OBJECTIVES: Tuberous sclerosis complex (TSC) is a rare genetic disorder associated with angiomyolipomata (non-malignant kidney lesions) in the majority of patients. Angiomyolipomata increase in size over time, present risk of acute hemorrhage, and can lead to progressive chronic kidney disease (CKD). Our objective was to document the association between angiomyolipomata and CKD, including the impact on health care resource utilization (HCRU) and health care costs. METHODS: This retrospective, longitudinal cohort study used medical chart data from patients with TSC treated at a specialty center in the Netherlands from January 1990 to April 2012. Patients were followed longitudinally and classified into open cohorts based on their CKD stage (estimated from serum creatinine levels) and size and number of angiomyolipomata. Average glomerular filtration rates (GFR) and the proportions of patients reaching advanced CKD stages were compared with a non-TSC reference population. HCRU rates and health care costs (2012€) per patient per year (PPPY) were compared across cohorts.  RESULTS: ), and more patients with TSC reached CKD stage 3 or higher (16% vs. 3% of patients <70 years old). Compared with CKD stage 1, CKD stages 2 to 5 were associated with larger and more numerous angiomyolipomata, higher overall HCRU rates (rate ratios=1.5 to 2.3, P≤0.01), and higher health care costs (incremental costs=€737 to €30,641 PPPY, P≤0.004). CONCLUSIONS: Our results suggest that impaired kidney function associated with angiomyolipomata imposes a significant burden and remains a key concern in patients with TSC. Treatments that slow the rate of kidney function decline in patients with TSC may substantially reduce the HCRU and costs associated with CKD and angiomyolipomata.