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 Epoetin alfa (EPO) and darbepoetin alfa (DPO) are erythropoiesis-stimulating agents that are widely and interchangeably used for the treatment of anemia in patients with advanced chronic ...kidney disease and end-stage renal disease. No study has specifically compared the risks of hard study outcomes between EPO and DPO, including mortality. Study Design Systematic review of the literature and meta-analysis. Setting & Population Patients enrolled in randomized trials comparing EPO versus DPO for the treatment of anemia in adults with chronic kidney disease, including those requiring dialysis. Selection Criteria for Studies We conducted a systematic search of the literature (PubMed, CENTRAL, SCOPUS, and EMBASE, all years) and industry resources, using predefined search terms and data abstraction tools. We then summarized key characteristics and findings of these trials and performed a random-effects meta-analysis of trials with at least 3 months’ duration to identify the summary OR of mortality between patients randomly assigned to DPO versus EPO. Intervention DPO versus EPO. Outcome All-cause mortality. Results We identified 9 trials that met the stated inclusion criteria. Overall, 2,024 patients were included in the meta-analysis, of whom 126 died during follow-up, which ranged from 20 to 52 weeks. We found no significant difference in mortality between patients randomly assigned to DPO versus EPO (OR, 1.33; 95% CI, 0.88-2.01). No treatment heterogeneity across studies was detected (Q statistic = 4.60; P = 0.8). Limitations Generalizability to nontrial populations is uncertain. Conclusions Few trials directly comparing DPO and EPO have been conducted and follow-up was limited. In aggregate, no effect of specific erythropoiesis-stimulating agent on mortality was identified, but the confidence limits were wide and remained compatible with considerable harm from DPO. Absent adequately powered randomized trials, observational postmarketing comparative effectiveness studies comparing these erythropoiesis-stimulating agents are required to better characterize the long-term safety profiles of these agents.
Abstract Background In patients undergoing percutaneous coronary intervention (PCI), drug-eluting stents (DES) reduce repeat revascularizations compared with bare-metal stents (BMS), but their ...effects on death and myocardial infarction (MI) are mixed. Few studies have focused on patients with end-stage renal disease. Objectives This study compared mortality and cardiovascular morbidity during percutaneous coronary intervention with DES and with BMS in dialysis patients. Methods We identified 36,117 dialysis patients from the USRDS (United States Renal Data System) who had coronary stenting in the United States between April 23, 2003, and December 31, 2010, and examined the association of DES versus BMS with 1-year outcomes: death; death or MI; and death, MI, or repeat revascularization. We also conducted a temporal analysis by dividing the study period into 3 DES eras: Transitional (April 23, 2003, to June 30, 2004); Liberal (July 1, 2004, to December 31, 2006); and Selective (January 1, 2007, to December 31, 2010). Results One-year event rates were high, with 38 deaths; 55 death or MI events; and 71 death, MI, or repeat revascularization events per 100 person-years. DES, compared with BMS, were associated with a significant 18% lower risk of death; 16% lower risk of death or MI; and 13% lower risk of death, MI, or repeat revascularization. DES use varied, from 56% in the Transitional era to 85% in the Liberal era and 62% in the Selective era. DES outcomes in the Liberal era were significantly better than in the Transitional Era, but not significantly better than in the Selective Era. Conclusions DES for percutaneous coronary intervention appears to be safe for use in U.S. dialysis patients and is associated with lower rates of death, MI, and repeat revascularization.
Abstract Objective The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and acute kidney injury is well established, but it is less clear whether this risk is focused with specific ...agents. We undertook a large pharmacoepidemiologic analysis of the risk of acute kidney injury among older adults using nonselective NSAIDs or cyclooxygenase (COX)-2 inhibitors. Methods Medicare beneficiaries from 2 large states with drug benefit were eligible for study. Patients were included if they filled a prescription for a nonselective NSAID or COX-2 inhibitor after more than 6 months without any such prescriptions and without a previous diagnosis of acute kidney injury. Incident acute kidney injury was ascertained from hospitalization claims within 45 days of initiating nonselective NSAID or COX-2 inhibitor therapy. Adjusted proportional hazards models estimated the relative risk of acute kidney injury associated with each agent compared with celecoxib. Results We included 183,446 patients whose mean age was 78 years; 80% were women. Acute kidney injury was identified in 870 (0.47%) of nonselective NSAID or COX-2 inhibitor users. The agents with significantly elevated risk compared with celecoxib were indomethacin (rate ratio RR = 2.23; 95% confidence interval CI, 1.70-2.93), ibuprofen (RR = 1.73; 95% CI, 1.36-2.19), and rofecoxib (RR = 1.52; 95% CI, 1.26-1.83). These findings were robust in several subgroups. Conclusion Acute kidney injury requiring hospitalization is a relatively rare adverse event among older adults after initiation of nonselective NSAIDs or COX-2 inhibitor treatment, observed in approximately 1 in 200 new users within 45 days. There seems to be a marked gradient of risk for acute kidney injury across agents, specifically for indomethacin, ibuprofen, and rofecoxib.
