key: cord-0861315-tk9g1wy6
authors: Patel, Niralee; Rein, Joshua L.; Sanchez-Russo, Luis; Winston, Jonathan; Uribarri, Jaime
title: COVID-19–Associated Acute Kidney Injury: A Case Series
date: 2020-07-17
journal: Kidney Med
DOI: 10.1016/j.xkme.2020.06.004
sha: f02773857e3a951f8ccc1afa846da7d64af2b1cf
doc_id: 861315
cord_uid: tk9g1wy6

nan

To the Editor:

During the peak of the coronavirus disease 2019 (COVID-19) pandemic in the New York area, nephrology consults in our intensive care units (ICUs) nearly tripled. The clinical epidemiology of COVID-associated acute kidney injury (AKI) across our health system has been reported (1), but here we highlight our experience from one hospital (Mount Sinai Hospital),

where we saw an unprecedented number of highly catabolic AKI cases, all due to infection with SARS-CoV19. Data collection was approved by the IRB at the Icahn School of Medicine at Mount Sinai.

All patients in this series were critically ill in the ICU with COVID pneumonia (COVID PNA) requiring ventilatory support. All experienced rapid rises in serum urea nitrogen (SUN) and serum creatinine with striking elevations in uric acid, phosphorous and potassium, lactate negative anion gap, metabolic acidosis and rapid falls in serum albumin. This could not be explained by low glomerular filtration rate alone and there was no evidence of tumor lysis syndrome or rhabdomyolysis (2,3).

At one particular day near the peak of the COVID-19 crisis (April 9, 2020), of 138 COVID positive ICU cases, 49 of 52 nephrology consult cases had AKI. We present three that typify the hypercatabolic state.

A 64 year-old man with no pre-existing conditions presented with COVID PNA.

Creatinine and SUN increased from 1.2 mg/dL and 21 mg/dL, respectively to 9.9 mg/dL and 160 mg/dL by day 4. Serum phosphorus at that time was 11.7 mg/dL. Creatine phosphokinase (CPK) was normal.

A 67 year-old man with background hypertension presented with COVID PNA. Over 4 days, serum creatinine increased from 1 mg/dL to 7.1 mg/dL, SUN from 12 mg/dL to 94 mg/dL, and calcium decreased from 8.1 mg/dL to 5.8 mg/dL, while serum phosphorus was 9.7 mg/dL (day 2) and peaked at 12.2 mg/dL on day 3.

A 50 year-old man with a history of asthma developed COVID PNA. Serum creatinine increased from 0.8 mg/dL to 7.8 mg/dL and SUN from 20 mg/dL to 102 mg/dL over 3 days. During that period serum phosphorus increased to 7.9 mg/dL. We considered the hyperphosphatemia and rapid rise in SUN to represent a highly catabolic state and sought to determine how prevalent this was in our COVID-infected ICU cohort. Not having a non-COVID patient population as comparators, we arbitrarily chose a serum phosphorous > 10 mg/dL early in the course of AKI as sufficiently unique to warrant reporting.

We found 9 of 49 such AKI patients, with mean duration of AKI before phosphorous reached 10 mg/dl being only 6 days. No patients were eating or receiving enough nutritional support that could explain exogenous phosphate loads. As summarized in Table 1 there was striking hyperuricemia and hypoalbuminemia, while SUN and creatinine reached levels that under ordinary circumstances take weeks to develop, not days. These changes can only come from muscle breakdown. CPK levels were normal or only slightly elevated. We reevaluated the same parameters in our nephrology ICU census 2 weeks later, for patients not included in Table 1 , and the frequency and degree of biochemical abnormalities was similarly abnormal.

In this report, we highlight a unique phenotype in a subset of critically ill COVID-infected patients. None of our patients required vasopressors, had elevated CPK levels, and only a few received steroids. Hypercatabolic patients in an ICU setting is not an unprecedented event, but such a high proportion of patients, all caused by the same infectious agent, and with an intact 3 muscle cell membrane is unprecedented. It supports the hypothesis of a unique cytokine release profile in COVID-19 (4).

Both IL-6 and TNFα have direct effect on muscle protein breakdown (5, 6) . There is a large literature supporting their role in muscle wasting associated with other inflammatory disorders (7, 8) . The increased release of muscle phosphorus and uric acid could cause or contribute to worsening AKI through intratubular deposition and tubular obstruction (2, 3) . We cannot definitely exclude other contributors to the laboratory abnormalities in individual patients, but as a group, the marked rise in phosphorus, urea nitrogen, and non-lactate acidosis all point towards COVID-associated tissue breakdown.

We considered whether such a hypercatabolic state could be useful as a marker for disease severity-predicting pulmonary or kidney outcomes, all-cause mortality or potentially a stratifier for selecting high risk patients to clinical trials. Given the wide range of COVID disease severity, the wide range of AKI disease severity, and the inherent limitations of clinical observations from a cross-sectional cohort, there simply is not enough power from this select cohort to make meaningful disease associations. Of the nine patients, six died, two recovered. Daily dialysis to manage hyperkalemia in the ICU cohort was often necessary.

A better understanding of the pathophysiologic causes of COVID-associated AKI is needed, particularly the role of cytokines. In anticipation of COVID-19 surges elsewhere, providers should be prepared for this hypercatabolic syndrome. Conventional intermittent hemodialysis alone may become a limited resource, because of an increased number of patients and increased dialysis demands. 

Acute Kidney Injury in Hospitalized Patients with COVID-19

Onco-nephrology: tumor lysis syndrome

Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review

SARS-CoV2: A storm is raging

Infusion of tumor necrosis factor/cachectin promotes muscle catabolism in the rat. A synergistic effect with interleukin 1

Interleukin-6 induces skeletal muscle protein breakdown in rats

TNF-α and cancer cachexia: Molecular insights and clinical implications

Cytokine signaling in skeletal muscle wasting

Reference ranges: Sodium=135-145 mEq/L, Potassium=3.5-5.2 mEq/L

mg/dL, Calcium=8.5-10.5 mg/dL, Phosphorus=2.4-4.7 mg/dL, Lactate=0.5-1.99 mmol/L, Albumin=3.5-4.9 g/dL, IL-6 (interleukin-6)=0-15 pg/mL, TNFα=0-22 pg/mL, CPK=30-200U/L, LDH=100-220 U/L, Urate (uric acid)=4-9 mg/dL, CRP (C reactive protein)=0-5 mg/L Conversion factors for units: creatinine in mg/dL to µmol/L, x88.4