COVID-19–Associated Acute Kidney Injury and Quantified Protein Catabolic Rate: A Likely Effect of Cytokine Storm on Muscle Protein Breakdown

Abstract

Rationale & ObjectivesPreviously 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 DesignDuring 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 & PopulationWe 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 Predictors8 patients with COVID-19–associated AKI undergoing acute PD.OutcomesUrea nitrogen generation rate in relation to daily protein intake.Analytical ApproachUrea 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.ResultsUrea 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.LimitationsSmall number of participants and assumptions in comparing urea nitrogen generation rate with protein intake.ConclusionsIn 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.