Renal manifestations of tuberous sclerosis complex
Renal manifestations of tuberous sclerosis complex
Angiomyolipoma (AML) is the most common renal lesion seen among ptns with tuberous sclerosis complex (TSC) that observed in 49-60 % of TSC ptns. Other commonly seen lesions include renal cysts & renal cell carcinoma (RCC). Most ptns with AML have few or no Sms attributed to kidney disease, and these lesions usually detected on routine imaging. However, some ptns may show severe hemorrhage, CKD, anemia, or HT. AMLs may cause significant & may be life-threatening hemorrhage. Dgx of renal AMLs is usually achieved by MRI imaging relying on demonstrating of👉 fat in the tumour. Lesions with poor fat are difficult to DD from RCC. When Dgx of renal AMLs cannot be properly established by imaging, biopsy is warranted to assure Dgx. We recommend renal surveillance with MRI at time of Dgx and at least every year in ptns with known AMLs. For females may need more frequent imaging if pregnant or on oestrogen therapy. With known renal lesion, SCr should be checked at least yearly.
CHRONIC KIDNEY DISEASE: Ptns with TSC develop CKD with non-nephrotic proteinuria progressing to ESKD in absence of large renal angiomyolipomas (AMLs) or extensive renal macrocystic disease. kidneys are seen small & echogenic on US. Kidney biopsy may show FSGS, with chronic interstitial disease that’s thought to be a secondary disorder induced by nephron loss. Proteinuria & renal insufficiency in secondary FSGS are 👉slowly developed. This’s in contrary to the primary FSGS that’s typically presented by acute or subacute onset of nephrotic syndrome.
Some ptns with TSC may show different type of chronic interstitial disease, there’s a diffuse, hyperplastic appearance of the interstitial stroma, with areas of spindle, smooth muscle, & fibroblastic cells. Pathogenesis still uncertain. It could be mediated partially at least by the genetic deficit in tuberin in TSC as it regulates the expression & promoter activity of the cell fibrosis protein a-smooth muscle cell actin. Findings typically include increased SCr, a benign urinary sediment, normal or mildly decreased kidney size, hyperechoic kidneys on US, & skin features of TSC that could be overlooked by both ptn & clinicians. Brain imaging show characteristic features of TSC e.g. multiple calcified subependymal nodules & tubers. There’s no definite therapy.
General principles of therapy: CKD of any cause can be observed with a variety of sequelae that nclude volume overload, electrolyte disorders e.g. metabolic acidosis & hyper-k+, hyperphosphatemia, renal osteodystrophy & HT. Adding to protection against CVS disease, the rate of CKD progress can be limited by BP reduction to the target and, in ptns with proteinuria, by decreasing protein excretion to < 1000 mg/d via an 👉ACEi and, other antihypertensive agents. Causes of ESKD may include polycystic kidneys, destruction of renal parenchyma by multiple renal AMLs, & nephrectomy to ttt life-threatening hemorrhage. CKD Ptns due to secondary FSGS can also progress to ESKD. Renal disease is also noticeable cause of mortality in TSC ptns.
Management ttt of neurologic manifestations & life expectancy improve in ptns with TSC, progression of CKD to ESKD will become a more crucial complication. Both DX & KTx provide adequate tools of survival in ptns developing ESKD, but the risk of kidney hemorrhage & malignant transformation in TSC is of importance. So, native kidney imaging should be continued, & bilateral nephrectomy could be performed when a ptn with TSC & ESKD commence DX or KTx preparation. Considering the beneficial effects of mTORi on the cutaneous, CNS, and pulmonary manifestations of TSC, a regimen including 👉everolimus or sirolimus are ttt of choice following Tx in ptns with TSC.
IMPACT OF RENAL DISEASE ON PROGNOSIS: renal disease is the 2nd leading cause of death in TSC, after neurologic disease, and is the most common cause of mortality in affected adults. Renal causes of death include ESKD, retroperitoneal hemorrhage & metastatic disease.
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