Micah L. Thorp

Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts

We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m² lower eGFR below a threshold of 45 ml/min per 1.73 m² was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.

Effect of ergocalciferol supplementation on serum parathyroid hormone and serum 25-hydroxyvitamin D in chronic kidney disease.

Aim:  To assess the impact of the administration of ergocalciferol on serum parathyroid hormone levels at different stages of chronic kidney disease (CKD).

Contemporary Prevalence and Correlates of Incident Heart Failure with Preserved Ejection Fraction

BACKGROUND We assessed the prevalence of preserved left ventricular ejection fraction in patients with incident heart failure and differences in the demographic and clinical characteristics that may differentiate patients presenting with heart failure with preserved versus reduced left ventricular ejection fraction. METHODS We identified all patients with newly diagnosed heart failure between 2005 and 2008 from 4 sites in the Cardiovascular Research Network on the basis of hospital discharge and ambulatory visit diagnoses, and assigned a category of preserved, borderline, or reduced left ventricular ejection fraction using data from electronic databases and chart review. RESULTS We identified 11,994 patients with incident heart failure; of these, 6210 (51.8%) had preserved left ventricular ejection fraction, 1870 (15.6%) had borderline systolic dysfunction, and 3914 (32.6%) had reduced left ventricular ejection fraction. For those with heart failure with preserved left ventricular ejection fraction, the mean age was 74.7 years and 57.1% were women; for those with borderline systolic dysfunction, the mean age was 71.6 years and 38.4% were women; and for those with reduced left ventricular ejection fraction, the mean age was 69.1 years and 32.6% were women. Compared with white patients, black patients were less likely to have heart failure with preserved systolic function. Those with a history of coronary artery bypass surgery, mitral or aortic valvular disease, atrial fibrillation or flutter, or a diagnosis of hypertension were more likely to have heart failure with preserved systolic function, as were those with a diverse range of noncardiac comorbid conditions, including chronic lung disease, chronic liver disease, a history of a hospitalized bleed, a history of a mechanical fall, a diagnosis of depression, and a diagnosis of dementia. Patients with a history of acute myocardial infarction and a history of ventricular fibrillation or ventricular tachycardia were less likely to have heart failure with preserved left ventricular ejection fraction. Patients with higher systolic blood pressures at baseline and lower low-density lipoprotein levels were more likely to have heart failure with preserved left ventricular ejection fraction, as were those with lower hemoglobin levels and the lowest glomerular filtration rates. CONCLUSIONS Heart failure with preserved left ventricular ejection fraction is the most common form of the heart failure syndrome among patients newly presenting with this condition, and women and older adults are especially affected. Evidence-based treatment strategies apply to less than one third of patients with newly diagnosed heart failure.

Chronic Kidney Disease and Outcomes in Heart Failure With Preserved Versus Reduced Ejection Fraction The Cardiovascular Research Network PRESERVE Study

Background— There is scant evidence on the effect that chronic kidney disease (CKD) confers on clinically meaningful outcomes among patients with heart failure with preserved left ventricular ejection fraction (HF-PEF). Methods and Results— We identified a community-based cohort of patients with HF. Electronic medical record data were used to divide into HF-PEF and reduced left ventricular EF on the basis of quantitative and qualitative estimates. Level of CKD was assessed by estimated glomerular filtration rate (eGFR) and by dipstick proteinuria. We followed patients for a median of 22.1 months for outcomes of death and hospitalization (HF-specific and all-cause). Multivariable Cox regression estimated the adjusted relative-risk of outcomes by level of CKD, separately for HF-PEF and HF with reduced left ventricular EF. We identified 14 579 patients with HF-PEF and 9762 with HF with reduced left ventricular EF. When compared with patients with eGFR between 60 and 89 mL/min per 1.73 m2, lower eGFR was associated with an independent graded increased risk of death and hospitalization. For example, among patients with HF-PEF, the risk of death was nearly double for eGFR 15 to 29 mL/min per 1.73 m2 and 7× higher for eGFR<15 mL/min per 1.73 m2, with similar findings in those with HF with reduced left ventricular EF. Conclusions— CKD is common and an important independent predictor of death and hospitalization in adults with HF across the spectrum of left ventricular systolic function. Our study highlights the need to develop new and effective interventions for the growing number of patients with HF complicated by CKD.

Epidemiology and healthcare costs of incident Clostridium difficile infections identified in the outpatient healthcare setting.

