Kidney Week

Abstract: PO1486

Anion Gap (AG) and Negative Osmotic Gap (OG) due to Remdesivir’s (R) Excipient

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Clinical - 2
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolyte, and Acid-Base Disorders

• 902 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

• Alqassimi, Sameer, USF Health Morsani College of Medicine, Tampa, United States

Sameer Alqassimi,

• Chavez, Octavio, USF Health Morsani College of Medicine, Tampa, Florida, United States

Octavio Chavez,

• Bassil, Claude, USF Health Morsani College of Medicine, Tampa, Florida, United States

Claude Bassil,

• Jain, Pranjal, Florida Kidney Physicians, Tampa, Florida, United States

Pranjal Jain,

• Durr, Jacques A., USF Health Morsani College of Medicine, Tampa, Florida, United States

Jacques A. Durr,

Group or Team Name

• USF Nephrology and Hypertension

Introduction

The FDA authorized R for COVID-19. Excess Na sulfobutylether (SBE) substituted β-cyclodextrin (CD) solubilizes R (PMID: 32376442). Minute accumulation of SBECD can cause an AG as n, its substitution in SBE is 6.5 (Captisol). The FDA advises against using R in adults with eGFR ≤30 mL/min unless the potential benefit outweighs the potential risks because SBECB accumulates. We report 2 cases of AG with the FDA protocol.

Case Description

Case A: 77 obese ♀ with bilateral AKA, and initial serum creatinine (Scr) of 1 mg/dL, currently decreasing (0.6 mg/dL). On day 5 R was initiated while a mild ketosis resolved (β OH-butyrate 0.6→0.3→0.1 mmol/L). An AG as high as 16 mmol/L (Alb ~2 g/dL) ensued, wherein the AG of the 1^st blood sample after each R infusion correlated inversely with the time elapsed after the infusion. Like ketones, lactate was low throughout R therapy. By the time R started, Scr had risen and plateaued at 1.8 mg/dL and the AG mirrored the subsequent increase and decrease in Scr, and vanished by day 9, when her Scr was < 1.7, after peaking at 2.6 mg/dL, in spite of continuing R, consistent with SBECD cleared by GFR, like cr. Her initial normal Scr already meant AKI in this elderly sedentary, bilateral AKA patient. Her OG, only 7 on day 2 of R, further decreased by 11, to a negative OG of –4 mOsm/Kg H₂O the next day, suggesting polyanion accumulation. The calculated osmolarity of a Na_nSBECD solution is ((n + 1)/n)*[Na] = 1.15*[Na], not 2*[Na] since n ≈ 6.5, which explains the negative OG. Case B: 42 ♀, with morbid obesity and initial Scr of 1 mg/dL. R started on day 2, as Scr rose fast but her AG was 10 mmol/L. Again, the AG rapidly rose to 16 mmol/L (Alb. ~2.5 g/dL), and paralleled the rise and drop in Scr. CRRT was started when Scr was 6 mg/dL. Here again, prior to CRRT the AGs of the 1^st samples following each R infusion were inversely related with the time from R infusion. While R was continued, CRRT caused parallel decreases in AG and Scr, since it clears cr and SBECD equally. The R loading dose contains 6 g and the 9 subsequent daily doses 3 g SBECD. Since the mass of SBE_6.5CD is 2163.3 D, the initial anion load is ~18 mmol, followed by 9 daily loads of ~ 9-10 mmol.

Discussion

Depending on plasma volume, rate of escape from plasma, GFR, and timing after the infusion, SBECD can cause an AG, and negative OG, when the GFR is low.