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Vahakn B Shahinian,
Elizabeth Hedgeman,
Brenda W Gillespie,
Eric W Young,
Bruce Robinson, Chi-Yuan Hsu,
Laura C Plantinga,
Nilka Ríos Burrows,
Paul Eggers,
Sharon Saydah,
Neil R Powe,
Rajiv Saran
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ABSTRACT: BACKGROUND: The feasibility of using health system data to estimate prevalence of chronic kidney disease (CKD) stages 3-5 was explored. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: A 5% national random sample of patients from the Veterans Affairs (VA) health care system, enrollees in a managed care plan in Michigan (M-CARE), and participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES). PREDICTOR: Observed CKD prevalence estimates in the health system population were calculated as patients with an available outpatient serum creatinine measurement with estimated glomerular filtration rate <60 mL/min/1.73 m(2), among those with at least one outpatient visit during the year. OUTCOMES & MEASUREMENTS: A logistic regression model was fitted using data from the 2005-2006 NHANES to predict CKD prevalence in those untested for serum creatinine in the health system population, adjusted for demographics and comorbid conditions. Model results then were combined with the observed prevalence in tested patients to derive an overall predicted prevalence of CKD within the health systems. RESULTS: Patients in the VA system were older, had more comorbid conditions, and were more likely to be tested for serum creatinine than those in the M-CARE system. Observed prevalences of CKD stages 3-5 were 15.6% and 0.9% in the VA and M-CARE systems, respectively. Using data from NHANES, the overall predicted prevalences of CKD were 20.4% and 1.6% in the VA and M-CARE systems, respectively. LIMITATIONS: Health system data quality was limited by missing data for laboratory results and race. A single estimated glomerular filtration rate value was used to define CKD, rather than persistence over 3 months. CONCLUSIONS: Estimation of CKD prevalence within health care systems is feasible, but discrepancies between observed and predicted prevalences suggest that this approach is dependent on data availability and quality of information for comorbid conditions, as well as the frequency of testing for CKD in the health care system.
American Journal of Kidney Diseases 03/2013; · 5.43 Impact Factor
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Nisha Bansal,
Martin Keane,
Patrice Delafontaine,
Daniel Dries,
Elyse Foster,
Crystal A Gadegbeku,
Alan S Go,
L Lee Hamm,
John W Kusek,
Akinlolu O Ojo,
Mahboob Rahman,
Kaixiang Tao,
Jackson T Wright,
Dawei Xie, Chi-Yuan Hsu
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ABSTRACT: Abnormal left ventricular structure and function are associated with increased risk of adverse outcomes among patients with CKD and ESRD. A better understanding of changes in left ventricular mass and ejection fraction during the transition from CKD to ESRD may provide important insights to opportunities to improve cardiac outcomes.
This was a longitudinal study of a subset of participants of the Chronic Renal Insufficiency Cohort who were enrolled from 2003 to 2007 and followed through January of 2011. Participants were included if they had serial echocardiograms performed at advanced CKD (defined as estimated GFR<20 ml/min per 1.73 m) and again after ESRD (defined as need for hemodialysis or peritoneal dialysis).
A total of 190 participants (44% female, 66% black) had echocardiograms during advanced CKD and after ESRD. Mean (SD) estimated GFR at advanced CKD was 16.9 (3.5) ml/min per 1.73 m. Mean (SD) time between the advanced CKD echocardiogram and ESRD echocardiogram was 2.0 (1.0) years. There was no significant change in left ventricular mass index (62.3-59.5 g/m, P=0.10) between advanced CKD and ESRD; however, ejection fraction significantly decreased (53%-50%, P=0.002). Interactions for age, race, dialysis modality, and diabetes status were not significant (P>0.05).
Mean left ventricular mass index did not change significantly from advanced CKD to ESRD; however, ejection fraction declined during this transition period. Although left ventricular mass index is fixed by advanced stages of CKD, ejection fraction decline during more advanced stages of CKD may be an important contributor to cardiovascular disease and mortality after dialysis.
