S KALLA1, R ELLIS1, B DOUCET1, S CAMPBELL1, N ISBEL1, B TIE1, D JEGATHEESAN1
1 Princess Alexandra Hospital, Brisbane , Australia
Background: The risk of developing renal cell carcinoma (RCC) is up to 6-fold higher in kidney transplant recipients (KTR). Pazopanib, a selective tyrosine kinase inhibitor (TKI), is an efficacious first line agent to treat metastatic RCC. Many TKIs are associated with thrombotic microangiopathy (TMA) due to inhibition of vascular endothelial growth factor; however, there are few reports linking pazopanib with TMA.
Case Report: A 52-year-old gentleman 5-years post his second kidney transplant for IgA nephropathy presented with hypertension, fluid overload and worsening graft function (peak creatinine 275µmol/L, baseline 130-160µmol/L) and nephrotic range proteinuria two months after commencing pazopanib for metastatic RCC. His maintenance immunosuppression included ciclosporin, mycophenolate, and prednisolone. Haematological parameters and liver function were unremarkable, there was no evidence of BK viraemia, and no allograft renal artery stenosis or venous thrombosis on ultrasound. Allograft biopsy demonstrated glomerular and arteriolar changes consistent with chronic active TMA and features of borderline cellular rejection. ADAMTS13 activity was normal. He was treated with intravenous methylprednisolone 250mg for three days and commenced on irbesartan 75mg daily. Drug-induced TMA from pazopanib was suspected, particularly given the documented associations with other TKIs. In consultation with his medical oncologist, pazopanib was ceased, and an alternate TKI cabozantinib was commenced. Serum creatinine remained <200µmol/L three months after admission.
Conclusion: This is the first reported biopsy-proven case of TMA attributed to pazopanib in a KTR. With increasing clinical indications for and availability of TKIs, clinicians need to be aware of their association with TMA events in KTRs, who are already susceptible to TMA due to abnormal vasculature, infectious triggers, ischaemia-reperfusion injury, and calcineurin inhibitor use.
Dr Shabana Kalla is a third year Basic Physician Trainee, currently completing her training in Princess Alexandra Hospital. She graduated from Monash University in 2015.
She aspires to become a nephrologist and with special interest in Transplant medicine/ immunology. She is currently awaiting to sit for her clinical exams 2020/2021 before applying for the Nephrology Advanced Trainee Network