Effects of Dietary Modification on Albumin Excretion Rate

Lifestyle modification is an important component in the management of most hypertensive patients. This includes limitation of dietary salt intake, use of the Dietary Approaches to Stop Hypertension (DASH) diet, regular aerobic exercise, maintenance of suitable body weight, smoking cessation, and minimizing alcohol intake.1 These interventions can successfully decrease blood pressure and may be equivalent to the effects of a single antihypertensive medication. However, there are limited data about the effects of lifestyle modification on target-organ damage related to hypertension. In addition, it is likely that many of these interventions have a salutary effect on overall cardiovascular health; how much of the long-term beneficial effect is independent of blood pressure lowering is unclear.

In this issue of the American Journal of Kidney Diseases, Jacobs et al2 report urinary albumin excretion rates of individuals in each of the 3 controlled feeding arms of the DASH trial: those consuming a control diet, a fruit/vegetable (FV) diet, or the DASH diet itself. The DASH diet favors fruits and vegetables (with more servings of vegetables than the FV diet), is rich in low-fat dairy products, and is low in saturated and total fat. It comprises 4 to 5 servings of fruit, 4 to 5 servings of vegetables, 2 to 3 servings of low-fat dairy, and less than 25% fat per day. Sodium, potassium, and protein contents of these 3 diets are listed in Table 1.

Table 1. Nutrient Targets of Control, Fruit/Vegetable, and DASH Diets

		Control	Fruit/Vegetable	DASH
	Protein (% kcal)	15	15	18
	Potassium (mg/d)	1,700	4,700	4,700
	Sodium (mg/d)	3,000	3,000	3,000

Note: One gram of sodium corresponds to 43 mEq, and 1 g of potassium corresponds to 25 mEq. Abbreviation: DASH, Dietary Approaches to Stop Hypertension. Data from Appel et al.3

The DASH diet has been well studied in carefully designed prospective clinical trials and was shown to decrease blood pressure by 5.5/3.0 mm Hg.3 In the DASH trial, 378 participants with entry diastolic blood pressure of 80 to 95 mm Hg and systolic blood pressure less than 160 mm Hg were randomly assigned to 1 of these dietary patterns for an 8-week period. For the article published in this issue of AJKD, stored urine samples were used to assess albumin excretion rates in DASH participants. The majority of participants (n = 285; 76%) had very low albumin excretion rates (<7 mg/24 h), and in this subgroup, albumin excretion rate did not differ significantly among the 3 diet groups at the end of the 8-week study period. However, in the subgroup of participants with albumin excretion rates greater than 7 mg/24 h (still less than the microalbuminuric range), albumin excretion rates were lowest at the end of the study period in participants assigned to the FV diet (6.6 mg/24 h) compared with the DASH (11.7 mg/24 h) and control diets (11.4 mg/24 h). Interestingly, the decrease in blood pressure was larger in participants assigned to the DASH diet (−4.9/−2.1 mm Hg) compared with the FV (−3.6/−1.4 mm Hg) and control diets (−0.7/0.1 mm Hg). Because albumin excretion varies on a day-to-day basis, current guidelines recommend the use of repeated samples to verify quantitation of albuminuria.4 Therefore, use of a single sample, particularly with very low levels of albumin excretion, is a methodologic limitation of this study.

These data stimulate 2 lines of thought: (1) how does this impact on the use of the DASH diet versus an FV diet, and (2) what are the implications of decreasing urinary albumin excretion in patients with “normal” levels of urinary albumin excretion? We attempt to discuss both these issues.

To put these results in perspective for an audience of nephrologists, it is important to note that patients in the DASH study had either mild hypertension or prehypertension and very low levels of urinary albumin excretion. Patients with chronic kidney disease (CKD; defined as reduced kidney function) were excluded from the study. Therefore, care needs to be taken before extrapolating these results to patients with greater severity of hypertension or evidence of target-organ damage. In addition, increased fruit and vegetable intake has the potential to increase dietary potassium intake, necessitating appropriate laboratory monitoring in a population with substantially reduced kidney function.

This study mitigates any theoretical concerns about whether the DASH diet may increase albuminuria because of its relatively high protein content. The dissociation of changes in albuminuria with changes in blood pressure suggests that mechanisms other than decreasing blood pressure mediate the albuminuria reduction seen with the FV diet. As discussed by the investigators, the altered balance of animal and plant protein may be associated with increased antioxidant and possibly anti-inflammatory properties that have a beneficial effect on endothelial function and therefore improve albuminuria. In addition, whether some of the beneficial effects seen may relate to the increased fiber intake is unclear.

Albuminuria is a robust predictor of increased risk of both progression of kidney disease and development of cardiovascular disease (CVD). Several studies indicate a strong graded relationship between CVD events and albumin excretion lower than the traditional albumin-creatinine ratio threshold of 30 mg/g used in the definition of CKD.5, 6 It also is emerging, mostly from post hoc analyses of large studies, that decreasing proteinuria from high levels is associated with improved outcomes. Therefore, some have suggested the use of proteinuria as a surrogate marker for progression of CKD.7 However, whether changes in albuminuria within the normal range will translate into lower risk of adverse outcomes of CKD and CVD is unresolved.

It is unlikely that low levels of albumin excretion per se directly cause kidney disease progression or CVD. It generally is believed that albuminuria is associated with several other risk factors that may themselves be causal or linked with causal processes.5 These include hyperglycemia, hypertension, decreased glomerular filtration rate, dyslipidemia, smoking, and inflammatory markers of an acute-phase response. Albuminuria may reflect increased renal endothelial permeability and may reflect diffuse endothelial dysfunction. If so, albuminuria would be an easily measured marker of other CVD factors, as well as of existing endothelial dysfunction, that likely reflect underlying macrovascular and microvascular disease.

The ability to affect albumin excretion at low levels presents an intriguing opportunity. Whether these changes can be sustained over time and in a real-world setting needs to be determined. These studies were conducted in the setting of research kitchens under the supervision of trained dieticians, evidenced by findings that the DASH diet was less effective in decreasing blood pressure when patients prepared their own food.8 Unfortunately, many clinicians do not have access to frequent dietary consultations, and reimbursement for nutritional services is problematic. The dissociation of changes in albuminuria with changes in blood pressure suggests that mechanisms other than blood pressure mediate albuminuria. Other ways of decreasing albuminuria, alone or in combination with inhibitors of the renin-angiotensin axis, need to be explored. These represent important opportunities for research regarding the larger objective of slowing progression and decreasing the risk of CVD in the setting of CKD.

What are the clinical implications of this study? In addition to well-recognized interventions that decrease albumin excretion, such as blockade of the renin-angiotensin-aldosterone system, blood pressure control, and glycemic control, these data support the concept of increasing fruits and vegetables in the dietary intake of individuals with hypertension. This is consistent with other benefits of increasing fruit and vegetables, as widely recognized in current guideline recommendations.9 Given the beneficial effects of these dietary interventions on blood pressure and now perhaps on markers of target-organ damage, changes in reimbursement practices and system-level changes to allow increased focus on dietary interventions may be supported. If additional studies support improvement in manifestations of target-organ damage related to hypertension, in the long term, cost savings may overcome the increased expenditure required to efficiently and successfully implement dietary changes. In addition, novel ways of implementing lifestyle modification in clinical practice will be invaluable in the future, particularly in the context of dietary changes.