OBJECTIVE To describe the epidemiology and healthcare costs of Clostridium difficile infection (CDI) identified in the outpatient setting. DESIGN Population-based, retrospective cohort study. PATIENTS Kaiser Permanente Colorado and Kaiser Permanente Northwest members between June 1, 2005, and September 30, 2008. METHODS We identified persons with incident CDI and classified CDI by whether it was identified in the outpatient or inpatient healthcare setting. We collected information about baseline variables and follow-up healthcare utilization, costs, and outcomes among patients with CDI. We compared characteristics of patients with CDI identified in the outpatient versus inpatient setting. RESULTS We identified 3,067 incident CDIs; 56% were identified in the outpatient setting. Few strong, independent predictors of diagnostic setting were identified, although a previous stay in a nonacute healthcare institution (odds ratio [OR], 1.45 [95% confidence interval (CI), 1.13-1.86]) was statistically associated with outpatient-identified CDI, as was age from 50 to 59 years (OR, 1.64 [95% CI, 1.18-2.29]), 60 to 69 years (OR, 1.37 [95% CI, 1.03-1.82]), and 70 to 79 years (OR, 1.36 [95% CI, 1.06-1.74]), when compared with persons aged 80-89 years. CONCLUSIONS We found that more than one-half of incident CDIs in this population were identified in the outpatient setting. Patients with outpatient-identified CDI were younger with fewer comorbidities, although they frequently had previous exposure to healthcare. These data suggest that practitioners should be aware of CDI and obtain appropriate diagnostic testing on outpatients with CDI symptoms.

Systolic Blood Pressure and Mortality Among Older, Community-Dwelling Adults With CKD

BACKGROUND Chronic kidney disease (CKD) is an increasingly common condition, especially in older adults. CKD manifests differently in older versus younger patients, with a risk of death that far outweighs the risk of CKD progressing to the point that dialysis is required. Current CKD guidelines recommend a blood pressure target <130/80 mm Hg for all patients with CKD; however, it is unknown how lower versus higher baseline blood pressures may affect older adults with CKD. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS Older patients (aged ≥ 75 years) with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2)) in a community-based health maintenance organization. PREDICTOR Baseline systolic blood pressure (SBP) < 130, 130-160 (reference group), and > 160 mm Hg. OUTCOMES Participants were followed up for 5 years to examine rates of mortality (primary outcome) and cardiovascular disease hospitalizations (secondary outcome). RESULTS At baseline, 3,099 participants (38.5%) had SBP < 130 mm Hg, 3,772 (46.9%) had SBP of 131-160 mm Hg, and 1,171 (14.6%) had SBP >160 mm Hg. A total of 3,734 (46.4%) died and 2,881 (35.8%) were hospitalized. Adjusted HRs for mortality in the groups with SBP < 130 and > 160 mm Hg were 1.22 (95% CI, 1.11-1.34) and 1.06 (95% CI, 0.93-1.22), respectively. Adjusted HRs for cardiovascular hospitalization in these groups were 1.10 (95% CI, 0.99-1.23) and 1.26 (95% CI, 1.09-1.45), respectively. LIMITATIONS Although causality should not be inferred from this retrospective analysis, results from this study can generate hypotheses for future randomized controlled trials to investigate the relationship between blood pressure and outcomes in older patients with CKD. CONCLUSIONS Our study suggests that lower baseline SBP (≤ 130 mm Hg) may predict poorer outcomes in terms of both mortality and cardiovascular hospitalizations in older adults with CKD. Conversely, higher baseline SBP (> 160 mm Hg) may predict increased risk of cardiovascular hospitalizations, but does not predict mortality. Clinical trials are required to test this hypothesis.

Systolic BP and Mortality in Older Adults with CKD

BACKGROUND AND OBJECTIVES Optimal BP targets for older adults with CKD are unclear. This study sought to determine whether a nonlinear relationship between BP and mortality-as described for the broader CKD population and for older adults in the general population-is present for older adults with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A cohort of 21,015 adults age 65-105 years with a moderate or severe reduction in eGFR (<60 ml/min per 1.73 m(2)) were identified within the Kaiser Permanente Northwest Health Maintenance Organization population. The relationship between baseline systolic BP (SBP; ≤120, 121-130, 131-140, 141-150, >150 mmHg; referent, 131-140 mmHg) and all-cause mortality across age groups (65-70, 71-80, and >80 years) was examined; patients were followed for up to 11 years after cohort entry. RESULTS The median times at risk were 3.15 years, 3.53 years, and 2.76 years for adults age 65-70, 71-80, and >80 years, respectively. Mortality during follow-up was 19.6% for those age 65-70 years, 33.4% for those age 71-80 years, and 55.7% for those age >80 years. The relationship between SBP and mortality varied as a function of age. The risk of death was highest for patients with the lowest SBP in all age groups. Only among adults age 65-70 years was an SBP>140 mmHg associated with a higher risk of death compared with the referent category. Patterns of age modification of the relationship between SBP and mortality were consistent in all sensitivity analyses. CONCLUSIONS In a cohort of older adults, the relationship between SBP and mortality varied systematically with age. A relationship between higher SBP and mortality was present only for younger members of this cohort and not for those older than 70. These results raise the question of whether the relative benefits and harms of lowering BP to recommended targets for older adults with CKD may vary as a function of age.

