Alterations of Type IV Collagen α Chains in Patients with Chronic Acquired Glomerulopathies: mRNA Levels, Protein Expression and Urinary Loss

Background: Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated. Methods: Urinary levels of col(IV)α1, col(IV)α3 and col(IV)α5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)α chains, from col(IV)α1 to col(IV)α5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls. Results: Urinary levels of col(IV)α1, col(IV)α3, col(IV)α5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)α1 and col(IV)α3 urinary excretion correlated with the degree of chronic histological damage [col(IV)α1 R = 0.44, p < 0.001; col(IV)α3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)α5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)α3, col(IV)α4 and col(IV)α5 chains [p < 0.01 for all]. Conclusion: Patients with chronic acquired glomerulopathies show important alterations in the col(IV)α chain network mimicking some molecular features of the X-linked Alport’s syndrome. Further studies are needed to show whether urinary levels of the col(IV)α chains may be used as markers for monitoring renal injury.