Increased mesangial expansion is one of the most characteristic histological changes in diabetic nephropathy (DN). Although the pathogenesis of DN remains unclear, recent studies associate interleukin (IL) 6 with mesangial proliferative glomerulonephritis. To elucidate the expression and localization of IL-6 mRNA in renal tissues of patients with DN, a high-resolution in situ hybridization using digoxigenin-labeled oligonucleotide was performed. Patients were divided into three groups based on light microscopy findings: mild (group 1), moderate (group 2), and severe (group 3) mesangial expansion. The relationship between the expression of IL-6 mRNA and the degree of glomerular mesangial expansion in DN was examined. Individual cells positive for IL-6 mRNA were observed in glomeruli. These cells were mesangial cells, glomerular epithelial cells, and Bowman's capsule. The signal intensity was strongest in tissues from group 2 but was weak in those from groups 1 and 3. Most cells in the area of mesangial proliferation were strongly stained for IL-6 mRNA, and few positive cells were found in the Kimmelstiel-Wilson nodular lesion. In the interstitium, some tubules, particularly atrophic tubules, and some infiltrating cells were positively stained for IL-6 mRNA. The interstitial expression of IL-6 mRNA correlated significantly with the degree of interstitial injury and was remarkable in tissues from groups 2 and 3. We conclude that IL-6 mRNA is expressed by glomerular resident cells and interstitial cells in the renal tissue of patients with DN and that its expression may be associated with mesangial proliferation and may be involved in the tissue injury of DN.

Progressive expansion of the mesangial matrix is one of the most characteristic histological features of diabetic nephropathy (DN). To determine the balance between the turnover and degradation of extracellular matrix (ECM) in renal tissue of patients with DN, we examined the expression of matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1) and type IV collagen (IV-C) mRNAs using a high-resolution in situ hybridization. Patients were divided into three grades: mild (grade I), moderate (grade II) and severe (grade III) mesangial expansion and tubulointerstitial injury. The relationship between the expression of these mRNAs and degree of glomerular mesangial expansion and interstitial injury was also examined. Cells positive for each mRNA were observed in glomerular resident cells, including glomerular mesangial, epithelial and endothelial cells and cells of Bowman's capsule. A number of tubular epithelial cells and some infiltrating cells in the interstitium also expressed these mRNAs. The expression of MMP-3 mRNA and TIMP-1 mRNA was strongest in glomeruli of grade I and inversely correlated with mesangial expansion. In contrast, the expression of all three types of mRNA was correlated with the degree of interstitial injury. Our results indicate that IV-C, MMP-3 and TIMP-1 mRNAs are expressed in glomerular resident cells, tubular epithelial cells and infiltrating cells in renal tissue of DN, and suggest that their expression changes with the degree of mesangial expansion and interstitial injury. Altered expression of MMP-3 and TIMP-1 may be associated with the progression of DN.

Objective To evaluate the usefulness of renal biopsy in the overall managementof patients with diabetes mellitus (DM), we examined the relationship between the clinical parameters and histopathological findings of renal biopsy samples.MethodsRenal biopsy specimens were obtained from 109 type 2 diabetic patients with proteinuria. Samples were divided into the following two groups: Diabetic Nephropathy (DN) group (n=80) had typical diabetic lesions without other renal diseases, complication group (n=29) had diabetic lesions with other renal diseases. Furthermore, DN group was subdivided into two subgroups: slow progressive group (SP group, n=32), the level of serum creatinine (s-Cr) was normal at the time of renal biopsy and three years after renal biopsy, and fast progressive group (FP group, n=14), the level of s-Cr was normal at the time of renal biopsy but more than doubled three years after renal biopsy.Results The level of total protein was significantly lower and HbAlc significantly higher in the DNgroup than in the Complication group. However, other clinical parameters were not significantly different between the two groups. Urinary protein, systolic and diastolic blood pressure in FP group were significantly higher than in SP group. The percentage of sclerotic glomeruli, the severity of mesangial expansion, tubular injury and cell infiltration were significantly greater in FP than in SP group. Conclusions Ourresults indicated that a complete evaluation of renal pathology in DMcould not be made by clinical parameters only, and that the progression of DNcould be accurately predicted by histopathological evaluation. Therefore, this study emphasizes the importance of renal biopsy in the overall management of patients with DMand/ orDN.

No abstract

To investigate the changes of renal type IV collagen turnover in diabetic nephropathy, urinary type IV collagen was measured by a highly sensitive one-step sandwich enzyme immunoassay (EIA). Urinary samples were obtained from 698 diabetic patients and 191 healthy adults. Among the patients, 264 had urinary albumin levels of less than 29 mg/g.creatine (Cr) (Stage I: normoalbuminuric stage), 169 had microalbuminuria from 30 to 299 mg/g.Cr (Stage II: microalbuminuric stage), 84 patients had macroalbuminuria of more than 300 mg/g.Cr and serum Cr of less than 1.1 mg/dl (Stage IIIA: macroalbuminuric stage without renal dysfunction), 97 had macroalbuminuria of more than 300 mg/g.Cr and serum Cr of more than 1.2 mg/dl (Stage IIIB: macroalbuminuric stage with renal dysfunction), and 84 had renal failure (Stage IV). The levels of urinary type IV collagen in Stages II, IIIA, IIIB, and IV were significantly higher than those in Stage I (P < 0.0001). The level of urinary type IV collagen in Stage I (5.00 +/- 0.23 microg/g.Cr; mean +/- SE) was also higher than that in normal adults (3.44 +/- 0.11 microg/g.Cr; mean +/- SE). These levels increased gradually due to progression of the clinical stage of diabetic nephropathy. It appears that the levels of urinary type IV collagen can be a useful marker for detecting renal injuries in diabetes according to our Asian multicenter trials.