Table 2.

Naranjo adverse drug reaction probability scale applied to the present case

Question	Answer	Score
1. Are there previous conclusive reports on this reaction?	Yes — prior case reports (Menon, Hoffmanová) and a population-based cohort (Wang).	+ 1
2. Did the adverse event appear after the suspected drug was administered?	Yes — onset within one month of starting brinzolamide/timolol.	+ 2
3. Did the adverse reaction improve when the drug was discontinued or a specific antagonist administered?	Yes — full normalisation within one week of withdrawal and alkali therapy.	+ 1
4. Did the adverse reaction reappear when the drug was re-administered?	Not done; rechallenge ethically inappropriate.	0
5. Are there alternative causes that could on their own have caused the reaction?	No — extensive work-up excluded alternative causes. AKI on CKD alone does not plausibly explain the severity (HCO3 − 8.9 mmol/L).	+ 2
6. Did the reaction reappear when a placebo was given?	Not done.	0
7. Was the drug detected in blood or other fluids in concentrations known to be toxic?	Not measured.	0
8. Was the reaction more severe when the dose was increased, or less severe when the dose was decreased?	Not assessed.	0
9. Did the patient have a similar reaction to the same or similar drugs in any previous exposure?	No prior CAI exposure documented.	0
10. Was the adverse event confirmed by any objective evidence?	Yes — arterial blood gas, electrolyte, and urine indices.	+ 1
Total score	Probable adverse drug reaction.	7

Naranjo cut-offs: ≥ 9 definite; 5–8 probable; 1–4 possible; ≤ 0 doubtful. ADR, adverse drug reaction; AKI, acute kidney injury; CAI, carbonic anhydrase inhibitor; CKD, chronic kidney disease