Clinical Journal of the American Society of Nephrology 03/2013; 8(3):355-62. · 5.23 Impact Factor
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ABSTRACT: Background/Aims: The association between chronic kidney disease (CKD) awareness and healthy behaviors is unknown. We examined whether CKD self-recognition is associated with healthy behaviors and achieving risk-reduction targets known to decrease risk of cardiovascular morbidity and CKD progression. Methods: CKD awareness, defined as a 'yes' response to 'Has a doctor or other health professional ever told you that you had kidney disease?', was examined among adults with CKD (eGFR <60 ml/min/1.73 m(2)) who participated in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Odds of participation in healthy behaviors (tobacco avoidance, avoidance of regular nonsteroidal anti-inflammatory drug use, and physical activity) and achievement of risk-reduction targets (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, systolic blood pressure control and glycemic control among those with diabetes) among those aware versus unaware of their CKD were determined by logistic regression, controlling for sociodemographics, access to care and comorbid conditions. Systolic blood pressure control was defined as <130 mm Hg (primary definition) or <140 mm Hg (secondary definition). Results: Of 2,615 participants, only 6% (n = 166) were aware of having CKD. Those who were aware had 82% higher odds of tobacco avoidance compared to those unaware (adjusted OR = 1.82, 95% CI 1.02-3.24). CKD awareness was not associated with other healthy behaviors or achievement of risk-reduction targets. Conclusions: Awareness of CKD was only associated with participation in one healthy behavior and was not associated with achievement of risk-reduction targets. To encourage adoption of healthy behaviors, a better understanding of barriers to participation in CKD-healthy behaviors is needed.
American Journal of Nephrology 01/2013; 37(2):135-143. · 2.54 Impact Factor
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Kathleen D Liu,
Wei Yang,
Amanda H Anderson,
Harold I Feldman,
Sevag Demirjian,
Takayuki Hamano,
Jiang He,
James Lash,
Eva Lustigova,
Sylvia E Rosas,
Michael S Simonson,
Kaixiang Tao, Chi-Yuan Hsu
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ABSTRACT: Novel biomarkers may improve our ability to predict which patients with chronic kidney disease (CKD) are at higher risk for progressive loss of renal function. Here, we assessed the performance of urine neutrophil gelatinase-associated lipocalin (NGAL) for outcome prediction in a diverse cohort of 3386 patients with CKD in the Chronic Renal Insufficiency Cohort study. In this cohort, the baseline mean estimated glomerular filtration rate (eGFR) was 42.4 ml/min per 1.73 m(2), the median 24-h urine protein was 0.2 g/day, and the median urine NGAL concentration was 17.2 ng/ml. Over an average follow-up of 3.2 years, there were 689 cases in which the eGFR was decreased by half or incident end-stage renal disease developed. Even after accounting for eGFR, proteinuria, and other known CKD progression risk factors, urine NGAL remained a significant independent risk factor (Cox model hazard ratio 1.70 highest to lowest quartile). The association between baseline urine NGAL levels and risk of CKD progression was strongest in the first 2 years of biomarker measurement. Within this time frame, adding urine NGAL to a model that included eGFR, proteinuria, and other CKD progression risk factors led to net reclassification improvement of 24.7%, but the C-statistic remained nearly identical. Thus, while urine NGAL was an independent risk factor of progression among patients with established CKD of diverse etiology, it did not substantially improve prediction of outcome events.Kidney International advance online publication, 23 January 2013; doi:10.1038/ki.2012.458.
Kidney International 01/2013; · 6.61 Impact Factor
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ABSTRACT: Individuals with acute heart failure exacerbation often experience a deterioration in renal function. We sought to determine whether this deterioration is ischemic in nature and detectable by sensitive urine biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). We measured serial biomarker levels and evaluated the associations of these biomarkers with renal recovery in a cohort of hospitalized patients with acute heart failure exacerbation.
Biomarker insights 01/2013; 8:15-8.
