Acute kidney injury (AKI) following cardiac surgery is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether pre-operative brain natriuretic peptide (BNP) levels predict postoperative AKI among patients undergoing cardiac surgery.
Methods and Results
The TRIBE-AKI Consortium enrolled 1,139 adults undergoing cardiac surgery at six hospitals from 2007–2009, who were selected for high AKI risk. Pre-operative BNP was categorized into quintiles. AKI was common using Acute Kidney Injury Network definitions; at least mild AKI was a ≥0.3mg/dL or 50% rise in creatinine, n=407 (36%), and severe AKI was either a doubling of creatinine or the requirement of acute renal replacement therapy, n=58 (5.1%). In analyses adjusted for pre-operative characteristics, pre-operative BNP was a strong and independent predictor of mild and severe AKI. Compared with the lowest BNP quintile the highest quintile had significantly higher risk of at least mild AKI (risk ratio [RR] 1.87; 1.40–2.49) and severe AKI (RR 3.17; 1.06–9.48). After adjustment for clinical predictors, addition of BNP improved the area under the curve to predict at least mild AKI (0.67 to 0.69, p=0.02) and severe AKI (0.73 to 0.75, p=0.11). Compared with clinical parameters alone, BNP modestly improved risk prediction of AKI cases into lower and higher risk (continuous net reclassification index at least mild AKI 0.183; 0.061, 0.314; severe AKI 0.231; 0.067, 0.506).
Pre-operative BNP level is associated with post-operative AKI in high-risk patients undergoing cardiac surgery. If confirmed in other types of patients and surgeries, pre-operative BNP may be a valuable component of future efforts to improve pre-operative risk stratification and discrimination among surgical candidates.
brain natriuretic peptide; cardiac surgery; acute renal failure; creatinine
Moderate kidney disease may predispose to infection. We sought to determine whether decreased kidney function, as estimated by serum cystatin C, was associated with the risk of infection-related hospitalization in older individuals.
Setting & Participants
5,142 Cardiovascular Health Study participants with measured serum creatinine and cystatin C and without eGFR <15 ml/min/1.73 m2 at enrollment.
The primary exposure of interest was estimated glomerular filtration rate using serum cystatin C (eGFRSCysC).
Infection-related hospitalizations during a median follow-up of 11.5 years.
In adjusted analyses, eGFRSCysC categories of 60–89, 45–59, and 15–44 ml/min/1.73 m2 were associated with 16%, 37%, and 64% greater risk of all-cause infection-related hospitalization, respectively, compared with an eGFRSCysC ≥90 ml/min/1.73 m2. When cause specific infection was examined, an eGFRSCysC of 15–44 ml/min/1.73 m2 was associated with an 80% greater risk of pulmonary and 160% greater risk of genitourinary infection compared with an eGFRSCysC ≥90 ml/min/1.73 m2.
No measures of urinary protein, study limited to principal discharge diagnosis.
Lower kidney function, estimated using cystatin C, was associated with a linear and graded risk of infection-related hospitalization. These findings highlight that even moderate degrees of reduced kidney function are associated with clinically significant higher risks of serious infection in older individuals.
renal disease; chronic kidney disease; infection; clinical epidemiology
Pentraxin-3 is an inflammatory marker thought to be more specific to vascular inflammation than C-reactive protein (CRP). Whether pentraxin-3 is independently associated with adverse events among persons with stable coronary heart disease (CHD), independently of CRP, and whether kidney dysfunction influences these associations, is not known.
We evaluated the associations of baseline pentraxin-3 levels with all-cause mortality, cardiovascular events (myocardial infarction, stroke or CHD death), and incident heart failure during 37 months among ambulatory persons with stable CHD participating in the Heart and Soul Study. Cox proportional hazards models were adjusted for age, sex, race, hypertension, diabetes, smoking, and CRP.
Among 986 persons with stable CHD, each one unit increase in log pentraxin-3 at baseline was associated with an 80% increased risk of all-cause mortality (HR 1.8, 95% CI 1.5–2.1), a 50% increased risk of cardiovascular events (HR 1.5, 95% CI, 1.2–1.9), and an 80% greater risk of incident heart failure (HR 1.8, 95% CI, 1.3–2.5). Further adjustment for estimated glomerular filtration rate (eGFR) attenuated these associations to 1.6 (1.3–1.9) for mortality, 1.3 (1.0–1.6) for cardiovascular events and 1.5 (1.1–2.1) for incident heart failure. Stratification by eGFR above or below 60 ml/min/1.73m2 did not affect these associations (p interaction >0.3 for all outcomes).
Among persons with stable CHD, higher pentraxin-3 concentrations were associated with increased risk for all-cause mortality, cardiovascular events and incident heart failure independently of systemic inflammation. Adjustment for eGFR modestly attenuated these associations, suggesting that future studies of pentraxin-3 should adjust for kidney function.
cardiovascular diseases; heart failure; coronary disease; kidney
Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2,312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations: 2 events per 10,000 for 25-OHD ≥ 20 ng/ml and 4 events per 10,000 for 25-OHD < 20 ng/ml. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations: 2 events per 10,000 for PTH ≤ 65 pg/ml and 4 events per 10,000 for PTH > 65 pg/ml. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a more than 2-fold risk of SCD after adjustment (hazard ratio 2.19, 95% confidence interval 1.17, 4.10, p=0.017) compared to participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease.
