Case Presentation: A 64-year-old female with hereditary transthyretin amyloidosis (hATTR) and hypothyroidism presented with three days of dull pain localized bilaterally to the biceps femorum, recurrent emesis, and anorexia. Her past medical history includes complications of hATTR (being treated with patisirtan and tafamidis); polyneuropathy, small bowel enteropathy, and cardiomyopathy with associated recent bioprosthetic mitral and tricuspid valvular replacements, complicated by atrial fibrillation requiring warfarin anticoagulation. Her physical exam was notable for tenderness at the biceps femorum insertion points, but otherwise there were no focal neurologic deficits. Laboratory studies were remarkable for elevated creatinine of 3.9 mg/dL (baseline of 1.5 mg/dL), uremia, hypoalbuminemia, mild leukocytosis, and supratherapeutic INR. Initial diagnostics studies included CT chest/abdomen/pelvis which showed mild pulmonary edema, anasarca, and small volume ascites while CT of the L-spine showed circumferential disc bulging at L4-5, L5-S1 causing mild stenosis and mild neural foraminal narrowing. Over the patient’s hospital course, her renal function declined to oliguric acute kidney injury stage III (creatinine peaked at 6.94 mg/dL) with symptomatic hyperkalemia requiring two sessions of emergent dialysis via tunneled dialysis catheter. A kidney biopsy was performed and was positive for fibrillary glomerulopathy with focal fibrinoid necrosis. The patient was started empirically on a course of intravenous methylprednisolone for three days which was transitioned to oral prednisone at 1mg/kg. Shortly after, the patient had recovery of renal function (creatinine at discharge was 1.53 mg/dL), after which her tunneled dialysis catheter was removed, and she was discharged with a maintenance dose of oral prednisone while awaiting additional expert opinion and potential rituximab therapy.

Discussion: This patient’s hereditary transthyretin amyloidosis was the overshadowing diagnosis at admission and was initially suspected to be the cause of her renal injury. However, there were several atypical features of this presentation that warranted additional workup in search of an alternative diagnosis. Notably, the patient had a rapidly progressive disease course that would be unexpected with amyloid induced kidney disease, which should follow a subacute to chronic course. The histopathologic diagnosis, fibrillary glomerulopathy with focal fibrinoid necrosis, was highly unexpected because fibrillary glomerulonephritis is diagnosed in only 0.5%–1% of native kidney biopsies. (1) Fibrillary glomerulonephritis is an immune-complex mediated GN with amyloid like fibrils larger than amyloid which are IgG positive and Congo red negative. Approximately 30% to 50% of patients have underlying malignancy or autoimmune disease, and the most common presentations include hematuria, proteinuria, hypertension, and renal injury. (2) The prognosis is poor, with 40% to 50% of patients developing end-stage renal disease within two to six years. (3) Treatment usually involves immunosuppression, but no therapies have demonstrated clear benefit.

Conclusions: The primary learning point of this case is the importance of maintaining a broad differential. While a unifying diagnosis is often sought in patients with multi-organ disease, symptomatology and natural disease course may indicate whether two or more distinct pathological processes are occurring, and prompt a more comprehensive workup.