Background: The phase-3 MONALEESA-2,-3 and -7 randomized trials showed improved progression-free survival (PFS) and overall survival (OS) with the addition of cyclin D-cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib to endocrine therapy in women with advanced-stage breast cancer. However, ribociclib induced acute renal injury is not recognized in these studies. In this report, we explore ribociclib-induced acute kidney injury (AKI) in breast cancer patients receiving ribociclib. Methods: We performed a retrospective chart review of all breast cancer patients who received ribociclib at our institution between April 2019 and September 2021. Patients and disease characteristics were collected, details of creatinine kinetics in relation to administration of ribociclib and other nephrotoxic drugs were obtained. Acute kidney injury grades (AKI-KDIGO classification) were captured. Results: 145 females, median age 60.0 years, all with advanced-stage breast cancer treated with aromatase inhibitors (AI) or fulvestrant plus ribociclib were reviewed. A total of 26 (17.9%) patients developed AKI; 3 were grade-I, 21 grade-II and 2 were grade-III. Rate of AKI was significantly higher (n = 15, 48.4%) among 31 patients on other concomitant nephrotoxic drugs, compared to 11 (9.6%) of 114 other patients, p = 0.001. Nephrotoxic drugs include non-steroidal anti-inflammatory (38%), metformin (30%), angiotensin-II receptor blockers (26%), and angiotensin-converting enzyme inhibitors (11%). Median time to develop AKI was 54 (range, 21-168) days, while the median time for creatinine recovery was 5 (range, 4-7) days after holding the drugs. Average creatinine increment for affected patients was 2.28 times the baseline level. Time to AKI was shorter, but not statistically significant, among patients on nephrotoxic drugs and recovery was faster after stopping these drugs (Table). Conclusions: Ribociclib-induced AKI is not uncommon and not adequately addressed. Though reversable in majority of patients, some patients may develop grade-III AKI or require treatment interruption. Nephrotoxic medications seem to significantly enhance ribociclib-associated renal injury. Withhold these medications with periodical assessment by nephrologist is strongly recommended in these patients. Larger studies are warranted to validate our findings.