Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization

West Virginia University

Status and phase: Terminated; Phase 4

Conditions: AKI; Acute Kidney Injury; COVID; Coronavirus Infection; Coronavirus

Treatments: Other: Standard of Care; Drug: Sodium bicarbonate

Study type: Interventional

Funder types: Other

Identifiers

NCT04530448

2005006707

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 3 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3 participants in 2 patient groups

Standard of Care

Active Comparator group

Description:

Standard of Care treatment

Treatment:

Other: Standard of Care

Sodium Bicarbonate

Active Comparator group

Description:

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.

Treatment:

Drug: Sodium bicarbonate