Cystoscopy is the most appropriate diagnostic test to perform next in this patient. He has painless hematuria with a history of granulomatosis with polyangiitis (formerly known as Wegener granulomatosis), which was treated with the nonbiologic disease-modifying antirheumatic alkylating agent cyclophosphamide. Both the underlying rheumatologic condition and the medication used for its treatment are associated with increased risk of malignancy, especially bladder cancer. Bladder cancer usually presents with painless frank (usually not microscopic) hematuria, and cystoscopy with biopsy is most likely to lead to the correct diagnosis. In contrast, kidney involvement due to the disease is associated with glomerulonephritis, and urinalysis shows erythrocyte casts or dysmorphic erythrocytes, which is not the case here. The risk of bladder cancer is higher if the patient has received oral cyclophosphamide because there is prolonged daily exposure to the metabolites associated with causing mucosal irritation and metaplasia. The incidence of cystitis and bladder cancer is lower with intermittent intravenous cyclophosphamide, especially when given with mesna, an adjuvant therapy given with cyclophosphamide to detoxify urotoxic metabolites. Importantly, bladder cancers associated with cyclophosphamide exposure may be more aggressive and should be urgently evaluated even when suspicion is low.

CT and ultrasonography may show large lesions affecting the kidneys and gastrointestinal tract but do not detect small and superficial lesions, which can only be detected on cystoscopy.

The patient had no new drug exposure, and urinalysis does not show significant findings of nephritis; therefore, there is no reason to suspect a drug reaction or interstitial nephritis and obtain urine eosinophils.

Urine protein-creatinine ratio to look for glomerular disease is not helpful in evaluating a patient with hematuria when suspicion for the underlying vasculitis is low, as seen in this patient with a negative p-ANCA.