Sudden cardiac death; Vitamin D; Parathyroid hormone; Elderly; Risk Factors
Changes in body fat distribution and abnormal glucose metabolism are common in HIV-infected patients. We hypothesized that HIV-infected participants would have a higher prevalence of impaired glucose tolerance (IGT) compared with control subjects.
RESEARCH DESIGN AND METHODS
A total of 491 HIV-infected and 187 control participants from the second examination of the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) underwent glucose tolerance testing (GTT). Multivariable regression was used to identify factors associated with GTT parameters.
The prevalence of impaired fasting glucose (IFG) (>110 mg/dL) was similar in HIV-infected and control participants (21 vs. 25%, P = 0.23). In those without IFG, the prevalence of IGT was slightly higher in HIV-infected participants compared with control subjects (13.1 vs. 8.2%, P = 0.14) and in HIV+ participants with lipoatrophy versus without (18.1 vs. 11.5%, P = 0.084). Diabetes detected by GTT was rare (HIV subjects 1.3% and control subjects 0%, P = 0.65). Mean 2-h glucose levels were 7.6 mg/dL higher in the HIV-infected participants (P = 0.012). Increased upper trunk subcutaneous adipose tissue (SAT) and decreased leg SAT were associated with 2-h glucose and IGT in both HIV-infected and control participants. Adjusting for adipose tissue reduced the estimated effects of HIV. Exercise, alcohol use, and current tenofovir use were associated with lower 2-h glucose levels in HIV-infected participants.
In HIV infection, increased upper trunk SAT and decreased leg SAT are associated with higher 2-h glucose. These body fat characteristics may identify HIV-infected patients with normal fasting glucose but nonetheless at increased risk for diabetes.
M[ND1]enopause is associated with urine phosphorus retention, which is mitigated by estrogen therapy. Fibroblast growth factor 23 (FGF-23) is a hormone originating from bone that regulates urine phosphorus excretion. Whether sex or estrogen therapy is associated with different FGF-23 levels is unknown.
Study Design & Setting
Cross-sectional study among ambulatory individuals with prevalent cardiovascular disease.
Sex, and among women, use or non-use of estrogen.
Serum phosphorus, tubular maximum reabsorption of phosphorus indexed to GFR (TMP/GFR), and plasma FGF-23 concentrations.
Among 987 participants, the mean age was 67 ± 11 years, 182 (18%) were female; 46 (25%) were taking estrogen. The mean eGFR was 71 ± 23 (SD) ml/min/1.73m2. Compared to women who were not taking estrogen, both women on estrogen therapy and men had significantly lower serum phosphorus concentrations, lower TMP/GFR (indicating higher urine phosphorus excretion), and lower FGF-23 concentrations with adjustment for age, demographics, and kidney function (P < 0.001 for each). Mean FGF-23 in RU/ml were 68.7 (95% CI, 59.7–79.0) in non estrogen using women, 43.8 (95% CI, 41.2–46.5) in men, and 45.1 (95% CI, 35.2–57.4) in women using estrogen in adjusted analysis (P< 0.001).
The majority of participants were men. Estrogen therapy was not randomly assigned.
Older women who are not taking estrogen have higher FGF-23 levels than either men or women taking estrogen. In the context of prior literature, these data suggest that post-menopausal phosphorus retention may stimulate higher FGF-23 concentrations after menopause.
Menopause; fibroblast growth factor-23; phosphorus; estradiol; sex hormones
Vitamin D deficiency and parathyroid hormone (PTH) excess are common among older adults and may adversely impact cardiovascular health. We evaluated associations of 25-hydroxyvitamin D (25-OHD) and PTH concentrations, separately, and in combination, with incident cardiovascular events and mortality during 14 years of follow-up in the Cardiovascular Health Study.
Methods and results
We studied 2,312 participants who were free of cardiovascular disease at baseline. We measured 25-OHD and intact PTH from previously frozen serum using mass spectrometry and a two-site immunoassay. Outcomes were adjudicated cases of myocardial infarction, heart failure, cardiovascular death, and all cause mortality. There were 384 participants (17%) who had serum 25-OHD concentrations <15 ng/ml and 570 (25%) who had serum PTH concentrations ≥ 65 pg/ml. After adjustment, each 10-ng/ml lower 25-OHD concentration was associated with a 9% greater (95% CI 2% to 17% greater) relative hazard of mortality and a 25% greater (95% CI 8% to 44% greater) relative hazard of myocardial infarction. Serum 25-OHD concentrations <15 ng/ml, were associated with a 29% greater (95% CI 5% to 55% greater) risk of mortality. Serum PTH concentrations ≥ 65 pg/ml were associated with a 30% greater risk of heart failure (95% CI 6% to 61% greater), but not other outcomes. There was no evidence of an interaction between serum 25-OHD and PTH concentrations and cardiovascular events.
Among older adults, 25-OHD deficiency is associated with myocardial infarction and mortality; PTH excess is associated with heart failure. Vitamin D and PTH might influence cardiovascular risk through divergent pathways.
