Objectives

This study sought to compare the association of microalbuminuria with outcomes in patients with different comorbidities.

Background

The risk of adverse outcomes associated with lower levels proteinuria has been found to be linearly decreasing with even low-normal levels of microalbuminuria. It is unclear whether comorbid conditions change these associations.

Methods

We examined the association of urine microalbumin-creatinine ratio (UACR) with mortality and the slopes of estimated glomerular filtration rate (eGFR) in a nationally representative cohort of 298,875 U.S. veterans. Associations of UACR with all-cause mortality overall and in subgroups of patients with and without diabetes mellitus, hypertension, cardiovascular disease, congestive heart failure, and advanced chronic kidney disease (CKD) were examined in Cox models, and with the slopes of eGFR in linear and logistic regression models.

Results

Very low levels of UACR were linearly associated with decreased mortality and less progression of CKD overall: adjusted mortality hazard ratio and estimated glomerular filtration rate slope (95% confidence interval [CI]) associated with UACR ≥200 μg/mg, compared to <5 μg/mg were 1.53 (95% CI: 1.38 to 1.69, p < 0.001) and -1.59 (95% CI: -1.83 to -1.35, p < 0.001). Similar linearity was present in all examined subgroups, except in patients with CKD in whom a U-shaped association was present and in whom a UACR of 10 to 19 was associated with the best outcomes.

Conclusions

The association of UACR with mortality and with progressive CKD is modified in patients with CKD, who experience higher mortality and worse progression of CKD with the lowest levels of UACR. Proteinuria-lowering interventions in patients with advanced CKD should be implemented cautiously, considering the potential for adverse outcomes.

Background

Black dialysis patients have significantly lower mortality compared to white patients, in contradistinction to the higher mortality seen in blacks in the general population. It is unclear if a similar paradox exists in non–dialysis-dependent CKD, and if it does, what its underlying reasons are.

Study Design

Historical cohort.

Setting & Participants

518,406 white and 52,402 black male US veterans with non-dialysis dependent CKD stages 3–5.

Predictor

Black race.

Outcomes & Measurements

We examined overall and CKD stage-specific all-cause mortality using parametric survival models. The effect of sociodemographic characteristics, comorbidities and laboratory characteristics on the observed differences was explored in multivariable models.

Results

Over a median follow-up of 4.7 years 172,093 patients died (mortality rate, 71.0 [95% CI, 70.6–71.3] per 1000 patient-years). Black race was associated with significantly lower crude mortality (HR, 0.95; 95% CI, 0.94–0.97; p<0.001). The survival advantage was attenuated after adjustment for age (HR, 1.14; 95% CI, 1.12–1.16), but was even magnified after full multivariable adjustment (HR, 0.72; 95% CI, 0.70–0.73; p<0.001). The unadjusted survival advantage of blacks was more prominent in those with more advanced stages of CKD, but CKD stage-specific differences were attenuated by multivariable adjustment.

Limitations

Exclusively male patients.

Conclusions

Black patients with CKD have lower mortality compared to white patients. The survival advantage seen in blacks is accentuated in patients with more advanced stages of CKD, which may be explained by changes in case mix and laboratory characteristics occurring during the course of kidney disease.

Background and objectives

Depression is common and is associated with higher mortality in patients with ESRD or CKD (stage 5). Less information is available on earlier stages of CKD. This study aimed to determine the prevalence of depression and any association with all-cause mortality in patients with varying severity of nondialysis-dependent CKD.

Design, setting, participants, & measurements

This is a retrospective study of a national cohort of 598,153 US veterans with nondialysis-dependent CKD stages 1-5 followed for a median of 4.7 years in the US Department of Veterans Affairs Health System. Diagnosis of depression was established as a result of systematic screening and administration of antidepressants. Association of depression with all-cause mortality overall and stratified by CKD stages were examined with the Kaplan-Meier method and in Cox models.

Results

There were 179,441 patients (30%) with a diagnosis of depression. Over median follow-up of 4.7 years, depression was associated with significantly higher age-adjusted mortality overall (hazard ratio, 1.55; 95% confidence interval, 1.54-1.57; P<0.001). Sequential adjustments for sociodemographic characteristics and especially for comorbid conditions attenuated this association, which nevertheless remained significant (hazard ratio, 1.25; 95% confidence interval, 1.23-1.26).

Conclusions

In this large cohort of predominantly elderly male patients with CKD, prevalence of depression and antidepressant use is high (30%) and is associated with significantly higher all-cause mortality independent of comorbid conditions.

Objectives

The study objective was to assess the association between angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use and mortality in patients with chronic kidney disease (CKD).

Background

There is insufficient evidence about the association of ACEI or ARBs with mortality in patients with CKD.

Methods

A logistic regression analysis was used to calculate the propensity of ACEI/ARB initiation in 141,413 U.S. veterans with nondialysis CKD who were previously unexposed to ACEI/ARB treatment. We examined the association of ACEI/ARB administration with all-cause mortality in patients matched by propensity scores using the Kaplan-Meier method and Cox models in "intention-to-treat" analyses and in generalized linear models with binary outcomes and inverse probability of treatment weights in "as-treated" analyses.

Results

The age of the patients at baseline was 75 ± 10 years, 8% of patients were black, and 22% were diabetic. ACEI/ARB administration was associated with a significantly lower risk of mortality both in the intention-to-treat analysis (hazard ratio: 0.81, 95% confidence interval: 0.78 to 0.84; p < 0.001) and the as-treated analysis with inverse probability of treatment weights (odds ratio: 0.37, 95% confidence interval: 0.34 to 0.41; p < 0.001). The association of ACEI/ARB treatment with lower risk of mortality was present in all examined subgroups.

Conclusions

In this large contemporary cohort of nondialysis-dependent patients with CKD, ACEI/ARB administration was associated with greater survival.

Background

Hyponatremia is common in patients with conditions such as congestive heart failure and is associated with increased mortality in hospitalized patients. Congestive heart failure is common in patients with chronic kidney disease, but the association of serum sodium concentration with mortality in such patients is not well characterized.

Methods and results

We examined the association of serum sodium concentration with all-cause mortality in a nationally representative cohort of 655 493 US veterans with non-dialysis-dependent chronic kidney disease (95 961 [15%] of them with congestive heart failure). Associations were examined in time-dependent Cox models with adjustment for potential confounders. During a median follow-up of 5.5 years, a total of 193 956 patients died (mortality rate, 62.5/1000 patient-years; 95% confidence interval, 62.2-62.8). The association of serum sodium level with mortality was U-shaped, with the lowest mortality seen in patients with sodium level of 140 mEq/L and with both lower and higher levels showing significant associations with increased mortality. Patients with serum sodium levels of <130, 130 to 135.9, 145.1 to 150, and ≥150 mEq/L compared with 136 to 145 mEq/L had multivariable-adjusted mortality hazard ratios (95% confidence interval) of 1.93 (1.83-2.03), 1.28 (1.26-1.30), 1.33 (1.28-1.38), and 1.56 (1.33-1.83) (P<0.001 for all). The associations remained consistent in subgroups of patients with and without congestive heart failure.

Conclusions

Both lower and higher serum sodium levels are independently associated with higher mortality in patients with non-dialysis-dependent chronic kidney disease, irrespective of the presence or absence of congestive heart failure.