Background Prevalence and factors associated with obstructive and restrictive lung function in people with chronic kidney disease (CKD) are unknown. Study Design Cross-sectional and longitudinal ...analyses. Setting & Participants Participants aged 40 to 79 years from NHANES (National Health and Nutrition Examination Survey) 2007 to 2012 who underwent spirometry testing. Predictor CKD (estimated glomerular filtration rate eGFR >15-<60 mL/min/1.73 m2 or urinary albumin-creatinine ratio ≥ 30 mg/g). Outcomes Restrictive lung function (defined as FEV1 /FVC ≥ 0.70 and baseline FVC < 80% predicted), obstructive lung function (defined as FEV1 /FVC < 0.70 based on postbronchodilator spirometric results), and mortality data (available for 2007-2008 and 2009-2010 survey periods). Results 7,610 participants (CKD = 1,338; non-CKD = 6,272) were included. Prevalences of obstructive lung function adjusted to the mean age of 55 years and 50% men in the CKD and non-CKD groups were 15.6% and 13.3%, respectively ( P = 0.2). Similarly, adjusted prevalences of restrictive lung function in the CKD and non-CKD groups were 9.8% and 6.7%, respectively ( P = 0.01). Presence of albumin-creatinine ratio ≥ 30 mg/g was associated with obstructive (OR, 1.42; 95% CI, 1.07-1.88) and restrictive lung function (OR, 1.43; 95% CI, 1.01-2.03) in the entire study cohort. eGFR < 60 mL/min/1.73 m2 was associated with higher odds of obstructive lung function. In a multivariable Cox model, age (HR, 1.07; 95% CI, 1.04-1.11) and presence of obstructive lung function (HR, 2.68; 95% CI, 1.80-3.97), but not CKD measures, were associated with death. Limitations Small proportion of participants with advanced kidney disease. Conclusions In a representative sample of US adults, impaired lung function is common in those with and without CKD. Albuminuria was independently associated with both obstructive and restrictive lung function, and eGFR < 60 mL/min/1.73 m2 was associated with higher odds of obstructive lung function. Older age and obstructive lung function were associated with higher likelihood of death. Further studies examining the burden of lung disease in advanced CKD are needed.
Background Diabetes is the leading cause of end-stage renal disease (ESRD) and a significant contributor to mortality in the general population. We examined the associations of hemoglobin A1c (HbA1c ...) levels with ESRD and death in a population with diabetes and chronic kidney disease (CKD). Study Design Cohort study. Setting & Participants 6,165 patients with diabetes (treated with oral hypoglycemic agents and/or insulin) and CKD stages 1 to 5 at a large health care system. Predictor HbA1c level (examined as a categorical and continuous measure). Outcomes All-cause and cause-specific mortality ascertained from the Ohio Department of Health mortality files and ESRD ascertained from the US Renal Data System. Results During a median 2.3 years of follow-up, 957 patients died (887 pre-ESRD deaths) and 205 patients reached ESRD. In a Cox proportional hazards model, after multivariable adjustment including for kidney function, HbA1c level < 6% was associated with higher risk for death when compared with HbA1c levels of 6% to 6.9% (HR, 1.23; 95% CI, 1.01-1.50). Similarly, HbA1c level ≥ 9% was associated with higher risk for all-cause death (HR, 1.34; 95% CI, 1.06-1.69). In competing-risk models, baseline HbA1c level was not associated with ESRD. For cause-specific mortality, diabetes accounted for >12% of deaths overall and >19% of deaths among those with HbA1c levels > 9%. Limitations Small proportion of participants with advanced kidney disease; single-center population. Conclusions In this cohort of patients with CKD with diabetes, HbA1c levels < 6% and ≥9% were associated with higher risk for death. HbA1c levels were not associated with ESRD in this specific CKD population. Diabetes-related deaths increased with higher HbA1c levels.
Background β-Trace protein (BTP) and β2 -microglobulin (B2M) are novel glomerular filtration markers that have stronger associations with adverse outcomes than creatinine. Comparisons of BTP and B2M ...to creatinine and cystatin C are limited by the absence of rigorously developed glomerular filtration rate (GFR) estimating equations for the novel markers. Study Design Study of diagnostic test accuracy. Setting & Participants Pooled database of 3 populations with chronic kidney disease (CKD) with mean measured GFR of 48 mL/min/1.73 m2 (N = 3,551; MDRD Modification of Diet in Renal Disease Study, AASK African American Study of Kidney Disease and Hypertension, and CRIC Chronic Renal Insufficiency Cohort Study). Index Tests GFR estimated using creatinine, cystatin C, BTP, or B2M level. Reference Test GFR measured as the urinary clearance of iothalamate. Results For BTP and B2M, coefficients for age, sex, and race were smaller than for creatinine and were similar or smaller than for cystatin C. For B2M, coefficients for sex, age, and race were smaller than for creatinine and were similar (age and race) or smaller (sex) than for cystatin C. The final equations with BTP (BTP, age, and sex) or B2M (B2M alone) were less accurate than either the CKD-EPI (CKD Epidemiology Collaboration) creatinine or cystatin C equations. The combined BTP-B2M equation (BTP and B2M alone) had similar accuracy to the CKD-EPI creatinine or cystatin C equation. The average of the BTP-B2M equation and the CKD-EPI creatinine–cystatin C equation was not more accurate than the CKD-EPI creatinine–cystatin C equation. Limitations No external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race. Conclusions BTP and B2M are less influenced by age, sex, and race than creatinine and less influenced by race than cystatin C, but provide less accurate GFR estimates than the CKD-EPI creatinine and cystatin C equations. The CKD-EPI BTP and B2M equation provides a methodological advance for their study as filtration markers and in their associations with risk and adverse outcomes, but further study is required before clinical use.
