Differences in Kidney Function and Incident Hypertension: The Multi-Ethnic Study of Atherosclerosis

1 April 2008 | Volume 148 Issue 7 | Pages 501-508

Background: Kidney disease and hypertension commonly coexist, yet the direction of their association is still debated.

Objective: To evaluate whether early kidney dysfunction, measured by serum cystatin C levels and urinary albumin excretion, predates hypertension in adults without clinically recognized kidney or cardiovascular disease.

Design: Observational cohort study using data from 2000 to 2005.

Setting: The MESA (Multi-Ethnic Study of Atherosclerosis), a community-based study of subclinical cardiovascular disease in adults age 45 to 84 years.

Participants: 2767 MESA participants without prevalent hypertension, cardiovascular disease, or clinically recognized kidney disease (an estimated glomerular filtration rate <60 mL/min per 1.73 m² or microalbuminuria).

Measurements: Cystatin C was measured by using a nephelometer, and urinary albumin and creatinine were measured from a spot morning collection. The primary outcome was incident hypertension, defined as systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or use of an antihypertensive medication.

Results: During a median follow-up of 3.1 years, 19.7% of the cohort (545 participants) developed hypertension. After adjustment for established hypertension risk factors, each 15-nmol/L increase in cystatin C was associated with a statistically significant 15% greater incidence of hypertension (P = 0.017). The highest sex-specific quartile of urinary albumin–creatinine ratio was associated with a statistically insignificant 16% greater incidence of hypertension (P = 0.192) compared with the lowest quartile. No statistical evidence suggested a multiplicative interaction.

Limitations: Unmeasured characteristics may have confounded observed associations of kidney markers with hypertension. Follow-up was relatively short. Hypertension that may have occurred between study visits or hypertension that was not captured by standard cuff measurements may have been missed.

Conclusion: Differences in kidney function, indicated by cystatin C levels, are associated with incident hypertension among individuals without clinical kidney or cardiovascular disease. These population-based findings complement experimental work implicating early kidney damage in the pathogenesis of essential hypertension.

Editors' Notes Context Evidence about whether early kidney dysfunction predates hypertension is scant. Contribution In this study, 2767 adults who were middle-aged or older and did not have clinically recognized hypertension or kidney or cardiovascular disease at baseline were followed for about 3 years. About 20% developed hypertension. Higher baseline levels of cystatin C were associated with higher incidence of hypertension, independent of other risk factors. Spot baseline measures of the urinary albumin–creatinine ratio were not associated with hypertension incidence, independent of other risk factors. Implication Early renal impairment marked by higher cystatin C levels may play a role in the pathogenesis of hypertension. —The Editors

 

Author and Article Information

From the University of Washington, Harborview Medical Center, Seattle, Washington; San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California; Veterans Affairs Pittsburgh Healthcare System and Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Columbia University, New York, New York; and Amgen, Thousand Oaks, California.

Acknowledgment: The authors thank the other investigators, the staff, and the participants of MESA for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.

Grant Support: By contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute and by a National Institutes of Health Career Development Award (K23 DK63274-01).

Potential Financial Conflicts of Interest: Employment: C. Stehman-Breen (Amgen). Grants pending: L.F. Fried (Merck).

Reproducible Research Statement: Study protocol: The complete MESA protocol is available online at http://www.mesa-nhlbi.org/moreinfo.aspx. Statistical code: Statistical code for these analyses is available from Dr. Kestenbaum (e-mail, brk{at}u.washington.edu). Data set: The MESA data are available for researchers with a MESA sponsor and approved manuscript proposal. A list of participating institutions and principal investigators can be found at http://www.mesa-nhlbi.org/institutions.aspx.

Requests for Single Reprints: Bryan Kestenbaum, MD, MS, University of Washington, Division of Nephrology, Harborview Medical Center, Room 10EH11, 325 Ninth Avenue, Seattle, WA 98104-2499; e-mail, brk{at}u.washington.edu.

Current Author Addresses: Dr. Kestenbaum: University of Washington, Division of Nephrology, Harborview Medical Center, Room 10EH11, 325 Ninth Avenue, Seattle, WA 98104.

Dr. Rudser: University of Washington, 1705 Northeast Pacific Street, Box 357232, Seattle WA 98195.

Dr. de Boer: University of Washington, 1959 Northeast Pacific Street, Box 356521, Seattle, WA 98195.

Dr. Peralta: University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143.

Dr. Fried: Veterans Affairs Pittsburgh Healthcare System, University Drive, Pittsburgh, PA 15240.

Dr. Shlipak: San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 111A-1, San Francisco, CA 94131.

Dr. Palmas: Columbia University, 622 West 168th Street, New York, NY 10032.

Dr. Stehman-Breen: Amgen, 1 Amgen Center Drive, Thousand Oaks, CA 91320.

Dr. Siscovick: Cardiovascular Health Research Unit, Metropolitan Park, East Tower, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101.

Author Contributions: Conception and design: B. Kestenbaum, K.D. Rudser, I.H. de Boer, C. Stehman-Breen.

Analysis and interpretation of the data: B. Kestenbaum, K.D. Rudser, I.H. de Boer, C.A. Peralta, L.F. Fried, M.G. Shlipak, C. Stehman-Breen, D.S. Siscovick.

Drafting of the article: B. Kestenbaum, K.D. Rudser, W. Palmas, C. Stehman-Breen.

Critical revision of the article for important intellectual content: B. Kestenbaum, K.D. Rudser, I.H. de Boer, C.A. Peralta, L.F. Fried, M.G. Shlipak, W. Palmas, C. Stehman-Breen, D.S. Siscovick.

Final approval of the article: B. Kestenbaum, K.D. Rudser, I.H. de Boer, C.A. Peralta, L.F. Fried, M.G. Shlipak, W. Palmas, C. Stehman-Breen, D.S. Siscovick.

Provision of study materials or patients: M.G. Shlipak, D.S. Siscovick.

Statistical expertise: B. Kestenbaum, K.D. Rudser.

Collection and assembly of data: W. Palmas.

Read all Rapid Responses

Incident hypertension or masked hypertension?

Iddo Z. Ben-Dov

Annals Online, 7 Apr 2008 [Full text]

Response to Letter

Bryan Kestenbaum

Annals Online, 10 Jun 2008 [Full text]