We selected as eligible all adult patients (≥18 years of age) who tested positive by polymerase chain reaction (PCR) testing of a nasopharyngeal sample for COVID-19 and were admitted at the UICIVE from March 1st to May 31st of 2020. For patients who had multiple qualifying hospital admissions, we included only the first hospitalization. Exclusion criteria comprised (a) chronic kidney disease (CKD) patients on renal replacement therapy, (b) patients who underwent renal replacement therapy one week prior to admission, (c) patients who had less than 2 determinations of SCr and (d) patients who were discharged or died less than two days after admission.

Data was collected from individual electronic clinical records. The following variables were analyzed: patient demographic characteristics (age, gender, ethnicity, body weight and height); comorbidities [diabetes mellitus, hypertension, chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), cirrhosis, CKD and/or active malignancy]; current treatment with RAAS inhibitors; disease severity according to the Sequential Organ Failure Assessment (SOFA)19 score and Brescia-COVID Respiratory Severity Scale (BCRSS) at admission20; laboratory values at admission [serum hemoglobin, hematocrit, neutrophil, lymphocyte count and platelet count, serum albumin, serum ferritin, SCr, procalcitonin (PCT) and C-reactive protein (CRP), arterial blood gas and pH analysis, lactic acid dehydrogenase (LDH)]; exposure to nephrotoxins during the first week of admission [non-steroidal anti-inflammatory drugs (NSAIDS), radiocontrast, vancomycin, aminoglycosides]; need for intensive care unit (ICU) admission; need for mechanical ventilation; vasopressor use; treatment options used for COVID-19 (hydroxychloroquine, lopinavir/ritonavir, corticosteroids, tocilizumab).

Diagnosis of COVID-19 was based on the WHO interim guidelines as a positive PCR test.21

AKI, developing during hospital stay, was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) classification, using the serum creatinine (SCr) criteria, as follows: Stage 1: increase in SCr by 0.3mg/dL within 48h or a 1.5–1.9 times increase in SCr from baseline within 7 days; Stage 2: 2.9 times increase in SCr within 7 days; Stage 3: 3 times or more increase in SCr within 7 days or initiation of renal replacement therapy (RRT).22 Patients were stratified according to the highest AKI stage attained during their hospital stay. Persistent AKI was defined as continuance of AKI beyond 48h according to the consensus report of the ADQI 16 Workgroup.23 Transient AKI was defined as AKI of less than 48h duration.23

Pre-admission SCr (mean SCr within the previous three months) was considered as baseline value. The estimated glomerular filtration rate (eGFR) for patients with previous baseline SCr was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation.24 When unavailable, baseline SCr was estimated from the MDRD equation, accepting the lower limit of a normal baseline GFR of 75mL/min/1.73m2, as previously proposed.22

Presence of CKD was estimated according to the baseline SCr as an estimated GFR of lower than 60mL/min/1.73m2.25

Diabetes mellitus was diagnosed according to the American Diabetes Association criteria.26 Hypertension diagnosed according to the 2018 European Society of Cardiology (ESC) and European Society of Hypertension Guidelines.27 COPD comprised emphysema and chronic bronchitis. CVD was considered whenever a history of cerebrovascular disease, chronic heart failure of any cause, cardiac ischemic disease and/or peripheral arterial disease was documented. Acidemia was defined as blood gas PH<7.35.28 N/L ratio at admission was calculated as: Neutrophil count/Lymphocyte count.

The analyzed outcomes were the development of AKI during the first week of admission and in-hospital mortality.

The Shapiro–Wilk test was used to assess the normal distribution of variables. Categorical variables were described as the total number and percentage for each category, whereas continuous variables were described as the mean±standard deviation or median and range. Continuous variables were compared with the Student's t-test and categorical variables were compared with the Chi-square test.

All variables underwent univariate analysis to determine statistically significant factors which may have contributed to AKI development and in-hospital mortality. Subsequently, only variables with a significant statistical difference in the univariate analysis were included in the multivariate analysis using the logistic regression method.

Data were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was defined as a p-value <0.05. Statistical analysis was performed with the statistical software package SPSS for windows (version 21.0).

From March 1st to May 31st, 217 patients were admitted to UICIVE with a diagnosis of COVID-19 on admission. We focused on 192 patients after excluding 25 patients as depicted in Fig. 1.

Fig. 1.

Flow-chart of patient selection.

(0.09MB).

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. Baseline creatinine was estimated in 5.7% of patients (n=11). 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, median SCr was 1.00 (0.37–19.10)mg/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±0.59g/dL and more than 70% of patients had hypoalbuminemia, median serum ferritin was 707.0 (66.0–7884.0)μg/L, mean CRP was 9.71±8.72mg/dL, mean lactate level was 15.65±10.60mg/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 hydroxychloroquine (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.

Median length of hospital stay was 15 (0–136) days. Baseline characteristics of this cohort are described in Table 1.

In this cohort of COVID-19 patients, 55.2% developed AKI during the first week of admission (n=106). Of these, 64.2% of patients (n=68) presented AKI during the first 48h admission and the remaining developed AKI during the remaining period. 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), were more likely to have pre-existing hypertension (78.3% vs. 56.5%, p=0.001), CKD (28.3% vs. 9.4%, p=0.001) and COPD (19.8% vs. 7.1%, p=0.012), and to be medicated with RAAS inhibitors (51.9% vs. 30.6%, p=0.002). Mean baseline SCr was higher in AKI patients (1.02±0.47 vs. 0.84±0.26, p=0.002). Patients with BCRSS score higher than 2 developed more frequently AKI (34.5% vs. 18.8%, p=0.019).

At admission, patients with AKI had higher SCr (1.23 (0.43–19.10) vs. 0.80 (0.37–1.38), 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) and were more likely acidemic (34.0% vs. 20%, p=0.032).

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).

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 hydroxychloroquine (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.

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).

Overall, in-hospital mortality was 18.2% (n=35). Older age (83.6±12.6 vs. 69.6±16.1, p<0.001), pre-existing CVD (60% vs. 29.9%, p=0.001) and CKD (42.9% vs. 14.6%, p<0.001); lower Hb (11.8±2.4 vs. 13.2±1.9, p<0.001), higher SCr (2.49±4.00 vs. 1.08±0.54, p<0.001), lower albumin (3.14±0.56 vs. 3.42±0.58, p=0.014) and acidemia (45.7% vs. 23.6%, p=0.008) at admission were associated with mortality (Table 2).

Mortality was higher in AKI patients (28.3% vs. 5.9%, p<0.001), and 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 two sensitivity analysis, one including only patients with persistent AKI and another assessing the impact of AKI severity in the multivariate model.

In this multivariate analysis, older age (adjusted OR 1.07 (95% CI 1.02–1.11), p=0.004), lower Hb level (adjusted OR 0.78 (95% CI 0.60–0.98), p=0.035), duration of AKI (adjusted OR 7.34 for persistent AKI (95% CI 2.37–22.72), p=0.001) and severity of AKI (adjusted OR 2.65 per increase in KDIGO stage (95% CI 1.32–5.33), p=0.006) were independent predictors of mortality (Table 3).