Behzad Najafian | Search PubMed

PubMed2003

Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy.

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 +/- 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 < 0.00001) and mesangial fractional volume (P < 0.0001) and decreased filtration surface density (P < 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 < 0.05). Fractional volume of proximal (P < 0.01) and distal (P <0.01) tubules per cortex were decreased, while fractional volume of cortical interstitium (P <0.00001) and atrophic tubules (P <0.01) 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 <0.05). Thus, AG and glomerulotubular junction abnormalities may be important in the development and progression of DN.

Adult↗

PubMed2002

Estimating mean glomerular volume using two arbitrary parallel sections.

The most reliable method for estimation of mean glomerular volume (MGV), the disector/Cavalieri method, is technically demanding and time consuming. Other methods suffer either from a lack of precise correlation with the gold standard or from the need for a large number of glomeruli in the sample. Here, a new method (the 2-profile method) is described; it provides a reliable estimate of MGV by measuring the profile area of glomeruli in two arbitrary parallel sections. MGV was estimated in renal biopsies from 16 diabetic patients and 13 normal subjects using both the Cavalieri and the 2-profile methods. The range of individual glomerular volumes based on the Cavalieri measurements was 0.31 to 4.02 x10(6) micro m(3). There was a high correlation between the two methods for MGV (r = 0.97; P < 0.0001). However, the 2-profile method systematically overestimated MGV (P = 0.0005, paired t test). This overestimation was corrected by introducing a multiplication factor of 0.91, after which statistical criteria of interchangeability with the Cavalieri method were met. The optimal distance between two sections was determined as 20 micro m with a coefficient of variation of 7.4% in repeated measurements of MGV. On the basis of findings that values for MGV stabilize after ten glomeruli are measured by the disector/Cavalieri method, it was determined that the accuracy of MGV by the 2-profile method obtained by eight glomeruli was less than 7% different from ten in all cases. Thus, the 2-profile method is a practical alternative to the disector/Cavalieri method for estimating MGV, especially in small samples and blocks with limited residual tissue.

Adolescent↗