Assessment of epidemiology and outcomes of adult patients with kidney-limited thrombotic microangiopathies.

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.

Covariates adjustment questioned conclusions of predictive analyses: an illustration with the Kidney Donor Risk Index.

OBJECTIVES: We aimed to illustrate that considering covariates can lead to meaningful interpretation of the discriminative capacities of a prognostic marker. For this, we evaluated the ability of the Kidney Donor Risk Index (KDRI) to discriminate kidney graft failure risk. STUDY DESIGN AND SETTING: From 4114 French patients, we estimated the adjusted area under the time-dependent ROC curve by standardizing the marker and weighting the observations. By weighting the contributions, we also studied the impact of KDRI-based transplantations on the patient and graft survival. RESULTS: The covariate-adjusted AUC varied from 55% (95% confidence interval [CI]: 51-60%) for a prognostic up to 1 year post-transplantation to 56% (95% CI: 52-59%) up to 7 years. The Restricted Mean Survival Time (RMST) was 6.44 years for high-quality graft recipients (95% CI: 6.30-6.56) and would have been 6.31 years (95% CI: 6.13-6.46) if they had medium-quality transplants. The RMST was 5.10 years for low-quality graft recipients (95% CI: 4.90-5.31) and would have been 5.52 years (95% CI: 5.17-5.83) if they had medium-quality transplants. CONCLUSION: We demonstrated that the KDRI discriminative capacities were mainly explained by the recipient characteristics. We also showed that counterfactual estimations, often used in causal studies, are also interesting in predictive studies, especially regarding the new available methods.

Horizontal mixture model for competing risks: a method used in waitlisted renal transplant candidates.

When a patient is registered on renal transplant waiting list, she/he expects a clear information on the likelihood of being transplanted. Nevertheless, this event is in competition with death and usual models for competing events are difficult to interpret for non-specialists. We used a horizontal mixture model. Data were extracted from two French dialysis and transplantation registries. The "Ile-de-France" region was used for external validation. The other patients were randomly divided for training and internal validation. Seven variables were associated with decreased long-term probability of transplantation: age over 40 years, comorbidities (diabetes, cardiovascular disease, malignancy), dialysis longer than 1 year before registration and blood groups O or B. We additionally demonstrated longer mean time-to-transplantation for recipients under the age of 50, overweight recipients, recipients with blood group O or B and with pre-transplantation anti-HLA class I or II immunization. Our model can be used to predict the long-term probability of transplantation and the time in dialysis among transplanted patients, two easily interpretable parts. Discriminative capacities were validated on both the internal and external (AUC at 5 years = 0.72, 95% CI from 0.68 to 0.76) validation samples. However, calibration issues were highlighted and illustrated the importance of complete re-estimation of the model for other countries. We illustrated the ease of interpretation of horizontal modelling, which constitutes an alternative to sub-hazard or cause-specific approaches. Nevertheless, it would be useful to test this in practice, for instance by questioning both the physicians and the patients. We believe that this model should also be used in other chronic diseases, for both etiologic and prognostic studies.

Comparison of survival outcomes between Expanded Criteria Donor and Standard Criteria Donor kidney transplant recipients: a systematic review and meta-analysis.

In 2002, the United Network for Organ Sharing proposed increasing the pool of donor kidneys to include Expanded Criteria Donor (ECD). Outside the USA, the ECD definition remains the one used without questioning whether such a graft allocation criterion is valid worldwide. We performed a meta-analysis to quantify the differences between ECD and Standard Criteria Donor (SCD) transplants. We paid particular attention to select studies in which the methodology was appropriate and we took into consideration the geographical area. Thirty-two publications were included. Only five studies, all from the USA, reported confounder-adjusted hazard ratios comparing the survival outcomes between ECD and SCD kidney transplant recipients. These five studies confirmed that ECD recipients seemed to have poorer prognosis. From 29 studies reporting appropriate survival curves, we estimated the 5-year pooled nonadjusted survivals for ECD and SCD recipients. The relative differences between the two groups were lower in Europe than in North America, particularly for death-censored graft failure. It is of primary importance to propose appropriate studies for external validation of the ECD criteria in non-US kidney transplant recipients.

Comparisons of the performance of different statistical tests for time-to-event analysis with confounding factors: practical illustrations in kidney transplantation.

Confounding factors are commonly encountered in observational studies. Several confounder-adjusted tests to compare survival between differently exposed subjects were proposed. However, only few studies have compared their performances regarding type I error rates, and no study exists evaluating their type II error rates. In this paper, we performed a comparative simulation study based on two different applications in kidney transplantation research. Our results showed that the propensity score-based inverse probability weighting (IPW) log-rank test proposed by Xie and Liu (2005) can be recommended as a first descriptive approach as it provides adjusted survival curves and has acceptable type I and II error rates. Even better performance was observed for the Wald test of the parameter corresponding to the exposure variable in a multivariable-adjusted Cox model. This last result is of primary interest regarding the exponentially increasing use of propensity score-based methods in the literature.