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Tuberous sclerosis complex (TSC) is a rare, autosomal dominant disease, characterized by the presence of benign tumors in several organs, including the kidneys. Cystic disease and angiomyolipomas (AML) are the most frequent TSC-related renal lesions, which may be present since childhood. Renal AMLs, present in up to 80% of patients, may grow over time, leading to serious complications, such as bleeding and chronic kidney disease (CKD). mTOR inhibitors (mTOR-i) have been proved to be a safe and effective therapy for TSC patients, leading to AMLs regression, reducing their risk of bleeding and preserving renal function.
This is a cross-sectional, retrospective and observational study of patients with TSC in follow-up at the genetic kidney disease unit of the Hospital de Clínicas of the Federal University of Paraná and of the University of São Paulo from January 2010 to September 2023. Clinical, laboratory, imaging, and mTOR-i therapy data of the first nephrology appointment were collected from the patients’ medical records. Glomerular filtration rate (eGFR) based on creatinine levels was estimated by the CKD-EPI or by Schwartz equations for adult or pediatric patients, respectively. Patients were divided into two groups, adult or pediatric (<18 years).
A total of 165 patients were included, 35 pediatric (11±4 years, 57.1% males) and 130 adult patients (30±11 years, 32.3% males). Renal AML was more frequent than cystic disease in both adult (AML, 90%; cystic disease 40%) and pediatric patients (AML, 45.7%; cystic disease 34.2%), being the most prevalent lesion in both groups. The presence of renal AML was significantly higher in adults than in children (p<0.01), whereas there was no difference regarding the presence of cystic disease between the patients group. One episode of retroperitoneal hemorrhage due to spontaneous rupture of renal AML occurred in pediatric patients and 11 in adult patients; two adults died from hemorrhagic shock. Strikingly, 5 episodes of surgical treatment were reported between pediatric patients: partial nephrectomy in 60% and total nephrectomy in 40%. Among adults, partial nephrectomy was the most frequent intervention (n=27, 57.4%), followed by arterial embolization (n=11; 23.4%) and total nephrectomy (n=9; 19.2%). Regarding pharmacological treatment, 31.4% and 35.4% of pediatric and adult patients were on mTOR-i, respectively. Regarding renal function, none of the pediatric patients had CKD (eGFR:137±21ml/min/1.73m2). Even though adult patients had an overall normal mean eGFR (115±31 ml/min/1.73m2), it was noticed a high prevalence of CKD (G2, 17.7%; G3, 4.9%; G4, 1.6%; G5, 0.8%; RRT, 0.8%). Table 1 summarizes the main findings of the study.
TSC-related renal involvement occurs since childhood, reinforcing the important role of the nephrologist in the care of these patients over lifetime. Only a low percentage of the study population were receiving the standard therapy, i.e. mTOR-i and renal-sparing surgical procedure, which might have contributed to the high rate of severe renal adverse events, as hemorrhage, loss of renal function and premature death. It is of paramount importance to enhance disease awareness for TSC to improve the medical care offered to these patients.