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ABSTRACT: BACKGROUND: Atrial fibrillation (AF) frequently occurs in patients with chronic kidney disease (CKD). However, the long-term impact of development of AF on the risk of adverse renal outcomes in patients with CKD is unknown. In this study, we determined the association between incident AF and risk of end-stage renal disease (ESRD) among adults with CKD. METHODS AND RESULTS: We studied adults with CKD (defined as persistent glomerular filtration rate [eGFR] <60 ml/min/1.73 m(2) by the CKD-EPI equation) enrolled in Kaiser Permanente Northern California who were identified between 2002-2010 and who did not have prior ESRD or previously documented AF. Incident AF was identified using primary hospital discharge diagnoses and/or two or more outpatient visits for AF. Incident ESRD was ascertained from a comprehensive health plan registry for dialysis and renal transplant. Among 206,229 adults with CKD, 16,463 developed incident AF. During a mean follow-up of 5.1±2.5 years, there were 345 cases of ESRD that occurred after development of incident AF (74 per 1000 person-years) compared with 6505 cases of ESRD during periods without AF (64 per 1000 person-years, P<0.001). After adjustment for potential confounders, incident AF was associated with a 67% increase in rate of ESRD (hazard ratio 1.67, 95% confidence interval: 1.46-1.91). CONCLUSIONS: Incident AF is independently associated with increased risk of developing ESRD in adults with CKD. Further study is needed to identify potentially modifiable pathways through which AF leads to a higher risk of progression to ESRD.
Circulation 12/2012; · 14.74 Impact Factor
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ABSTRACT: The population epidemiology of AKI is not well described. Here, we analyzed data from the Nationwide Inpatient Sample, a nationally representative dataset, to identify cases of dialysis-requiring AKI using validated International Classification of Diseases, Ninth Revision (ICD-9) codes. From 2000 to 2009, the incidence of dialysis-requiring AKI increased from 222 to 533 cases per million person-years, averaging a 10% increase per year (incidence rate ratio=1.10, 95% CI=1.10-1.11 per year). Older age, male sex, and black race associated with higher incidence of dialysis-requiring AKI. The rapid increase in incidence was evident in all age, sex, and race subgroups examined. Temporal changes in the population distribution of age, race, and sex as well as trends of sepsis, acute heart failure, and receipt of cardiac catheterization and mechanical ventilation accounted for about one third of the observed increase in dialysis-requiring AKI among hospitalized patients. The total number of deaths associated with dialysis-requiring AKI rose from 18,000 in 2000 to nearly 39,000 in 2009. In conclusion, the incidence of dialysis-requiring AKI increased rapidly in all patient subgroups in the past decade in the United States, and the number of deaths associated with dialysis-requiring AKI more than doubled.
Journal of the American Society of Nephrology 12/2012; · 9.66 Impact Factor
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ABSTRACT: Background: Telomere attrition is a novel risk factor for cardiovascular disease. Studies of telomere length in relation to kidney function are limited. We explored the association of kidney function with telomere length and telomere shortening. Methods: The Heart and Soul Study is a longitudinal study of patients with stable coronary heart disease. Measures of baseline kidney function included: serum creatinine, creatinine-derived estimated glomerular filtration rate (eGFR(CKD-EPI)), 24-hour urine measured creatinine clearance, cystatin C, cystatin C-derived estimated glomerular filtration rate (eGFRcys) and urine albumin to creatinine ratio. Telomere length was measured from peripheral blood leukocytes at baseline (n = 954) and 5 years later (n = 608). Linear regression models were used to test the association of kidney function with (i) baseline telomere length and (ii) change in telomere length over 5 years. Results: At baseline, mean eGFR(CKD-EPI) was 72.6 (±21.5) ml/min/1.73 m(2), eGFRcys was 71.0 (±23.1) ml/min/1.73 m(2) and ACR was 8.6 (±12.3) mg/g. Only lower baseline eGFR(CKD-EPI) was associated with shorter baseline telomere length (9.1 (95% CI 1.2-16.9) fewer base pairs for every 5 ml/min/1.73 m(2) lower eGFR(CKD-EPI)). Lower baseline eGFR(CKD-EPI) (and all other measures of kidney function) predicted more rapid telomere shortening (10.8 (95% CI 4.3-17.3) decrease in base pairs over 5 years for every 5 ml/min/1.73 m(2) lower eGFR(CKD-EPI)). After adjustment for age, these associations were no longer statistically significant. Conclusions: In patients with coronary heart disease, reduced kidney function is associated with (i) shorter baseline telomere length and (ii) more rapid telomere shortening over 5 years; however, these associations are entirely explained by older age.
