TSC can present itself as one of several different types of lesions in the kidneys: simple cysts, angiomyolipomas and renal cell carcinoma. About 70-80% of people with TSC develop some other abnormality in their kidneys, but frequently these don't cause any symptoms, especially during childhood.

Renal lesions occur in over half of all children at the time of initial evaluation. Simple cysts, which account for 25% of the abnormalities, may appear or disappear at any time. Multiple renal cysts with damage to the kidney tissue may lead to arterial hypertension and renal failure.

Renal angiomyolipomas, which account for 75% of abnormalities, are benign lesions (hamartomas) made up of vascular tissue, smooth muscle, and fat. Angiomyolipomas begin in childhood in many individuals with TSC, but they usually grow very slowly and may not be problematic until young adulthood. By the third decade of life, they may cause lumbar pain and hematuria (blood in the urine) from slow bleeding, and rarely they may result in sudden internal bleeding.

Renal cell carcinoma, a tumor that originates in the same hyperplastic epithelium that forms renal cysts, is the only malignancy associated with tuberous sclerosis complex. It occurs with an increased frequency in patients with TSC.