It is also absorbed from your belly, small bowel and colon [8]. with metastatic disease, up to 50% of patients will develop metastases following nephrectomy [2]. Age is a key risk factor, with incidence rates in the UK highest in those between 85 and 89?years old, and these patients are more likely to have other comorbidities (CRUK, 2019). Consequently, it is more likely for newly diagnosed patients to present with other medical problems that increase the complexity of their care. We present an unusual cause of renal failure in a patient undergoing systemic treatment for metastatic renal carcinoma with the tyrosine kinase inhibitor (TKI) pazopanib. Over the course of 30?months, he demonstrated a good response to treatment but developed progressive renal failure, eventually commencing haemodialysis. The unexpected cause of his renal failure demonstrates the importance of critically evaluating seemingly benign symptoms on TKIs and pursuing the true pathology. Case statement An 84-year-old man who had previously undergone a right radical nephrectomy for renal cell carcinoma offered to his general INCA-6 practitioner 15?years later with iron deficiency anaemia (haemoglobin 95 d/dL, mean cell volume 79.2?fl, ferritin 16.5?g/l, transferrin saturation 6%). His co-morbidities included type 2 diabetes mellitus, asthma, ischaemic heart disease (coronary artery bypass graft 13?years previously) and a hip replacement. His medication included ramipril, bisoprolol, simvastatin, metformin, aspirin, vitamin B12, ferrous sulphate and a fentanyl patch. An oesophago-gastroduodenoscopy (OGD) revealed an ulcerating duodenal mass, and the biopsy confirmed metastatic obvious cell renal carcinoma. A CT scan demonstrated the large 110?mm duodenal mass was centred in the head of the pancreas and was causing gastric outlet obstruction with moderate pancreatic duct dilatation (Fig. ?(Fig.2).2). His amylase was 23?IU/L. In addition, there were multiple, bilateral pulmonary metastases, and a 25?mm left renal nodule in keeping with a second renal tumour. Open in a separate windows Fig. 2 Graph of serum creatinine against time. Black bars symbolize the periods during which the patient required pazopanib At his initial oncology assessment his ECOG overall performance status was 1, he was living independently and was managing all activities of daily living without assistance. He therefore commenced palliative systemic therapy with pazopanib at a dose of 800?mg once daily as first-line treatment for his metastatic renal cell carcinoma. A re-staging CT scan after 3?months of treatment indicated disease response. However, he developed reduced appetite, grade 2 diarrhoea and grade 3 fatigue and his ECOG overall performance status deteriorated to 3. Therefore, after a short treatment break, his INCA-6 pazopanib was reduced to 400?mg once daily. A further CT scan after 6?months of treatment demonstrated ongoing disease response, and at that time his only persisting toxicity remained grade 1C2 diarrhoea, which was managed with loperamide. However, after 9?months of treatment, he developed a severe bout of diarrhoea, accompanied by dehydration and severe postural hypotension. His renal function deteriorated (Fig.?1 C Point C) and his creatinine rose from a baseline of 84?mol/L to 158?mol/L (Fig. ?(Fig.2)2) and his estimated glomerular filtration rate (eGFR) fell from 80?ml/min/1.73m2 to 37?ml/min/1.73m2. An ultrasound scan of his single remaining kidney revealed no evidence of obstruction. Urinalysis was unfavorable for blood and a urine-to-creatinine ratio of 16?mg/mmol demonstrated negligible proteinuria. Serum electrophoresis and immunoglobulins, auto-antibody titres and match levels were all unremarkable. Open in a separate windows Fig. 1 CT scan at re-presentation INCA-6 (a) 11?cm enhancing mass in the head of the pancreas, compressing the duodenum and leading to dilatation of the pancreatic duct with two smaller lesions in the body of the pancreas. b Multiple bilateral pulmonary metastases. c Exophytic lesion in the left kidney A working diagnosis of acute kidney injury (AKI) from acute tubular SKP1A necrosis (ATN) due to hypovolaemia and hypertension as a result of his diarrhoea was made. His pazopanib and antihypertensive brokers were temporarily withheld and he was rehydrated. His renal function improved and his creatinine fell to 119?mol/L and his eGFR rose to 53?ml/min/1.73m2, although failed to return to his previous baseline. Given the ongoing response of his metastatic RCC to pazopanib, the drug was re-introduced. Over the ensuing 12 months his eGFR remained stable INCA-6 on this medication INCA-6 with continued oncological response. Following this period of stable renal function, his creatinine subsequently began to progressively rise again. This time, there was no identifiable disruption of fluid balance, haemodynamic disturbance or exacerbation of his gastrointestinal symptoms. Other than pazopanib, he was not.