Alteration of Collagen Metabolism in Hereditary Nephritis

Abstract

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 Corti). 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 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.sibly, tectorial membrane of the organ of Corti). Collagen recently shown to be present in these basement membranes have very similar biochemical composition (10). Collagen changes have been reported in the organ of Corti in HN. (12).On the basis of these observations we studied collagen metabolism in patients with HN by measuring urinary hydroxylysine glycosides. The hyl glyc are hydroxylysyl galactose glucose (HGG) and hydroxylysyl galactose (HG). These two glycosides are basic units in basement membrane collagen as well as a large number of other collagens. They are metabolized only to a minor degree before excretion and have a high threshold of clearance. MATERIALS AND METHODSEarly morning specimens were collected and stored without preservative at -70°C pending analysis. Informed consent for the study was obtained from the parents. Seven patients (M-4, F-3) ages 6-13 with HN were studied. All patients had positive family and clinical history. Two of four affected males were brothers with neurosensory hearing loss and were both azotemic. One girl was uremic without hearing loss at the time of the study. No other abnormalities were obse...

Glomerular Basement Membrane Changes in Hereditary Glomerular Diseases

“…By immunoelectrophoresis, Lubec et al [18] detected an abnor mal GBM antigen in the urine of patients with Alport's syndrome. The finding of high levels of urinary hydroxylysine glycosides supports the hypothesis of increased colla gen turnover [19], The fact that glomeruli of patients with Alport's syndrome [20,21] do not bind antiglomerular basement mem brane antibodies (from Goodpasture's syn drome) is evidence that the normal GBM antigen(s) is lacking in their basement mem brane. This data is especially interesting since young infants lack the same GBM antigen(s).…”

Urinary Excretion of Hydroxylysine and Its Glycosides in Alport’s Syndrome and Several Other Glomerulopathies

“…This finding could suggest a maturation defect, although others have contra dicted the absence of Goodpasture antigen in young children [14]. In urine, an increased excretion of hydroxylysylglycosides has been reported [3,4], In the present study of a considerably larger patient group we were unable to confirm these findings. Other urinary abnor malities have been reported.…”

“…As collagen type IV, present in glomerular basement membrane, is relatively rich in glycosylated hydroxylysine (HYL) [2] compared to other collagen types; the urinary excretion of the hydroxylysylglycosides, glucosylgalactosylhydroxylysine (GGH) and galactosylhydroxylysine (GH), might be altered in this disease and might form a tool in diagnosis. Increased excretion of these compounds has been reported [3,4].…”

The Urinary Excretion of Total Hydroxylysine and Its Glycosides in Normal Persons, and in Patients Suffering from Alport’s Syndrome -Contribution of the Peptide-Bound Fraction

“…In a former study, no marked differences in excretion rates of the free compounds between normals and pa tients suffering from Alport's syndrome could be estab lished [5], in contrast to data from the literature [2,3]. It was suggested in that study, that investigation of the peptide-bound fraction of urinary glycosides might be a better diagnostic approach of Alport's syndrome.…”

“…In diseases, such as Alport's syndrome, in which a molecular defect in glomerular basement membrane composition is assumed, an altered excretion of the glycosides of hydroxylysine, glucosylgalactosylhydroxylysine (GGH) and galactosylhydroxylysine (GH), can be expected. Increased excretion rates of GGH and GH have been reported in this syndrome [2,3]. In a former study, however, we were unable to distinguish clearly Alport patients and patients with other glomeru lopathies from normals [4,5].…”