, 80%, and 72% versus 87%, 55%, and 30% at 1, 3, and 5 years, respectively. After RT survival at 5 years was 37% higher for patients with CCI ≥ 3, and 46% higher in those with CCI < 3, compared with patients remaining on the WL. On univariate and multivariate analysis, patient survival was independently associated with a CCI of ≥3 (hazard ratio 1.62; confidence interval 1.09-2.41; P < 0.02) and the use of calcineurin-based therapy maintenance therapy (hazard ratio 0.53; confidence interval 0.34-0.82; P < 0.004). CONCLUSIONS: Our study showed that RT improved survival in patients older than 60 years even those with high comorbidities. The survival after transplantation was also affected by comorbidities.

Outbreak of OXY-2-Producing Klebsiella oxytoca in a renal transplant unit.

We describe a Klebsiella oxytoca infection outbreak in a renal transplant unit that involved seven patients. All strains belonged to a single pulsed-field gel electrophoresis pattern and were resistant to amoxicillin-clavulanate, cefuroxime, piperacillin-tazobactam, and aztreonam but susceptible to ceftriaxone, ceftazidime, cefepime, and imipenem. Chromosomal beta-lactamase hyperproduction was caused by a point mutation in the bla(OXY-2) gene promoter region.

Nonprogrammed Vascular Access Is Associated With Greater Mortality in Patients Who Return to Hemodialysis With a Failing Renal Graft.

BACKGROUND: In incident hemodialysis (HD) patients, the use of catheters is associated with a worse prognosis when compared with those with an arteriovenous fistula, but the role of vascular access (VA) type in the morbidity and mortality of patients returning to HD with a failing renal allograft is unknown. We aimed to determine the associations between the type of VA and mortality in this population. METHODS: This was a retrospective observational cohort study of 138 patients who initiated dialysis after kidney transplant failure between 1995 and 2014. We recorded access type, laboratory values at entry, stratified patients per risk, and determined the effect on mortality of programmed VA (PVA), (arteriovenous fistula or PTFE graft) and nonprogrammed VA (UPVA) (tunneled or nontunneled catheters) at the initiation of HD. RESULTS: Eighty-five (61.6%) and 53 (38.4%) patients initiated therapy with PVA and UPVA, respectively. Overall mortality was 14.6% at 1 year. Patients using catheters had greater mortality than those with a PVA (log rank P <0.0001). At 24 months, 7 patients died in PVA group versus 22 in UPVA group. Multivariate Cox analysis showed that initiation of HD with a catheter (hazard ratio, 5.90; 95%, confidence interval, 2.83-12.31) was independently associated with greater mortality after adjusting for confounders. CONCLUSIONS: Nonprogrammed VA with a catheter predicted all-cause mortality among patients with transplant failure reentering HD.