0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Original Research |

Estimated Glomerular Filtration Rate and Albuminuria as Predictors of Outcomes in Patients With High Cardiovascular Risk: A Cohort Study

Catherine M. Clase, MB, BChir, MSc; Peggy Gao, MSc; Sheldon W. Tobe, MD; Matthew J. McQueen, MBChB, PhD; Anja Grosshennig, MD; Koon K. Teo, MBBCH, PhD; Salim Yusuf, MD, DPhil; Johannes F.E. Mann, MD, on behalf of the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in Angiotensin-Converting-Enzyme-Inhibitor Intolerant Subjects with Cardiovascular Disease) Investigators
[+] Article and Author Information

From McMaster University and Population Health Research Institute, Hamilton, and University of Toronto, Toronto, Ontario, Canada, and Schwabing General Hospital and KfH Kidney Center, Munich, and Friedrich Alexander University, Erlangen, Germany.


Acknowledgment: The authors thank the study patients, as well as the investigators on whose behalf we publish (6).

Grant Support: By Boehringer Ingelheim, the Population Health Research Institute, and the European Commission (grant 241544, SysKid; Dr. Mann). Dr. Clase is supported by the clinical work of her colleagues.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-1426.

Reproducible Research Statement:Study protocol: Outlined in reference (26) and available from Dr. Teo (e-mail, teok@mcmaster.ca). Statistical code and data set: Not available.

Requests for Single Reprints: Catherine M. Clase, MB, BChir, MSc, St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario L8P 4A6, Canada; e-mail, clase@mcmaster.ca.

Current Author Addresses: Dr. Clase: St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario L8P 4A6, Canada.

Ms. Gao and Drs. McQueen, Teo, and Yusuf: Population Health Research Institute, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.

Dr. Tobe: Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Room A2 40, Toronto, Ontario M4N 3M5, Canada.

Drs. Grosshennig and Mann: Schwabing General Hospital, Kölner Platz 1, 80804 Munich, Germany.

Author Contributions: Conception and design: C. Clase, S. Yusuf, J.F.E. Mann.

Analysis and interpretation of the data: C. Clase, P. Gao, M.J. McQueen, A. Grosshennig, S. Yusuf, J.F.E. Mann.

Drafting of the article: C. Clase, S.W. Tobe, M.J. McQueen, J.F.E. Mann.

Critical revision of the article for important intellectual content: C. Clase, S.W. Tobe, M.J. McQueen, K.K. Teo, S. Yusuf, J.F.E. Mann.

Final approval of the article: C. Clase, S.W. Tobe, K.K. Teo, S. Yusuf, J.F.E. Mann.

Provision of study materials or patients: M.J. McQueen.

Obtaining of funding: J.F.E. Mann.

Administrative, technical, or logistic support: M.J. McQueen, K.K. Teo, J.F.E. Mann.

Collection and assembly of data: K.K. Teo, J.F.E. Mann.


Ann Intern Med. 2011;154(5):310-318. doi:10.7326/0003-4819-154-5-201103010-00005
Text Size: A A A

Background: Glomerular filtration rate and albuminuria are risk factors for cardiovascular disease and markers of renal function.

Objective: To examine the contribution of estimated glomerular filtration rate (eGFR) and urinary albumin–creatinine ratio beyond that of traditional cardiovascular risk factors to classification of patient risk for cardiovascular and renal outcomes.

Design: Prospective cohort study that pooled all patients of ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in Angiotensin-Converting-Enzyme-Inhibitor Intolerant Subjects with Cardiovascular Disease).

Patients: 27 620 patients older than 55 years with documented cardiovascular disease, who were followed for a mean of 4.6 years.

Measurements: Baseline eGFR, urinary albumin–creatinine ratio, and cardiovascular risk factors. Outcomes were all-cause mortality; a composite of cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure; long-term dialysis; and a composite of long-term dialysis and doubling of serum creatinine level.

Results: Lower eGFRs and higher urinary albumin–creatinine ratios were associated with the primary cardiovascular composite outcome (for example, an adjusted hazard ratio of 2.53 [95% CI, 1.61 to 3.99] for an eGFR <30 mL/min per 1.73 m2 and a very high urinary albumin–creatinine ratio). However, adding information about eGFR and urinary albumin–creatinine ratio to the risk reclassification analyses led to no meaningful decrease in the proportion of patients assigned to the intermediate-risk category (31% without vs. 32% with renal information). In contrast, eGFR and urinary albumin–creatinine ratio were strongly associated with risk for long-term dialysis and greatly improved both model calibration and risk stratification capacity when added to traditional cardiovascular risk factors (65% assigned to intermediate-risk categories without renal information vs. 18% with renal information).

Limitation: Creatinine levels were not standardized.

Conclusion: In patients with high vascular risk, eGFR and urinary albumin–creatinine ratio add little to traditional cardiovascular risk factors for stratifying cardiovascular risk but greatly improve risk stratification for renal outcomes.

