Renal Involvement in Sarcoidosis

Sarcoidosis is a clinicopathologic syndrome resulting from dispersed organ involvement by a noncaseating granulomatous process of unknown cause. The clinical manifestations of sarcoidosis are protean, depending on the affected organs; however, the principal targets of sarcoidosis are the lungs and thoracic lymph nodes, which almost always are involved. As a rule, it is a disease of insidious onset that pursues a chronic course, with episodic remissions and exacerbations. The severity and diversity of its clinical manifestations depend on the extent of infiltrating granulomatous lesions of the involved organs and that of the number of affected organs. When diffuse and widespread the disease may pursue an acute fulminant course. Diagnosis depends on demonstration of the characteristic pathologic lesion of noncaseating granulomas within the affected organ. Sarcoidosis is a common (1 to 40 cases per 100,000 population) disease of the relatively young (mean age 40 years), with a proclivity for racial (3.5 times more in blacks), ethnic (Scandinavian), and seasonal occurrence (summer rather than winter). Reports of community outbreaks, work-related risks, familial clustering, occurrence after organ transplantation, and experimental induction in animals by injection of affected tissue homogenates from humans strongly suggests an infective cause that remains to be identified. Two associated metabolic abnormalities of diagnostic and clinical import are elevated levels of calcitriol (1,25-dihydroxy-vitamin D3) and angiotensin-converting enzyme (ACE). Neither is unique to sarcoidosis. Elevated levels of calcitriol are consequent to the capacity of the infiltrating macrophages of the granulomas to synthesize calcitriol. Elevated levels of ACE are consequent to that of the multinucleated giant and epithelioid cells that ultimately develop in the granulomas, along with that of the infiltrating macrophages, to produce ACE. Of these, the elevated levels of calcitriol are the more important because they account for the abnormal calcium metabolism that occurs in most patients. Elevated levels of ACE are of no known clinical consequence Garabed Eknoyan