# The effects of urine alkalinization on kidney function in critically ill patients with COVID-19: a proof-of-concept randomized clinical trial

## TL;DR

This study tested urine alkalinization in critically ill COVID-19 patients to see if it could prevent kidney injury, but found no significant benefits.

## Contribution

A proof-of-concept trial exploring urine alkalinization as a potential strategy to prevent acute kidney injury in critically ill COVID-19 patients.

## Key findings

- Urine alkalinization increased urine pH but did not significantly reduce acute kidney injury rates.
- Patients receiving alkalinization had higher rates of hypernatremia and metabolic alkalosis.
- Elevated urine TIMP-2 and IGFBP7 concentrations were linked to higher ICU and 60-day mortality.

## Abstract

Acute kidney injury (AKI) is a common complication of COVID-19. While the exact mechanisms remain unclear, direct viral infection of renal tubular epithelial cells is hypothesized. Given the pH-dependent entry of coronaviruses into host cells, urine alkalinization was proposed as a potential preventive strategy.

This was a proof-of-concept prospective, randomized clinical trial in critically ill patients with COVID-19. Patients were randomized to urine alkalinization versus usual care. The intervention group received intravenous 8.4% sodium bicarbonate to achieve a urine pH ≥ 7.5 up to 10 days after randomization. The primary outcome was the proportion of patients achieving target urine pH. Secondary outcomes included changes in urine tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), AKI development, renal replacement therapy, and adverse effects.

The trial was terminated early due to slow recruitment and the end of the COVID-19 pandemic. Sixteen patients were enrolled (median age 48 years old, 75% male). More patients in the intervention group achieved target urine pH than in the control group (75% vs 37.5%, P = 0.315). There was a separation of urine pH between both groups throughout 10 days (P = 0.097 for interaction). However, the intervention did not significantly impact urine [TIMP-2]x[IGFBP7] concentrations (P = 0.813 for interaction) or clinical outcomes, including AKI occurrence (risk ratio 0.6 (95% confidence interval 0.21, 1.70), P = 0.619). More patients in the intervention group experienced hypernatremia and metabolic alkalosis. Notably, patients with elevated urine [TIMP-2]x[IGFBP7] concentrations and AKI had higher ICU and 60-day mortality.

While urine alkalinization is feasible and can increase urine pH, we could not demonstrate differences in AKI rates or changes in urine [TIMP-2]x[IGFBP7] concentrations in critically ill COVID-19 patients.

The online version contains supplementary material available at 10.1186/s40635-025-00739-7.