ABSTRACT
Background: Acute kidney injury (AKI) is a common complication of COVID-19. Several etiologies have been identified, including pigment deposition likely associated with myopathic damage. Nevertheless, the relationship between longitudinal creatine-kinase trends and renal outcomes is uncertain. Aim: To correlate longitudinal changes in serum creatine-kinase levels with hospital-acquired AKI (beyond 48 h of hospital admission) in severe COVID-19 patients. Methods: This is a retrospective cohort study, and creatine-kinase levels were assessed over time in 1551 hospitalized patients with normal renal function at the time of hospital admission. Results: In subjects who developed hospital-acquired AKI (n = 126, 8.1%), the serum creatine-kinase concentration before AKI onset was not different when compared to patients without AKI (slope of log creatine-kinase/day = -0.09 [95% CI -0.17 to +0.19] vs. +0.03 [95% CI -0.1 to +0.1]). After AKI diagnosis, serum creatine-kinase levels showed a significantly ascendent slope (slope of log creatine-kinase/day after AKI diagnosis = +0.14; 95% CI + 0.05 to +0.3). The AKI evolution was the main factor associated with the creatine-kinase trend. Subjects with persistent AKI (n = 40, 32%) had rising creatine-kinase levels during hospitalization (slope of log creatine-kinase/day = +0.30 95% CI + 0.19 to +0.51). A rising creatine-kinase trend (n = 114, 8%) was associated with a 1.89-fold higher risk of in-hospital death (95% CI 1.14 to 3.16). Nevertheless, this association disappeared after adjusting AKI evolution and LDH baseline levels. Conclusion: In severe COVID-19 patients, a slight increase in creatine-kinase levels was observed after AKI occurrence but not before. Our results show that, at least for the appearance of hospital-acquired AKI, the CK rise does not meet the temporality criterion of causality regarding the occurrence of AKI. Rising creatine-kinase trends were associated with a higher risk of mortality, but this association was modified by AKI evolution and inflammation. There is a limited efficiency for AKI prognosis in the serial follow-up of CK levels in severe COVID-19 patients with normal renal function.
ABSTRACT
BACKGROUND: There is controversy regarding the association between hypovitaminosis D and COVID-19 outcomes. AIM OF THE STUDY: We assessed the association between 25-hydroxyvitamin D levels and COVID-19 outcomes in hospitalized subjects with severe SARS-CoV-2 infection. METHODS: Retrospective cohort study. Serum 25-hydroxyvitamin D levels of subjects with severe COVID-19 pneumonia were measured at hospital admission, between March 17th, 2020, and March 1st, 2021. RESULTS: Out of 2,908 patients, 571 (19.6%) had vitamin D deficiency (defined as a serum 25-hydroxyvitamin D level <12.5 ng/mL [<31.25 nmol/L]), and 1069 (36.7%) had levels between 12.5 ng/mL (31.25 nmol/L) and 20 ng/mL 850 nmol/L). Compared to subjects without vitamin D deficiency, those with 25-hydroxyvitamin D level <12.5 ng/mL had higher rates of in-hospital mortality at 30 d (28.0 vs. 17.3%; p <0.001), global mortality (31.9 vs. 20.8%; p <0.001), mechanical ventilation requirement (23.8 vs. 17.2%; p <0.001), and significantly longer hospital stay (median [interquartile range] of 9 [6-17 d] vs. 7 [5-12 d], p <0.001). In the unadjusted analysis, the risk of in-hospital death was greater for patients with vitamin D deficiency (HR 1.43; 95% CI, 1.20-1.70; p <0.001). After adjusting for confounders, the risk of in-hospital death within 30 d remained significantly greater in patients with vitamin D deficiency (HR 1.46; 95% CI, 1.21-1.76; p <0.001). The risk was reduced but remained significant with 25-hydroxyvitamin D levels between 12.5 ng/mL and 20 ng/mL (HR 1.31; 95% CI 1.10-1.55, p = 0.02). In comparison with other clinical biomarkers, vitamin D deficiency was an independent predictive marker of in-hospital mortality after adjusting for confounders. CONCLUSION: Very low 25-hydroxyvitamin D levels measured at hospital admission were significantly associated with in-hospital mortality and are a useful prognostic biomarker in severe COVID-19 patients.