Vitamin D; parathyroid hormone; myocardial infarction; cardiovascular death; heart failure; mortality; mineral metabolism
The evidence for the effectiveness of antihypertensive medication use for slowing decline in kidney function in older persons is sparse. We addressed this research question by the application of novel methods in a marginal structural model.
Change in kidney function was measured by two or more measures of cystatin C in 1,576 hypertensive participants in the Cardiovascular Health Study over 7 years of follow-up (1989–1997 in four U.S. communities). The exposure of interest was antihypertensive medication use. We used a novel estimator in a marginal structural model to account for bias due to confounding and informative censoring.
The mean annual decline in eGFR was 2.41 ± 4.91 mL/min/1.73 m2. In unadjusted analysis, antihypertensive medication use was not associated with annual change in kidney function. Traditional multivariable regression did not substantially change these estimates. Based on a marginal structural analysis, persons on antihypertensives had slower declines in kidney function; participants had an estimated 0.88 (0.13, 1.63) ml/min/1.73 m2 per year slower decline in eGFR compared with persons on no treatment. In a model that also accounted for bias due to informative censoring, the estimate for the treatment effect was 2.23 (−0.13, 4.59) ml/min/1.73 m2 per year slower decline in eGFR.
In summary, estimates from a marginal structural model suggested that antihypertensive therapy was associated with preserved kidney function in hypertensive elderly adults. Confirmatory studies may provide power to determine the strength and validity of the findings.
aged; kidney function; hypertension; marginal structural model
Acute kidney injury (AKI) following cardiac surgery is associated with poor outcomes, but is challenging to predict from information available prior to surgery.
Prospective cohort study
Setting & Participants
The TRIBE-AKI Consortium enrolled 1,147 adults undergoing cardiac surgery at six hospitals from 2007–2009; participants were selected for high AKI risk.
Pre-surgical cystatin C, creatinine, and creatinine-based estimated glomerular filtration rate (eGFR) were categorized into quintiles and grouped as ‘Best’ (quintiles 1–2), ‘Intermediate’ (quintiles 3–4), and ‘Worst’ (quintile 5) kidney function.
The primary outcome was AKI Network (Acute Kidney Injury Network) Stage 1 or higher; ≥0.3mg/dL or 50% rise in creatinine.
Analyses were adjusted for characteristics used clinically for pre-surgical risk stratification.
The average age and kidney function were: 71±10 years (mean ± standard deviation), serum creatinine 1.1±0.3 mg/dL, eGFR-Cr, 74±9 mL/min/1.73m2, and cystatin C, 0.9 ±0.3 mg/L. A total of 407 (36%) participants developed AKI during hospitalization. Adjusted odds ratios for intermediate and worst kidney function by cystatin C were 1.9 (95% CI, 1.4–2.7) and 4.8 (95% CI, 2.9–7.7) compared with 1.2 (95% CI, 0.9–1.7) and 1.8 (95% CI, 1.2–2.6) for creatinine and 1.0 (95% CI, 0.7–1.4) and 1.7 (95% CI, 1.1–2.3) for eGFR-Cr categories, respectively. After adjustment for clinical predictors, the C statistic to predict AKI was 0.70 without kidney markers, 0.69 with creatinine, and 0.72 with cystatin C. Cystatin C also substantially improved AKI risk classification compared to creatinine, based on a net reclassification index of 0.21 (p<0.001).
The ability of these kidney biomarkers to predict risk for dialysis-requiring AKI or death could not be reliably assessed in our study due to a small number of patients with either outcome.
Pre-surgical cystatin C is better than creatinine or creatinine-based eGFR at forecasting the risk of AKI after cardiac surgery.
acute renal failure; creatinine; prognosis
Background. Chronic kidney disease (CKD) is associated with insulin resistance (IR). Prior studies have found that in individuals with CKD, leptin is associated with fat mass but resistin is not and the associations with adiponectin are conflicting. This suggests that the mechanism and factors associated with IR in CKD may differ.
Methods. Of the 2418 individuals without reported diabetes at baseline, participating in the Health, Aging and Body Composition study, a study in older individuals aged 70–79 years, 15.6% had CKD defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 based on cystatin C. IR was defined as the upper quartile of the homeostasis model assessment. The association of visceral and subcutaneous abdominal fat, percent body fat, muscle fat, lipids, inflammatory markers and adiponectin were tested with logistic regression. Interactions were checked to assess whether the factors associated with IR were different in those with and without CKD.
Results. Individuals with IR had a lower eGFR (80.7 ± 20.9 versus 75.6 ± 19.6, P < 0.001). After multivariable adjustment, eGFR (odds ratio per 10 mL/min/1.73m2 0.92, 95% confidence interval 0.87–0.98) and CKD (1.41, 1.04–1.92) remained independently associated with IR. In individuals with and without CKD, the significant predictors of IR were male sex, black race, higher visceral fat, abdominal subcutaneous fat and triglycerides. In individuals without CKD, IR was associated with lower high-density lipoprotein and current nonsmoking status in multivariate analysis. In contrast, among individuals with CKD, interleukin-6 (IL-6) was independently associated with IR. There was a significant interaction of eGFR with race and IL-6 with a trend for adionectin but no significant interactions with CKD (P > 0.1). In the fully adjusted model, there was a trend for an interaction with adiponectin for eGFR (P = 0.08) and significant for CKD (P = 0.04 ), where adiponectin was associated with IR in those without CKD but not in those with CKD.
