Importance

Older adults are often excluded from clinical trials. The benefit of preventive interventions tested in younger trial populations may be reduced when applied to older adults in the clinical setting if they are less likely to survive long enough to experience those outcomes targeted by the intervention.

Objective

To extrapolate a treatment effect similar to those reported in major randomized clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of end-stage renal disease (ESRD) to a real-world population of older patients with chronic kidney disease.

Design, setting, and participants

Simulation study in a retrospective cohort conducted in Department of Veterans Affairs medical centers. We included 371 470 patients 70 years or older with chronic kidney disease.

Exposure

Level of estimated glomerular filtration rate (eGFR) and proteinuria.

Main outcomes and measures

Among members of this cohort, we evaluated the expected effect of a 30% reduction in relative risk on the number needed to treat (NNT) to prevent 1 case of ESRD over a 3-year period. These limits were selected to mimic the treatment effect achieved in major trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of ESRD. These trials have reported relative risk reductions of 23% to 56% during observation periods of 2.6 to 3.4 years, yielding NNTs to prevent 1 case of ESRD of 9 to 25.

Results

The NNT to prevent 1 case of ESRD among members of this cohort ranged from 16 in patients with the highest baseline risk (eGFR of 15-29 mL/min/1.73 m(2) with a dipstick proteinuria measurement of ≥ 2+) to 2500 for those with the lowest baseline risk (eGFR of 45-59 mL/min/1.73 m(2) with negative or trace proteinuria and eGFR of ≥ 60 mL/min/1.73 m2 with dipstick proteinuria measurement of 1+). Most patients belonged to groups with an NNT of more than 100, even when the exposure time was extended over 10 years and in all sensitivity analyses.

Conclusions and relevance

Differences in baseline risk and life expectancy between trial subjects and real-world populations of older adults with CKD may reduce the marginal benefit to individual patients of interventions to prevent ESRD.

Objective

This study aims to determine whether menopausal symptoms differed between women with chronic kidney disease (CKD) and women without CKD, and whether CKD modified associations of late vasomotor symptoms (VMS) with mortality and/or cardiovascular events.

Methods

CKD, defined as estimated glomerular filtration rate lower than 60 mL/minute/1.73 m (using the Chronic Kidney Disease Epidemiology Collaboration equation), was determined in 17,891 postmenopausal women, aged 50 to 79 years at baseline, in the multiethnic Women's Health Initiative cohort. Primary outcomes were presence, severity, and timing/duration of VMS (self-reported hot flashes and night sweats) at baseline. We used polytomous logistic regression to test for associations among CKD and four VMS categories (no VMS; early VMS-present before menopause but not at study baseline; late VMS-present only at study baseline; persistent VMS-present before menopause and study baseline) and Cox regression to determine whether CKD modified associations between late VMS and mortality or cardiovascular events.

Results

Women with CKD (1,017 of 17,891; mean estimated glomerular filtration rate, 50.7 mL/min/1.73 m) were more likely to have had menopause before age 45 years (26% vs 23%, P = 0.02) but were less likely to experience VMS (38% vs 46%, P < 0.001) than women without CKD. Women with CKD were not more likely than women without CKD to experience late VMS. Late VMS (hazard ratio, 1.16; 95% CI, 1.04-1.29) and CKD (hazard ratio, 1.74; 95% CI, 1.54-1.97) were each independently associated with increased risk for mortality, but CKD did not modify the association of late VMS with mortality (Pinteraction = 0.53), coronary heart disease (Pinteraction = 0.12), or stroke (Pinteraction = 0.68).

Conclusions

Women with mild CKD experience earlier menopause and fewer VMS than women without CKD.

Urine biomarker concentrations reflecting kidney tubule injury and dysfunction were not associated with brain MRI measures.Higher eGFR was associated with lower total brain cerebral blood flow.This is the first evaluation of the relationship of kidney tubule biomarkers with brain imaging by MRI in patients with CKD.

Background

Often, patients with chronic kidney disease are reported to be unaware of it. We prospectively evaluated the association between awareness of kidney disease to end-stage renal disease and mortality.

Methods

We utilized 2000-2009 data from the National Kidney Foundation's Kidney Early Evaluation Program. Mortality was determined by cross reference to the Social Security Administration Death Master File and development of end stage by cross reference with the United States Renal Data System.

