Our overarching goal is to improve the outcomes of critically ill COVID-19 patients with or at risk for development of acute kidney injury (AKI). The objective of this study is to determine the role of a protocol to manage urine alkalization using a simple medication that has been used for a very long time, is safe, and without significant side-effects. We aim to determine the feasibility and safety of a urine alkalinization protocol for the prevention of AKI in patients testing positive for COVID-19.
Emerging evidence suggests that acute kidney injury (AKI) secondary to COVID-19 (COV-AKI)
might result from direct infection of renal tubule epithelial cells (RTEC). A variety of
epithelial cells express the ACE2 receptor which contains the receptor-binding domain (RBD)
used by SARS-CoV-1 and SARS-CoV-2 to enter the cells. While direct infection of RTEC has not
yet been proven data from multiple laboratories show virus in the kidney. It is this direct
viral involvement of the RTEC that this proposal seeks to address.
One relatively simple approach would be to perturb the ability of the RBD to bind to its
cellular (hACE2) receptor. Changes in pH may cause each amino acid residue, in the RBD, to
assume a slightly different 'microscopic' conformation-dependent pKa value. Urine pH is
normally 5.5- 6.5 (not too dissimilar to alveolar fluid-6.4-6.86) and can be easily and
safely manipulated. In fact, urine alkalinization protocols have been used for decades to
reduce renal toxicity from various compounds (especially chemotherapy) and are recommended by
US and European toxicology societies. Here, the strategy will be deployed not for ion
trapping but to inhibit the virus from infecting RTEC. Alkalinizing the urine using IV
sodium-bicarbonate solution to pH of 7.5 or more can be easily and safely achieved.
While severe AKI does not appear to be a major part of the SARS-CoV-2 syndrome for most
patients, when severe AKI does occur, mortality is very high and preventing early AKI may
reduce AKI severity as the disease progresses.
Drug: Sodium bicarbonate
Sodium bicarbonate 225 mEq (225 mL of an 8.4% solution) intravenously over 1 hour. Sodium bicarbonate 8.4% solution should not exceed 900 ml (4 boluses) in 24 hours.
Other: Standard of Care
Standard of Care treatment
Inclusion Criteria:
- Confirmed COVID-19 positive
- Admission to ICU or step-down unit
- Age ≥ 18 years old
Exclusion Criteria:
- Stage 3 AKI by KDIGO criteria
- CKD stage 4-5
- Contraindications to Na bicarbonate therapy (e.g. met. alkalosis, severe heart
failure)
- Urine pH > 7.0
WVU Medicine Heart & Vascular Institute
Morgantown, West Virginia, United States