Introduction: One of the worst clinical outcomes of the coronavirus disease 2019 (COVID-19) pandemic was acute kidney injury (AKI). Methods: This manuscript presents results from a population-based registry study assessing treatment, comorbidities, and predictors of hospital death among COVID-19 patients with AKI from March 1st to May 31th, 2020. Death, oxygen delivery and ventilation, acute dialysis need, use of medications, and various clinical outcomes, in addition to the length of stay in the hospital and intensive care unit (ICU), were evaluated. Results: In Castile and Leon, the largest region of Spain, 10.87% of the patients admitted for COVID-19 (n = 7,307) developed AKI. These patients were known by having hypertension (57.93%), cardiovascular disease (48.99%), diabetes (26.7%) and chronic kidney disease (14.36%), and they used antibiotics (90.43%), antimalarials (60.45%), steroids (48.61%), antivirals (33.38%), anti-systemic inflammatory response syndrome (SIRS) drugs (9.45%), and tocilizumab (8.31%). Mortality among patients with AKI doubled that observed in patients without AKI (46.1 vs. 21.79%). Predictors of hospital death in COVID-19 patients with AKI were ventilation needs (OR = 5.9), treatment with steroids (OR = 1.7) or anti-SIRS (OR = 2.4), severe acute respiratory syndrome (SARS) occurrence (OR = 2.8), and SIRS occurrence (OR = 2.5). Conclusions: Acute kidney injury is a frequent and serious complication among COVID-19 patients, with a very high mortality, that requires more attention by treating physicians, when prescribing medications, by looking for manifestations particular to the disease, such as SARS or SIRS.