A Novel Metabolic Signature To Predict the Requirement of Dialysis or Renal Transplantation in Patients with Chronic Kidney Disease.

Identification of chronic kidney disease patients at risk of progressing to end-stage renal disease (ESRD) is essential for treatment decision-making and clinical trial design. Here, we explored whether proton nuclear magnetic resonance (NMR) spectroscopy of blood plasma improves the currently best performing kidney failure risk equation, the so-called Tangri score. Our study cohort comprised 4640 participants from the German Chronic Kidney Disease (GCKD) study, of whom 185 (3.99%) progressed over a mean observation time of 3.70 ± 0.88 years to ESRD requiring either dialysis or transplantation. The original four-variable Tangri risk equation yielded a C statistic of 0.863 (95% CI, 0.831-0.900). Upon inclusion of NMR features by state-of-the-art machine learning methods, the C statistic improved to 0.875 (95% CI, 0.850-0.911), thereby outperforming the Tangri score in 94 out of 100 subsampling rounds. Of the 24 NMR features included in the model, creatinine, high-density lipoprotein, valine, acetyl groups of glycoproteins, and Ca2+-EDTA carried the highest weights. In conclusion, proton NMR-based plasma fingerprinting improved markedly the detection of patients at risk of developing ESRD, thus enabling enhanced patient treatment.

Simulation shows undesirable results for competing risks analysis with time-dependent covariates for clinical outcomes.

BACKGROUND: We evaluate three methods for competing risks analysis with time-dependent covariates in comparison with the corresponding methods with time-independent covariates. METHODS: We used cause-specific hazard analysis and two summary approaches for in-hospital death: logistic regression and regression of the subdistribution hazard. We analysed real hospital data (n=1864) and considered pneumonia on admission / hospital-acquired pneumonia as time-independent / time-dependent covariates for the competing events 'discharge alive' and 'in-hospital death'. Several simulation studies with time-constant hazards were conducted. RESULTS: All approaches capture the effect of time-independent covariates, whereas the approaches perform differently with time-dependent covariates. The subdistribution approach for time-dependent covariates detected effects in a simulated no-effects setting and provided counter-intuitive effects in other settings. CONCLUSIONS: The extension of the Fine and Gray model to time-dependent covariates is in general not a helpful synthesis of the cause-specific hazards. Cause-specific hazard analysis and, for uncensored data, the odds ratio are capable of handling competing risks data with time-dependent covariates but the use of the subdistribution approach should be neglected until the problems can be resolved. For general right-censored data, cause-specific hazard analysis is the method of choice.

Encouraging Self-Management in Cardiovascular Disease Prevention.

BACKGROUND: Cardiovascular diseases are among the most common causes of death in industrialized countries. The goal of the DECADE study ("decision aid, action planning, and follow-up support for patients to reduce the 10-year risk of cardiovascular diseases") is to improve patient activation and health-related behavior by means of structured cardiovascular risk counseling and DECADE brochures. In this pilot study, the applicability of DECADE and the potential effects of the intervention on patients with cardiovascular risk factors were investigated. METHODS: 87 patients were included in the two-arm, randomized, controlled pilot study. All of them participated in four structured counseling sessions. The A+D group received DECADE brochures (intervention group), while the A group did not (control group). The change in patient activation four months later (PAM13-D) was the primary endpoint. Secondary endpoints included, among others, changes in health status and health-related behavior, goal achievement, and patient satisfaction. These changes were studied in an intention-to-treat analysis. RESULTS: Endpoint data were available for 78 patients (38 in the A+D group and 40 in the A group) at four months. The use of DECADE brochures had a significant beneficial effect on PAM13-D scores (an increase of 3.30 points, p = 0.023), corresponding to a moderate effect size of 0.54. Positive trends were seen in most of the other endpoints. The improved patient activation was associated with an overall reduction of risk factors. CONCLUSION: This pilot study shows that DECADE can support patient activation. The effects can be expected to be stronger in a larger study and in comparison to usual care. If this can be confirmed, DECADE should be embedded in routine patient care.