Topical Carbonic Anhydrase Inhibitors May Trigger Life-Threatening Acidosis in CKD Patients: Study
A new study published in the journal of BMC Nephrology showed that in individuals with chronic kidney disease (CKD), topical carbonic anhydrase inhibitors (CAIs) used in ophthalmology can be substantially absorbed into the systemic circulation, avoiding first-pass metabolism and perhaps resulting in potentially fatal metabolic acidosis.
As the kidneys lose their capacity to eliminate daily acid loads, metabolic acidosis in chronic kidney disease usually develops gradually. Clinicians must look at exogenous causes, such as topical carbonic anhydrase inhibitors, such as dorzolamide, used for glaucoma, if the acidosis is unusually severe in comparison to the patient's renal baseline.
Although the goal of these drops is intraocular pressure, systemic absorption is unavoidable. Toxicity is avoided in healthy persons by quick renal clearance. The medication builds up systemically in CKD due to poor clearance. This causes a severe normal-anion gap (hyperchloremic) metabolic acidosis by preventing proximal tubule bicarbonate reabsorption.
During acute-on-chronic kidney damage (AKI), diagnosing this is infamously challenging. AKI can readily conceal the underlying CAI-induced normal-anion gap component since it usually produces a large anion gap acidosis due to retained uremic toxins, potentially postponing the critical stopping of the offending eye drops.
In this case report, one month after beginning fixed-combination brinzolamide 1%/timolol 0.5% eye drops, a 73-year-old Asian guy with stage 3 CKD and glaucoma had increasing dyspnea, anorexia, and a 3-kg weight loss. A laboratory test showed acute-on-chronic renal damage (creatinine 3.9 mg/dL against baseline ~2.0 mg/dL) and severe metabolic acidosis (pH 7.29; serum bicarbonate 8.9 mmol/L, from a pre-exposure baseline of 20.3 mmol/L). A significant non-anion-gap (hyperchloremic) component was superimposed on a smaller high-anion-gap component, as indicated by a delta-delta ratio of 0.42 (calculated using a reference normal serum bicarbonate of 24 mmol/L). During established acidosis (without bicarbonate loading), hypokalemia (K+ 3.3 mmol/L), hyperchloremia (Cl-107 mmol/L), positive urine anion gap (+33.4 mmol/L), and a fractional excretion of bicarbonate of 4.3%. Researchers methodically ruled out other causes of metabolic acidosis. The Naranjo Adverse Drug Reaction Probability Scale's causality evaluation resulted in a score of 7 (probably). Within a week of stopping the ophthalmic solution and alkali treatment, the acidosis was resolved and renal function returned to baseline, which persisted at the one-year follow-up.
Overall, topical CAIs can have high systemic absorption, bypassing first-pass metabolism and causing life-threatening acidosis in individuals with little renal reserve. Clinicians must keep a high suspicion for ocular medicines as potential causes of mixed acid-base problems in CKD patients.
Source:
Chao, M.-Y. V., & Wang, Y.-C. (2026). Severe metabolic acidosis with renal tubular acidosis features attributed to topical brinzolamide in a patient with stage 3 chronic kidney disease: a case report. BMC Nephrology. https://doi.org/10.1186/s12882-026-05167-7