Background Previous observational studies examining outcomes associated with the timing of dialysis therapy initiation in the United States have often been limited by lead time and survivor bias. ...Study Design Retrospective cohort study comparing the effectiveness of early versus later (conventional) dialysis therapy initiation in advanced chronic kidney disease (CKD). The analysis used inverse probability weighting to account for an individual's contribution to different exposure groups over time in a pooled logistic regression model. Patients contributed risk to both exposure categories (early and later initiation) until there was a clear treatment strategy (ie, dialysis therapy was initiated early or estimated glomerular filtration rate eGFR decreased to <10 mL/min/1.73 m2 ). Setting & Participants Patients with CKD who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider as of January 1, 2005, and at least 3 eGFRs in the range of 20-30 mL/min/1.73 m2 measured at least 180 days apart. Predictors Timing of dialysis therapy initiation as determined using model-based interpolation of eGFR trajectories over time. Timing was defined as early (interpolated eGFR at dialysis therapy initiation ≥ 10 mL/min/1.73 m2 ) or later (eGFR < 10 mL/min/1.73 m2 ) and was time-varying. Outcomes Death from any cause occurring from the time that eGFR was equal to 20 mL/min/1.73 m2 through September 15, 2009. Results The study population consisted of 652 patients meeting inclusion criteria. Most (71.3%) of the study population did not initiate dialysis therapy during follow-up. Patients who did not initiate dialysis therapy (n = 465) were older, more likely to be white, and had more favorable laboratory profiles than those who started dialysis therapy. Overall, 146 initiated dialysis early and 80 had eGFRs decrease to <10 mL/min/1.73 m2 . Many participants (n = 426) were censored prior to attaining a clear treatment strategy and were considered undeclared. There was no statistically significant survival difference for the early compared with later initiation strategy (OR, 0.85; 95% CI, 0.65-1.11). Limitations Interpolated eGFR, moderate sample size, and likely unmeasured confounders. Conclusions In patients with advanced CKD, timing of dialysis therapy initiation was not associated with mortality when accounting for lead time bias and survivor bias.
Background Elevated total serum alkaline phosphatase (ALP) levels have been associated with mortality in the general population and in dialysis patients. Study Design Retrospective cohort study. ...Setting & Participants 28,678 patients with chronic kidney disease (CKD) stages 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2 ) were identified using the Cleveland Clinic CKD Registry. CKD was defined as 2 estimated glomerular filtration rate values <60 mL/min/1.73 m2 drawn more than 90 days apart using the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation. Predictor ALP levels measured using the calorimetric assay were examined as quartiles (quartile Q1, <66 U/L; Q2, 66-81 U/L; Q3, 82-101 U/L; and Q4, ≥102 U/L) and as a continuous measure. Outcomes & Measurements All-cause mortality and end-stage renal disease (ESRD) were ascertained using the Social Security Death Index and US Renal Data System. Results After a median follow-up of 2.2 years, 588 patients progressed to ESRD and 4,755 died. There was a graded increase in risk of mortality with higher ALP quartiles (Q2, Q3, and Q4) compared to the reference quartile (Q1) after adjusting for demographics, comorbid conditions, use of relevant medications, and liver function test results. The highest ALP quartile was associated with an HR for ESRD of 1.38 (95% CI, 1.09-1.76). Each 1-SD (42.7 U/L) higher ALP level was associated with 15% (95% CI, 1.09-1.22) and 16% (95% CI, 1.14-1.18) increased risk of ESRD and mortality, respectively. Limitations Single-center observational study; lack of complete data, including parathyroid hormone level, for all study participants, and attrition bias. Conclusions Higher serum ALP levels in patients with CKD stages 3-4 were associated independently with all-cause mortality and ESRD.
