These data demonstrate that T cell depletion can improve the course of experimental renal IRI. However, more aggressive T cell depletion strategies were required compared with that needed to prevent experimental allograft rejection.

Abstract. X-linked Alport syndrome (XLAS) is a progressive disorder of basement membranes caused by mutations in the COL4A5 gene, encoding the ␣5 chain of type IV collagen. A mouse model of this disorder was generated by targeting a human nonsense mutation, G5X, to the mouse Col4a5 gene. As predicted for a nonsense mutation, hemizygous mutant male mice are null and heterozygous carrier female mice are mosaic for ␣5(IV) chain expression. Mutant male mice and carrier female mice are viable through reproductive age and fertile. Mutant male mice died spontaneously at 6 to 34 wk of age, and carrier female mice died at 8 to 45 wk of age, manifesting proteinuria, azotemia, and progressive and manifold histologic abnormalities of the kidney glomerulus and tubulointerstitium. Ultrastructural abnormalities of the glomerular basement membrane, including lamellation and splitting, were characteristic of human XLAS. The mouse model described here recapitulates essential clinical and pathologic findings of human XLAS. With ␣5(IV) expression reflecting X-inactivation patterns, it will be especially useful in studying determinants of disease variability in the carrier state.

Abstract. Atubular glomeruli (AG) have been described in several renal disorders. However, little attention has been paid to AG in diabetic nephropathy (DN). Preliminary studies suggested that tip lesions were frequently present in type 1 diabetic (D) patients with proteinuria. The aim of this study was to determine the frequency of AG and their possible relationship with tip lesions in DN. Renal biopsies from eight proteinuric type 1 D patients with normal to moderately reduced GFR (76 Ϯ 26 ml/min per 1.73 m 2 ) and eight normal subjects were studied by light (LM) and electron microscopy (EM). Glomerular volume, volume of the glomerular corpuscle, which is tuft, and the fractional volumes of proximal, distal, and atrophic tubules per cortex were estimated using appropriate stereologic methods. Glomerulotubular junctions were examined on serial sections and classified into glomeruli attached to: normal tubules (NT); short atrophic tubules (SAT); long atrophic tubules (LAT); atrophic tubules with no observable glomerular opening (ATNO); and atubular glomeruli (AG). EM studies showed typical diabetic changes in biopsies, including increased GBM width (P Ͻ 0.00001) and mesangial fractional volume (P Ͻ 0.0001) and decreased filtration surface density (P Ͻ 0.01) compared with normal subjects. Seventeen percent of glomeruli in the D patients were atubular, and 51% were attached to atrophic tubules. Tip lesions were present in all SAT, 64% of LAT, 82% of ATNO, and only 9% of NT and were never observed in normal subjects. The relative volume of AG was smaller than glomeruli in other categories (P Ͻ 0.05). Fractional volume of proximal (P Ͻ 0.01) and distal (P Ͻ0.01) tubules per cortex were decreased, while fractional volume of cortical interstitium (P Ͻ0.00001) and atrophic tubules (P Ͻ0.01) were increased in D patients. Fractional volume of atrophic tubules, %AG, and percent of glomeruli with tip lesion explained 94% of the GFR variability in diabetic patients (P Ͻ0.05). Thus, AG and glomerulotubular junction abnormalities may be important in the development and progression of DN.Atubular glomeruli (AG) have been described in several renal disorders (1,2). AG, by definition, have open circulation but no observable tubular attachment and are thus presumably nonfunctioning (3). This phenomenon, first described by Oliver (4) as a finding in chronic Bright disease in humans, had been confirmed in experimental chronic pyelonephritis (5,6). Marcussen et al. (7-13) studied atubular glomeruli in cisplatin-and lithium-induced nephropathies in rats and chronic pyelonephritis and renal artery stenosis in humans. More recently, this phenomenon was documented in Adriamycin-induced nephrosis and the remnant kidney model in rats (14,15). An important contribution of AG to renal function impairment has been hypothesized (2,15). However, despite that 44% of all new cases of end-stage renal disease in the United States are due to diabetes, little attention has been paid to the possible role of this entity in diabetic nephropathy (1,2). ...