Differential Bias for Creatinine- and Cystatin C- Derived Estimated Glomerular Filtration Rate in Critical COVID-19

Anders O Larsson; Michael Hultström; Robert Frithiof; Ulf Nyman; Miklos Lipcsey; Mats B Eriksson

doi:10.3390/biomedicines10112708

Differential Bias for Creatinine- and Cystatin C- Derived Estimated Glomerular Filtration Rate in Critical COVID-19

Biomedicines. 2022 Oct 26;10(11):2708. doi: 10.3390/biomedicines10112708.

Authors

Anders O Larsson¹, Michael Hultström^{2

3

4

5}, Robert Frithiof², Ulf Nyman⁶, Miklos Lipcsey^{2

7}, Mats B Eriksson^{2

8}

Affiliations

¹ Department of Medical Sciences, Section of Clinical Chemistry, Uppsala University, 751 85 Uppsala, Sweden.
² Department of Surgical Sciences, Anaesthesiology and Intensive Care Medicine, Uppsala University, 751 85 Uppsala, Sweden.
³ Department of Medical Cell Biology, Integrative Physiology, Uppsala University, 751 23 Uppsala, Sweden.
⁴ Department of Epidemiology, McGill University, Montréal, QC H3A 0G4, Canada.
⁵ Lady Davis Institute of Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, Canada.
⁶ Department of Translational Medicine, Division of Medical Radiology, Lund University, 221 85 Malmö, Sweden.
⁷ Hedenstierna Laboratory, Department of Surgical Sciences, Uppsala University, 751 85 Uppsala, Sweden.
⁸ NOVA Medical School, New University of Lisbon, 1099-085 Lisbon, Portugal.

Abstract

COVID-19 is a systemic disease, frequently affecting kidney function. Dexamethasone is standard treatment in severe COVID-19 cases, and is considered to increase plasma levels of cystatin C. However, this has not been studied in COVID-19. Glomerular filtration rate (GFR) is a clinically important indicator of renal function, but often estimated using equations (eGFR) based on filtered metabolites. This study focuses on sources of bias for eGFRs (mL/min) using a creatinine-based equation (eGFR_LMR) and a cystatin C-based equation (eGFR_CAPA) in intensive-care-treated patients with COVID-19. This study was performed on 351 patients aged 18 years old or above with severe COVID-19 infections, admitted to the intensive care unit (ICU) in Uppsala University Hospital, a tertiary care hospital in Uppsala, Sweden, between 14 March 2020 and 10 March 2021. Dexamethasone treatment (6 mg for up to 10 days) was introduced 22 June 2020 (n = 232). Values are presented as medians (IQR). eGFR_CAPA in dexamethasone-treated patients was 69 (37), and 74 (46) in patients not given dexamethasone (p = 0.01). eGFR_LMR was not affected by dexamethasone. eGFR_LMR in females was 94 (20), and 75 (38) in males (p = 0.00001). Age and maximal CRP correlated negatively to eGFR_CAPA and eGFR_LMR, whereas both eGFR equations correlated positively to BMI. In ICU patients with COVID-19, dexamethasone treatment was associated with reduced eGFR_CAPA. This finding may be explained by corticosteroid-induced increases in plasma cystatin C. This observation is important from a clinical perspective since adequate interpretation of laboratory results is crucial.

Keywords: COVID-19; SARS-CoV-2; biomarkers; corticosteroids; creatinine; cystatin C; eGFR; intensive care; kidney.

Abstract

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