American Journal of Nephrology 10/2012; 36(5):405-411. · 2.54 Impact Factor
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Clinical Journal of the American Society of Nephrology 10/2012; · 5.23 Impact Factor
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Meyeon Park, Chi-Yuan Hsu,
Yongmei Li,
Rakesh K Mishra,
Martin Keane,
Sylvia E Rosas,
Daniel Dries,
Dawei Xie,
Jing Chen,
Jiang He,
Amanda Anderson,
Alan S Go,
Michael G Shlipak
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ABSTRACT: Heart failure is a common consequence of CKD, and it portends high risk for mortality. However, among patients without known heart failure, the associations of different stages of estimated GFR (eGFR) with changes in cardiac structure and function are not well described. Here, we performed a cross-sectional analysis to study these associations among 3487 participants of the Chronic Renal Insufficiency Cohort Study. We estimated GFR using cystatin C. The prevalence of left ventricular hypertrophy (LVH) assessed by echocardiography was 32%, 48%, 57%, and 75% for eGFR categories ≥60, 45-59, 30-44, and <30 ml/min per 1.73 m(2), respectively. In fully adjusted multivariable analyses, subjects with eGFR levels of <30 ml/min per 1.73 m(2) had twofold higher odds of LVH (OR=2.20, 95% CI=1.40-3.40; P<0.001) relative to subjects with eGFR≥60 ml/min per 1.73 m(2). This reduction in kidney function also significantly associated with abnormal LV geometry but not diastolic or systolic dysfunction. An eGFR of 30-44 ml/min per 1.73 m(2) also significantly associated with LVH and abnormal LV geometry compared with eGFR≥60 ml/min per 1.73 m(2). In summary, in this large CKD cohort, reduced kidney function associated with abnormal cardiac structure. We did not detect significant associations between kidney function and systolic or diastolic function after adjusting for potential confounding variables.
Journal of the American Society of Nephrology 08/2012; 23(10):1725-34. · 9.66 Impact Factor
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ABSTRACT: Whether automated estimated glomerular filtration rate (eGFR) reporting for patients is associated with improved provider recognition of chronic kidney disease (CKD), as measured by diagnostic coding of CKD in those with laboratory evidence of the disease, has not been explored in a poor, ethnically diverse, high-risk urban patient population. A retrospective cohort of 237 adult patients (≥20 years) with incident CKD (≥1 eGFR ≥60 ml/min/1.73 m(2), followed by ≥2 eGFRs <60 ml/min/1.73 m(2) ≥3 months apart)-pre- or postautomated eGFR reporting-was identified within the San Francisco Department of Public Health Community Health Network (January 2005-July 2009). Patients were considered coded if any ICD-9-CM diagnostic codes for CKD (585.x), other kidney disease (580.x-581.x, 586.x), or diabetes (250.4) or hypertension (403.x, 404.x) CKD were present in the medical record within 6 months of incident CKD. Multivariable logistic regression was used to obtain adjusted odds ratios (ORs) for CKD coding. We found that, pre-eGFR reporting, 42.5 % of incident CKD patients were coded for CKD. Female gender, increased age, and non-Black race were associated with lower serum creatinine and lower prevalence of coding but comparable eGFR. Prevalence of coding was not statistically significantly higher overall (49.6 %, P = 0.27) or in subgroups after the institution of automated eGFR reporting. However, gaps in coding by age and gender were narrowed post-eGFR, even after adjustment for sociodemographic and clinical characteristics: 47.9 % of those <65 and 30.3 % of those ≥65 were coded pre-eGFR, compared to 49.0 % and 52.0 % post-eGFR (OR = 0.43 and 1.16); similarly, 53.2 % of males and 25.4 % of females were coded pre-eGFR compared to 52.8 % and 44.0 % post-eGFR (OR 0.28 vs. 0.64). Blacks were more likely to be coded in the post-eGFR period: OR = 1.08 and 1.43 (P (interaction) > 0.05). Automated eGFR reporting may help improve CKD recognition, but it is not sufficient to resolve underidentification of CKD by safety net providers.
Journal of Urban Health 06/2012; · 2.13 Impact Factor
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Amanda Hyre Anderson,
Wei Yang, Chi-yuan Hsu,
Marshall M Joffe,
Mary B Leonard,
Dawei Xie,
Jing Chen,
Tom Greene,
Bernard G Jaar,
Patricia Kao,
John W Kusek,
J Richard Landis,
James P Lash,
Raymond R Townsend,
Matthew R Weir,
Harold I Feldman
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ABSTRACT: Glomerular filtration rate (GFR) is considered the best measure of kidney function, but repeated assessment is not feasible in most research studies.
