TY - JOUR
T1 - A Urine pH-Ammonium Acid/Base Score and CKD Progression
AU - Svendsen, Samuel Levi
AU - Rousing, Amalie Quist
AU - Carlsen, Rasmus Kirkeskov
AU - Khatir, Dinah
AU - Jensen, Danny
AU - Hansen, Nikita Misella
AU - Salomo, Louise
AU - Birn, Henrik
AU - Buus, Niels Henrik
AU - Leipziger, Jens
AU - Sorensen, Mads Vaarby
AU - Berg, Peder
PY - 2024/11
Y1 - 2024/11
N2 - 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 NH41 excretion associates with poor kidney outcomes in CKD and is proposed as a marker for subclinical acidosis. However, low NH41 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 (N582), a variation cohort (N558), and a validation cohort (N573). A urine acid/base score was derived and calculated from urinary pH and [NH41]. 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 (n554/82, 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 NH41 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.
AB - 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 NH41 excretion associates with poor kidney outcomes in CKD and is proposed as a marker for subclinical acidosis. However, low NH41 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 (N582), a variation cohort (N558), and a validation cohort (N573). A urine acid/base score was derived and calculated from urinary pH and [NH41]. 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 (n554/82, 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 NH41 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.
KW - acid-base disorders
KW - acidosis CKD progression proximal tubule ESKD fluid
KW - electrolyte
UR - http://www.scopus.com/inward/record.url?scp=85199385689&partnerID=8YFLogxK
U2 - 10.1681/ASN.0000000000000447
DO - 10.1681/ASN.0000000000000447
M3 - Journal article
C2 - 39018119
SN - 1046-6673
VL - 35
SP - 1533
EP - 1545
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 11
ER -