Abstract: FR-PO1086
Subclinical Acidosis Assessed by a New Urine Acid-Base Score Is an Independent Risk Factor for CKD Progression
Session Information
- CKD Mechanisms: Progression, Fibrosis, and Beyond
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Svendsen, Samuel L.C., Aarhus Universitet Faculty of Health, Aarhus, Denmark
- Carlsen, Rasmus, Aarhus Universitetshospital, Aarhus, Denmark
- Buus, Niels Henrik, Aarhus Universitetshospital, Aarhus, Denmark
- Birn, Henrik, Aarhus Universitetshospital, Aarhus, Denmark
- Leipziger, Jens G., Aarhus Universitet Faculty of Health, Aarhus, Denmark
- Berg, Peder, Aarhus Universitet Faculty of Health, Aarhus, Denmark
- Sorensen, Mads Vaarby, Aarhus Universitet Faculty of Health, Aarhus, Denmark
Background
Acidosis is reported to exacerbate the gradual loss of kidney function in patients with chronic kidney disease (CKD). Current guidelines advise assessing acid-base (AB) status of CKD patients by plasma bicarbonate, although covert acidosis may be present before it is reflected in this. Indeed, others have found a correlation between subclinical acidosis (SA), evidenced by low urinary NH4+ excretion, and progression of kidney disease. However, low NH4+ excretion may also be present in physiological states with low demand for acid elimination. To identify a sensitive and specific marker of SA, we analyzed several AB markers in urine samples from CKD patients. We hypothesized that a measure incorporating both pHu and [NH4+]u would reflect the demand and capacity for sufficient renal acid excretion in CKD patients, and that this would be associated with CKD progression.
Methods
We included biobanked urine samples from CKD patients from two clinical studies (RENVAS, development cohort, 81 CKD patients and 25 healthy controls and PUMA, validation cohort, 65 CKD patients). Outcomes included mGFR at 18 months and composite outcome of 50% eGFR reduction or kidney failure defined by initiation of dialysis or kidney transplantation. AB-score was calculated from [NH4+]u and pHu. Patients were stratified as SA if their AB score was below the 2.5th percentile of the control group or non-SA if their score was above.
Results
In the development cohort (mean eGFR 34.1mL/min, age 61.7y) 62% had SA. A higher baseline AB score was associated with a slower decrease in mGFR (p=0.002) and patients with SA had a greater mGFR decline after 18 months (p=0.039). Renal events were more frequent in patients with SA (p<0.001, mean follow-up 5.1y). When adjusted for covariates, including tCO2 and eGFR, the hazard ratio (HR) of reaching the composite outcome was 0.41(95%CI 0.21-0.79, p=0.009) per SD higher AB score and in patients with SA 5.3 (95%CI 1.2-24.2, p=0.039). In the validation cohort (mean eGFR 36.8mL/min, age 68.0y, mean follow-up 3.4y) 65% had SA. Adjusted HR was 0.27 (95%CI 0.1-0.76, p=0.013) per SD higher AB score and in patients with SA 15.5 (95%CI 1.9-129.4, p=0.011).
Conclusion
SA associates with greater mGFR decrease after 18 months and an increased risk of kidney failure or a >50% reduction of eGFR.
Funding
- Private Foundation Support