105 - Sodium Glucose Cotransporter 2 inhibitor (SGLT2i) Use in a Pediatric Patient Receiving Cisplatin

Publication Number: 105.6931

Esraa Elsamny, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Amr Elgehiny, MD Anderson Cancer Center, Houston, TX, United States; Douglas J. Harrison, University of Texas MD Anderson Cancer Center, Houston, TX, United States; Rita D. Swinford, McGovern Medical School at the University of Texas Health Science Center at Houston, HOUSTON, TX, United States

Background: Cisplatin (CP) is a cornerstone chemotherapeutic for treating pediatric germ cell tumors; however, its dose-dependent nephrotoxicity can limit use, as the drug is primarily eliminated through the kidneys. Hypomagnesemia is a challenging side effect. Patients often remain hypomagnesemic despite IV and oral magnesium (Mg) supplementation. Considering the challenges and side effects associated with IV Mg and its oral forms, there is a need for therapeutics that effectively reduce excessive urinary Mg losses. The SGLT2is have been shown to reduce urinary Mg wasting in a dose dependent fashion. Despite a growing interest in SGLT2i's for kidney protection in adults, their use for treating hypomagnesemia is off-label and experience is limited in pediatrics.

Objective: We aim to demonstrate the utility of SGLT2is in a child with CP-induced nephrotoxicity and Mg depletion.

Design/Methods: We report a case of an adolescent male diagnosed with a high-risk metastatic testicular germ cell tumor, treated extensively with CP, bleomycin, and etoposide for 10 months in attempt to induce remission. During his treatment, he developed hypomagnesemia and a declining glomerular filtration rate (GFR) concomitantly with the CP therapy. He required irbesartan up to 300 mg daily for hypertension. Dapagliflozin, an SGLT2i, (10mg/d) was started 3 months into treatment. His stem cell transplant (SCT) course was complicated by septic shock, non-dialysis requiring acute kidney injury (AKI) and proteinuria (figures 1 and 2).

Results: Our patient’s GFR stabilized at 60 ml/min/1.73 m²(CKiD U25), allowing him to continue CP therapy along with carboplatin for SCT (cumulative dose >60mg/m2). (Figure1). With the addition of the SGLT2i, he discontinued IV Mg supplementation while maintaining adequate Mg levels on oral Mg-Protein-Complex (Figure 3). Moreover, his blood pressure improved and eventually discontinued all antihypertensives. The SGLT2i was held during the AKI episode and resumed with recovery, his kidney function stabilized, as indicated by a return of serum creatinine to baseline and his proteinuria subsequently resolved to allow the continuation of his Oncology treatment plan. (Figures 1 and 2). During the time of SGLT2i use, glucosuria was noted on urinalysis.

Conclusion(s): This case highlights an important potential of the SGLT2i in pediatric oncology for CP-induced nephrotoxicity and hypomagnesemia. Our report was not designed prospectively and despite numerous confounding factors, we found the SGLT2i stabilized our patient’s kidney function and Mg loss despite extensive treatment with CP.

Elsamny Verification of Trainee Status 11.4.24.pdf

Urine protein to creatinine ratio (figure2)
This graph shows the changes in patient's urine protein to creatinine ratio over time.

Serum magnesium levels (figure 3)
This graph shows the changes in patient's serum Magnesium levels over time.