Targeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition: A Case Report and Review of the Literature

Rationale: Targeted cancer therapies have revolutionized the field of oncology by selecting for specific molecular pathways, thus improving overall clinical prognosis. However, many of these targeted treatments have been reported to have adverse kidney effects, including acute kidney injury, interstitial nephritis, and glomerular disease. Furthermore, some of these targeted therapies have also been found to cause an asymptomatic rise in serum creatinine levels through inhibition of active tubular secretion. Presenting concerns: A 79-year-old woman was being followed for stage 4 A2 chronic kidney disease secondary to type 2 diabetes and longstanding hypertension. She was diagnosed with invasive mammary carcinoma and was initiated on letrozole, an aromatase inhibitor, and palbociclib, a selective cyclin-dependent kinase inhibitor, was subsequently added. Prior to the initiation of her treatments, her baseline estimated glomerular filtration rate (eGFR) fluctuated between 25 and 28 mL/min/1.73 m 2 over the previous year. After initiating palbociclib, her serum creatinine progressively increased, despite having well-controlled blood pressure and diabetes. In addition, there was no history of pre-renal events nor any sonographic evidence of obstruction. Within 7 months, her eGFR based on serum creatinine had decreased down to 12 mL/min/1.73 m 2 . Interventions: Given that there were no clinical or other biochemical changes suggestive of worsening renal function, a serum cystatin C was measured using an immunoturbidimetric assay, which was 1.71 mg/L and correlated with an eGFR of 33 mL/min/1.73 m 2 based on the chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C equation (2012). This value was consistent with her previous baseline. Based on these findings, the significant decrease in eGFR measured by serum creatinine was attributed to the inhibitory effects of palbociclib on tubular creatinine secretion, rather than representing true kidney damage. Thus, a kidney biopsy was not performed in this context. Outcomes: Seven months later, a repeat serum cystatin C was repeated to assess for any worsening of the patient’s kidney function and revealed an eGFR of 35 mL/min/1.73 m 2 based on the CKD-EPI cystatin C equation (2012), thus revealing stable kidney function and reinforcing the inhibitory effects of palbociclib on tubular creatinine secretion through its direct effects on kidney transporters. Teaching points: This case report and literature review acknowledges the importance of using alternative methods of assessing kidney function when patients are undergoing targeted cancer therapies known to affect tubular creatinine secretion, which include cyclin-dependent kinase 4/6 inhibitors, poly(adenosine diphosphate-ribose) polymerase inhibitors, tyrosine kinase inhibitors, and mesenchymal-epithelial transition inhibitors. The use of non–creatinine-based markers of glomerular filtration rate (GFR), such as cystatin C and nuclear renal scans, will allow for more accurate estimation of kidney function in the appropriate setting, thus avoiding invasive diagnostic tests and unnecessary adjustments of treatment plans. However, certain targeted cancer therapies have also been proven to cause true kidney injury; therefore, physicians must still maintain a high degree of suspicion and consider invasive investigations and/or cessation or reduction of treatments when alternative measurements of kidney function do not suggest an underestimation of GFR via serum creatinine.

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