Serum Bicarbonate and Kidney Disease Progression and Cardiovascular Outcome in Patients With Diabetic Nephropathy: A Post Hoc Analysis of the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study and IDNT (Irbesartan Diabetic Nephropathy Trial).

Abstract

BACKGROUND:

Low serum bicarbonate level has been reported to be an independent predictor of kidney function decline and mortality in patients with chronic kidney disease. Mechanisms underlying low serum bicarbonate levels may differ in patients with and without diabetes. We aimed to specifically investigate the association of serum bicarbonate level with kidney disease progression and cardiovascular outcome in a cohort of patients with type 2 diabetes and nephropathy.

STUDY DESIGN:

Post hoc analysis of 2 multicenter randomized controlled trials.

SETTING & PARTICIPANTS:

2,628 adults with type 2 diabetes and nephropathy.

FACTOR:

Serum bicarbonate level.

OUTCOMES:

Incidence of: (1) end-stage renal disease (ESRD), (2) ESRD or doubling of serum creatinine level, (3) all-cause mortality, (4) cardiovascular events (fatal/nonfatal stroke/myocardial infarction), and (5) heart failure.

MEASUREMENTS:

Serum bicarbonate was measured at baseline as total carbon dioxide. Associations of baseline serum bicarbonate level with end points were investigated using Cox regression models. Serum bicarbonate levels were studied as a continuous variable and stratified in quartiles. Follow-up was 2.8±1.0 (SD) years.

RESULTS:

Cox regression analyses showed that serum bicarbonate level had inverse associations with incident ESRD (HR, 0.91; 95% CI, 0.89-0.93; P<0.001) and incidence of the combined end point of ESRD or serum creatinine doubling (HR, 0.94; 95% CI, 0.92-0.96; P<0.001). These associations were independent of age, sex, and cardiovascular risk factors, but disappeared after adjustment for baseline estimated glomerular filtration rate (all P>0.05). Analysis of bicarbonate quartiles showed similar results for the quartile with the lowest bicarbonate (≤21 mEq/L) versus the quartile with normal bicarbonate levels (24-26 mEq/L). There was no association of bicarbonate level with cardiovascular events and heart failure.

LIMITATIONS:

Post hoc analysis and single measurement of serum bicarbonate.

CONCLUSIONS:

In this cohort of patients with type 2 diabetes with nephropathy, serum bicarbonate level associations with kidney disease end points were not retained after adjustment for estimated glomerular filtration rate, which is in contrast to results of earlier studies in nondiabetic populations.

• Authors: Elise Schutte, Hiddo J Lambers Heerspink, Helen L Lutgers, Stephan J L Bakker, Priya Vart, Bruce H R Wolffenbuttel, Kausik Umanath, Julia B Lewis, Dick de Zeeuw, Ron T Gansevoort
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 66 Issue 3 Pg. 450-8 (Sep 2015) ISSN: 1523-6838 [Electronic] United States
• PMID: 25987260 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Bicarbonates
• Biphenyl Compounds
• Tetrazoles
• Irbesartan
• Losartan

Topics

• Adult
• Aged
• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Bicarbonates (blood)
• Biphenyl Compounds (therapeutic use)
• Diabetes Mellitus, Type 2 (blood)
• Diabetic Angiopathies (epidemiology)
• Diabetic Nephropathies (blood, drug therapy)
• Disease Progression
• Female
• Humans
• Irbesartan
• Kidney Failure, Chronic (blood)
• Losartan (therapeutic use)
• Male
• Middle Aged
• Renal Insufficiency, Chronic (blood)
• Risk Factors
• Tetrazoles (therapeutic use)