Kidney Week

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

Samuel L.C. Svendsen,

• Carlsen, Rasmus, Aarhus Universitetshospital, Aarhus, Denmark

Rasmus Carlsen,

• Buus, Niels Henrik, Aarhus Universitetshospital, Aarhus, Denmark

Niels Henrik Buus,

• Birn, Henrik, Aarhus Universitetshospital, Aarhus, Denmark

Henrik Birn,

• Leipziger, Jens G., Aarhus Universitet Faculty of Health, Aarhus, Denmark

Jens G. Leipziger,

• Berg, Peder, Aarhus Universitet Faculty of Health, Aarhus, Denmark

Peder Berg,

• Sorensen, Mads Vaarby, Aarhus Universitet Faculty of Health, Aarhus, Denmark

Mads Vaarby Sorensen,

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 pH_u 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 pH_u. Patients were stratified as SA if their AB score was below the 2.5^th 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