Non-dietary factors may affect net acid excretion

New evidence suggests that, contrary to popular clinical belief, non-dietary factors such as body composition, medications, and insulin resistance may also contribute to a patient's net acid excretion (NAE).

This new evidence was presented by Landon C. Brown, MD, of Duke, in a poster displayed at the American Society of Nephrology's annual meeting held October 31 to November 5, 2017, in New Orleans, LA. Other Duke investigators involved in the research included Myles S. Wolf, MD, MMSc, and Julia J. Scialla, MD.

Researchers analyzed data from the Chronic Renal Insufficiency Cohort (CRIC), a multicenter prospective study of racially and ethnically diverse patients with chronic kidney disease (CKD). CRIC was established in 2001 by the National Institute of Diabetes, Digestive, and Kidney Diseases to improve understanding of chronic renal insufficiency and related cardiovascular illnesses. To be included in CRIC, patients had to have an estimated glomerular filtration rate (eGFR) of 20 to 70 mL/min/1.73 m2.

The analyses conducted by Brown and colleagues' were inspired by a previous finding made by members of the same research group that patients with diabetes who had high NAE actually demonstrated a lower risk of CKD progression—the opposite of what one would expect, Brown explained. "It used to be that everyone thought diet was the only thing that could throw off NAE, but that finding made us want to go back and look at other factors that might be affecting metabolic acidosis," said Brown.

To explore the relationship of NAE with other possible factors, investigators measured NAE in 24-hour urine as the sum of the urine ammonium and titratable acidity. Linear regression was used to identify individual variables and sets of variables associated with NAE across the domains of demographics, comorbidities, laboratory measurements, diet, body composition, and medications.

Mean NAE was 33.2 ± 17.4 mEq/day and was higher in patients with diabetes (n = 496; 34.4 ± 18.7 mEq/day; P < .05) than it was in those without diabetes (n = 482; 31.9 ± 15.9 mEq/day; P = .02); this was especially the case in patients with diabetes who were taking biguanide drugs. Multiple variables were shown to be associated with NAE, including body size, insulin resistance, kidney function, acid-base status, nutrition (serum albumin and diet), and several drugs.

To their surprise, researchers found the most variance in NAE to be explained by the domains of laboratory values (kidney function, serum bicarbonate), body composition (body mass index, body surface area, free fat mass, waist size), and demographics (age, sex, race, education). Diet (total protein, total calories, dietary potassium, dietary sodium, potential renal acid load) only explained a moderate degree of variance, the study concluded (Table 1).

TABLE 1. Variable Domains Associated With NAE

Domain Variance explained (adjusted R2)
Laboratory values 13.4%
Body composition 13.0%
Demographics 9.9%
Diet 6.6%
Comorbidities 2.9%
Medications 2.7%

If these findings are confirmed, they could affect patient management. For example, because alkali supplements are often used to slow the progression of CKD and reduce NAE, nephrologists may need to adjust clinical goals to take these other factors into account. Brown noted: "It's much more complicated than just what we eat, which has been the primary hypothesis for years."

Source: Brown LC, Rahman M, Miller ER, et al. Predictors of net acid excretion in the chronic renal insufficiency cohort (CRIC) study. Presented at: American Society of Nephrology annual meeting, Kidney Week, 2017; October 31-November 5, 2017; New Orleans, LA. Poster 428.