SummaryHereditary nephritis (HN) is a progressive renal disease not uncommonly seen in children. Asymptomatic hematuria is an early and consistent finding with or without proteinuria. Distinctive abnormalities frequently associated with this condition involve basement membranes primarily (glomerular basement membrane, lens capsule, and possibly, tectorial membrane of the organ of Cord). These basement membranes contain collagen with similar biochemical composition suggesting that this association may be pathogenetically related. On the basis of this observation, we studied collagen metabolism in patients with HN by utilizing urinary hydroxylysine glycosides (hyl glyc) as an index of collagen metabolism. The hyl glyc hydroxylysine galactose glucose and hydroxylysine galactose are basic units in basement membrane as well as a large number of other collagen. We studied 25 normal children, seven patients with HN, and six HN siblings with hematuria. The mean excretion of total hyl glyc are 64 ± 5.5, 93 ± 14, and 123 ± 15.6 umoles/g creatinine, respectively. The difference in the mean excretion level of total hyl glyc between patients with HN and normal controls is statistically different (P< 0.05). The siblings of HN patients differed significantly from normal (P> 0.005), but was comparable to the HN patients. Two of 16 additional patients studied had the Nail Patella syndrome and showed increased urinary hyl glyc. The elevated urinary hyl glyc in HN patients and their siblings strongly suggests an altered rate of collagen degradation during the natural course of the disease. The origin of collagen is presently unknown because no data exists describing the biochemical composition of basement membrane collagen in HN. To elucidate further the pathogenesis of this important disease, studies should investigate the biosynthesis and metabolism of basement membrane collagen of involved structures.SpeculationCollagen metabolism in HN suspect patients will raise the index of suspicion if found to be altered. This observation may provide increased understanding of the pathogenesis of this disorder.