Predicting costs of care in heart failure patients

BackgroundIdentifying heart failure patients most likely to suffer poor outcomes is an essential part of delivering interventions to those most likely to benefit. We sought a comprehensive account of heart failure events and their cumulative economic burden by examining patient characteristics that predict increased cost or poor outcomes.MethodsWe collected electronic medical data from members of a large HMO who had a heart failure diagnosis and an echocardiogram from 1999–2004, and followed them for one year. We examined the role of demographics, clinical and laboratory findings, comorbid disease and whether the heart failure was incident, as well as mortality. We used regression methods appropriate for censored cost data.ResultsOf the 4,696 patients, 8% were incident. Several diseases were associated with significantly higher and economically relevant cost changes, including atrial fibrillation (15% higher), coronary artery disease (14% higher), chronic lung disease (29% higher), depression (36% higher), diabetes (38% higher) and hyperlipidemia (21% higher). Some factors were associated with costs in a counterintuitive fashion (i.e. lower costs in the presence of the factor) including age, ejection fraction and anemia. But anemia and ejection fraction were also associated with a higher death rate.ConclusionsClose control of factors that are independently associated with higher cost or poor outcomes may be important for disease management. Analysis of costs in a disease like heart failure that has a high death rate underscores the need for economic methods to consider how mortality should best be considered in costing studies.

Risk Factors for Adverse Outcomes by Left Ventricular Ejection Fraction in a Contemporary Heart Failure Population

Background—Although heart failure (HF) is a syndrome with important differences in response to therapy by left ventricular ejection fraction (LVEF), existing risk stratification models typically group all HF patients together. The relative importance of common predictor variables for important clinical outcomes across strata of LVEF is relatively unknown. Methods and Results—We identified all members with HF between 2005 and 2008 from 4 integrated healthcare systems in the Cardiovascular Research Network. LVEF was categorized as preserved (LVEF ≥50% or normal), borderline (41%–49% or mildly reduced), and reduced (⩽40% or moderately to severely reduced). We used Cox regression models to identify independent predictors of death and hospitalization by LVEF category. Among 30 094 ambulatory adults with HF, mean age was 74 years and 46% were women. LVEF was preserved in 49.5%, borderline in 16.2%, and reduced in 34.3% of patients. During a median follow-up of 1.8 years (interquartile range, 0.8–3.1), 8060 (26.8%) patients died, 8108 (26.9%) were hospitalized for HF, and 20 272 (67.4%) were hospitalized for any reason. In multivariable models, nearly all tested covariates performed similarly across LVEF strata for the outcome of death from any cause, as well as for HF-related and all-cause hospitalizations. Conclusions—We found that in a large, diverse contemporary HF population, risk assessment was strikingly similar across all LVEF categories. These data suggest that, although many HF therapies are uniquely applied to patients with reduced LVEF, individual prognostic factor performance does not seem to be significantly related to level of left ventricular systolic function.

Predicting the risk of end-stage renal disease in the population-based setting: a retrospective case-control study

BackgroundPrevious studies of predictors of end-stage renal disease (ESRD) have limitations: (1) some focused on patients with clinically recognized chronic kidney disease (CKD); (2) others identified population-based patients who developed ESRD, but lacked earlier baseline clinical measures to predict ESRD. Our study was designed to address these limitations and to identify the strength and precision of characteristics that might predict ESRD pragmatically for decision-makers--as measured by the onset of renal replacement therapy (RRT).MethodsWe conducted a population-based, retrospective case-control study of patients who developed ESRD and started RRT. We conducted the study in a health maintenance organization, Kaiser Permanente Northwest (KPNW). The case-control study was nested within the adult population of KPNW members who were enrolled during 1999, the baseline period. Cases and their matched controls were identified from January 2000 through December 2004. We evaluated baseline clinical characteristics measured during routine care by calculating the adjusted odds ratios and their 95% confidence intervals after controlling for matching characteristics: age, sex, and year.ResultsThe rate of RRT in the cohort from which we sampled was 58 per 100,000 person-years (95% CI, 53 to 64). After excluding patients with missing data, we analyzed 350 cases and 2,114 controls. We identified the following characteristics that predicted ESRD with odds ratios ≥ 2.0: eGFR<60 mL/min/1.73 m2 (OR = 20.5; 95% CI, 11.2 to 37.3), positive test for proteinuria (OR = 5.0; 95% CI, 3.5 to 7.1), hypertension (OR = 4.5; 95% CI, 2.5 to 8.0), gout/positive test for uric acid (OR = 2.5; 95% CI, 1.8 to 3.5), peripheral vascular disease (OR = 2.2; 95% CI, 1.4 to 3.6), congestive heart failure (OR = 2.1; 95% CI, 1.4 to 3.3), and diabetes (OR = 2.1; 95% CI, 1.5 to 2.9).ConclusionsThe clinical characteristics needed to predict ESRD--for example, to develop a population-based, prognostic risk score--were often documented during routine care years before patients developed ESRD and required RRT.