Primary Funding Source: Boehringer Ingelheim, Population Health Research Institute, and the European Commission.

Figures

Grahic Jump Location
Appendix Figure 1.
Derivation of patients for the current study from patients in ONTARGET and TRANSCEND.

ONTARGET = ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial; TRANSCEND = Telmisartan Randomized Assessment Study in Angiotensin-Converting-Enzyme-Inhibitor Intolerant Subjects with Cardiovascular Disease.

Grahic Jump Location
Grahic Jump Location
Figure.
Distribution of hazard ratios for the primary cardiovascular outcome and eGFR or UACR.

Values are adjusted for age, sex, diabetes, known coronary artery disease, previous stroke or transient ischemic attack, systolic and diastolic blood pressure, fasting blood glucose level, low-density and high-denisty lipoprotein cholesterol level, smoking status (current, former, or never smoker), study membership, and medication use. eGFR = estimated glomerular filtration rate; UACR = urinary albumin–creatinine ratio.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 2.
Hazard ratios for long-term dialysis and eGFR or UACR.

Values are adjusted for age, sex, diabetes, known coronary artery disease, previous stroke or transient ischemic attack, systolic and diastolic blood pressure, fasting blood glucose level, low-density and high-density lipoprotein cholesterol level, smoking status (current, former, or never smoker), study membership, and medication use. eGFR = estimated glomerular filtration rate; UACR = urinary albumin–creatinine ratio.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Chronic Kidney Disease in Patients with High Vascular Risk
Posted on March 13, 2011
Gen-Min Lin
Hualien-Armed Forces General Hospital, Hualien, Taiwan
Conflict of Interest: None Declared

To the Editor: We appreciate the work by Clase et al which reported that in patients with high vascular risk, estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio add little to traditional cardiovascular risk factors for stratifying cardiovascular risk but greatly improve risk stratification for renal outcomes (1). As is known, there are numberous etiologies contributing to chronic kidney disease including not only the traditional risk factors for ahteroslcerosis such as age, diabetes, dyslipidemia and hypertension but also chronic toxic/medical agents use, post-infectious/ autoimmune glomerulopathy, a dehydration status and chronic obstructive nephropathy. Among these facors, some may be heart protective but kidney hazardous. For example, a long-term use of alcohol or aspirin is believed to reduce ischemic cardiovascular events but possibly result in deterioration of renal function in chronic renal disease (2). Therefore, the underlying causes of chonic renal disease may not be involved in the process of atherosclerosis directly leading to increase cardiovascular risks which is compatible to the findings of the report. On the contrary, whether the etiology accounting for the renal damage is, a viscious cycle will be establised by renal hypertension via activation of renin-angiotensin-aldosterone system causing a negative feedback to deteriorate kidney function. Until now, there have been many clinical trials supporting the relationship between blood pressure control and the progression of end-stage renal disease in patients with chronic renal disease. Recently, in the African-American Study of Kidney Disease and Hypertension (AASK) trial, Appel and colleagues separated their participants with hypertensive chronic renal disease receiving either intensive or standard blood pressure control into those with a urine protein-to-creatinine ratio > 0.22 and that < 0.22 (3). We observed that in the higher ratio group, lower eGFR was observed at baseline and the incidence of progression to end-stage renal disease or doubling of serum creatinine level at follow-up was more than 3 times than that in the lower ratio group. In addition, although the AASK investigators did not emphasize the point that one-third of the study patients with a higher protein-to-creatinine ratio may potentially have severe hypertension,(4) we noticed that there were 25% of patients on intensive control but 60% of patients on standard control with blood pressure >140/90 mmHg at 4-year follow-up in the trial phase. This means that those on standard control in the high ratio group may not achieve the optimal blood pressure target and hence resulted in worse outcomes. According to these findings, we conclude that the severity of renal function itself should be a pivotal predictor to the progression of end-stage renal disease and adequate control of blood pressure is important to break down the vicious cycle in this setting.

References

1. Clase CM, Gao P, Tobe SW, et al. Estimated Glomerular Filtration Rate and Albuminuria as Predictors of Outcomes in Patients With High Cardiovascular Risk: A Cohort Study. Ann Intern Med. 2011; 154:310-318.

2. Fored CM, Ejerblad E, Lindblad P, et al. Acetaminophen, aspirin, and chronic renal failure. N Engl J Med. 2001; 345:1801-1808.

3. Appel LJ, Wright JT Jr, Greene T, et al. Intensive blood-pressure control in hypertensive chronic kidney disease. N Engl J Med 2010; 363: 918-929

4. Agarwal R, Light RP. GFR, proteinuria and circadian blood pressure. Nephrol Dial Transplant. 2009;24: 2400-2406

Conflict of Interest:

None declared

Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)