Two-hundred and thirty-seven patients with COVID-19 and without exclusion criteria required ICU admission. Fifty-two (21.4%) patients presented AKI ≥ 2 of the AKIN classification and were included in the study. The median follow-up was 35.5 (IQR 36.75) days. Table 1 summarizes the demographic and clinical characteristics of the patients at hospital admission.
Patients were mostly male (76.9%), with a median age of 71.5 (61–74.75) years. Regarding comorbidities, 73.08% of the patients presented at least one, with hypertension, diabetes and COPD being the most frequent (59.6%, 21.2% and 21.2%, respectively). Overweight was present in 17% of the patients, and 13.5% presented CKD stage 3. Twenty-one per cent of the patients (n = 11) were on treatment with ACEI, and 15.4% with ARBs at admission. Both antihypertensive drugs were discontinued in all patients at admission.
The median time from symptom onset to hospital and ICU admission were 7 (IQR 5) and 10 (IQR 4) days, respectively. Pneumonia was present in 94.2% of cases, with a mean PaO2/FiO2 of 243 ± 155 mmHg, and a mean SOFA at admission of 5.78 ± 3.26.
Table 2 summarizes the laboratory findings. At the time of AKI diagnosis, patients had a worse liver profile, higher levels of d-dimer, procalcitonin, leukocytes, and platelets than at admission. C-Reactive Protein (CRP) levels were lower at AKI diagnosis compared to admission values. SOFA scores also showed a significant increase between admission and AKI diagnosis (5.79 ± 3.26 and 8.38 ± 2.43, respectively, p < 0.01).
Thrombotic events occurred in ten patients (19.23%): eight pulmonary thromboembolisms and two peripheral arterial occlusions. On the other hand, hemorrhagic complications occurred in 11 patients (21.15%): four gastro-intestinal bleeds, three retroperitoneal bleeds, three muscle and one central nervous system bleeds.
Most of the patients received therapy with the combination of hydroxychloroquine, azithromycin (96.2%), and lopinavir/ritonavir (94.2%). Steroids were administered to 69.2% of the patients with a mean cumulative dose of 544 ± 496.38 mg of prednisone. Tocilizumab was used in 48.1% of cases; the median time between admission and tocilizumab administration was two days (1–4), mean dose 561 ± 276.24. Five (9.6%) patients with refractory inflammatory response were treated with Anakinra.
Regarding antithrombotic treatment, 5 (9.6%) patients were anticoagulated, 38 (73%) received antithrombotic prophylaxis, and 9 (17.3%) did not receive antithrombotic therapy at hospital admission. At diagnosis of AKI, 10 (19.2%) patients were on anticoagulant treatment, 38 (73%) with prophylaxis and 4 (7.7%) without antithrombotic therapy. Low molecular weight heparin was used in 40 (76.9%) and 43 (82.69%) patients at admission and at AKI diagnosis, respectively. Moreover, three and five patients received unfractionated heparin at hospital admission and AKI diagnosis, respectively. One patient received fondaparinux at AKI time because of heparin-induced thrombocytopenia.
AKI characteristics and evolution are described in Table 3. Most of the patients (84.6%) developed AKI during the ICU stay, within a median of 5 and 12 days from admission and the onset of symptoms, respectively. Twenty-six (50%) of the cases progressed to more severe AKI.
Patients were mostly non-oliguric at AKI diagnosis, but those who started RRT developed it more frequently (in the 24 h before RRT onset). Hyperkalemia was not a frequent finding at the time of AKI diagnosis.
At AKI diagnosis, 73% of the patients were on treatment with vasoactive drugs, with a median noradrenaline dose of 0.19 mcg/kg/min (IQR 0.46).
Suspected intrinsic AKI related to severe COVID-19, which accounted for 71.15% (n 37) of cases, was the most common form of kidney dysfunction. The other probable causes of AKI that were identified included: hemorrhagic shock related to anticoagulation treatment (4); contrast nephropathy (3); drug nephrotoxicity (2); cardiac arrest (2); liver failure (2); heart failure (1) and pancreatitis (1).
Fifteen patients (28.85%) required RRT, including 13 with continuous renal replacement therapy (CRRT). Median time from admission to RRT was 12 (IQR 10) days. RRT mean time was 10.87 ± 9.28 days. CRRT was the only modality in eight patients, while five patients received CRRT followed by intermittent modality, and two patients were treated with intermittent modalities alone. When CRRT was used, the modalities included continuous hemodialysis with medium cut-off dialyzers (MCO) (n = 5) and continuous hemodiafiltration with high-flux hemofilter (n = 8). Anticoagulation consisted of citrate in six patients and heparin in six patients.
At the end of follow-up, 31 (59.6%) patients recovered from the AKI episode.
Variables associated with RRT or mortality are described in Tables 4 and 5 and 6 (Supplementary material).
Baseline and admission creatinine was higher in patients who died, p 0.011 and 0.02, respectively (Table 6 supplementary materials). In univariate analysis, the variables associated with higher mortality in AKI patients were age > 60 years (p 0.017), and presence of one or more comorbidities (p 0.03). On the contrary, recovery from AKI was associated with less probability of death, p < 0.001. In the multivariate analysis, only AKI recovery retains significance (p 0.005).
Overall mortality among patients with COVID-19 diagnosis admitted to the ICUs during the study period, and without exclusion criteria, n = 237, was 16.87% (n = 40). In the non-AKI patients, mortality was 7.3% (n = 13), while in AKI patients it was 51.92% (n = 27), p < 0.001, OR 10.67 (95% CI 5.1–22.33). The median time to death after AKI diagnosis was eight days (IQR 13). AKI was also associated with longer hospital LOS, 35 (IQR 36.75) vs 18 (IQR 20) days in AKI vs non-AKI patients, respectively (p 0.018)).
Regarding RRT, in the univariate analysis, a SOFA score of 8 or more at AKI diagnosis was associated with the need for RRT, p 0.032, OR 4.52, with sensitivity and specificity of 73% and 62%, respectively. However, the non-renal SOFA score at AKI was not associated with RRT. Also the use of vasoactive drugs at AKI diagnosis was not associated with RRT requirement, p 0.06. On the contrary, the use of corticosteroids was associated with less requirement of RRT, p 0.03, OR 0.24.
In the multivariate analysis, a SOFA score of 8 or more and corticosteroid use at AKI diagnosis were associated with RRT, OR 6.15, p 0.015, and OR 0.16, p = 0.017 respectively.