MINIMAL CHANGE DISEASE ASSOCIATED WITH RIBOCICLIB: A NOVEL RENAL COMPLICATION OF CDK4/6 INHIBITOR THERAPY

Cyclin-dependent kinase (CDK) 4/6 inhibitors block cell-cycle progression from G1 to S phase, suppressing tumor growth. In combination with endocrine therapy, they significantly improve progression-free survival in hormone receptor–positive, HER2-negative metastatic breast cancer. The three FDA-approved agents-ribociclib, palbociclib, and abemaciclib-are oral therapies used long-term until disease progression. These agents can cause pseudo–AKI through inhibition of renal transporters such as OCT2, MATE-1, and MATE2-K, resulting in reversible creatinine elevations without structural damage. True nephrotoxicity, including acute tubular necrosis and, less commonly, interstitial nephritis have also been reported.

We describe a case report of minimal change disease associated with ribociclib, a manifestation not previously reported with CDK 4/6 inhibitor therapy.

A 70-year-old woman with long-standing type 2 diabetes and HTN presented with severe back pain and was found to have hypercalcemia (16.2 mg/dL) and diffuse spinal lesions on MRI. Bone biopsy confirmed metastatic breast carcinoma (ER 95%, PR-, HER2-). She was treated with anastrozole and palbociclib, but within two months developed AKI (Cr 1.93 mg/dL) with hypomagnesemia (0.5 mg/dL) and hypocalcemia (6.6 mg/dL), which resolved after discontinuation. 2 months after stopping palbociclib, she started abemaciclib but developed recurrent AKI (Cr 1.89 mg/dL) and persistent nausea, prompting discontinuation with recovery (Cr 1.03 mg/dL). Over the next 4 years, she received multiple courses of radiation and CyberKnife therapy for recurrent bone metastases and was then started on ribociclib 600 mg/day. Baseline creatinine was 1.0 mg/dL, with negative UA and UACR of 44 mg/g. 3 months later, a 24-hour urine protein was 374 mg/day, and creatinine increased to 1.5 mg/dL. 10 months into therapy, UPCR rose to 10.36 g/g, leading to discontinuation of ribociclib. Kidney biopsy showed diffuse podocyte injury consistent with minimal change disease, with mild diabetic glomerulopathy and arteriosclerosis. Ribociclib was not restarted, and the patient was treated with tacrolimus 2 mg twice daily; however, proteinuria increased to 20 g/g and remained 11 g/g after 1 month. With no improvement after 8 weeks, tacrolimus was switched to high-dose prednisone 60 mg daily. Over 4 months, prednisone was tapered as proteinuria decreased to 3.88 g/g and creatinine remained around 1.71 mg/dL. Prednisone was then discontinued and cyclosporine initiated, reducing UPCR to 1.01g/g by March 2025, but creatinine rose to 3.19 mg/dL with hypertension, hyperlipidemia, and headaches. Cyclosporine was stopped, and the patient received rituximab, after which UPCR improved to 0.6 g/g by September 2025. Her cancer has remained in remission since the time of ribociclib initiation. 

CDK4/6 inhibitors are increasingly used in hormone receptor–positive breast cancer and can affect kidney function through both functional and structural mechanisms. This is the first case to describe minimal change disease that occurred in association with starting ribociclib therapy.