Focal segmental glomerulosclerosis associated with mitochondrial cytopathy

Background. The nonspecific lesion of focal segmental glomerulosclerosis (F SGS) can occur as a primary disease or in a variety of secondary settings. In mitochondrial cytopathies (MCs), the phenotypic expression of the diseas e depends on the degree of cellular dysfunction, and this correlates with t he proportion of abnormal mitochondrial DNA in the cells and the dependence of tissues on oxidative metabolism. The most common renal manifestation in MCs is tubular dysfunction; little has been reported about glomerular dise ases. Methods. Cases of four adult patients with FSGS and MC are reported. Routin e histology and mitochondrial DNA analysis were carried out on renal biopsi es. Results. Family history and clinical manifestations in the four patients wi th FSGS suggested a diagnosis of MC. An A3243G transition in the mitochondr ial DNA tRNA(leu(UUR)) was found in lymphocytes and kidney. Glomerular lesi ons of FSGS were associated with unusual hyaline lesions, which appeared to represent individual myocyte necrosis in afferent arterioles and small art eries. Conclusion. FSGS is a renal manifestation of MCs. The renal lesion can prec ede other manifestations of the genetic disease by many years. The striking arteriolar lesions in these cases may have resulted in glomerular hyperten sion and hyperperfusion, leading to secondary epithelial cell abnormalities and, ultimately, FSGS. However, primary epithelial cell dys function cause d by mitochondrial defects could not be ruled out on morphological grounds. MCs should be considered in cases of so-called primary FSGS, particularly if there is a familial history of diabetes, neuromuscular disorders, or dea fness.