Conclusions. In mainly Stage 3 CKD, kidney function is associated with IR; except for adiponectin, the correlates of IR are similar in those with and without CKD.
chronic kidney disease; cystatin C; insulin resistance; subcutaneous fat
Recent reports have suggested a close relationship between education and health, including mortality, in the United States.
Setting and Participants
We studied 61,457 participants enrolled in a national health screening initiative, the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP).
Self-reported educational attainment
Chronic diseases (hypertension, diabetes, cardiovascular disease, reduced kidney function, and albuminuria) and mortality
We evaluated the cross-sectional associations between self-reported educational attainment with the chronic diseases listed above using logistic regression models adjusted for demographics, access to care, behaviors, and co-morbidities. The association of educational attainment with survival was determined by multivariable Cox proportional hazards regression.
Higher educational attainment was associated with lower prevalence of each of the chronic conditions listed above. In multivariable models, compared with persons not completing high school, college graduates had a lower risk of each chronic condition, ranging from 11% lower odds of reduced kidney function to 37% lower odds of cardiovascular disease. Over a mean follow-up time of 3.9 years (median, 3.7 years), 2,384 (4%) deaths occurred. In the fully adjusted Cox model, those who had completed college had a 24% lower mortality, compared to participants who had completed at least some high school.
A lack of income data does not allow us to disentangle the independent effects of education from income.
In this diverse, contemporary cohort, higher educational attainment was independently associated with lower prevalence of chronic diseases and short-term mortality among all age and race/ethnicity groups.
education; mortality; chronic kidney disease
Background. Acculturation affects health, but it has never been studied with kidney disease.
Methods. We studied the association of language spoken at home, generation and birth place with kidney function among Hispanics and Chinese in the Multi-Ethnic Study of Atherosclerosis (n = 2999). Kidney function was determined by cystatin C (eGFRcys) and albumin/creatinine ratio (ACR). We evaluated mediators in models: Model 1 = age, sex, income, education; Model 2 = Model 1 + behaviors; and Model 3 = Model 1 + comorbidities.
Results. Among Hispanics, speaking mixed Spanish/English was significantly associated with lower eGFRcys (− 2.83 mL/min/1.73 m2, − 5.69–0.04) and higher ACR (RD 40%, 17–68%) compared with speaking Spanish only; this was mildly attenuated by behaviors (− 2.29, − 5.33–0.75; RD 42%, 18–72%) but not comorbidities (− 3.04, − 5.83 to − 0.23); RD 35%, 14–59%). US-born Hispanics had lower eGFRcys compared with foreign-born Hispanics [1.83 mL/min/1.73 m2 lower (0.97–1.31) for Generation 1; 1.37 mL/min/1.73 m2 lower (0.75–1.57) for Generation ≥ 2].
In contrast, Chinese who spoke any English had higher eGFRcys (2.53, 95% CI: − 1.70–6.78), but similar ACR (RD − 5%, 95% CI: − 26–23%) compared with those speaking Chinese only, but associations were not statistically significant.
Conclusion. Higher acculturation was associated with worse kidney function in Hispanics, mediated perhaps by behavioral factors but not comorbidities. Associations may be in the opposite direction among Chinese. Future studies are needed to elucidate these mechanisms.
acculturation; cystatin C; kidney function
To examine the utility of using proteinuria in pre-operative risk stratification for acute kidney injury (AKI). AKI is a common and important complication for patients undergoing cardiac surgery. Proteinuria, which reflects structural damage to the glomeruli or renal tubules, may aid the prediction of AKI.
The ratio of urine albumin to creatinine (UACR) and dipstick proteinuria concentration were prospectively measured in 1159 patients undergoing cardiac surgery. The cohort was organized into four clinical risk categories based on the pre-operative UACR: UACR ≤ 10 mg/g (≤ 1.1 mg/mmol), 11–29 mg/g (1.2–3.3 mg/mmol), 30–299 mg/g (3.4–33.8 mg/mmol), and ≥ 300 mg/g (≥ 33.9 mg/mmol). The primary outcome was post-operative AKI, defined by the AKIN stage I criterion (serum creatinine rise by ≥50% or ≥ 0.3 mg/dL (26.5 μmol/L)).
An increase in the incidence of AKI was noted across the UACR categories. Adding UACR to the clinical model to predict AKI improved the AUC from 0.64 to 0.67 (p < 0.001) and the continuous net reclassification improvement (NRI) was 30% (p < 0.001). UACR was also independently associated with risk of in-hospital dialysis, and ICU and hospital length of stay. Surgery status and pre-operative GFR were effect modifiers; the association was stronger amongst those undergoing elective surgery and those with eGFR ≥ 45 mL/min per 1.73 m2.
Pre-operative proteinuria provides graded stratification risk for AKI and is an independent predictor of other outcomes in patients undergoing cardiac surgery.
