The Cox model is a regression technique for performing survival analyses in epidemiological and clinical research. This model estimates the hazard ratio (HR) of a given endpoint associated with a specific risk factor, which can be either a continuous variable like age and C‐reactive protein level or a categorical variable like gender and diabetes mellitus. When the risk factor is a continuous variable, the Cox model provides the HR of the study endpoint associated with a predefined unit of increase in the independent variable (e.g., for every 1‐year increase in age, 2 mg/L increase in C‐reactive protein). A fundamental assumption underlying the application of the Cox model is proportional hazards; in other words, the effects of different variables on survival are constant over time and additive over a particular scale. The Cox regression model, when applied to etiological studies, also allows an adjustment for potential confounders; in an exposure‐outcome pathway, a confounder is a variable which is associated with the exposure, is not an effect of the exposure, does not lie in the causal pathway between the exposure and the outcome, and represents a risk factor for the outcome.

Studies performed in the field of oxidative medicine and cellular longevity frequently focus on the association between biomarkers of cellular and molecular mechanisms of oxidative stress as well as of aging, immune function, and vascular biology with specific time to event data, such as mortality and organ failure. Indeed, time‐to‐event analysis is one of the most important methodologies used in clinical and epidemiological research to address etiological and prognostic hypotheses. Survival data require adequate methods of analyses. Among these, the Kaplan‐Meier analysis is the most used one in both observational and interventional studies. In this paper, we describe the mathematical background of this technique and the concept of censoring (right censoring, interval censoring, and left censoring) and report some examples demonstrating how to construct a Kaplan‐Meier survival curve and how to apply this method to provide an answer to specific research questions.

Older adults dialysis patients represent the frailest subgroup of the End Stage Renal Disease (ESRD) population and physical exercise program may mitigate the age-related decline in muscle mass and function. Dialysis patients of the EXCITE trial aged > 65 years (n = 115, active arm, n = 53; control arm, n = 62) were submitted in random order to a home based, low intensity physical exercise program. At baseline and 6 months after exercise training 6-min walking distance (6MWD) and 5-time sit-to-stand test (5STS) were performed, and quality of life (QoL) was tested. The training program improved both the 6MWD (6-months: 327 ± 86 m versus baseline: 294 ± 74 m; P < 0.001) and the 5STS time (6-months: 19.8 ± 5.6 s versus baseline: 22.5 ± 5.1 s; P < 0.001) in the exercise group whereas they did not change in the control group (P = 0.98 and 0.25, respectively). The between-arms differences (6 months-baseline) in the 6MWD (+ 34.0 m, 95% CI: 14.4 to 53.5 m) and in the 5STS time changes (− 1.9 s, 95% CI: -3.6 to − 0.3 s) were both statistically significant (P = 0.001 and P = 0.024, respectively). The cognitive function dimension of QoL significantly reduced in the control arm (P = 0.04) while it remained unchanged in the active arm (P = 0.78) (between groups difference P = 0.05). No patient died during the trial and the training program was well tolerated. This secondary analysis of the EXCITE trial shows that a home-based, exercise program improves physical performance and is well tolerated in elderly ESRD patients. The trial was registered in ClinicalTrials.Gov ( Clinicaltrials.gov identifier: NCT01255969) on December 8, 2010.

Background: Accruing evidence suggests that Xanthine Oxidase inhibitors (XOis) may bring direct renal benefits, besides those related to their hypo-uricemic effect. We hence aimed at performing a systematic review of randomized controlled trials (RCTs) to verify if treatment with XOis may improve renal outcomes in individuals with chronic kidney disease (CKD). Methods: Ovid-MEDLINE, PubMed and CENTRAL databases were searched for RCTs comparing any XOi to standard therapy or placebo. The primary endpoint of interest was progression to End-Stage Kidney Disease (ESKD); secondary endpoints were changes in serum creatinine, glomerular filtration rate (eGFR), proteinuria and albuminuria. Results: XOis treatment significantly reduced the risk of ESKD compared to the control (3 studies, 204 pts; RR = 0.42; 95% CI, 0.22, 0.80) and also improved eGFR in data pooled from RCTs with long follow-up times (>3 mo.) (4 studies, 357 pts; mean difference (MD) 6.82 mL/min/1.73 m²; 95% CI, 3.50, 10.15) and high methodological quality (blind design) (3 studies, 400 pts; MD 2.61 mL/min/1.73 m²; 95% CI, 0.23, 4.99). Conversely, no definite effects were apparently noticed on serum creatinine, proteinuria and albuminuria. Conclusions: XOis may represent a promising tool for retarding disease progression in CKD patients. Future trials are awaited to confirm the generalizability of these findings to the whole CKD population.

Intestinal dysbiosis is highly pervasive among chronic kidney disease (CKD) patients and may play a key role in disease progression and complications. We performed a systematic review and meta-analysis to evaluate effects of biotic supplements on a large series of outcomes in renal patients. Ovid-MEDLINE, PubMed and CENTRAL databases were searched for randomized controlled trials (RCTs) comparing any biotic (pre-, pro- or synbiotics) to standard therapy or placebo. Primary endpoints were change in renal function and cardiovascular events; secondary endpoints were change in proteinuria/albuminuria, inflammation, uremic toxins, quality of life and nutritional status. Seventeen eligible studies (701 participants) were reviewed. Biotics treatment did not modify estimated glomerular filtration rate (eGFR) (mean difference (MD) 0.34 mL/min/1.73 m²; 95% CI −0.19, 0.86), serum creatinine (MD −0.13 mg/dL; 95% confidence interval (CI) −0.32, 0.07), C-reactive protein (MD 0.75 mg/dL; 95% CI −1.54, 3.03) and urea (standardized MD (SMD) −0.02; 95% CI −0.25, 0.20) as compared to control. Outcome data on the other endpoints of interest were lacking, sparse or in an unsuitable format to be analyzed collectively. According to the currently available evidence, there is no conclusive rationale for recommending biotic supplements for improving outcomes in renal patients. Large-scale, well-designed and adequately powered studies focusing on hard rather than surrogate outcomes are still awaited.