The Alport nephropathy: clinicopathological correlations

Abstract

The alleged dominance of diffuse attenuation of the glomerular basement membrane (GBM) in young children and females with Alport's Syndrome (AS) suggests that it might be the initial ultrastructural manifestation of type IV collagen defects. We carried out a 'blind' review of 130 renal biopsies obtained from 100 patients with AS, emphasizing the electron microscopy changes, and related the findings to the clinical presentation and outcome. The intracapillary distribution of (1) thickened, (2) attenuated and (3) normal GBM was assessed individually as: none (grade 0), <25% (grade 1), 25-50% (grade 2) and >50% (grade 3). Deafness was defined as persistent loss of > or =30 dBs. Proteinuria was measured as protein/creatinine ratios in early morning urine. Heavy proteinuria (> or =200 mg/mmol) correlated significantly with the presence of segmental and global glomerulosclerosis and foam cells. Comparing grades 0+1 vs. 3 GBM changes, using a 2x2 chi(2) test, there were significant correlations between grade 3 GBM thickening and male sex (P =0.005), heavy proteinuria (P =0.02) and deafness (P <0.001). GBM thickening did not correlate with age at the initial biopsy, but repeat biopsies demonstrated increasing thickening with age. The grades of GBM attenuation did not correlate with either age at biopsy or sex. In 11 biopsies with atypical lamina densa changes in thickened GBM segments, there were no differences in clinicopathological correlations compared with classical biopsies. Our data indicate that diffuse GBM attenuation can be an ultrastructural variant of the Alport nephropathy, but do not support the contention that it is the initial lesion.

Presence of Foam Cells in Kidney Interstitium Is Associated with Progression of Renal Injury in Patients with Glomerular Diseases

“…A large amount of protein was filtered from glomeruli and reabsorbed by renal tubular cells, contributing to renal interstitial damage. Previous studies have already demonstrated that hyperlipidemia and gross proteinuria are two crucial factors leading to renal interstitial FCs formation in some cases of glomerulonephritis [10, 14, 22]. …”

Hereditary nephritis mimicking immune complex–mediated glomerulonephritis

“…The remaining cases are autosomal recessive or autosomal dominant, caused by mutations in the genes encoding the a3 (COL4A3) or a4 chains (COL4A4) of collagen IV. New mutations may be responsible for some cases that lack family history of renal disease [1]. Hereditary nephritis is characterized clinically by persistent microhematuria, although proteinuria and renal insufficiency are commonly observed in the later stages of disease.…”

Histologic and Ultrastructural Studies of Juvenile Onset Renal Disease in Four Rottweiler Dogs

“…The GBM is less electron dense and of variable thickness because of a complex interwoven ''basket-weave'' replication of the lamina densa. 21 There may be podocyte foot process effacement, and the epithelial aspect of the capillary wall is typically irregular. 10 Canine models of Alport syndrome have been described in Samoyed, ''Navasota,'' Doberman Pinscher, Dalmatian, and Bull Terrier dogs.…”