Urine Acid/Base Score for Predicting CKD Progression

Acid/base status in CKD is currently determined using plasma measures, but acidosis may be present before it is observable in plasma. Low urine NH4+ excretion has been proposed as a marker for subclinical acidosis, but low NH4+ excretion could be due to a low capacity or low demand for acid excretion. 

Samuel Levi Svendsen and colleagues proposed that a urine acid/base score accounting for both the demand and capacity for acid excretion would better predict CKD progression. They examined 24-hour urine collections from three clinical studies of CKD stage 3-4 patients, divided into a development cohort (n=82), a variation cohort (n=58), and a validation cohort (n=73).  

Urinary pH and NH4+ were used to determine a urine acid/base score. Subclinical acidosis was defined as an acid/base score below the lower limit of the 95% prediction interval of healthy controls. Primary outcomes were the change in measured GFR after 18 months and CKD progression (≥50% decline in eGFR, initiation of long-term dialysis, or kidney transplantation) during a follow-up period of up to 10 years. 

Subclinical acidosis was common among the development (n=54), variation (n=40), and validation cohorts (n=48), with 67% prevalence across all three. Subclinical acidosis was associated with an 18% (95% CI, 2-32) greater decrease in measured GFR after 18 months and with a higher risk of CKD progression during a median follow-up of 6 years. Adjusted HRs were 9.88 (95% CI, 1.27-76.7) for the development cohort and 11.1 (95% CI, 2.88-42.5) for the validation cohort. 

The urine acid/base score using urinary pH and NH4+ had a higher predictive value for CKD progression than NH4+ excretion alone. Subclinical acidosis was associated with a higher risk of CKD progression in patients with CKD stages 3-4. 

Source: Journal of the American Society of Nephrology.