Cross-sectional study of 1,433 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study (ie, the GFR subcohort) to derive an internal GFR estimating equation using a split-sample approach.
Adults from 7 US metropolitan areas with mild to moderate chronic kidney disease; 48% had diabetes and 37% were black.
CRIC GFR estimating equation. REFERENCE TEST OR OUTCOME: Urinary (125)I-iothalamate clearance testing (measured GFR [mGFR]). OTHER MEASUREMENTS: Laboratory measures, including serum creatinine and cystatin C, and anthropometrics.
In the validation data set, the model that included serum creatinine level, serum cystatin C level, age, sex, and race was the most parsimonious and similarly predictive of mGFR compared with a model additionally including bioelectrical impedance analysis phase angle, CRIC clinical center, and 24-hour urinary creatinine excretion. Specifically, root mean square errors for the separate models were 0.207 versus 0.202, respectively. Performance of the CRIC GFR estimating equation was most accurate for the subgroups of younger participants, men, nonblacks, non-Hispanics, those without diabetes, those with body mass index <30 kg/m(2), those with higher 24-hour urine creatinine excretion, those with lower high-sensitivity C-reactive protein levels, and those with higher mGFRs.
Urinary clearance of (125)I-iothalamate is an imperfect measure of true GFR; cystatin C level is not standardized to certified reference material; lack of external validation; small sample sizes limit analyses of subgroup-specific predictors.
The CRIC GFR estimating equation predicts mGFR accurately in the CRIC cohort using serum creatinine and cystatin C levels, age, sex, and race. Its performance was best in younger and healthier participants.
American Journal of Kidney Diseases 06/2012; 60(2):250-61. · 5.43 Impact Factor
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ABSTRACT: Clinical heart failure (HF) is associated with CKD and faster rates of kidney function decline. Whether subclinical abnormalities of cardiac structure are associated with faster kidney function decline is not known. The association between cardiac concentricity and kidney function decline was evaluated.
This is a longitudinal study of 3866 individuals from the Multi-Ethnic Study of Atherosclerosis (2000-2007) who were free of clinical cardiovascular disease, with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m(2) at baseline and 5 years of follow-up. Concentricity, a measurement of abnormal cardiac size, was assessed by magnetic resonance imaging and evaluated as a continuous measurement and in quartiles. GFR was estimated by creatinine (eGFRcr) and cystatin C (eGFRcys). The association of concentricity with annual eGFR decline, incident CKD, and rapid kidney function decline (>5% per year) was investigated using linear mixed models as well as Poisson and logistic regression, respectively. Analyses adjusted for demographics, BP, diabetes, and inflammatory markers.
Median decline was -0.8 (interquartile range, -3.1, -0.5) by eGFRcr. Compared with the lowest quartile of concentricity, persons in the highest quartile had an additional 21% (9%-32%) decline in mean eGFRcr in fully adjusted models. Concentricity was also associated with incident CKD and with rapid kidney function decline after adjustment.
Subclinical abnormalities in cardiac structure are associated with longitudinal kidney function decline independent of diabetes and hypertension. Future studies should examine mechanisms to explain these associations.
Clinical Journal of the American Society of Nephrology 05/2012; 7(7):1137-44. · 5.23 Impact Factor
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ABSTRACT: Urine dopamine (DA) is produced in the proximal tubule and has been found to increase in response to dietary phosphorus intake, and to contribute to greater urinary phosphorus excretion in animal models. Whether urine DA is associated with phosphorus homeostasis in humans is uncertain.
This was a cross-sectional study of 884 outpatients. DA was measured from 24-hour urine collections. We examined cross-sectional associations between urine DA and serum phosphorus, 24-hour urine phosphorus (as an indicator of dietary phosphorus absorption), fractional excretion of phosphorus (FEphos), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). Models were adjusted for age, sex, race, eGFR, albuminuria, hypertension, heart failure, tobacco use, body mass index, and diuretic use.