Background Low 25-hydroxyvitamin D (25OHD) levels are common in patients with non–dialysis-dependent chronic kidney disease (CKD). The associations between low 25(OH)D levels and mortality in ...non–dialysis-dependent patients with CKD are unclear. Study Design Retrospective cohort study. Setting & Participants Patients with stages 3-4 CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2 ; n = 12,673) who had 25(OH)D levels measured after the diagnosis of CKD in the Cleveland Clinic Health System. Predictor 25(OH)D levels categorized into 3 groups: <15, 15-29, and ≥30 ng/mL. Outcomes We examined factors associated with low 25(OH)D levels and associations between low 25(OH)D levels and all-cause mortality (ascertained using the Social Security Death Index and our electronic medical record) using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves. Measurements 25(OH)D was measured using chemiluminescence immunoassay. Results Of 12,763 patients with CKD, 15% (n = 1,970) had 25(OH)D levels <15 ng/mL, whereas 45% (n = 5,749) had 25(OH)D levels of 15-29 ng/mL. Male sex, African American race, diabetes, coronary artery disease, and lower estimated glomerular filtration rate were associated significantly with 25(OH)D level <30 ng/mL. A graded increase in risk of 25(OH)D level <30 ng/mL was evident across increasing body mass index levels. Patients who had 25(OH)D levels measured in fall through spring had higher odds for 25(OH)D levels <30 ng/mL. After covariate adjustment, patients with CKD with 25(OH)D levels <15 ng/mL had a 33% increased risk of mortality (95% CI, 1.07-1.65). The group with 25(OH)D levels of 15-29 ng/mL did not show a significantly increased risk of mortality (HR, 1.03; 95% CI, 0.86-1.22) compared with patients with 25(OH)D levels ≥30 ng/mL. Limitations Single-center observational study, lack of data for albuminuria and other markers of bone and mineral disorders, and attrition bias. Conclusions 25(OH)D level <15 ng/mL was associated independently with all-cause mortality in non–dialysis-dependent patients with CKD.
Background A recent cross-sectional analysis of Kidney Early Evaluation Program (KEEP) participants suggested that obesity is a heterogeneous disease state in African Americans and whites with ...chronic kidney disease (CKD). Study Design In longitudinal analyses spanning 8 years of follow-up, we examined whether race and body mass index (BMI) influence end-stage renal disease (ESRD) and mortality rates in participants with CKD stages 3-4. Setting & Participants KEEP participants were included in this analysis if they met the following criteria: (1) estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1.73 m2 , (2) white or African American race, and (3) no previous dialysis or transplantation. Outcomes & Measurements Survival analyses were performed for the outcomes of ESRD, death, and combined outcome of ESRD or death. Results Of 14,631 participants with CKD stages 3-4, 28% were African American and 72% were white. African American participants had higher rates of obesity and hypertension, with a higher baseline mean eGFR, higher prevalence of albuminuria, and greater degree of anemia compared with whites. In multivariable models, African American race increased the risk of ESRD (HR, 1.66; 95% CI, 1.26-2.07), but not death (HR, 0.89; 95% CI, 0.76-1.03). In these models, male sex, hypertension, diabetes, lower baseline eGFR, and albuminuria were predictive of higher rates of ESRD; age, male sex, diabetes, lower baseline eGFR, and albuminuria were predictive of overall mortality. There was no significant interaction between race and BMI in the adjusted model for outcomes of ESRD ( P = 0.7) or death ( P = 0.3). Limitations Baseline values used in the analysis are from a cross-sectional data set. Dyslipidemia and secondary hyperparathyroidism were not accounted for in the analysis. Conclusions African American race was associated with a higher incidence of ESRD, but not mortality. Although obesity may be a heterogeneous disease state in African Americans and whites with CKD, there does not appear to be a significant interaction between race and BMI in progression to ESRD or death.
Rationale and Objective: Chronic kidney disease is a risk enhancing factor for cardiovascular disease (CVD) and mortality, and the role of aspirin use is unclear in this population. We investigated ...the risk and benefits of aspirin use in primary and secondary prevention of CVD in the Chronic Renal Insufficiency Cohort Study. Study Design: Prospective observational cohort. Setting & Participants: 3,664 Chronic Renal Insufficiency Cohort participants. Exposure: Aspirin use in patients with and without preexisting CVD. Outcomes: Mortality, composite and individual CVD events (myocardial infarction, stroke, and peripheral arterial disease), kidney failure (dialysis and transplant), and major bleeding. Analytical Approach: Intention-to-treat analysis and multivariable Cox proportional hazards model to examine associations of time varying aspirin use. Results: The primary prevention group was composed of 2,578 (70.3%) individuals. Mean age was 57 ± 11 years, 46% women, 42% Black, and 47% had diabetes. The mean estimated glomerular filtration rate was 45 mL/min/1.73 m2. Median follow-up was 11.5 (IQR, 7.4-13) years. Aspirin was not associated with all-cause mortality in those without preexisting cardiovascular disease (CVD) (HR, 0.84; 95% CI, 0.7-1.01; P = 0.06) or those with CVD (HR, 0.88; 95% CI, 0.77-1.02, P = 0.08). Aspirin was not associated with a reduction of the CVD composite in primary prevention (HR, 0.97; 95% CI, 0.77-1.23; P = 0.79) and in secondary prevention because the original study design was not meant to study the effects of aspirin. Limitations: This is not a randomized controlled trial, and therefore, causality cannot be determined. Conclusions: Aspirin use in chronic kidney disease patients was not associated with reduction in primary or secondary CVD events, progression to kidney failure, or major bleeding.
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