Journal of the American Society of Nephrology : JASN · 2024
A Urine pH-Ammonium Acid/Base Score and CKD Progression.
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Svendsen Samuel Levi, Rousing Amalie Quist, Carlsen Rasmus Kirkeskov, Khatir Dinah, Jensen Danny, Hansen Nikita Misella, Salomo Louise, Birn Henrik, Buus Niels Henrik, Leipziger Jens, Sorensen Mads Vaarby, Berg Peder
Аннотация
KEY POINTS: This study developed a urine acid/base score to assess tubular acid excretion capacity and identify early acid retention in CKD. The results show that early signs of acid retention (a low acid/base score) are associated with a higher risk for CKD progression. Future research should address if a low urine acid/base score can be improved and if this translates into clinically meaningful effects.
BACKGROUND: Acidosis is associated with exacerbated loss of kidney function in CKD. Currently, acid/base status is assessed by plasma measures, although organ-damaging covert acidosis, subclinical acidosis, may be present before reflected in plasma. Low urine NH4+ excretion associates with poor kidney outcomes in CKD and is proposed as a marker for subclinical acidosis. However, low NH4+ excretion could result from either a low capacity or a low demand for acid excretion. We hypothesized that a urine acid/base score reflecting both the demand and capacity for acid excretion would better predict CKD progression.
METHODS: Twenty-four–hour urine collections were included from three clinical studies of patients with CKD stage 3 and 4: a development cohort (N=82), a variation cohort (N=58), and a validation cohort (N=73). A urine acid/base score was derived and calculated from urinary pH and [NH4+]. Subclinical acidosis was defined as an acid/base score below the lower limit of the 95% prediction interval of healthy controls. The main outcomes were change in measured GFR after 18 months and CKD progression (defined as ≥50% decline in eGFR, initiation of long-term dialysis, or kidney transplantation) during up to 10 years of follow-up.
RESULTS: Subclinical acidosis was prevalent in all cohorts (n=54/82, 48/73, and 40/58, respectively, approximately 67%). Subclinical acidosis was associated with an 18% (95% confidence interval [CI], 2 to 32) larger decrease of measured GFR after 18 months. During a median follow-up of 6 years, subclinical acidosis was associated with a higher risk of CKD progression. Adjusted hazard ratios were 9.88 (95% CI, 1.27 to 76.7) in the development cohort and 11.1 (95% CI, 2.88 to 42.5) in the validation cohort. The acid/base score had a higher predictive value for CKD progression than NH4+ excretion alone.
CONCLUSIONS: Subclinical acidosis, defined by a new urine acid/base score, was associated with a higher risk of CKD progression in patients with CKD stage 3 and 4.
BACKGROUND: Acidosis is associated with exacerbated loss of kidney function in CKD. Currently, acid/base status is assessed by plasma measures, although organ-damaging covert acidosis, subclinical acidosis, may be present before reflected in plasma. Low urine NH4+ excretion associates with poor kidney outcomes in CKD and is proposed as a marker for subclinical acidosis. However, low NH4+ excretion could result from either a low capacity or a low demand for acid excretion. We hypothesized that a urine acid/base score reflecting both the demand and capacity for acid excretion would better predict CKD progression.
METHODS: Twenty-four–hour urine collections were included from three clinical studies of patients with CKD stage 3 and 4: a development cohort (N=82), a variation cohort (N=58), and a validation cohort (N=73). A urine acid/base score was derived and calculated from urinary pH and [NH4+]. Subclinical acidosis was defined as an acid/base score below the lower limit of the 95% prediction interval of healthy controls. The main outcomes were change in measured GFR after 18 months and CKD progression (defined as ≥50% decline in eGFR, initiation of long-term dialysis, or kidney transplantation) during up to 10 years of follow-up.
RESULTS: Subclinical acidosis was prevalent in all cohorts (n=54/82, 48/73, and 40/58, respectively, approximately 67%). Subclinical acidosis was associated with an 18% (95% confidence interval [CI], 2 to 32) larger decrease of measured GFR after 18 months. During a median follow-up of 6 years, subclinical acidosis was associated with a higher risk of CKD progression. Adjusted hazard ratios were 9.88 (95% CI, 1.27 to 76.7) in the development cohort and 11.1 (95% CI, 2.88 to 42.5) in the validation cohort. The acid/base score had a higher predictive value for CKD progression than NH4+ excretion alone.
CONCLUSIONS: Subclinical acidosis, defined by a new urine acid/base score, was associated with a higher risk of CKD progression in patients with CKD stage 3 and 4.