Mean age was 66.6 ± 11 years and mean eGFR was 71 ± 21.3 ml/min/1.73 m(2). The mean urine DA was 193 ± 86 µg/day, mean serum phosphorus was 3.6 ± 0.6 mg/dl, mean daily urine phosphorus excretion was 671 ± 312 mg/day, and mean FEphos was 17 ± 9%. In adjusted models, each standard deviation higher DA was associated with 78.4 mg/day higher urine phosphorus and 0.9% lower FEphos (p < 0.05 for both). There was no statistically significant association between urine DA, serum phosphorus, FGF-23 or PTH in adjusted models.
Higher dietary phosphorus absorption is associated with higher urine DA in humans, consistent with animal models. However, higher urine DA is not associated with FGF-23 or PTH, suggesting that known mechanisms of renal tubular handling of phosphorus may not be involved in the renal dopamine-phosphorus regulatory pathway in humans.
American Journal of Nephrology 05/2012; 35(6):483-90. · 2.54 Impact Factor
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Paul M Palevsky,
Bruce A Molitoris,
Mark D Okusa,
Adeera Levin,
Sushrut S Waikar,
Ron Wald,
Glenn M Chertow,
Patrick T Murray,
Chirag R Parikh,
Andrew D Shaw, [......],
Aliza M Thompson,
B Taylor Thompson,
Christof S Westenfelder,
James A Tumlin,
David G Warnock,
Sudhir V Shah,
Yining Xie,
Emily G Duggan,
Paul L Kimmel,
Robert A Star
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ABSTRACT: Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.
Clinical Journal of the American Society of Nephrology 03/2012; 7(5):844-50. · 5.23 Impact Factor
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Mark D Okusa,
Bruce A Molitoris,
Paul M Palevsky,
Vernon M Chinchilli,
Kathleen D Liu,
Alfred K Cheung,
Steven D Weisbord,
Sarah Faubel,
John A Kellum,
Ron Wald, [......],
Aliza M Thompson,
B Taylor Thompson,
Christof S Westenfelder,
James A Tumlin,
David G Warnock,
Sudhir V Shah,
Yining Xie,
Emily G Duggan,
Paul L Kimmel,
Robert A Star
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ABSTRACT: AKI is an important clinical problem that has become increasingly more common. Mortality rates associated with AKI remain high despite advances in supportive care. Patients surviving AKI have increased long-term mortality and appear to be at increased risk of developing CKD and progressing to ESRD. No proven effective pharmacologic therapies are currently available for the prevention or treatment of AKI. Advances in addressing this unmet need will require the development of novel therapeutic agents based on precise understanding of key pathophysiological events and the implementation of well designed clinical trials. To address this need, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored the "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" workshop in December 2010. The event brought together representatives from academia, industry, the National Institutes of Health, and the US Food and Drug Administration. We report the discussions of workgroups that developed outlines of clinical trials for the prevention of AKI in two patient populations: patients undergoing elective surgery who are at risk for or who develop AKI, and patients who are at risk for contrast-induced AKI. In both of these populations, primary prevention or secondary therapy can be delivered at an optimal time relative to kidney injury. The workgroups detailed primary and secondary endpoints for studies in these groups, and explored the use of adaptive clinical trial designs for trials of novel preventive strategies to improve outcomes of patients with AKI.
Clinical Journal of the American Society of Nephrology 03/2012; 7(5):851-5. · 5.23 Impact Factor
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Bruce A Molitoris,
Mark D Okusa,
Paul M Palevsky,
Lakhmir S Chawla,
James S Kaufman,
Prasad Devarajan,
Robert M Toto, Chi-yuan Hsu,
Tom H Greene,
Sarah G Faubel, [......],
Aliza M Thompson,
B Taylor Thompson,
Christof S Westenfelder,
James A Tumlin,
David G Warnock,
Sudhir V Shah,
Yining Xie,
Emily G Duggan,
Paul L Kimmel,
Robert A Star
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ABSTRACT: AKI remains an important clinical problem, with a high mortality rate, increasing incidence, and no Food and Drug Administration-approved therapeutics. Advances in addressing this clinical need require approaches for rapid diagnosis and stratification of injury, development of therapeutic agents based on precise understanding of key pathophysiological events, and implementation of well designed clinical trials. In the near future, AKI biomarkers may facilitate trial design. To address these issues, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a meeting, "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers," in December of 2010 that brought together academic investigators, industry partners, and representatives from the National Institutes of Health and the Food and Drug Administration. Important issues in the design of clinical trials for interventions in AKI in patients with sepsis or AKI in the setting of critical illness after surgery or trauma were discussed. The sepsis working group discussed use of severity of illness scores and focus on patients with specific etiologies to enhance homogeneity of trial participants. The group also discussed endpoints congruent with those endpoints used in critical care studies. The second workgroup emphasized difficulties in obtaining consent before admission and collaboration among interdisciplinary healthcare groups. Despite the difficult trial design issues, these clinical situations represent a clinical opportunity because of the high event rates, severity of AKI, and poor outcomes. The groups considered trial design issues and discussed advantages and disadvantages of several short- and long-term primary endpoints in these patients.
