The Decrement of Hemoglobin Concentration with Angiotensin II Receptor Blocker Treatment Is Correlated with the Reduction of Albuminuria in Non-Diabetic Hypertensive Patients: Post-Hoc Analysis of ESPECIAL Trial

Jung Nam An, Jin Ho Hwang, Jung Pyo Lee, Ho Jun Chin, Sejoong Kim, Dong Ki Kim, Suhnggwon Kim, Jung Hwan Park, Sung Joon Shin, Sang Ho Lee, Bum Soon Choi, Chun Soo Lim, Jung Nam An, Jin Ho Hwang, Jung Pyo Lee, Ho Jun Chin, Sejoong Kim, Dong Ki Kim, Suhnggwon Kim, Jung Hwan Park, Sung Joon Shin, Sang Ho Lee, Bum Soon Choi, Chun Soo Lim

Abstract

Blockade of the renin-angiotensin-aldosterone system exhibits a renoprotective effect; however, blockade of this system may also decrease hemoglobin (Hb) and erythropoietin (EPO) levels. We evaluated the correlation between reduced albuminuria and decreased hemoglobin concentrations after treatment with an angiotensin II receptor blocker (ARB). Two hundred forty-five non-diabetic hypertensive participants with established albuminuria and relatively preserved renal function were treated with an ARB (40 mg/day olmesartan) for eight weeks. Subsequent changes in various clinical parameters, including Hb, EPO, and albuminuria, were analyzed following treatment. After the 8-week treatment with an ARB, Hb and EPO levels significantly decreased. Patients with a greater decrease in Hb exhibited a greater reduction in 24-hour urinary albumin excretion compared with patients with less of a decrease or no decrease in Hb, whereas no associations with a decline in renal function and EPO levels were noted. Multivariate logistic regression analysis demonstrated a correlation between the reduction of urine albumin excretion and the decrease in Hb levels (after natural logarithm transformation, adjusted odds ratio 1.76, 95% confidence interval 1.21-2.56, P = 0.003). Linear regression analysis also supported this positive correlation (Pearson correlation analysis; R = 0.24, P < 0.001). Decreased Hb concentrations following ARB treatment were positively correlated with reduced albuminuria in non-diabetic hypertensive patients, regardless of decreased blood pressure and EPO levels or renal function decline.

Trial registration: ClinicalTrials.gov NCT01552954.

Conflict of interest statement

Competing Interests: This study was funded by Daiichi Sankyo Korea Co. Ltd., and Daewoong Pharmaceutical Co. Ltd., Seoul, Korea. Olmesartan medoxomil was also provided by the same pharmaceutical companies for all participants. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Correlation between the decrease in…
Fig 1. Correlation between the decrease in hemoglobin level and the decline in eGFR levels.
A. Changes in eGFR levels following angiotensin receptor blocker treatment do not correlate with decreased hemoglobin levels (P = 0.627). GFR, glomerular filtration rate. B. Correlation between the decrease in hemoglobin level and the decline in EPO levels. Changes in EPO levels following angiotensin receptor blocker treatment do not correlate with decreased hemoglobin levels (P = 0.378). EPO, erythropoietin.
Fig 2. Correlation between the reduction in…
Fig 2. Correlation between the reduction in 24-hour urine albumin excretion and hemoglobin levels.
Hemoglobin levels significantly decreased as the 24-hour urine albumin excretion decreased (Pearson’s correlation analysis; R = 0.24, P < 0.001).

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