# Acid-base balance and kidney, bone, and muscle health in Veterans with preserved renal function

> **NIH VA I01** · VA SALT LAKE CITY HEALTHCARE SYSTEM · 2020 · —

## Abstract

Chronic kidney disease (CKD) is a common, morbid, and costly condition that significantly impacts Veteran
health. Apart from diabetes and hypertension control, there are no other therapies that prevent CKD. Results
from large cohort studies suggest that diets that are higher in acid content increase the risk of CKD and end-
stage renal disease. Further, dietary acid excess and metabolic acidosis are linked with bone demineralization,
muscle catabolism, and physical dysfunction, which could be impacting Veteran health as well. One of the
challenges translating these findings into the clinic is that dietary acid excess is typically determined from
dietary histories, which are often inaccurate and impractical in clinical practice. Another is that the most
commonly measured acid-base indicator, serum bicarbonate, is likely to be in the normal range even in the
setting of a high acid diet. This is because urinary ammonium excretion increases in response to dietary acid to
facilitate acid excretion and formation of new bicarbonate, which ultimately maintains serum bicarbonate and
pH in the normal range. Further, enhanced intrarenal ammonia production causes kidney fibrosis in animal
models. Thus, high urinary ammonium excretion might signal acid-mediated organ injury in the setting of a
normal serum bicarbonate concentration. The hypothesis of this study is that urinary ammonium excretion, as
a direct measurement of dietary acid load, is better associated with kidney injury and impaired bone and
muscle health in Veterans with preserved kidney function than serum bicarbonate concentration. A cross-
sectional study of 260 Veterans with preserved kidney function and diabetes or hypertension is proposed to
investigate this hypothesis. Participants will collect 24-hour urine samples at home while consuming their usual
diet. Urinary ammonium excretion from 24-hour urine collections and venous bicarbonate concentration will be
measured. Adjusted linear and logistic regression analyses will be performed to compare the strength of the
associations of urinary ammonium and serum bicarbonate with kidney, bone, and muscle health markers. The
primary kidney, bone, and muscle outcomes are urinary transforming growth factor-b1, bone mineral density at
the total hip, and quadriceps strength, respectively. Exploratory analyses will compare associations of urinary
ammonium and serum bicarbonate with urinary kidney injury molecule-1 and neutrophil gelatinase-associated
lipocalin levels; lumbar spine bone mineral density, urinary calcium excretion, and serum levels of cross-linked
telopeptide of type 1 collagen and procollagen type I intact N-terminal propeptide; hand-grip strength and Short
Physical Performance Battery score; and frailty. It is hypothesized that urinary ammonium, but not serum
bicarbonate, identifies subclinical kidney injury and impaired muscle and bone health. If the expected results
are observed, they would support urinary ammonium as a practical means...

## Key facts

- **NIH application ID:** 9979783
- **Project number:** 5I01CX001695-03
- **Recipient organization:** VA SALT LAKE CITY HEALTHCARE SYSTEM
- **Principal Investigator:** Kalani Lukela Raphael
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979783

## Citation

> US National Institutes of Health, RePORTER application 9979783, Acid-base balance and kidney, bone, and muscle health in Veterans with preserved renal function (5I01CX001695-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979783. Licensed CC0.

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