Background Controversy exists about any differences in longer-term safety across different intravenous iron formulations routinely used in hemodialysis (HD) patients. We exploited a natural ...experiment to compare outcomes of patients initiating HD therapy in facilities that predominantly (in ≥90% of their patients) used iron sucrose versus sodium ferric gluconate complex. Study Design Retrospective cohort study of incident HD patients. Setting & Participants Using the US Renal Data System, we hard-matched on geographic region and center characteristics HD facilities predominantly using ferric gluconate with similar ones using iron sucrose. Subsequently, incident HD patients were assigned to their facility iron formulation exposure. Intervention Facility-level use of iron sucrose versus ferric gluconate. Outcomes Patients were followed up for mortality from any, cardiovascular, or infectious causes. Medicare-insured patients were followed up for infectious and cardiovascular (stroke or myocardial infarction) hospitalizations and for composite outcomes with the corresponding cause-specific deaths. Measurements HRs. Results We matched 2,015 iron sucrose facilities with 2,015 ferric gluconate facilities, in which 51,603 patients (iron sucrose, 24,911; ferric gluconate, 26,692) subsequently initiated HD therapy. All recorded patient characteristics were balanced between groups. Over 49,989 person-years, 10,381 deaths (3,908 cardiovascular and 1,209 infectious) occurred. Adjusted all-cause (HR, 0.98; 95% CI, 0.93-1.03), cardiovascular (HR, 0.96; 95% CI, 0.89-1.03), and infectious mortality (HR, 0.98; 95% CI, 0.86-1.13) did not differ between iron sucrose and ferric gluconate facilities. Among Medicare beneficiaries, no differences between ferric gluconate and iron sucrose facilities were observed in fatal or nonfatal cardiovascular events (HR, 1.01; 95% CI, 0.93-1.09). The composite infectious end point occurred less frequently in iron sucrose versus ferric gluconate facilities (HR, 0.92; 95% CI, 0.88-0.96). Limitations Unobserved selection bias from nonrandom treatment assignment. Conclusions Patients initiating HD therapy in facilities almost exclusively using iron sucrose versus ferric gluconate had similar longer-term outcomes. However, there was a small decrease in infectious hospitalizations and deaths in patients dialyzing in facilities predominantly using iron sucrose. This difference may be due to residual confounding, random chance, or a causal effect.
Background Adequately powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking. Study Design ...Observational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis therapy in facilities (almost) exclusively using DPO versus EPO. Setting & Participants Nonchain US hemodialysis facilities; each facility switching from EPO to DPO (2003-2010) was matched for location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis therapy in these facilities were assigned their facility-level exposure. Intervention DPO versus EPO. Outcomes All-cause mortality, cardiovascular mortality; composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke. Measurements Unadjusted and adjusted HRs from Cox proportional hazards regression models. Results Of 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9,465 47.5%; EPO: 10,467 52.5%) incident hemodialysis patients were followed up for 21,918 person-years during which 5,550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was 1.06 (95% CI, 1.00-1.13) and was materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99-1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94-1.16). Nonfatal outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542 (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363 person-years, 248 and 372 events were recorded, respectively, for strokes and MIs. We found no differences in adjusted stroke or MI rates or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96-1.25). Limitations Nonrandom treatment assignment, potential residual confounding. Conclusions In incident hemodialysis patients, mortality and cardiovascular event rates did not differ between patients treated at facilities predominantly using DPO versus EPO.
Background Kidney disease disproportionately affects minority populations, including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular ...(CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women’s Health Initiative. Study Design Prospective cohort study. Setting & Participants Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n = 8,921), African American (n = 7,436), or Hispanic (n = 3,054) were used to calculate estimated glomerular filtration rates (eGFRs). Predictors Categories of eGFR (exposure); race/ethnicity (effect modifier). Outcomes The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death. Measurements We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity. Results During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race ( P = 0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship, with lower eGFR being associated with higher CV risk, and higher eGFR, with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFRs and very few events occurring in these categories. Limitations Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics. Conclusions In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women.
Background Persons with end-stage renal disease (ESRD) on hemodialysis carry an exceptionally high burden of cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEIs) are recommended ...for patients on dialysis, but there are few data regarding their effectiveness in ESRD. Methods We conducted a secondary analysis of results of the HEMO study, a randomized trial of dialysis dose and membrane flux in patients on maintenance hemodialysis. We focused on the nonrandomized exposure of ACEI use, using proportional hazards regression and a propensity score analysis. The primary outcome was all-cause mortality. Secondary outcomes examined in the present analysis were cardiovascular hospitalization, heart failure hospitalization, and the composite outcomes of death or cardiovascular hospitalization and death or heart failure hospitalization. Results In multivariable-adjusted analyses, there were no significant associations among ACEI use and mortality (hazard ratio 0.97, 95% CI 0.82-1.14), cardiovascular hospitalization, and either composite outcome. Angiotensin-converting enzyme inhibitor use was associated with a higher risk of heart failure hospitalization (hazard ratio 1.41, 95% CI 1.11-1.80). In the propensity score–matched cohort, ACEI use was not significantly associated with any outcomes, including heart failure hospitalization. Conclusions In a well-characterized cohort of patients on maintenance hemodialysis, ACEI use was not significantly associated with mortality or cardiovascular morbidity. The higher risk of heart failure hospitalization associated with ACEI use may not only reflect residual confounding but also highlights gaps in evidence when applying treatments proven effective in the general population to patients with ESRD. Our results underscore the need for definitive trials in ESRD to inform the treatment of cardiovascular disease.
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