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BackgroundThe high mortality and cardiovascular disease (CVD) burden in patients with end-stage renal disease (ESRD) is well-documented. Recent literature suggests that acute kidney injury is also associated with CVD. It is unknown whether patients with incident ESRD due to dialysis-requiring acute kidney injury (AKI-D) are at higher short-term risk for death and CVD events, compared with incident ESRD patients without preceding AKI-D. Few studies have examined the impact of recovery from AKI-D on subsequent CVD risk.MethodsIn this retrospective cohort study, we evaluated adult members of Kaiser Permanente Northern California who initiated dialysis from January 2009 to September 2015. Preceding AKI-D and subsequent outcomes of death and CVD events (acute coronary syndrome, heart failure, ischemic stroke or transient ischemic attack) were identified from electronic health records. We performed multivariable Cox regression models adjusting for demographics, comorbidities, medication use, and laboratory results.ResultsCompared to incident ESRD patients who experienced AKI-D (n = 1865), patients with ESRD not due to AKI-D (n = 3772) had significantly lower adjusted rates of death (adjusted hazard ratio [aHR] 0.56, 95% CI: 0.47-0.67) and heart failure hospitalization (aHR 0.45, 0.30-0.70). Compared to AKI-D patients who did not recover and progressed to ESRD, AKI-D patients who recovered (n = 1347) had a 30% lower adjusted relative rate of death (aHR 0.70, 0.55-0.88).ConclusionsPatients who transition to ESRD via AKI-D are a high-risk subgroup that may benefit from aggressive monitoring and medical management, particularly for heart failure. Recovery from AKI-D is independently associated with lower short-term mortality.

Renal recovery after dialysis-requiring acute kidney injury (AKI-D) is an important clinical and patient-centered outcome. Here we examined whether the pre-admission proteinuria level independently influences risk for non-recovery after AKI-D in a community-based population. All adult members of Kaiser Permanente Northern California who experienced AKI-D between January 1, 2009 and September 30, 2015 were included. Pre-admission proteinuria levels were determined by dipstick up to four years before the AKI-D hospitalization and the outcome was renal recovery (survival and dialysis-independence four weeks and more) at 90 days after initiation of renal replacement therapy. We used multivariable logistic regression to adjust for baseline estimated glomerular filtration rate (eGFR), age, sex, ethnicity, short-term predicted risk of death, comorbidities, and medication use. Among 5,347 adults with AKI-D, the mean age was 66 years, 59% were men, and 50% were white. Compared with negative/trace proteinuria, the adjusted odds ratios for non-recovery (continued dialysis-dependence or death) were 1.47 (95% confidence interval 1.19-1.82) for 1+ proteinuria and 1.92 (1.54-2.38) for 2+ or more proteinuria. Among survivors, the crude probability of recovery ranged from 83% for negative/trace proteinuria with baseline eGFR over 60 mL/min/1.73m2 to 25% for 2+ or more proteinuria with eGFR 15-29 mL/min/1.73m2. Thus, the pre-AKI-D level of proteinuria is a graded, independent risk factor for non-recovery and helps to improve short-term risk stratification for patients with AKI-D.

BackgroundThe clinical effects of age occur over an age continuum, yet age as a primary predictor is often analyzed using arbitrary age cut-points.ObjectiveTo assess whether transformation of a continuous variable such as age using a spline function can uncover nonlinear associations between age and cardiovascular outcomes.DesignObservational retrospective cohort study in 1015 Kaiser Permanente Northern California patients with end-stage renal disease after index coronary revascularization. Age, the primary predictor, was modeled by 5 different techniques: 1) dichotomized at 65 years or older; 2) at 80 years or older (as a sensitivity analysis); 3) categorized as younger than 55 years (reference), 55 to 64, 65 to 74, and 75 years or older; 4) linear (every 5 years) variable; and 5) nonlinear by transformation into a cubic spline. Age categories were changed in a sensitivity analysis.Main outcome measuresPrimary and secondary outcomes were all-cause mortality and repeat revascularization, respectively.ResultsGraphical assessment demonstrated that age dichotomized at either 65 years and older or 80 years and older led to loss of information. Categorized age underestimated or overestimated risk at the extremes of age. A sensitivity analysis demonstrated that an arbitrary change in the age category led to a different conclusion. Age modeled linearly adequately represented mortality risk but was suboptimal with repeat revascularization. Only the cubic spline demonstrated the nonlinear association between age and repeat revascularization.ConclusionEmploying the continuous variable age as a case study, we have demonstrated that the use of flexible transformations, such as spline functions, can unearth clinically meaningful associations that would not have been possible otherwise. Future research should determine whether incorporation of these methods can improve decision making at a population level.