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Updated: Nov 27, 2025

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
COVID-19-Associated Acute Kidney Injury and Quantified Protein Catabolic Rate: A Likely Effect of Cytokine Storm on
Jaime Uribarri1, Osama El Shamy2, Shuchita Sharma1
1Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
Rationale & Objectives:
Previously we reported a cohort of patients with coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) with striking biochemical evidence of tissue breakdown in the absence of apparent rhabdomyolysis. We sought to quantify the extent of tissue catabolism in similar patients.
Study Design:
During acute peritoneal dialysis (PD) in patients with COVID-19-associated AKI, we measured urea Kt/V adequacy and calculated the daily urea nitrogen generation rate while quantifying daily protein intake.
Setting & Population:
We did calculations in 8 patients with COVID-9-associated AKI undergoing acute PD at Mount Sinai Hospital in New York City. As a comparator, we obtained urea kinetic parameters from our database of ambulatory patients receiving maintenance PD.
Exposure Or Predictors:
8 patients with COVID-19-associated AKI undergoing acute PD.
Outcomes:
Urea nitrogen generation rate in relation to daily protein intake.
Analytical Approach:
Urea nitrogen generation rate from urea kinetics was related to measured daily dietary protein intake in these patients and we compared it with this relationship in ambulatory maintenance PD patients for whom both parameters were calculated from urea kinetics.
Results:
Urea nitrogen generation rate in patients with AKI was 10.2 ± 5 g/d, which is more than 2-fold higher than for stable outpatients receiving maintenance PD (4.7 ± 3 g/d) despite similar dietary protein intake (74.8 ± 11 vs 67.2 ± 29 g/d, respectively). This strongly suggests endogenous protein breakdown, probably from muscle. Urea nitrogen generation rate in these patients with AKI corresponds to 315 g/d of ongoing muscle breakdown and cumulative 2.5 kg of muscle breakdown during the early course of AKI.
Limitations:
Small number of participants and assumptions in comparing urea nitrogen generation rate with protein intake.
Conclusions:
In highly catabolic patients, an endogenous source of urea generation such as muscle protein breakdown seems to be the most likely explainable cause for our findings. This is the first study that we are aware of to quantify the degree of endogenous protein breakdown induced by COVID-19-related cytokine storm.
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