Participants
From March 1st to May 31st, 236 patients were admitted to UICIVE with a diagnosis of COVID-19 on admission. We focused on 192 patients after excluding 44 patients as depicted in Figure 1.
A majority of Caucasian (n=174, 90.6%) males (n=100, 52.1%) were hospitalized with a mean age of 72.2±16.4 years. There was a large prevalence of hypertensive (n=131, 68.2%), CVD (n=68, 35.4%), diabetic (n=54, 28.1%) and CKD (n=38, 19.8%) patients. Forty-two percent of patients were medicated with RAAS inhibitors. Almost 20% of hospitalized patients (n=38) required admission to an intensive care unit (ICU) mostly due to respiratory failure, 15.1% of patients fulfilled ARDS criteria and 16.7% of patients required mechanical ventilation. Most patients had a SOFA score of at least 2 (57.8%), and 12.5% of patients had a SOFA score of at least 4. Almost 30% of patients had a BCRSS score of at least 2.
At admission, mean SCr was 1.33±1.82mg/dL, mean hemoglobin was 13.0±2.1 and almost 40% of patients were anemic, mean NL ratio was 6.49±5.71, mean serum albumin was 3.37±0.59 g/dL and more than 70% of patients had hypoalbuminemia, mean serum ferritin was 1100.6±1298.3 ug/L, mean CRP was 9.71±8.72mg/dL, mean lactate level was 15.65±10.60 mg/dL and 27% of patients were acidemic.
During the first week of admission, 20.8% of patients were exposed to nephrotoxins, namely NSAIDS, radiocontrast, vancomycin or aminoglycosides. Concerning treatment, a vast majority of patients were medicated with hydroxycloroquine (n=140, 72.9%) and lopinavir/ritonavir (n=128, 66.7%). Only 3 patients were treated with tocilizumab and 10.9% of patients required corticosteroids. Mean time to ICU admission was 3.2±1.8 days.
Mean length of hospital stay was 22.3±23.9 days. Baseline characteristics of this cohort are described in Table 1.
AKI
In this cohort of COVID-19 patients, 55.2% developed AKI (n=106). Of these, 64.2% of patients (n=68) presented AKI at admission and the remaining developed AKI within the first week of hospitalization. Mean time to AKI development was 2.2±0.9 days. Patient characteristics according to AKI development are described in Table 1.
Patients with AKI were older (75.6±14.6 vs 67.6±17.4, p=0.001; unadjusted OR 1.03 (95% CI 1.01-1.05), p=0.001), were more likely to have pre-existing hypertension (78.3% vs 56.5%, p=0.001; unadjusted OR 2.78 (95% CI 1.48-5.22), p=0.001), CKD (28.3% vs 9.4%, p=0.001; unadjusted OR 3.96 (95% CI 1.70-9.19), p=0.001) and COPD (19.8% vs 7.1%, p=0.012; unadjusted OR 3.25 (95% CI 1.25-8.48). p=0.016), and to be medicated with RAAS inhibitors (51.9% vs 30.6%, p=0.002; unadjusted OR 2.60 (95% CI 1.42-4.75), p=0.002). Mean baseline SCr was higher in AKI patients (1.02±0.47 vs 0.84±0.26, p=0.002; unadjusted OR 4.40 (95% CI 1.64-11.83), p=0.003).
At admission, these patients had higher SCr (1.72±2.37 vs 0.84±0.25, p=0.001; unadjusted OR 35.81 (95% CI 10.48-122.38). p<0.001), higher NL ratio (7.8±6.5 vs 4.9±4.0, p<0.001; unadjusted OR 1.13 (95% CI 1.05-1.21), p=0.001) and were more likely acidemic (34.0% vs 20%, p=0.032; unadjusted OR 2.06 (95% CI 1.06-4.01)).
During the first week of hospitalization, patients more exposed to nephrotoxins were more likely to develop AKI (27.4% vs 12.9%, p=0.015; unadjusted OR 2.53 (95% CI 1.18-5.44), p=0.017).
