tHe USual Suspects

A 72-year-old man presented with a short history of headaches with reduced visual acuity in his right eye. His general practitioner then referred him to the ophthalmologist who found Grade IV hypertensive retinopathy with bilateral papilloedema on fundoscopy. He was referred to a medical team for further assessment. Eleven months prior to this current presentation, the patient developed painless jaundice, pale stools and weight loss. Computed tomography revealed a 7-cm mass in the pancreas. Intraoperatively, metastatic deposits were discovered in the small bowel mesentery. Palliative gastroenterostomy, bilioenteric anastomosis and enteroenterostomy were performed. Histology confirmed adenocarcinoma. He underwent seven monthly cycles of Gemcitabine chemotherapy, the last of which was 6 weeks prior to his current admission. On admission, his blood pressure was 210/124 mmHg. There was reduced air entry and dullness to percussion bibasally on examination of the chest. Chest X-ray showed cardiomegaly and bilateral effusions. An electrocardiogram showed evidence of left ventricular hypertrophy. A recent echocardiogram had shown mild left ventricular impairment as well as a pericardial effusion that was not haemodynamically relevant. An ultrasound scan showed normal-sized kidneys without chronic parenchymal changes. Serum biochemistry revealed evidence of acute kidney injury, with serum creatinine 230 lmol/L (1 month previously serum creatinine had been within normal range). The urinary protein creatinine ratio was 470 mg/mmol creatinine. Full blood count showed anaemia and thrombocytopaenia (haemoglobin 8.8 g/dL, white blood count 8.8 3 10/L, platelets 70 3 10/L, reticulocyte count 3.7%). The serum lactate dehydrogenase was markedly elevated at 1919 U/L and serum haptoglobin was <0.01 g/L consistent with haemolysis. The blood film revealed fragmented red blood cells. Serum immunoglobulins and complement C3 and C4 were normal. Anti-neutrophil cytoplasmic antibodies, anti-neutrophil antibodies and antibodies to extractable nuclear antigens, including Scl-70, were all negative. A renal biopsy was performed. The biopsy showed some glomeruli with increased mesangial matrix and eosinophilic material in the capillary lumina, indicating intraluminal thrombus (Figure 1). Periodic acid-Schiff stain showed a fibrillary appearance of the mesangium (Figure 2). Silver stain showed focal splitting of the glomerular basement membrane. A diagnosis of thrombotic microangiopathy with renal involvement was made and both the underlying malignant disease and the chemotherapy with Gemcitabine were seen as possible underlying causes. Gemcitabine was stopped. Plasma exchange was briefly considered but not done after a review of the evidence. Treatment with amlodipine and atenolol was started to control blood pressure. An assay of von Willebrand factor-cleaving protease came back as normal, as did assays for Factors H and I. Escherichia. coli 0157:H7 serology was positive. The patient had no diarrhoea at this point in time nor did he recall any previous episode of loose stools. Stool culture was negative. The patient did well subsequently and he was discharged from hospital. When last seen in clinic, he was well with stable renal function (serum creatinine 289 lmol/L). He is under regular review by the oncology team, currently there is no evidence of disease progression and no further chemotherapy is planned.