Association of dietary acid load with cardiovascular disease risk factors in patients with diabetic nephropathy

Highlights

• We assessed the association of dietary acid load with cardiovascular risk factors.

• We found negative association for fruit with acid load but positive for meat.

• We found that both potential renal acid load (PRAL) and the ratio of protein to potassium were positively related to hemoglobin A_1c.

• Other risk factors were differently related to acid load indices.

Abstract

Objective

An association between dietary acid load and cardiovascular disease risk has been reported in epidemiologic studies; however, there are no reports to our knowledge of this association in patients with diabetic nephropathy (DN). Therefore, the aim of this study was to examine the association between dietary acid load, based on potential renal acid load (PRAL) and protein:potassium ratio (Pro:K) scores, and cardiovascular disease risk factors in individuals with DN.

Methods

In this cross-sectional study, we randomly enrolled 547 patients with DN. Dietary intake was assessed using a validated food frequency questionnaire. Biochemical and anthropometric measures were assessed using standard methods.

Results

Participants had a mean age of 66.8 y and body mass index of 24 kg/m². After controlling for potential confounders, participants in the low PRAL group had lower hemoglobin (Hb)A_1c (5.7% ± 0.5% versus 7.8% ± 0.5%; P = 0.01), triacylglycerols (246.9 ± 2.3 mg/dL versus 257.4 ± 2.3 mg/dL; P = 0.006), systolic blood pressure (103.6 ± 0.7 mm Hg versus 106.1 ± 0.7 mm Hg; P = 0.03), and lower creatinine and fasting blood sugar compared with the high PRAL group. Pro:K was positively related to HbA_1c (5.8% ± 0.5% versus 7.6% ± 0.5%; P = 0.03), but inversely associated with low-density lipoprotein and waist circumference.

Conclusions

We found that both PRAL and Pro:K were positively related to HbA_1c in the setting of DN, whereas other biochemical and kidney-related markers varied with PRAL and Pro:K status. Future studies are warranted to clarify the clinical outcomes of dietary acid load in older populations as well as in patients with chronic kidney disease.

Introduction

Diabetic nephropathy (DN) is a common complication in patients with poorly controlled diabetes [1]. Findings from a recent systematic review suggest that the prevalence of DN in Iranian adults ranges between 7% and 26% [2]. Both diabetes and nephropathy are independent risk factors for cardiovascular disease (CVD) [3]. Genetic and dietary factors [4], [5] are determinants of poor glycemic control, insulin resistance (IR), and elevated glycated hemoglobin (Hb)A_1c, which are the primary determinants of microalbuminuria [6], a prognostic marker of kidney disease.

A focus on identifying dietary approaches that improve insulin sensitivity may delay the onset of nephropathy in patients with diabetes. Furthermore, the published literature suggests that even a small increase metabolic acidosis increases IR [7]. Therefore, reducing the dietary acid load may offer one solution to improve health outcomes in patients with diabetes. Moreover, several cross-sectional and longitudinal studies have found a positive association between dietary acid load and increased risk for various chronic diseases, including diabetes, IR, nonalcoholic fatty liver, and cardiometabolic factors [8], [9], [10], [11], but not hypertension [12].

An understanding of the effect of dietary acid load in individuals with kidney disease is relevant not only because the kidney plays an active role in acid–base homeostasis, but the acid-excretion capacity is diminished, which may intensify metabolic acidosis [13]. Additionally, acid-inducing diets increase kidney tubular toxicity by elevating ammonium production to excrete H+ and activating the renin-angiotensin system [14], which contribute further declines in kidney function. Thus, the consumption of alkaline-rich foods may contribute to amelioration of the metabolic profile in patients with kidney diseases [13].

Dietary acid load has been estimated by two approaches in epidemiologic studies. The potential renal acid load (PRAL) is based on the intestinal absorption rates of five nutrients including protein, potassium, phosphorus, magnesium, and calcium [15], [16]. The second is determined by net endogenous acid production (NEAP), which takes into account the total amount of ingested protein and potassium [17]. The significant association between 24-h urinary net acid excretion (NAE) with PRAL and NEAP has been validated in renal transplant recipients [18]. Therefore, both PRAL and NEAP may be useful indicators of dietary acid load status in patients with DN.

To date, most studies examining the association between dietary acid load and CVD risk have been conducted with healthy young participants. To our knowledge, there is only one published study in renal transplant recipients; however, little else is known about the relationship between dietary acid load and kidney-related and inflammatory markers in renal patients. Additionally, many Iranians consume lower than recommended servings of fruits and vegetables or milk and meat products. However, consumption of soft drinks has increased among Iranian adults [19]. Iranians primarily meet their daily energy requirements from simple and refined carbohydrates, and only 22% is derived from fat [20]. Therefore, in the present study, we assessed the relationship between two markers of dietary acid load on CVD factors, high-sensitivity C-reactive protein (hs-CRP), and kidney-related biomarkers in patients with DN.