A Urine pH-Ammonium Acid/Base Score and CKD Progression

Samuel Levi Svendsen, Amalie Quist Rousing, Rasmus Kirkeskov Carlsen, Dinah Khatir, Danny Jensen, Nikita Misella Hansen, Louise Salomo, Henrik Birn, Niels Henrik Buus, Jens Leipziger, Mads Vaarby Sorensen, Peder Berg

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
JournalJournal of the American Society of Nephrology
Volume35
Issue11
Pages (from-to)1533-1545
Number of pages13
ISSN1046-6673
DOIs
Publication statusPublished - Nov 2024

Keywords

  • acid-base disorders
  • acidosis CKD progression proximal tubule ESKD fluid
  • electrolyte

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