In this multicenter, prospective study of 288 children (half under 2 years of age) undergoing cardiac surgery, we evaluated whether the measurement of pre- and postoperative serum cystatin C (CysC) improves the prediction of acute kidney injury (AKI) over that obtained by serum creatinine (SCr). Higher preoperative SCr-based estimated glomerular filtration rates predicted higher risk of the postoperative primary outcomes of stage 1 and 2 AKI (adjusted odds ratios (ORs) 1.5 and 1.9, respectively). Preoperative CysC was not associated with AKI. The highest quintile of postoperative (within 6 h) CysC predicted stage 1 and 2 AKI (adjusted ORs of 6 and 17.2, respectively). The highest tertile of percent change in CysC independently predicted AKI, whereas the highest tertile of SCr predicted stage 1 but not stage 2 AKI. Postoperative CysC levels independently predicted longer duration of ventilation and intensive care unit length of stay, whereas the postoperative SCr change only predicted longer intensive care unit stay. Thus, postoperative serum CysC is useful to risk-stratify patients for AKI treatment trials. More research, however, is needed to understand the relation between preoperative renal function and the risk of AKI.
acute renal failure; cardiovascular; creatinine; epidemiology and outcomes; renal function
The effect of mild chronic kidney disease (CKD) on depression, stress, quality of life (QOL), and health status is not well understood. We compared these outcomes in subjects with and without CKD.
We performed a cross-sectional study of 967 outpatients enrolled in the Heart and Soul Study. CKD was defined as a measured creatinine clearance <60 ml/min. Outcome measures included depressive symptoms measured using the Patient Health Questionnaire (PHQ), stress measured using the Perceived Stress Scale (PSS), and QOL and overall health rated as excellent, very good, good, fair, or poor.
The prevalence of depressive symptoms (17 vs. 19%, p = 0.4) or perceived stress (11 vs. 16%, p = 0.09) did not vary significantly by CKD. The prevalence of fair or poor QOL was not significantly different in subjects with CKD, compared with those without CKD (24 vs. 23%, p = 0.65). Age-adjusted analyses revealed a significant association of CKD with QOL (p = 0.003), however, this association no longer reached statistical significance after adjustment for confounders (p = 0.06). Subjects with CKD were more likely to report poor or fair overall health than subjects without CKD (42 vs. 34%, p = 0.03). After multivariate adjustment, CKD remained significantly associated with worse overall health (OR = 1.65, 95% CI 1.21–2.24, p = 0.001), and modestly associated with QOL (OR = 1.31, 95% CI 0.99–1.75, p = 0.06), but had no association with depression (p = 0.48) or stress (p = 0.24).
In this study of persons with coronary artery disease, subjects with CKD had reduced overall health and modestly reduced QOL; however, mental health was similar in those with and without CKD. These findings suggest that self-assessed overall health may decline at earlier stages of renal dysfunction than mental health outcomes or QOL.
Chronic kidney disease; Kidney disease, depression; Kidney disease, stress; Kidney disease, quality of life
Chronic kidney disease (CKD) and anemia are common conditions in the outpatient setting, but their independent and additive effects on physical capacity have not been well characterized. The association of CKD and anemia with self-reported physical function was evaluated and exercise capacity was measured in patients with coronary disease. A cross-sectional study of 954 outpatients enrolled in the Heart and Soul study was performed. CKD was defined as a measured creatinine clearance <60 ml/min, and anemia was defined as a hemoglobin level of <12g/dl. Physical function was self-assessed using the physical limitation subscale of the Seattle Angina Questionnaire (0 to 100), and exercise capacity was defined as metabolic equivalent tasks achieved at peak exercise. In unadjusted analyses, CKD was associated with lower self-reported physical function (67.6 versus 74.9; P < 0.001) and lower exercise capacity (5.5 versus 7.9; P < 0.001). Similarly, anemia was associated with lower self-reported physical function (62.6 versus 74.3; P < 0.001) and exercise capacity (5.7 versus 7.5; P < 0.001). After multivariate adjustment, CKD (69.4 versus 74.2; P = 0.003) and anemia (67.5 versus 73.6; P = 0.009) each remained associated with lower mean self-reported physical function. In addition, patients with CKD (6.3 versus 7.7; P < 0.001) or anemia (6.5 versus 7.4; P = 0.004) had lower adjusted mean exercise capacities. Participants with both CKD and anemia had lower self-reported physical function and exercise capacity than those with either alone. CKD and anemia are independently associated with physical limitation and reduced exercise capacity in outpatients with coronary disease, and these effects are additive. The broad impact of these disease conditions merits further study.
