A review of all native kidney biopsies at our center from 1974 to 1993 identified 43 cases of idiopathic focal segmental glomerulosclerosis (FSGS) with predominantly collapsing features and lacking evidence of HIV-1 infection or intravenous drug use. No case was identified before 1979 and the incidence of this entity has progressively increased over the past two decades. Compared to 50 age-matched controls of idiopathic FSGS with typical perihilar scars, the group of idiopathic collapsing FSGS displayed black racial predominance, a higher serum creatinine and more severe features of nephrotic syndrome at biopsy. Morphologic features of visceral epithelial cell hypertrophy and hyperplasia, tubular microcysts, tubular epithelial degenerative and regenerative features and interstitial edema were more prevalent and severe in collapsing FSGS. Median time to ESRD was rapid in collapsing FSGS versus controls (13.0 months vs. 62.5 months, P < 0.05). Correlates of progression to ESRD included a higher initial serum creatinine and failure to undergo remission of proteinuria. Both glomerulosclerosis and certain features of tubular damage were independent predictors of the level of renal function at time of biopsy, but not of the rate of progression of renal insufficiency. Although three patients had partial or complete spontaneous remissions, none of 26 patients treated with steroids alone responded. Idiopathic collapsing FSGS is a variant of FSGS with increasing incidence, distinct clinicopathologic features, black racial predominance, a rapidly progressive course and relative steroid resistance.

C1q nephropathy falls within the clinical-pathologic spectrum of MCD/FSGS. Although further studies are needed to determine the pathomechanism of C1q deposition, we hypothesize that it may be a non-specific marker of increased mesangial trafficking in the setting of glomerular proteinuria.

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We report the first case of a mitochondrial DNA (mtDNA) deletion diagnosed by renal biopsy. An eight-year-old girl with megaloblastic anemia and severe growth retardation developed progressive renal insufficiency accompanied by partial Fanconi syndrome. Histologic examination of the renal biopsy disclosed nonspecific chronic tubulointerstitial disease characterized by tubular atrophy and interstitial fibrosis. On ultrastructural examination, tubular cell mitochondria were extremely dysmorphic with prominent size variation, abnormal arborization, disorientation of the cristae and osmiophilic electron-dense inclusions. Functional histochemical stains for mitochondrial enzymes performed on cryostat renal sections revealed focal tubular absence of cytochrome C oxidase (COX), a respiratory chain enzyme partially encoded by mtDNA, with preservation of succinate dehydrogenase (SDH), a respiratory chain enzyme entirely encoded by nuclear DNA (nDNA). Immunoreactivity for COX subunit 2 (encoded by mtDNA) was weak to undetectable in most tubular cells, whereas reactivity for subunit 4 (encoded by nDNA) was intense in all cells. Molecular analysis of the mtDNA of kidney and peripheral blood leukocytes was performed using Southern blot and PCR. Both techniques disclosed a 2.7 kb mtDNA deletion located between nucleotide (nt) 9700 and nt 13700, a common site for mtDNA deletions associated with encephalomyopathies. Mitochondrial DNA deletions may be an under-recognized cause of idiopathic tubulointerstitial nephropathy in children lacking neurologic or myopathic manifestations.

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