Clinical Journal of the American Society of Nephrology 03/2012; 7(5):856-60. · 5.23 Impact Factor
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Archives of internal medicine 02/2012; 172(3):253-4. · 11.46 Impact Factor
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ABSTRACT: Awareness of chronic kidney disease (CKD) is low. Efforts are underway to increase recognition of CKD among patients, assuming that such an increase will lead to better outcomes through greater adherence to proven therapies. Few studies have tested this assumption.
CKD awareness, defined by a 'yes' answer to 'Have you ever been told by a healthcare provider you have weak or failing kidneys?', was assessed among 2,404 adults with CKD stages 1-4, who participated in the 2003-2008 National Health and Nutrition Examination Surveys. Odds of blood pressure (BP) control, self-reported use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), and glycemic control, were determined among those aware vs. unaware of their CKD.
Optimal BP control, ACEI/ARB use and glycemic control were low in the US adult population with CKD, although there was a recent increase in attainment of guideline-concordant BP control. Odds of BP control and ACEI/ARB use were not different among individuals aware of their CKD compared to those unaware (adjusted odds ratio (AOR) 0.91; 95% CI 0.52-1.58 and AOR 0.75; 0.44-1.30, respectively). CKD awareness among diabetic participants was not associated with glycemic control (AOR 0.41; 95% CI 0.14-1.18).
Awareness of CKD is not associated with more optimal BP control, ACEI/ARB use or glycemic control. Future efforts in this area should further explore the measurement of CKD awareness and behaviors associated with CKD awareness.
American Journal of Nephrology 01/2012; 35(2):191-7. · 2.54 Impact Factor
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ABSTRACT: The aim of this study was to examine whether kidney dysfunction is associated with the type of clinical presentation of coronary heart disease (CHD).
Reduced kidney function increases the risk for developing CHD, but it is not known whether it also influences the acuity of clinical presentation, which has important prognostic implications.
A case-control study was conducted of subjects whose first clinical presentation of CHD was either acute myocardial infarction or stable exertional angina between October 2001 and December 2003. Estimated glomerular filtration rate (eGFR) before the incident event was calculated using calibrated serum creatinine and the abbreviated MDRD (Modification of Diet in Renal Disease) equation. Patient characteristics and use of medications were ascertained from self-report and health plan databases. Multivariable logistic regression was used to examine the association of reduced eGFR and CHD presentation.
A total of 803 adults with incident acute myocardial infarctions and 419 adults with incident stable exertional angina who had baseline eGFRs ≤130 ml/min/1.73 m(2) were studied. Mean eGFR was lower in subjects with acute myocardial infarctions compared with those with stable angina. Compared with eGFR of 90 to 130 ml/min/1.73 m(2), a strong, graded, independent association was found between reduced eGFR and presenting with acute myocardial infarction, with adjusted odds ratios of 1.36 (95% confidence interval: 0.99 to 1.86) for eGFR 60 to 89 ml/min/1.73 m(2), 1.55 (95% confidence interval: 0.92 to 2.62) for eGFR 45 to 59 ml/min/1.73 m(2), and 3.82 (95% confidence interval: 1.55 to 9.46) for eGFR <45 ml/min/1.73 m(2) (p < 0.001 for trend).
An eGFR <45 ml/min/1.73 m(2) is a strong, independent predictor of presenting with acute myocardial infarction versus stable angina as the initial manifestation of CHD.
Journal of the American College of Cardiology 10/2011; 58(15):1600-7. · 14.16 Impact Factor