AKI patients required more ICU admission (30.2% vs 7.1%, p<0.001), mechanical ventilation (26.4% vs 4.7%, p<0.001) and vasopressor use (7.5% vs 0%, p=0.008) and fulfilled more ARDS criteria (22.6% vs 5.9%, p=0.001). More AKI patients were treated with hydroxycloroquine (78.3% vs 67.1%, p=0.047) and corticosteroids (16.2% vs 4.7%, p=0.009).
The majority of AKI patients had persistent AKI (n=64, 60.4%). According to AKI severity, most patients were KDIGO stage 1 (n=66, 60.0%), followed by KDIGO stage 3 (n=24, 21.8%) and KDIGO stage 2 (n=20, 18.2%). Ten percent of AKI patients required renal replacement therapy (RRT), five patients required continuous RRT and the remaining intermittent RRT.
On a multivariate analysis, admission SCr (adjusted OR 48.01 (95% CI 10.46-220.45), p<0.001) and exposure to nephrotoxins (adjusted OR 3.60 (95% CI 1.30-9.94), p=0.014) were independent predictors of AKI.
Transient versus Persistent AKI
There were no statistically significant differences between transient versus persistent AKI concerning demographic and clinical characteristics, nor laboratory values at admission.
Compared with transient AKI, patients with persistent AKI had a higher proportion of patients with more severe AKI (KDIGO stage 3 31.3% vs 7.1%, KDIGO stage 2 21.9% vs 14.3%, KDIGO stage 1 45.3% vs 78.6%, p=0.002), required more often ICU admission (37.5% vs 19.0, p=0.045), and RRT (14.1% vs 2.4%, p=0.044). These patients had higher mortality rate than transient AKI patients (37.5% vs 11.9%, p=0.004).
AKI and outcomes
Overall, in-hospital mortality was 18.2% (n=35). Mortality was associated with older age (83.6±12.6 vs 69.6±16.1, p<0.001; unadjusted OR 1.08 (95% CI 1.04-1.12), p<0.001), pre-existing CVD (60% vs 29.9%, p=0.001, unadjusted OR 3.51 (95% CI 1.65-7.49), p=0.001) and CKD (42.9% vs 14.6%, p<0.001, unadjusted OR 5.14 (95% CI 2.26-11.71), p<0.001); lower Hb (11.8±2.4 vs 13.2±1.9, p<0.001, unadjusted OR 0.73 (0.61-0.88), p=0.001), higher SCr (2.49±4.00 vs 1.08±0.54, p<0.001, unadjusted OR 2.42 (95% CI 1.44-4.06), p=0.001), lower albumin (3.14±0.56 vs 3.42±0.58, p=0.014, unadjusted OR 0.45 (95% CI 0.23-0.87), p=0.018) and acidemia (45.7% vs 23.6%, p=0.008, unadjusted OR 2.73 (95% CI 1.28-5.84), p=0.001) at admission. (Table 2)
Mortality was also associated with AKI (28.3% vs 5.9%, p<0.001, unadjusted OR 6.03 (2.22-16.37), p<0.001). AKI patients also had a more prolonged length of hospital stay (26.5±26.2 days vs 17.1±19.6 days, p=0.007).
On a multivariate analysis, AKI was not an independent predictor of mortality (adjusted OR 3.00 (95% CI 0.86-10.52), p=0.086). Thus, we performed a sensitivity analysis to include only patients with persistent AKI. On a multivariate analysis, older age (adjusted OR 1.08 (95% CI 1.02-1.13), p=0.004), lower Hb level (adjusted OR 0.69 (95% CI 0.53-0.91), p=0.007), acidemia (adjusted OR 5.53 (95% CI 1.70-18.63), p=0.005), duration of AKI (adjusted OR 7.91 for persistent AKI (95% CI 2.39-26.21), p=0.001) and severity of AKI (adjusted OR 2.30 per increase in KDIGO stage (95% CI 1.10-4.82), p=0.027) were independent predictors of mortality. (Table 3)