Metabolic acidosis is associated with an increased risk for chronic kidney disease (CKD) progression and the need for renal replacement therapy (RRT) and a within-individual increase in serum bicarbonate lowered the risk of CKD progression, according to study findings presented at the American Society of Nephrology’s Kidney Week 2020 Reimagined virtual conference.

The study, by Vandana S. Mathur, MD, of Mathur Consulting in Woodside, California, and colleagues, included 51,558 patients with nondialysis CKD stages 3 to 5 who had at least 2 serum bicarbonate tests 28 to 365 days apart, 3 or more estimated glomerular filtration rate (eGFR) values less than 60 mL/min/1.73 m2, and at least 2 years of post-index data or who died during that period. The investigators defined progression to renal replacement therapy (RRT) as initiation of dialysis, receipt of a kidney transplant, or an eGFR of 9 mL/min/1.73 m2 or less.1

The study population included 17,350 patients with metabolic acidosis and 3208 with normal serum bicarbonate at baseline. The unadjusted rates of progression to RRT within 2 years were significantly higher among patients with metabolic acidosis than among those without the condition (19.6% vs 5.5%; P <.001), Dr Mathur and colleagues reported. Each 1 mEq/L increase in serum bicarbonate between 12 and 29 mEq/L was significantly associated with a 2.5% decrease in the 2-year risk of initiating RRT and a 4.5% decreased risk up to 10 years.


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The increased risk for CKD progression to RRT associated with metabolic acidosis was independent of age, race, sex, preexisting comorbidities, baseline eGFR, and albumin-to-creatinine ratio, the study found.

For the study, the investigators relied on 2007 to 2017 data from de-identified Optum® electronic medical records (EMR).

In a separate analysis of 136,067 patients with nondialysis CKD stages 3-5 with up to 11.5 years of follow-up, which also involved use of Optum® EMR data, the same investigators found that 75,127 (55%) progressed 1 or more CKD stages within 2 years.2 In this analysis, the investigators evaluated exposure variables both of baseline bicarbonate as well as the time-dependent change from patients’ baseline at each post-index serum bicarbonate (until the outcome) to evaluate risk of CKD progression.

The incidence of CKD progression, separately measured as at least a 40% decline from baseline eGFR of 1 or more CKD stages within 2 years was significantly higher among patients with metabolic acidosis (serum bicarbonate less than 22 mEq/L) than those with normal serum bicarbonate levels. CKD progression defined as a 40% or greater decline in eGFR occurred in 38.3% of patients with metabolic acidosis compared with 20.4% of those without the condition (P <.0001). Progression of at least 1 CKD stage occurred in 66.7% and 54.5%, respectively (P <.0001). All differences were statistically significant.

During up to 11.5 years of follow-up (median 4.2 years), each 1 mEq/L increase in serum bicarbonate was significantly associated with a 3.1% decreased risk for a 40% or greater decline in eGFR and a 2.5% decreased risk of progressing 1 or more CKD stages, after controlling for age, race, sex, preexisting comorbidities, baseline eGFR, and albumin-to-creatinine ratio.

Disclosure: This clinical trial was commercially supported. Please see the original reference for a full list of authors’ disclosures.

References

  1. Mathur VS, Funk SE, Reaven NL, Tangri, N. Metabolic acidosis and progression to renal replacement therapy. Presented at: Kidney Week 2020 Reimagined virtual conference, October 19 to 25. Poster PO0467.
  2. Mathur VS, Reaven NL, Funk SE, Tangri, N. Metabolic acidosis is associated with CKD progression: A longitudinal analysis of >100,000 US community-based patients. Presented at: Kidney Week 2020 Reimagined virtual conference, October 19 to 25. Poster PO0469.