The most likely diagnosis is renal cell carcinoma. The patient has acquired cystic kidney disease (ACKD), which becomes more common and progresses during the course of end-stage kidney disease (ESKD); the incidence of ACKD rises dramatically as time on dialysis increases. Patients with ACKD typically have a large number of small bilateral kidney cysts and reduced kidney size. For unclear reasons, patients with ACKD have an approximately 30-fold increased risk for developing renal cell carcinoma; despite this, routine screening for this malignancy is not recommended. However, clinicians should have a high level of suspicion for renal cell carcinoma in patients with ESKD who have flank pain or hematuria that may be suggestive of the diagnosis. Despite the relatively high prevalence of renal cell carcinoma in patients with ACKD, it is an uncommon cause of death in patients with ESKD.

The hallmark of autosomal dominant polycystic kidney disease (ADPKD) is large kidneys with multiple kidney cysts, usually originating in the renal collecting duct. Most patients with ADPKD have a positive family history for cystic kidney disease and/or chronic kidney disease. Diagnosis may be complicated by the fact that a hemorrhagic kidney cyst is usually indistinguishable from a solid renal mass on ultrasound. However, in this patient without a family history, small kidneys on ultrasound, and cysts scattered throughout the renal parenchyma, ADPKD with a hemorrhagic renal cyst is unlikely.

Renal angiomyolipomas and bilateral renal cysts are associated with tuberous sclerosis complex (TSC). However, because this is an autosomal dominant disease, there is almost always a positive family history. Additionally, TSC is a systemic disorder with lesions typically present in various organs and tissues and would be a far less common cause of kidney tumors in a patient with ESKD.

Transitional cell or urothelial carcinomas arise from the mucosal surfaces of the urethra, bladder, and ureters and may also occur in the renal pelvis and calyces; in the upper urinary tract, transitional cell carcinomas also tend to be multifocal and only uncommonly form mass lesions within the kidney. This patient's mass is located in the renal parenchyma, and there is not an increased risk of transitional cell carcinoma with ACKD, making this a less likely diagnosis.