Magalhães et al. demonstrated that the incidence of acute kidney injury was high in hospitalized patients with COVID-19 and that the second wave was associated with greater severity; however, the mortality rates were similar between the two periods. This may reflect both the effectiveness of vaccines and the constant learning that frontline professionals gained throughout the pandemic to provide greater support to their patients. ◼ Renal involvement was frequent in patients with COVID-19 and related to worse outcomes. ◼ Diuretic use, mechanical ventilation, proteinuria, hematuria, age, and creatine phosphokinase and D-dimer levels were risk factors for acute kidney injury. ◼ Acute kidney injury, mechanical ventilation, elevated SOFA Score, and elevated ATN-ISS were associated with mortality. ◼ The second wave was associated with greater severity; however, the mortality rates were similar between the two periods. ◼ This may reflect the effectiveness of vaccines and the constant learning that frontline professionals gained throughout the pandemic. This study aimed to evaluate the incidence of acute kidney injury in hospitalized Brazilian patients with COVID-19 and identify the risk factors associated with its development and prognosis during the two waves of the disease. We performed a prospective cohort study of hospitalized patients with COVID-19 at a public university hospital in São Paulo from March 2020 to May 2021. Of 887 patients hospitalized with COVID-19, 54.6% were admitted to the intensive care unit. The incidence of acute kidney injury was 48.1%, and the overall mortality rate was 38.9%. Acute kidney replacement therapy was indicated for 58.8% of the patients. The factors associated with acute kidney injury were diuretic use (odds ratio [OR] 2.2, 95%CI= 1.2-4.1, p=0.01), mechanical ventilation (OR= 12.9, 95%CI= 4.3-38.2, p<0.0001), hematuria(OR= 2.02, 95%CI= 1.1-3.5, p<0.0001), chronic kidney disease (OR= 2.6, 95%CI= 1.2-5.5, p=0.009), age (OR= 1.03, 95%CI= 1.01-1.07, p=0.02), and elevated creatine phosphokinase (OR= 1.02, 95%CI= 1.01-1.07, p=0.02) and D-dimer levels (OR= 1.01, 95%CI= 1.01-1.09, p<0.0001). Mortality was higher among those with acute kidney injury (OR= 1.12, 95%CI= 1.02-2.05, p=0.01), elevated Sequential Organ Failure Assessment Scores (OR= 1.35, 95%CI= 1.1-1.6, p=0.007), elevated Acute Tubular Necrosis-Injury Severity Score (ATN-ISS; (OR= 96.4, 95%CI= 4.8-203.1, p<0.0001), and who received mechanical ventilation (OR= 12.9, 95%CI= 4.3-38.2, p<0.0001). During the second wave, the number of cases requiring mechanical ventilation (OR= 1.57, 95%CI= 1.01-2.3, p=0.026), with proteinuria (OR= 1.44, 95%CI= 1.01-2.1, p=0.04), and with higher ATN-ISS Scores (OR= 40.9, 95%CI= 1.7-48.1, p=0.04) was higher than that during the first wave. Acute kidney injury was frequent in hospitalized patients with COVID-19, and the second wave was associated with greater severity. However, mortality rates were similar between the two periods, which may reflect both the effectiveness of vaccines and the constant learning that frontline professionals gained throughout the pandemic to provide greater support to their patients. RBR-62y3h7.