Results

Of 109,285 participants, 28,244 (26%) had chronic kidney disease defined by albuminuria or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). Only 9% (n=2660) reported being aware of kidney disease. Compared with those who were not aware, participants aware of chronic kidney disease had lower eGFR (49 vs 62 mL/min/1.73 m(2)) and a higher prevalence of albuminuria (52% vs. 46%), diabetes (47% vs 42%), cardiovascular disease (43% vs 28%), and cancer (23% vs 14%). Over 8.5 years of follow-up, aware participants compared with those unaware had a lower rate of survival for end stage (83% and 96%) and mortality (78% vs 81%), P <.001. After adjustment for demographics, socioeconomic factors, comorbidity, and severity of kidney disease, aware participants continued to demonstrate an increased risk for end-stage renal disease (hazard ratio 1.37; 95% confidence interval, 1.07-1.75; P <.0123) and mortality (hazard ratio 1.27; 95% confidence interval, 1.07-1.52; P <.0077) relative to unaware participants with chronic kidney disease.

Conclusions

Among patients identified as having chronic kidney disease at a health screening, only a small proportion had been made aware of their diagnosis previously by clinicians. This subgroup was at a disproportionately high risk for mortality and end-stage renal disease.

Background

Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied.

Study design

Cross-sectional analysis.

Settings & participants

Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008.

Measurement

Depressive symptoms measured by Beck Depression Inventory (BDI).

Predictors

Demographic and clinical factors.

Outcomes

Elevated depressive symptoms (BDI score ≥11) and antidepressant medication use.

Results

Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each).

Limitations

Absence of clinical diagnosis of depression and use of nonpharmacologic treatments.

Conclusions

Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications.

Background

Studies in the general population suggest that atrial fibrillation (AF) is an independent risk factor for decline in cognitive function, but this relationship has not been examined in adults with chronic kidney disease (CKD). We investigated the association between incident AF and changes in cognitive function over time in this population.

Methods and results

We studied a subgroup of 3254 adults participating in the Chronic Renal Insufficiency Cohort Study. Incident AF was ascertained by 12-lead electrocardiogram (ECG) obtained at a study visit and/or identification of a hospitalization with AF during follow-up. Cognitive function was assessed biennially using the Modified Mini-Mental State Exam. Linear mixed effects regression was used to evaluate the association between incident AF and longitudinal change in cognitive function. Compared with individuals without incident AF (n = 3158), those with incident AF (n = 96) were older, had a higher prevalence of cardiovascular disease and hypertension, and lower estimated glomerular filtration rate. After median follow-up of 6.8 years, we observed no significant multivariable association between incident AF and change in cognitive function test score.

Conclusion

In this cohort of adults with CKD, incident AF was not associated with a decline in cognitive function.

Background

Cognitive impairment is common among patients with chronic kidney disease (CKD); however, its prognostic significance is unclear. We assessed the independent association between cognitive impairment and CKD progression in adults with mild to moderate CKD.

Study design

Prospective cohort.

Setting & participants

Adults with CKD participating in the CRIC (Chronic Renal Insufficiency Cohort) Study. Mean age of the sample was 57.7±11.0 years and mean estimated glomerular filtration rate (eGFR) was 45.0±16.9mL/min/1.73m(2).

Predictor

Cognitive function was assessed with the Modified Mini-Mental State Examination at study entry. A subset of participants 55 years and older underwent 5 additional cognitive tests assessing different domains. Cognitive impairment was defined as a score > 1 SD below the mean score on each test. Covariates included demographics, kidney function, comorbid conditions, and medications.

Outcomes

Incident end-stage renal disease (ESRD) and incident ESRD or 50% decline in baseline eGFR.

Results

In 3,883 CRIC participants, 524 (13.5%) had cognitive impairment at baseline. During a median 6.1 years of follow-up, 813 developed ESRD and 1,062 developed ESRD or a ≥50% reduction in eGFR. There was no significant association between cognitive impairment and risk for ESRD (HR, 1.07; 95% CI, 0.87-1.30) or the composite of ESRD or 50% reduction in eGFR (HR, 1.06; 95% CI, 0.89-1.27). Similarly, there was no association between cognitive impairment and the joint outcome of death, ESRD, or 50% reduction in eGFR (HR, 1.06; 95% CI, 0.91-1.23). Among CRIC participants who underwent additional cognitive testing, we found no consistent association between impairment in specific cognitive domains and risk for CKD progression in adjusted analyses.

Limitations

Unmeasured potential confounders, single measure of cognition for younger participants.

