Lymphocytes are dispensable for glomerulonephritis but required for renal interstitial fibrosis in matrix defect-induced Alport renal disease.

One current theory for the emergence of glomerular nephritis implicates Th1-type cellular responses associated with delayed-type hypersensitivity, involving T cells and macrophages. Using a mouse model for progressive glomerulonephritis, we investigate the role of B and T cells in the pathogenesis of glomerular inflammation. Deletion of alpha3 chain of type IV collagen in mice (alpha3(IV) collagen null mice) results in GBM defects, glomerulonephritis and tubulointerstitial inflammation, fibrosis and significant immune infiltration including activated B- and T-lymphocytes. To evaluate the contribution of lymphocytes to the pathogenesis of glomerulonephritis and renal fibrosis, we generated mice that are deficient in both the alpha3(IV) collagen and Rag-1 (alpha3/Rag-1 DKO). Lymphocyte deficiency significantly reduces fibrosis in the renal interstitium, but ultrastructural GBM defects persist. Interestingly, glomerulonephritis in the double null mice persists at a similar level with comparable proteinuria. Here we demonstrate that despite the presence of B-cell and T-cells in the inflamed glomeruli, their deletion does not impede the emergence of glomerulonephritis but has a negative impact on the progression of renal interstitial fibrosis.

Discordance between skin biopsy and kidney biopsy in an X-linked carrier of Alport syndrome.

Alport syndrome (AS) is the most common form of hereditary nephritis. Females with X-linked AS are heterozygous carriers of the disease mutation. Carrier status in females without a family history has traditionally been diagnosed by kidney biopsy; more recently skin biopsy has been utilized. We report on a 14-year-old girl with long-standing hematuria and intermittent proteinuria who underwent kidney and skin biopsy to establish a definitive diagnosis. Electron microscopy showed extensive thinning of glomerular basement membrane (GBM), with no evidence of lamination. Immunofluorescence staining showed continuous GBM staining for the alpha3(IV) and alpha5(IV) collagen chains, whereas the epidermal basement membrane showed discontinuous alpha5(IV) collagen staining consistent with an X-linked carrier of AS. Few reports have shown discordance between kidney and skin biopsy findings as seen in this case, presumably due to X chromosome lyonization. We therefore suggest that simultaneous kidney and skin biopsies may be more accurate in the assessment of potential female carriers of AS than either kidney biopsy or skin biopsy alone.

Peritubular capillary changes in alport syndrome, diabetic glomerulopathy, Balkan endemic nephropathy and hemorrhagic fever with renal syndrome.

The morphology of peritubular capillary has been mostly studied in relation to chronic transplant rejection, where an association has been found between transplant glomerulopathy and reduplication of peritubular capillary basement membranes (PCBM). This electron microscopy study of peritubular capillaries was done on kidney biopsies performed on patients with conditions involving primarily glomeruli (diabetic glomerulopathy (23), Alport syndrome (37)) or causing more or less isolated changes of nephron structures outside the glomeruli (Balkan endemic nephropathy (15) and hemorrhagic fever with renal syndrome (19)). The aim was to explore the ultrastructural features of the PCBM. In patients with diabetic glomerulopathy, the PCBM was homogeneous, with a width ranging from normal to evidently increased (55-355 nm). In patients with Alport syndrome, the PCBM was homogeneous, with no substantial splitting or prominent thickening. Mean thickness varied between 80 (85-100) nm in children and 120 (46-250) nm in adults. Mean PCBM thickness in patients with Balkan endemic nephropathy was 209 (90-1270) nm. The thickened PCBM was also often split. In patients with hemorrhagic fever with renal syndrome, peritubular capillaries and medular vasa recta were generally extremely congested and focally ruptured, and their basal lamina showed prevailing thinning and focal discontinuities.