Chronic renal insufficiency (CRI) is a predictor of stroke, cardiovascular, and all-cause mortality, but the mechanisms responsible for these associations are unclear. Whether CRI was associated with severity of coronary artery disease (CAD) as measured by exercise stress echocardiography among outpatients with stable CAD was evaluated. This study is a cross-sectional analysis of the Heart and Soul study, a prospective cohort of patients with known CAD. Renal function was assessed by 24-h urine collection, and CRI was defined as measured creatinine clearance ≤60 ml/min. Exercise stress echocardiography was used to identify inducible ischemia, defined as any wall motion abnormality seen at stress but not at rest. Logistic regression was used to evaluate the association of CRI with exercise-induced ischemia after adjustment for cardiovascular risk factors. Participants with CRI composed 97 (23%) of the 431 participants and were characterized by older age, worse CAD, lower ejection fraction, greater left ventricular mass and higher C-reactive protein values. The prevalence of exercise-induced ischemia was also substantially greater in the participants with CRI (42% versus 23%; odds ratio [OR], 2.3; 95% confidence interval [CI], 1.4 to 3.8; P < 0.001). This association was minimally changed by adjustment for traditional cardiovascular risk factors and coronary disease history (OR, 2.0; 95% CI, 1.3 to 3.3; P < 0.01) and remained strong even after adjustment for C-reactive protein (OR, 2.3; 95% CI, 1.0 to 5.1; P < 0.04). CRI is strongly associated with exercise-induced ischemia in patients with CAD. The greater severity of atherosclerotic disease observed in patients with CRI may in part explain the association of CRI with increased cardiovascular risk among individuals with CAD.
To characterize the inflammatory and coagulopathic response after endovascular thoracoabdominal aortic aneurysm (TAAA) repair and to evaluate the effect of the response on post-operative renal function.
From 7/2005 to 6/2008, 42 patients underwent elective endovascular repair of a TAAA using custom designed multi-branched stent-grafts at a single academic institution. 4 patients were excluded from the analysis. White blood cell count (WBC), platelet count, prothrombin time (PT), and creatinine were measured in all patients. In the last 9 patients, interleukin-6 (IL-6), protein C, Factor V, d-dimers, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) levels were also measured. Change in lab values were expressed as a percentage of baseline values.
The 30-day mortality rate was 5% (2/38). All patients (n=38) had a higher WBC (mean±SD: 139 ± 80%, P<0.0001), lower platelet count (56 ± 15%, P<0.0001), and higher PT (median: 17%, IQR 12 - 22%, P<0.0001) after stent-graft insertion. Twelve of 38 patients (32%) developed postoperative acute renal insufficiency (>50% rise in creatinine). Patients with renal insufficiency had significantly larger changes in WBC (178 ± 100% vs 121 ± 64%, p=0.04) and platelet count (64 ± 17% vs 52 ± 12%, p=0.02) compared to those without renal insufficiency. All patients (n=9) had significant increases in NGAL (182 ± 115%, p=0.008) after stent-graft insertion. 6/9 patients (67%) had increased cystatin C (35 ± 43%, p = 0.04) after stent-graft insertion, with a greater rise in those with postoperative renal insufficiency (87 ± 32% vs 8 ± 13%, p = 0.02). IL-6 levels were markedly increased in all patients (n=9) after repair (9,840 ± 6,160%, p=0.008). Protein C (35 ± 10%, p=0.008) and Factor V levels (28 ± 20%, p=0.008) were uniformly decreased, while d-dimers were elevated after repair in all patients (310 ± 213%, p=0.008).
Leukocytosis and thrombocytopenia were uniform following endovascular TAAA repair, and the severity of the response correlated with post-operative renal dysfunction. Elevation of a sensitive marker of renal injury (NGAL) suggests that renal injury may occur in all patients after stent-graft insertion.
Epidemiological studies typically diagnose heart failure (HF) at the time of hospitalization, and have not evaluated the prevalence of HF symptoms in CKD patients without a prior HF diagnosis.
Methods and Results
We modified the Kansas City Cardiomyopathy Questionnaire (KCCQ) to detect and quantify symptoms characteristic of HF (dyspnea, edema, and fatigue) among 2,883 CKD patients without diagnosed heart failure in the Chronic Renal Insufficiency Cohort (CRIC). The KCCQ is a 23-item instrument that quantifies the impact of dyspnea, fatigue and edema on physical, social, and emotional functions (scored 0–100). The median KCCQ score was 92, and 25% had KCCQ scores < 75. Compared with cystatin C-based eGFR >50ml/min/1.73m2 (reference), eGFR 40–50, 30–40, and <30 were independently associated with lower KCCQ scores (<75); adjusted odds ratios and (95% CI): 1.38 (1.06–1.78), 1.39 (1.09–1.82), and 2.15 (1.54–3.00), respectively. Lower hemoglobin (Hb) levels also had independent associations with KCCQ <75: Hb > 14 g/dL (reference), Hb 13–14 g/dL (1.03; 0.76–1.40), Hb 12–13 g/dL (1.41; 1.04–1.91), Hb 11–12 g/dL (1.56; 1.12–2.16); and Hb<11 g/dL (1.65; 1.15–2.37).
CKD patients without diagnosed HF have a substantial burden of symptoms characteristic of HF, particularly among those with lower eGFR and hemoglobin levels.
hemoglobin; glomerular filtration rate
Background. Despite a higher incidence of end-stage renal disease (stage 5), blacks have been shown to have the same or lower prevalence of chronic kidney disease (CKD stages 3 and 4). Current creatinine-based glomerular filtration rate (GFR)-estimating equations may misclassify young, healthy blacks.