Conclusions

Among adults with CKD, cognitive impairment is not associated with excess risk for CKD progression after accounting for traditional risk factors.

BACKGROUND:Advanced chronic kidney disease is associated with elevated risk for cognitive impairment. However, it is not known whether and how cognitive impairment is associated with planning and preparation for end-stage renal disease. STUDY DESIGN:Retrospective observational study. SETTING & PARTICIPANTS:630 adults participating in the CRIC (Chronic Renal Insufficiency Cohort) Study who had cognitive assessments in late-stage CKD, defined as estimated glome-rular filtration rate ≤ 20mL/min/1.73m2, and subsequently initiated maintenance dialysis therapy. PREDICTOR:Predialysis cognitive impairment, defined as a score on the Modified Mini-Mental State Examination lower than previously derived age-based threshold scores. Covariates included age, race/ethnicity, educational attainment, comorbid conditions, and health literacy. OUTCOMES:Peritoneal dialysis (PD) as first dialysis modality, preemptive permanent access placement, venous catheter avoidance at dialysis therapy initiation, and preemptive wait-listing for a kidney transplant. MEASUREMENTS:Multivariable-adjusted logistic regression. RESULTS:Predialysis cognitive impairment was present in 117 (19%) participants. PD was the first dialysis modality among 16% of participants (n=100), 75% had preemptive access placed (n=473), 45% avoided using a venous catheter at dialysis therapy initiation (n=279), and 20% were preemptively wait-listed (n=126). Predialysis cognitive impairment was independently associated with 78% lower odds of PD as the first dialysis modality (adjusted OR [aOR], 0.22; 95% CI, 0.06-0.74; P=0.02) and 42% lower odds of venous catheter avoidance at dialysis therapy initiation (aOR, 0.58; 95% CI, 0.34-0.98; P=0.04). Predialysis cognitive impairment was not independently associated with preemptive permanent access placement or wait-listing. LIMITATIONS:Potential unmeasured confounders; single measure of cognitive function. CONCLUSIONS:Predialysis cognitive impairment is associated with a lower likelihood of PD as a first dialysis modality and of venous catheter avoidance at dialysis therapy initiation. Future studies may consider addressing cognitive function when testing strategies to improve patient transitions to dialysis therapy.

Rationale & objective

Among individuals with chronic kidney disease (CKD), poor self-reported health is associated with adverse outcomes including hospitalization and death. We sought to examine the association between health-related quality-of-life (HRQoL) and depressive symptoms in advanced CKD and subsequent access to the kidney transplant waiting list.

Study design

Prospective cohort study.

Setting & population

1,676 Chronic Renal Insufficiency Cohort (CRIC) study participants with estimated glomerular filtration rates ≤ 30 mL/min/1.73 m² at study entry or during follow-up.

Exposures

HRQoL ascertained by 5 scales of the Kidney Disease Quality of Life-36 Survey (Physical Component Summary [PCS], Mental Component Summary, Symptoms, Burdens, and Effects), with higher scores indicating better HRQoL, and depressive symptoms ascertained using the Beck Depression Inventory.

Outcomes

Time to kidney transplant wait-listing and time to pre-emptive wait-listing.

Analytic approach

Time-to-event analysis using Cox proportional hazards regression.

Results

During a median follow-up of 5.1 years, 652 (39%) participants were wait-listed, of whom 304 were preemptively wait-listed. Adjusted for demographics, comorbid conditions, estimated glomerular filtration rate slope, and cognitive function, participants with the highest scores on the Burden and Effects scales, respectively, had lower rates of wait-listing than those with the lowest scores on the Burden (wait-listing adjusted hazard ratio [aHR], 0.70; 95% CI, 0.57-0.85; P < 0.001) and Effects scales (wait-listing aHR, 0.74; 95% CI, 0.59-0.92; P = 0.007). Participants with fewer depressive symptoms (ie, Beck Depression Inventory score < 14) had lower wait-listing rates than those with more depressive symptoms (aHR, 0.81; 95% CI, 0.66-0.99; P = 0.04). Participants with lower Burden and Effects scale scores and those with higher Symptoms and PCS scores had higher pre-emptive wait-listing rates (aHR in highest tertile of PCS relative to lowest tertile, 1.58; 95% CI, 1.12-2.23; P = 0.01).

Limitations

Unmeasured confounders.

Conclusions

Self-reported health in late-stage CKD may influence the timing of kidney transplantation.