Dietary acid load and chronic kidney disease among adults in the United States

Diet can markedly affect the acid-base status [1–4] and it significantly influences the chronic kidney disease (CKD) and its progression [5–8]. Dietary acid load (DAL) is determined by the balance of acid-inducing foods which is rich in animal proteins (such as meats, eggs, and cheese) and base-inducing foods which is rich in fruits and vegetables (such as raisins, apples, peaches, spinach, and cauliflower). Intake of acid-inducing foods in high amounts for a sufficient period of time can induce metabolic acidosis [9, 10]. Acid-inducing diets are believed to impact the kidney via tubular toxicity of elevated ammonium concentrations and activation of the renin-angiotensin system [11, 12]. With increased dietary acid load, production of ammonia is increased in the proximal tubule and H⁺ excretion is increased distally to augment overall acid excretion [13, 14].

Prior studies have demonstrated that dietary acid-loading increased and base-loading decreased angiotensin II, endothelin-1, and aldosterone –mediated kidney injury [5, 6]. Some small translational studies in patients with early CKD demonstrated that oral alkali or base-inducing fruits and vegetables (e.g. raisins, apples, spinach) decreased urinary endothelin-1, aldosterone, and markers of tubulointerstitial injury in addition to slowing GFR decline [5, 11]. Although a study by Scialla et al. [15] conducted among African Americans with hypertension-attributed nephropathy found that higher net endogenous acid production was associated with faster GFR decline and Kanda et al. [16] found similar results in a cohort with older CKD adults, the degree to which DAL is associated with risk of CKD in large, representative populations has not been explored. Furthermore, the relation of DAL with characteristics of persons at risk for CKD is largely unknown. Understanding these relations could provide a foundation for dietary interventions in CKD. Therefore, we undertook a population-based study to investigate whether dietary acid content, which we quantified as net acid excretion (NAE_es) estimated from 24-hr dietary recall, is associated with advanced stages of CKD or albuminuria. We also investigated the relation between socio-demographic and clinical characteristics and DAL.

In this nationally representative cohort, we found that greater DAL, quantified by estimated NAE was associated with albuminuria among U.S. adults. Moreover, several socio-demographic factors (age 40–60 years, low income, and racial/ethnic minority status) were independently associated with high DAL.

Western diets, which are generally high in animal and grain products, are high in acid precursors. In general, common foods that impart a high DAL include cheese, meat, eggs, and grains; whereas fruits and vegetables provide alkali [1, 28]. The average American consumes approximately 15–17% of their energy as protein, predominantly from animal sources [29]. In addition, it is low in potassium-rich fruit and vegetables [30], resulting in an average DAL of approximately 1 mEq/kg/day [31]. Our findings raise the possibility of high acid containing diets playing a role in the development of CKD. They buttress the findings of smaller studies that have shown that dietary acid reduction with either NaHCO₃ and/or base-inducing fruits and vegetables slow GFR decline and reduce urinary parameters of kidney injury in CKD patients [32]. While this area is still being developed, there are studies that have suggested that high dietary acid load might mediate progressive GFR decline in those with moderately reduced GFR due to hypertensive nephropathy [7, 11]. Our results not only suggest higher risk of albuminuria and low eGFR in participants with hypertension but a similar magnitude effect was observed for participants without hypertension or diabetes.

In our study, we examined the association between protein intake and phosphorus intake with albuminuria. Although there is concern that high protein intake and phosphorus intake may promote renal damage by chronically increasing glomerular pressure and hyperfiltration [33–35], we did not find a significant association between them. This is not surprising in that Remer et al. [1, 2], Goraya et al. [8, 32], and Scialla et al. [36] show that the more important determinant of the effect of dietary protein on nephropathy progression is the quality of the ingested protein (i.e., whether it induces acid-production [like most animal protein] or base production [like most fruit and vegetable protein]) when ingested rather than the quantity of protein ingested. It is important to note that our results suggested a higher risk of albuminuria in adults with greater DAL than that suggested by the amount of either protein or phosphorus intake alone. A balance of protein intake with base-inducing fruits and vegetables may be important for containing renal damage.

