Jackson Heart Study: Dietary Acid Load and Risk of CKD Progression

Results of recent studies have shown that progression of chronic kidney disease (CKD), defined by estimated glomerular filtration rate (eGFR), can be affected by acid-base status. Research, including animal studies, observational epidemiology, and small clinical trials, has examined the impact of chronic metabolic acidosis on eGFR decline in individuals with moderately impaired kidney function. Diets high in sulfur-rich protein and low in fruit and vegetables have an adverse effect on human acid-base and may be a contributing factor to  CKD progression.

There are few data available on the relationship between participant characteristics, dietary acid load, and kidney injury in African Americans with high risk of CKD progression. The Jackson Heart Study offers an opportunity to examine the impact of diet, particularly dietary acid load, on renal function in that patient population. Tanushree Banerjee, PhD, and colleagues recently conducted an analysis of data from the Jackson Heart Study to assess (1) the association between participant characteristics (sociodemographic characteristics, cultural, behavioral determinants, violence, coping inventory,  global stress, and anger) and dietary acid load, and (2) the association between dietary acid load and impaired kidney function and albuminuria in participants ≥20 years of age in the Jackson Heart Study. Results of the analysis were reported in the Journal of Renal Nutrition [2018;28(4):251-258].

The Jackson Heart Study enrolled 5301 African Americans from the Jackson, Mississippi, area between September 2000 and March 2004. Following exclusion due to missing data, the current analysis included 3257 individuals. Compared with those with complete data, the 1928 excluded individuals tended to be older (58.3 vs 54.1 years), more likely to be male (37.8% vs 31.7%), to have lower education level (31.4% vs 37.4% college degree), and were less likely to have diabetes (21.3% vs 25.1%).

For the current analysis, participants were stratified into one of three groups by dietary acid load, mEq/d: Low, minimum-50.6, n=1075; (2) middle, 50.6-60.1, n=1108; and (3) high, 60.1-maximum, n=1074.

In unadjusted models, there was an association between high dietary acid load and younger age and male sex. There were also associations between high dietary acid load and less church support, higher body mass index (BMI), higher homeostasis model assessment: insulin resistance (HOMA-IR), more physical activity, lower likelihood of hypertension, and higher total energy intake per day. Results of adjusted models using multivariable analysis showed significantly higher dietary acid load among smokers, those with higher education level, those with higher BMI, and those with higher daily energy intake. In the adjusted model, following exclusion of diabetes, the researchers found significantly lower dietary acid load among those with higher HOMA-IR.

In further analysis of the association between dietary acid load as an independent predictor and insulin resistance as a primary outcome, there was a statistically significant association between the highest tertile of dietary acid load, quantified as potential renal acid load, and insulin resistance (b: –0.9 (95% confidence interval [CI], –1.5 to –0.02).

There was more albuminuria among participants with higher dietary load. Following adjustment for potential confounders, the odds of having albuminuria were 1.2 times higher in participants in highest tertile of dietary acid load compared with those in the lowest tertile (odds ratio [OR], 1.15; 95% CI, 0.75-1.70); the association was nonsignificant. The linear trends across tertiles also did not reach statistical significance (P for trend=.10). In a subset of participants with hypertension, there was an association between significant odds of albuminuria and the highest (vs the lowest) tertile of acid load. The association was no longer significant following adjustment for aldosterone, and was further attenuated after inclusion of endothelin.

There was no significant association between acid load and eGFR in unadjusted analyses. However, following multivariable adjustment for confounders, the highest and middle tertiles of acid load were associated with a nearly three times odds of reduced kidney function compared with the lowest tertile. There was also a statistically significant association between higher dietary acid load and reduced kidney function across tertiles after adjustment for potential confounders (P for trend=.02). In the subset of participants with hypertension, compared with the lowest tertile of dietary acid load, those in the middle and highest tertiles had statistically significant odds of reduced kidney function; the odds were attenuated after further adjustment for aldosterone and endothelin.

The association between dietary acid load and CKD was not significant in unadjusted analyses. In the multivariable model, the odds of CKD among those in the highest tertile of dietary acid load were 2.4 times higher than for those in the lowest tertile. Odds for CKD for participants in the middle tertile were nearly twice as high as for those in the lowest tertile. There was a significant trend of risk of CKD across tertiles with further dietary acid load (P for trend=.001). In the subset with hypertension, the odds of risk of CKD were twice as high for those in the highest tertile compared with those in the lowest tertile. The odds were attenuated following further adjustment for aldosterone and endothelin, and the association was no longer significant.

On analysis of only participants with 24-hour urine collection, there was an association between higher levels of dietary acid load and greater odds of albuminuria, compared with the lowest levels of dietary acid load (OR, 1.12; 95% CI, 1.02-1.70). Following adjustment for confounders, there was a significant association between greater dietary acid load and prevalent CKD. Results were similar in the subgroup with hypertension in the primary analysis for highest versus lowest tertile of dietary acid load and albuminuria (OR, 1.29; 95% CI, 1.10-2.52).

The researchers cited some limitations to the study, including the observational design that may allow for incompletely controlled confounding, assessing food intake by FFQ alone, not evaluating the effect of different types of ingested protein on acid production, and the inability to generalize the findings to a broader population of African Americans.

The researchers said, “In this high-risk population of African Americans from the South, in general, consumed diets were high in acid load. High dietary acid load was independently associated with increased odds of albuminuria and reduced kidney function. These data emphasize the likely role of nutrition in optimizing CKD outcomes and provide insight into dietary factors that may contribute to geographic and racial disparities in kidney disease risk in the United States.”

Takeaway Points

  1. Using data from the Jackson Heart Study, researchers conducted an analysis to examine the association of dietary acid load in African Americans at high risk of progression of chronic kidney disease (CKD).
  2. Dietary acid load was higher in younger adults, men, and in those with higher body mass index.
  3. Higher dietary acid load was associated with greater risk of CKD, even after adjustment for confounders. In a subgroup with hypertension, results were similar.