Dietary Acid Load is Associated With Serum Bicarbonate but not Insulin Sensitivity in Chronic Kidney Disease

Abstract

Objective In chronic kidney disease (CKD), dietary acid may promote metabolic acidosis and insulin resistance, which in turn may contribute to adverse clinical health outcomes. We examined associations between dietary acid load, serum bicarbonate, and insulin sensitivity in CKD. Design In a cross-sectional study, we collected 3-day prospective food diaries to quantify dietary acid load as net endogenous acid production (NEAP, the nonvolatile acid load produced by the diet’s acid balance) and potential renal acid load (PRAL). We measured urine net acid excretion (NAE) in 24-hour urine samples. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp. Subjects 42 patients with CKD stages 3–5 attending nephrology clinics in the Pacific Northwest and 21 control subjects (eGFR ≥60mL/min/1.73m2). Main outcome measures Serum bicarbonate and insulin sensitivity (SIclamp). Results Mean age was 60.8±13.6 years and 54% of participants were men. Mean eGFR and serum bicarbonate concentrations were 34.4±13.1 mL/min/1.73m2 and 24.1±2.9 mEq/L for participants with CKD and 88.6±14.5 mL/min/1.73m2 and 26.3±1.8 mEq/L for control subjects, respectively. Mean NEAP, PRAL, and NAE were 58.2±24.3, 9.7±18.4, and 32.1±19.8 mEq/day, respectively. Considering all participants, dietary acid load was significantly, inversely associated with serum bicarbonate, adjusting for age, sex, race, eGFR, BMI, and diuretic use: −1.2 mEq/L per SD NEAP (95% CI −1.8, −0.6, p<0.0001); −0.9 mEq/L bicarbonate per SD PRAL (95% CI −1.5, −0.4, p=0.0005); −0.7 mEq/L bicarbonate per SD NAE (95% CI −1.2, −0.1, p=0.01). These associations were similar in participants with and without CKD. However, neither NEAP, PRAL, nor NAE was significantly associated with SIclamp. Serum bicarbonate was also not significantly associated with SIclamp. Conclusions In CKD, dietary acid load is associated with serum bicarbonate, suggesting that acidosis may be improved by dietary changes, but not with insulin sensitivity. Practical application We observed that a diet with a greater acid load was associated with lower serum bicarbonate but not insulin resistance in patients with chronic kidney disease. It may be beneficial to limit dietary acid in patients with chronic kidney disease to improve metabolic acidosis and its long-term adverse health effects, but additional, experimental studies are needed to establish the safety and usefulness of such interventions.

Dietary acid load, blood pressure, fasting blood sugar and biomarkers of insulin resistance among adults: Findings from an updated systematic review and meta‐analysis

“…Several other studies also reported similar results of higher prevalence of HTN or higher SBP and DBP values in highest vs lowest PRAL or NEAP groupings . Only one study reported inverse association between HTN prevalence among NEAP quartiles and several other studies found no difference . In the data analysis of Rotterdam study by Engberink et al, SBP in the highest tertile of PRAL was significantly higher than the lowest.…”

“…Table presents the summary of systematically reviewed studies evaluated the association between dietary acid load (eg PRAL or NEAP), blood pressure and hypertension prevalence. Totally, 20 studies reported the association between HTN, blood pressure and PRAL or NEAP among the systematically reviewed literature . In the study by Akter et al evaluating the association between dietary acid load and prevalence of HTN in the Furukawa Nutrition and Health Study the odds of HTN in subjects in the highest tertile of PRAL and NEAP was 31% and 40% more than individuals in lowest tertile (PRAL; OR: 1.31; CI: 1.01‐1.70; NEAP OR: 1.40; CI: 1.08‐1.82) among 2028 working Japanese population.…”

“…12,18,39,40 Only one study reported inverse association between HTN prevalence among NEAP quartiles 4 and several other studies found no difference. 7,15,19,22,[31][32][33][35][36][37][38]42 In the data analysis of Rotterdam study by Engberink et al, 33 SBP in the highest tertile of PRAL was significantly higher than the lowest.…”

“…The association between dietary acid load and glycaemic markers, insulin resistance and the prevalence of diabetes or the odds of diabetes has been reported in 22 studies. 4,6,7,12,15,[17][18][19][20][21][22][31][32][33][34][35][37][38][39][40][41][42] In the study by Akter et al PRAL and NEAP scores were positively associated with HOMA-IR values (P-trend:…”

“…13,14 Numerous studies are available reporting the association between metabolic risk factors with dietary acid load as either PRAL or NEAP or both of them. 7,12,[15][16][17][18][19][20] The results of these studies are inconsistence; several reported the positive association between metabolic risk factors 5,6,21 while others not. 4,22 According to our literature review, only one meta-analysis was carried out evaluating the association between dietary acid load and risk of T 2 DM with literature review up to September 2017.…”