Our finding of an association between low socioeconomic-status (SES) and greater NAE_es is intriguing. Lower financial means and living in certain communities may affect the ability of individuals to obtain a diet rich in fruits and vegetables. Studies of the food and low SES environment suggest that low-income individuals often live in neighborhoods where there are few full-service grocery stores and may not have easy access to transportation to allow for shopping at such stores in outlying areas [37]. Limited access to nutritious food and relatively easier access to less nutritious food may be linked to poor diets and, ultimately, to diet-related diseases. Differences in access to food may create structural barriers in poor communities that lead to poor health behaviors and health inequalities [38].

Fresh fruits and vegetables can be expensive, and low-income individuals must weigh how they will use their scarce resources. Prior studies found that having a lower income and no greater than a high school education were associated with consumption of fewer servings of fruits and vegetables per day [39, 40]. Energy-dense foods composed of refined grains, added sugars, or fats may represent the lowest-cost option [41, 42]. The consumption of more fruits and vegetables typically lowers the DAL [32, 43]. In contrast, sugar consumption has been linked with an increase in uric acid levels, which in turn may promote kidney damage [44]. Thus, low SES might lead to greater CKD burden via this pathway [44, 45].

Although our findings are consistent with some prior studies [5–8] suggesting that the risk for CKD or its progression may be mitigated by a reduction in the DAL, this area remains controversial. Jara et al. found that the combination of chronic metabolic acidosis and phosphate loading in azotemic rats may protect against the progression of renal failure, because the harmful effects of acidosis and phosphate loading may be counterbalanced [46]. In a similar study, Mendoza et al. [47] found that metabolic acidosis inhibits vascular and soft-tissue calcifications in calcitriol-treated uremic rats. Since acidosis prevents upregulation of vascular Pit-1 expression, a possible mechanism for its anticalcifying effect may be reduced cellular uptake of phosphate [47].

Despite the strengths of a large study representative of the U.S. population, the detailed collection of nutritional parameters, and standardized laboratory testing that is integral to the design of the NHANES, our study had certain limitations. First, it was an observational study, and although we adjusted for potential confounders associated with both diet content and CKD, residual confounding is likely. Second, by design, the NHANES is cross-sectional; therefore, causality cannot be inferred and there is a possibility of misclassification of risk factors for CKD such as diabetes and hypertension which are defined from measurements at a single time point. Third, we lacked a measure of the neighborhood food environment which may affect individual dietary patterns [48]. We also did not assess health behaviors that may be closely associated with dietary practices, such as physical activity and adherence to medications. Fourth, we did not have any details available on the family history of kidney disease for these participants. Fifth, a 24-hour dietary recall was used to assess the usual intake which is subject to bias. However, previous literature has demonstrated the reliability of dietary intake measures from the 24-hour dietary recalls [49]. Sixth, we analyzed participants for whom we had complete data of their dietary recall interview, thus introducing the potential for selection bias. However, there was no significant difference in the socio-demographic and clinical characteristics in the participants whom we included in our study and those excluded, except age. Finally, we estimated NAE_es from dietary data using previously validated equations rather than directly measuring NAE_es in participants’ urine.

To our knowledge, this is one of the few studies to assess the relationship of dietary renal acid load with markers of CKD in a large, representative population, and to examine the association of socio-demographic characteristics with dietary renal acid load. Our findings suggest that high DAL is associated with greater risk of markers of CKD, and older age, poverty, racial/ethnic minority status, and limited education are independently associated with high DAL among U.S. adults. The findings have important implications, in that, if they are corroborated in other studies, altering diets may provide an adjunct approach to other strategies for treatment of CKD. Longitudinal studies in large representative populations should be conducted to examine a potential causal relationship between NAE_es and CKD.