Clinical grade albuminuria and microalbuminuria are associated with high risk of chronic renal insufficiency, cardiovascular disease and death. Recently the Heart Outcomes Prevention Evaluation (HOPE) study showed an association of risk of total mortality and cardiovascular disease incidence with urinary albumin excretion, even within the normal range of excretion. Albuminuria is known to be reduced by ACE-inhibitors and by certain low protein diets. Reduction occurs within 8 weeks. Low protein diets are often formed by increasing fruits, vegetables, whole grains, and dairy products, while reducing red meat and other sources of protein. Therefore diets previously shown to lower albumin excretion in normal participants and in patients with renal disease are consistent with the dietary pattern employed in the Dietary Approaches to Stop Hypertension Trial (DASH, 1994-96) study. We propose to study albumin excretion in the DASH diet using frozen urine samples. DASH was a parallel arm, randomized feeding study in over 400 persons with high normal blood pressure or stage I hypertension, designed to study dietary pattern influences on blood pressure. It employed a control diet, similar to that eaten by many Americans, and intervention diets, including one that increased intake of fruits and vegetables, but was otherwise similar to the control diet; and another, the DASH diet, that, in addition, increased other high fiber plant foods, increased protein from chicken and fish, and added low-fat dairy products. For 421 of the 459 DASH participants, 24-hour urine samples were stored at baseline and after 8 weeks on diet; an additional 64 participants provided samples after 4 weeks on diet. These samples have been stored at -70'C since 1994-96. Blood pressure reductions were seen in both the fruit and vegetable diet and the more comprehensive DASH diet, compared to the control diet. We propose to measure urinary albumin concentration in these samples (n ca. 1000). As a quality control measure, we will measure creatinine in a subset of these samples, for comparison with their originally measured values. Statistical analyses will assess the primary hypothesis that the DASH diet reduces albuminuria, even in the normal range. A secondary hypothesis is a dose-response pattern: that the fruit and vegetable diet has an influence on albuminuria intermediate between that of the DASH diet and the control diet. Thus we will test the hypothesis that the DASH dietary pattern ameliorates albuminuria. Reduction of albuminuria and the underlying defects that it represents is an important medical and public health goal.
| Jacobs Jr, David R; Gross, Myron D; Steffen, Lyn et al. (2009) The effects of dietary patterns on urinary albumin excretion: results of the Dietary Approaches to Stop Hypertension (DASH) Trial. Am J Kidney Dis 53:638-46 |
| Cummings, Rhett; Zhao, Yutong; Jacoby, David et al. (2004) Protein kinase Cdelta mediates lysophosphatidic acid-induced NF-kappaB activation and interleukin-8 secretion in human bronchial epithelial cells. J Biol Chem 279:41085-94 |
