Spectrum of disease in familial focal and segmental glomerulosclerosis

Background. Focal segmental glomerulosclerosis (FSGS) is the underlying pat hologic entity in 5% of adults and 20% of children with end-stage renal dis ease (ESRD). FSGS is generally considered to be sporadic in origin. Methods. Recently, we identified 60 families involving 190 individuals with familial FSGS, providing evidence for a subset of families in which a gene tic form is segregating. Each family had at least one member with renal bio psy-confirmed FSGS and at least one other member with either renal biopsy-c onfirmed FSGS or ESRD. Results. Twenty-six families had individuals affected in more than one gene ration [multigeneration (MG)], and the remaining 34 families had only a sin gle generation (SG) affected. There was equal representation of males and f emales among affected individuals. Ten percent of MG families were African American. and 52% of SG families were African American. The mean age of pre sentation was significantly higher in the MG families (32.5 +/- 14.6 years) compared with the SG families (20.1 +/- 12.1 years, P = 0.0001). SG cases had higher levels of proteinuria at presentation (7.0 +/- 5.6 g/24 hr, comp ared with 3.8 +/- 3.4 g/24 hr, for the MG families, P = 0.002). On renal bi opsy, tubulointerstitial damage was more severe in patients in the SG famil ies than in the MG families; however, the level of glomerular damage did no t differ between these groups. Fifty percent of the patients had progressed to ESRD by the age of 30 years. Variables measured at presentation that we re independently associated with poor renal survival were decreased age, in creased serum creatinine, and increased urinary protein excretion. Forty-on e patients underwent successful renal transplantation, with a 10-year graft survival rate of 62%. One patient developed clinical and biopsy evidence o f recurrence of FSGS in the allograft. Conclusion. These data confirm the existence of a non-Alport's form of here ditary glomerulonephritis, which has a morphological pattern of FSGS.