Methods. Among 3501 young adults (mean age 45), we compared the prevalence of CKD in blacks and whites using the Modification of Diet in Renal Disease (MDRD) and the CKD Epidemiology Collaboration (CKD-EPI) equations. In addition, we used measured creatinine excretion rates to determine the actual excretion ratio for CARDIA (race coefficient 12%) and applied this to the CKD-EPI equation. We also studied the prevalence of CKD risk factors among black and white participants near the CKD threshold cut-off (eGFR CKD-EPI 60–80 mL/min/1.73 m2) to estimate the relative likelihood of misclassification in blacks and whites.
Results. Using the MDRD equation, prevalence of CKD stages 4 and 5 was higher for blacks compared with whites (0.6% vs. 0.1%, P-value 0.05). In contrast, prevalence of eGFR <60 mL/min/1.73 m2 was significantly higher for whites (3.6%) compared with blacks (1.9%), due to higher prevalence of stage 3 among whites. Prevalence of CKD was similar for blacks and whites using CKD-EPI equation (1.2%), but was higher among blacks when using the CARDIA-derived race coefficient (1.6% vs.1.2%, P-value = 0.03). Among persons with eGFR by CKD-EPI of 60–80 mL/min/1.73 m2, blacks had higher levels of albuminuria, uric acid, systolic blood pressure and higher diabetes prevalence.
Conclusions. CKD classification among young blacks is very sensitive to the race coefficients. Despite whites having higher rates of CKD stage 3, blacks with eGFRs just above the CKD threshold had higher rates of CKD risk factors. Current equations used to define CKD may systematically miss a high-risk group of blacks at a time in the disease course when interventions are crucial.
chronic kidney disease; glomerular filtration rate; race
Compared with controls, HIV-infected persons have a greater prevalence of kidney disease as assessed by high levels of cystatin C and albuminuria, but not as assessed by creatinine level. However, the clinical importance of elevated cystatin C and albuminuria in the HIV-infected population has not been studied.
We conducted an observational cohort study to determine the association of kidney disease (measured by albuminuria, cystatin C, and serum creatinine) with mortality.
Setting & Participants
922 HIV-infected persons enrolled in the FRAM (Fat Redistribution and Metabolic Change in HIV infection) study.
Serum cystatin C and serum creatinine were used to estimate glomerular filtration rate (eGFR). Albuminuria was defined as a positive urine dipstick (≥1+) or a urine albumin-creatinine ratio > 30 mg/g.
At baseline, reduced kidney function (eGFRSCysC <60 mL/min/1.73m2) or albuminuria was present in 28% of participants. After five years of follow-up, mortality was 48% among those with both eGFRSCysC <60 mL/min/1.73m2 and albuminuria, 23% in those with eGFRSCysC <60 mL/min/1.73m2 alone, 20% in those with albuminuria alone, and 9% in those with neither condition. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, and inflammatory markers, eGFRSCysC <60 mL/min/1.73m2 and albuminuria were associated with nearly a twofold increase in mortality, whereas eGFRSCr <60 mL/min/1.73m2 did not appear to have any substantial association with mortality. Together, eGFRSCysC <60 mL/min/1.73m2 and albuminuria accounted for 17% of the population-level attributable risk for mortality.
Vital status was unknown in 261 participants from the original cohort.
Kidney disease marked by albuminuria or increased cystatin C levels appears to be an important risk factor for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on serum creatinine to estimate kidney function in clinical practice.
kidney disease; mortality; HIV infection
Microalbuminuria is associated with increased risk of cardiovascular disease and mortality. The objective of the study was to evaluate if HIV infection was an independent risk factor for microalbuminuria.
The relationship between HIV infection and microalbuminuria was assessed using subjects enrolled in the study of Fat Redistribution and Metabolic Change in HIV Infection, which consists of HIV-positive and control men and women. Participants with proteinuria (dipstick ≥1+) were excluded.
Microalbuminuria (urinary albumin/creatinine ratio, ACR>30 mg/g) was present in 11% of HIV infected, and 2% of control participants (P<0.001); a fivefold odds after multivariate adjustment (odds ratio, 5.11; 95% confidence interval, 1.97–13.31; P=0.0008). Several cardiovascular risk factors were associated with higher ACR in HIV participants: insulin resistance (HOMA>4; 32%, P<0.0001), systolic blood pressure (21%, P=0.01 for 120–140 versus <120 mmHg, and 43%, P <0.06 for >140 versus <120 mmHg), and family history of hypertension (17%, P=0.03). Higher CD4 cell count was associated with lower albumin/creatinine ratio (−24%, P=0.009 for 200–400 versus <200 cells/ml and −26%, P=0.005 for >400 versus <200 cells/ml).
HIV infection had a strong and independent association with microalbuminuria, the severity of which was predicted by markers of insulin resistance, hypertension, and advanced HIV infection. These associations warrant further investigation, as the increased prevalence of microalbuminuria in HIV infection may be a harbinger of future risk of cardiovascular and kidney diseases.
Microalbuminuria; kidney; urine protein; insulin resistance; lipodystrophy
Although studies have reported a high prevalence of end-stage renal disease in human immunodeficiency virus (HIV)-infected individuals, little is known about moderate impairments in kidney function. Cystatin C measurement may be more sensitive than creatinine for detecting impaired kidney function in persons with HIV.
