Supplementary Material for: Estimated Glomerular Filtration Rate: Fit for What Purpose?

There is important nosologic utility in staging chronic kidney disease (CKD) based on estimates of glomerular filtration rate (GFR). These equations have been optimized for estimating GFR at a single point in time. Risk assessment models used for prognosis of specified outcome events have commonly incorporated estimated GFR (eGFR), but the validity of this approach has not been evaluated. The current objective is to evaluate the risk of all-cause mortality over a 10-year follow-up period with multivariable-adjusted Cox regression analysis, comparing CKD stages based on eGFR to Cockcroft-Gault estimated creatinine clearance (eCrCl). There were significant differences between Stage 3A and Stage 3B-5 hazard ratios for all-cause mortality (p = 0.003) using eCrCl categories, but not for the same eGFR categories (p = 0.241). Discrimination analysis showed that a clinically significant difference (relative integrated discrimination improvement 778.6%; p = 0.001) was observed between the 2 models for the age strata ≤64. While eGFR is more precise and accurate than the Cockcroft Gault equation for estimating measured GFR at a single point in time, eGFR does not perform as well as eCrCl for assessing risk of all-cause mortality over 10-year follow-up intervals

Supplementary Material for: Acute Kidney Injury and Mortality in Hospitalized Patients

<i>Background:</i> The objective of this study was to determine the incidence of acute kidney injury (AKI) and its relation with mortality among hospitalized patients. <i>Methods:</i> Analysis of hospital discharge and laboratory data from an urban academic medical center over a 1-year period. We included hospitalized adult patients receiving two or more serum creatinine (sCr) measurements. We excluded prisoners, psychiatry, labor and delivery, and transferred patients, ‘bedded outpatients’ as well as individuals with a history of kidney transplant or chronic dialysis. We defined AKI as (a) an increase in sCr of ≥0.3 mg/dl; (b) an increase in sCr to ≥150% of baseline, or (c) the initiation of dialysis in a patient with no known history of prior dialysis. We identified factors associated with AKI as well as the relationships between AKI and in-hospital mortality. <i>Results:</i> Among the 19,249 hospitalizations included in the analysis, the incidence of AKI was 22.7%. Older persons, Blacks, and patients with reduced baseline kidney function were more likely to develop AKI (all p < 0.001). Among AKI cases, the most common primary admitting diagnosis groups were circulatory diseases (25.4%) and infection (16.4%). After adjustment for age, sex, race, admitting sCr concentration, and the severity of illness index, AKI was independently associated with in-hospital mortality (adjusted odds ratio 4.43, 95% confidence interval 3.68–5.35). <i>Conclusions:</i> AKI occurred in over 1 of 5 hospitalizations and was associated with a more than fourfold increased likelihood of death. These observations highlight the importance of AKI recognition as well as the association of AKI with mortality in hospitalized patients

Supplementary Material for: Healthy Behaviors, Risk Factor Control and Awareness of Chronic Kidney Disease

<b><i>Background/Aims:</i></b> The association between chronic kidney disease (CKD) awareness and healthy behaviors is unknown. We examined whether CKD self-recognition is associated with healthy behaviors and achieving risk-reduction targets known to decrease risk of cardiovascular morbidity and CKD progression. <b><i>Methods:</i></b> CKD awareness, defined as a ‘yes’ response to ‘Has a doctor or other health professional ever told you that you had kidney disease?’, was examined among adults with CKD (eGFR <60 ml/min/1.73 m²) who participated in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Odds of participation in healthy behaviors (tobacco avoidance, avoidance of regular nonsteroidal anti-inflammatory drug use, and physical activity) and achievement of risk-reduction targets (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, systolic blood pressure control and glycemic control among those with diabetes) among those aware versus unaware of their CKD were determined by logistic regression, controlling for sociodemographics, access to care and comorbid conditions. Systolic blood pressure control was defined as <130 mm Hg (primary definition) or <140 mm Hg (secondary definition). <b><i>Results:</i></b> Of 2,615 participants, only 6% (n = 166) were aware of having CKD. Those who were aware had 82% higher odds of tobacco avoidance compared to those unaware (adjusted OR = 1.82, 95% CI 1.02–3.24). CKD awareness was not associated with other healthy behaviors or achievement of risk-reduction targets. <b><i>Conclusions:</i></b> Awareness of CKD was only associated with participation in one healthy behavior and was not associated with achievement of risk-reduction targets. To encourage adoption of healthy behaviors, a better understanding of barriers to participation in CKD-healthy behaviors is needed

Supplementary Material for: Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

<b><i>Background:</i></b> Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. <b><i>Methods:</i></b> Patients in ­BEACON (<i>n</i> = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m², and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). <b><i>Results:</i></b> Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; <i>p</i> < 0.0001). <b><i>Conclusions:</i></b> Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD