Breast cancer is the most common cancer among the female population, of which the hormone-positive HR subtype+ (HER2+) comprises 75% of cases. Treatment with protein kinase inhibitors, specifically cyclin-dependent kinase 4/6 (CKD4/6) inhibitors have been successful in improving both prognosis and survival in combination with aromatase inhibitors.1–3 Ribociclib is a CKD4/6 inhibitor used in this disease, which has been associated with a number of adverse effects, including renal failure.4,5
Case reportA 69-year-old patient with a medical history of locally advanced infiltrating ductal carcinoma of the right breast with infraclavicular mediastinal lymph node involvement and bone+ HER+ in 2014. Initially, she underwent mastectomy and received maintenance letrozole. Subsequently in December 2022 she presented bone extension to L11 and lymph nodes with evidence of malignancy, so treatment was started with ribociclib 600 mg/every 24 h from January 2023 to June 2023, maintaining previous treatment with letrozole. Renal function was normal in January 2023 with baseline creatinine around 0.9−1 mg/dl. She was referred in June 2023 to nephrology for presenting a serum creatinine of 1.8 mg/dl (Fig. 1). The presence of prerenal disease was ruled out, and analytically she did not present proteinuria or alterations in the immunological study, in addition urea levels were normal. For this reason, cystatin C and creatinine clearance were requested, presenting a normal cystatin C of 1.0 mg/l, creatinine clearance 34.6 ml/min and glomerular filtration rate measured by cystatin C of 69.9 ml/min.
Discussion
Cases of creatinine elevation have been reported in patients treated with protein kinase inhibitors, specifically CKD4/6 in conjunction with letrozole1–3 this is because they inhibit the receptor of the transporters involved in the active secretion of creatinine in the proximal tubules, so they can cause creatinine elevations due to decreased creatinine excretion, and not due to parenchymal damage.6 In our case, normal cystatin C levels indicate that decreased clearance of creatinine is due to lack of creatinine excretion and not due to parenchymal damage, therefore in this case creatine clearance is affected by the lack of tubular creatine excretion.
This is the first reported case of inhibition of tubular creatinine secretion secondary to the use of ribociclib. For this reason, in the presence of increased creatinine levels in patients under treatment with this drug, we recommend the use of cystatin C to monitor renal function. If an inhibition of tubular creatinine secretion is confirmed, it would allow these patients to continue with a treatment that can improve their long-term prognosis.