We evaluated kidney function in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) cohort, a representative sample of 1008 HIV-infected persons and 290 controls from the Coronary Artery Risk Development in Young Adults (CARDIA) study in the United States.
Cystatin C level was elevated in HIV-infected individuals; the mean±SD cystatin C level was 0.92±0.22 mg/L in those infected with HIV and 0.76±0.15 mg/L in controls (P<.001). In contrast, both mean creatinine levels and estimated glomerular filtration rates appeared similar in HIV-infected individuals and controls (0.87±0.21 vs 0.85±0.19 mg/dL [to convert to micromoles per liter, multiply by 88.4] [P=.35] and 110±26 vs 106±23 mL/min/1.73 m2 [P=.06], respectively). Persons with HIV infection were more likely to have a cystatin C level greater than 1.0 mg/L (OR, 9.8; 95% confidence interval, 4.4-22.0 [P<.001]), a threshold demonstrated to be associated with increased risk for death and cardiovascular and kidney disease. Among participants with HIV, potentially modifiable risk factors for kidney disease, hypertension, and low high-density lipoprotein concentration were associated with a higher cystatin C level, as were lower CD4 lymphocyte count and coinfection with hepatitis C virus (all P<.001).
Individuals infected with HIV had substantially worse kidney function when measured by cystatin Clevel compared with HIV-negative controls, whereas mean creatinine levels and estimated glomerular filtration rates were similar. Cystatin C measurement could be a useful clinical tool to identify HIV-infected persons at increased risk for kidney and cardiovascular disease.
Background. Alcohol consumption appears to be protective for cardiovascular disease; however, its relationship with kidney disease is unclear.
Methods. This prospective cohort study included 4343 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged ≥65 from four US communities. We used previously defined categories based on weekly alcohol consumption: none, former, <1 drink, 1–6 drinks, 7–13 drinks and ≥14 drinks. Cystatin C was measured at baseline, year 3 and year 7; eligible subjects had at least two measures. Estimated GFRcys was calculated from cystatin C. The primary outcome was rapid kidney function as an annual estimated GFR (eGFRcys) loss >3 mL/min/1.73 m2/year.
Results. Eight percent of the cohort reported former alcohol use and 52% reported current alcohol consumption. During a mean follow-up of 5.6 years, 1075 (25%) participants had rapid kidney function decline. In adjusted logistic regression models, there was no association between alcohol use and kidney function decline (odds ratio, 95% confidence interval: none = reference; former = 1.18, 0.89–1.56; <1 drink = 1.20, 0.99–1.47; 1–6 = 1.18, 0.95–1.45; 7–13 = 1.10, 0.80–1.53; >14 = 0.89, 0.61–1.13). Results were similar with kidney function decline as a continuous outcome.
Conclusions. Our results suggest that moderate alcohol consumption has neither adverse nor beneficial effects on kidney function. Although clinicians will need to consider the potential deleterious effects associated with alcohol consumption, there does not appear to be a basis for recommending that older adults discontinue or initiate light to moderate alcohol consumption to protect against kidney disease.
alcohol; kidney disease; outcomes; progression
Introduction. Reduced kidney function, approximated by elevated cystatin C, is associated with diastolic dysfunction, heart failure, and cardiovascular mortality; however, the precise mechanism(s) that account for these relationships remains unclear. Understanding the relationship between cystatin C and subclinical left ventricular (LV) remodeling, across ethnically diverse populations, may help explain the mechanisms underlying the association of kidney dysfunction with heart failure and cardiovascular mortality. Methods. Measures of cystatin C and LV parameters were obtained from the multi-ethnic study of atherosclerosis (MESA) cohort at baseline (N = 4, 970 with complete data on cystatin C and LV parameters). LV parameters; LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), LV mass (LVM), concentricity (LV mass/LV end-diastolic volume), and LV ejection fraction (LVEF) were measured using magnetic resonance imaging. Nested linear models were used to examine the relationship between higher quartiles of cystatin C and LV parameters, with and without adjustment for demographics, height, and weight, and traditional cardiovascular risk factors. Similar analyses were performed stratified by ethnicity and gender. Results. A fully adjusted model demonstrated a linear relationship between higher quartiles of cystatin C and lower LVEDV, (Mean ± SE, 128 ± 0.7, 128 ± 0.7, 126 ± 0.7, 124 ± 0.8 mL; P = 0.0001). Associations were also observed between higher quartiles of cystatin C and lower LVESV (P = 0.04) and concentricity (P = 0.0001). In contrast, no association was detected between cystatin C and LVM or LVEF. In analyses stratified by race and gender, the patterns of association between cystatin C quartiles and LV parameters were qualitatively similar to the overall association. Conclusion. Cystatin C levels were inversely associated with LVEDV and LVESV with a disproportionate decrease in LVEDV compared to LVM in a multi-ethnic population. This morphometric pattern of concentric left ventricular remodeling, may in part explain the process by which kidney dysfunction leads to diastolic dysfunction, heart failure and cardiovascular mortality.