CKD: Low Urine Ammonium Excretion Linked to Death, ESRD

Troy Brown, RN

April 10, 2017

Patients with chronic kidney disease (CKD) who had the lowest urine ammonium excretion had a 46% higher risk of dying or needing dialysis when compared with patients with the highest levels of urine ammonium excretion, a new study found.

Kalani L. Raphael, MD, from the University of Utah, Salt Lake City, and VA Salt Lake City Health Care System, and colleagues report their findings in an article published online April 6 in the Journal of the American Society of Nephrology.

"These results suggest that low urine ammonium excretion identifies individuals at high risk of CKD progression or death irrespective of the serum bicarbonate concentration," Dr Raphael said in a news release. "Overall, acid levels in the urine provide important information about kidney health above and beyond acid measurements obtained from the blood."

The researchers evaluated data from 1044 participants in the African American Study of Kidney Disease and Hypertension to determine whether urine ammonium excretion is independently associated with long-term clinical endpoints in patients with CKD.

Secondary objectives were to determine whether daily urine ammonium excretion is associated with later acidosis and clinical events in a subgroup of patients with CKD and no acidosis.

Compared with those in the highest tertile of urine ammonium excretion, patients in the lowest tertile had a 46% higher (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.13 - 1.87) risk for death or end-stage renal disease (ESRD), after adjusting for demographics, measured glomerular filtration rate, proteinuria, net endogenous acid production, body mass index, serum potassium, and serum total carbon dioxide.

The risk was similar (HR, 1.50; 95% CI, 1.16 - 1.95) when the researchers adjusted for other potential confounders including smoking status, systolic blood pressure, heart disease, use of renin-angiotensin system inhibitors, and diuretics.

For patients in the middle tertile, the HR for death or ESRD was 1.14 (95% CI, 0.89 - 1.46) when compared with those in the highest tertile, after adjusting for demographics, measured glomerular filtration rate, proteinuria, net endogenous acid production, body mass index, serum potassium, and serum total carbon dioxide (tCO2).

Risks Higher Even Among Patients Without Acidosis

Patients without acidosis at baseline also were at increased risk for death or ESRD (adjusted HR for those with ammonium excretion <20 mEq/day, 1.36; 95% CI, 1.09 - 1.71) compared with patients with ammonium excretion 20 mEq/d or higher.

In addition, patients in lowest tertile of ammonium excretion had higher risk (adjusted odds ratio, 2.56; 95% CI, 1.04 - 6.27) of developing acidosis during the next year compared with those in the highest tertile.

Urine ammonium excretion is critical for maintaining normal total carbon dioxide, and reduced urine ammonium excretion is involved in the development of metabolic acidosis in patients with CKD, the researchers write. Therefore, they suggest, it may be an alternative, and possibly earlier, indicator of risk for these patients than tCO2.

"[Lower urine ammonium] excretion is a risk factor for acidosis and poor renal and survival outcomes among African Americans with hypertensive CKD irrespective of important confounders, tCO2, and nutritional determinants of acid-base status. Similar findings were observed in another CKD cohort," the authors explain. "Hence, [urine ammonium] excretion has prognostic value above and beyond tCO2. With accumulating interest in the potential use of alkaline therapy to slow CKD progression in patients without overt acidosis, the observation that lower daily [urine ammonium] excretion in this setting signals a higher risk of death or ESRD suggests that [urine ammonium] may better risk stratify these individuals," they conclude.

The authors have disclosed no relevant financial relationships.

J Am Soc Nephrol. Published online April 6, 2017. Abstract

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