Renal TMA Presenting After Eight Years of Sunitinib Therapy

Introduction: Thrombotic microangiopathy (TMA) is a rare side effect of Tyrosine Kinase Inhibitor (TKI) therapy that has almost always been reported as occurring within the first year of TKI initiation, with very few cases reported between two-three years. We report a case of renal-TMA occurring after eight years of TKI therapy. Case Description: A 70-year-old male was seen for worsening renal function and edema in early 2022. He had a history of metastatic renal clear cell carcinoma treated with left renal resection in 2013 and was started on Sunitinib (TKI) in 2014. His baseline serum creatinine was 151 umol/L and peaked to 260 umol/L with urine protein: creatinine ratio (UPCR) of 857 mg/mmol at the time of referral. Physical exam revealed hypertension and bilateral lower extremity pitting edema. Rheumatologic work up, complement levels, and paraproteinemia panel were unremarkable. Renal biopsy revealed hyaline occlusive glomerular microangiopathy. Sunitinib was discontinued and within one week, his serum creatinine decreased from 260 umol/L to 182 umol/L. He was switched to Nivolumab in late 2022. After a year of discontinuation of Sunitinib, his serum creatinine and UPCR decreased from 260 umol/l and 857 mg/mmol respectively at referral, to 135 umol/l and 50 mg/mmol. The only other treatment that was leveraged was the optimization of his renin-angiotensin blockade using Irbesartan. No recurrence of renal dysfunction was noted after a year of follow-up and his hypertension and edema had resolved. Discussion: To the best of our knowledge, our case is the first to highlight renal TMA occurring after three years TKI therapy. In previous case reports, renal recovery was seen with simply discontinuing the medication and supportive care such as reninangiotensin inhibition, as was seen with our case. Some reports have used steroid therapy however these cases have almost always included stopping the offending agent as well. Mixed results have been reported with re-introducing TKI therapy. Take-away points from this case include: (1) Renal TMA can occur even after many years of TKI therapy, and should be monitored for as a possible long term side effect (2) Management involves obtaining renal biopsy, stopping the TKI, and supportive care to optimize hypertension and proteinuria (3) Further work is needed to understand if steroid treatment is effective and if re-introducing TKI therapy is safe

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