Impact of COVID-19 on Renal Function: Analysis of Acute Kidney Injury Across Three Pandemic Waves

<b>Background/Objectives:</b> Coronavirus disease 2019 (COVID-19) has emerged as a multisystem disorder, with acute kidney injury (AKI) representing a frequent and severe complication associated with poor outcomes. This study assessed the incidence, risk factors, and outcomes of AKI in patients with severe COVID-19 across three pandemic waves. <b>Methods:</b> We retrospectively analyzed 561 patients with severe COVID-19 admitted to a tertiary hospital between March 2020 and December 2021. AKI was defined and staged according to KDIGO 2012 criteria. Demographic, clinical, laboratory, and imaging data were evaluated using univariate and multivariable logistic regression and ROC curve analyses to identify predictors of AKI. <b>Results:</b> AKI occurred in 71 patients (12.65%), most frequently during the third wave (40.9%). Stage 1 accounted for 62% of cases, while 23.9% progressed to stage 3 and 10% required dialysis. Compared with patients without AKI, those with AKI had longer hospital stays (15 vs. 11 days), more intense inflammatory responses (CRP 91.7 vs. 63.3 mg/L, <i>p</i> = 0.002), and higher mortality (35.2% vs. 10.2%, <i>p</i> < 0.001). Multivariable analysis identified elevated serum myoglobin (OR = 1.010, <i>p</i> = 0.001), prolonged corticosteroid therapy (OR = 1.096, <i>p</i> = 0.035), and lower hemoglobin (OR = 0.375, <i>p</i> < 0.001) as independent factors of AKI. <b>Conclusions:</b> AKI in severe COVID-19 is multifactorial, reflecting the interplay of systemic inflammation, cytolysis, coagulopathy, and renal microvascular dysfunction. The risk increases with higher myoglobin levels, longer corticosteroid exposure, and lower hemoglobin, highlighting the need for early identification and preventive strategies in high-risk patients.