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A common complication in patients with chronic kidney disease (CKD) and the presence of COVID-19 infection is the acute kidney injury (AKI). In 9 out of 10 cases, mortality occurs in patients presenting with AKI. The aim of this study is to determine whether there are sufficiently informative biomarkers for early prediction of these complications.
The study group included 160 patients: 70 COVID-19(+) CKD patients, 50 COVID-19(+) patients with no history of kidney disease, 20 COVID-19(-) CKD patients and 20 healthy controls. Data on patients’gender, age, co-morbidities and laboratory results from blood and urine samples were collected at admission into the emergency room (ER), whilst the healthy group were volunteers to whom the study was explained and have expressed in writing their willingness to participate.
Laboratory values included calculated eGFR (by the CKD-EPI 2021 formula), highly sensitive inflammatory markers, D-dimer, blood-cell counts, and changes in urine parameters. Co-morbidities included hypertension, obesity, diabetes mellitus, vascular disease and CKD. All patients had been treated by the official protocol of the Republic of Bulgaria for COVID-19 treatment. In total six biomarkers were examined:
· SAA, IL-6 and ACE2 from serum
· IL-18, KIM-1 and NGAL from fresh urine.
The levels of specific biomarkers were determined by ELISA.
Overall, serum creatinine level on admission was elevated in 40% of cases; eGFR was <60 mL/min/1.73 m2 in 37.5% of patients. Mean value of eGFR on admission was 82.3 mL/min/1.73 m2 for the non-CKD COVID-19(+) group, 49.5 mL/min/1.73 m2 for the CKD COVID-19(+) group, 62.3 mL/min/1.73m2 for the COVID-19(-) CKD patients, whilst for the healthy control group it was at 111.1 mL/min/1.73m2. In total, three patients needed renal-replacement therapy: two patients from the CKD group and one from the non-CKD group, all of them were COVID-19 positive.
AKI occurred in 38 patients with COVID-19 (23.7%). Overall, in the 160 COVID-19(+) patients, the in-hospital mortality rate was 14.3% (23 patients) with 19 of these patients having an AKI.
We assessed all of the six biomarkers in the different groups. We found that at admission patients who had AKI at later stage during the hospital treatment had significantly higher levels of SAA (p-value=0.0272), IL-6 (p-value=0.0069), NGAL (p-value=0.002) and KIM-1 (p-value=0.0361) in comparison to the patients who had no evidence of impaired kidney function. Subsequently, a similar analysis was conducted to estimate cohort mortality. Two of the biomarkers were significantly associated with death, i.e., SAA (p-value=0.001) and IL-6 (p-value=0.002).
Serum ACE2 enzyme levels and urinary IL-18 levels did not show any significant results in the statistical analyses performed, either for AKI or for mortality rate.
We found that some of the examined biomarkers are reliable in predicting AKI and mortality rate in COVID-19(+) CKD and non-CKD patients. Such biomarkers are IL-6, SAA, KIM-1 and NGAL. These biomarkers are highly informative and have strong predictive value in the setting of ER, allowing to have an early prognosis of disease outcome.