Takahiro Kawano

Discordance between Retinopathy and Nephropathy in Type 2 Diabetes

The aim of this study was to investigate the relationship between the grade of retinopathy and the severity of glomerular lesions in patients with type 2 diabetes and to describe 5 patients without diabetic retinopathy for whom renal biopsy specimens demonstrated advanced diabetic nephropathy. A total of 221 patients with type 2 diabetes (139 males and 82 females) who consectively underwent renal biopsy between 1982 and 1996 were investigated. The severity of diffuse glomerular lesions was graded using the criteria of Gellman and coworkers, and diabetic retinopathy was classified as absent, nonproliferative, or proliferative. The incidence of advanced nephropathy without retinopathy for all 221 cases was 2.3%. Advanced nephropathy was present in 5 of the 122 (4.1%) patients without retinopathy. These 5 patients were all males and aged 50–70 (mean 61) years. Their clinical characteristics were not uniform, and no special clinical features distinguished the patients who were regarded as having possible advanced nephropathy without retinopathy. In our study, although concordance of retinopathy and nephropathy is relatively common, a little discordance was pronounced in Japanese type 2 diabetic patients. Our findings are consistent with the hypothesis that there are important differences in some aspects of the pathogenesis of retinopathy and nephropathy.

Association of Chlamydia pneumoniae infection with diabetic nephropathy.

We evaluated the association of Chlamydia pneumoniae (CP) infection with progression of diabetic nephropathy. Type 2 diabetic patients (60) were divided into two groups, those with incipient nephropathy and those with advanced nephropathy, based on the severity of diffuse glomerular lesions using Gellmans criteria. Type 2 (34) diabetic patients without nephropathy (normoalbuminuria) and 59 nondiabetics served as control groups. Serum IgG-antibody against CP was measured using ELISA. CP antibody was detected in 45.8% of nondiabetic controls, in 47.1% of diabetic patients without nephropathy, in 52.6% of diabetic patients with incipient nephropathy, and 78% of diabetic patients with advanced nephropathy. There was 4.22-fold increase in the risk of advanced nephropathy associated with the presence of CP antibody. Our findings indicate an association between chronic CP infection and advanced diabetic nephropathy.

Serum IgA levels in patients with diabetic nephropathy and IgA nephropathy superimposed on diabetes mellitus

The aim of this study was to examine the relationship between serum immunoglobulin A (IgA) levels and diabetic nephropathy in patients with type 2 diabetes mellitus, and to describe the role of IgA nephropathy superimposed on diabetes mellitus. A total of 127 type 2 diabetic patients were studied. Of these diabetics, 74 had no proteinuria, 35 had diabetic glomerulosclerosis confirmed by renal biopsy, 13 had superimposed IgA nephropathy, and five had superimposed non-IgA nephropathy. We also studied 93 non-diabetic patients with IgA nephropathy, 24 non-diabetic patients with non-IgA nephropathy, and 38 non-diabetic controls. Serum IgA levels were significantly higher in IgA nephropathy patients (350+/-130 mg/dl) than in non-diabetic controls (228+/-56 mg/dl) and diabetics without proteinuria (268+/-104 mg/dl). Serum IgA levels were also significantly higher in diabetics with superimposed IgA nephropathy (470+/-208 mg/dl) than in non-diabetic controls, non-IgA nephropathy patients (270+/-133 mg/dl), diabetics without proteinuria, diabetic glomerulosclerosis alone (302+/-126 mg/dl), and diabetics with superimposed non-IgA nephropathy (248+/-137 mg/dl). The prevalence of high serum IgA levels was significantly higher in diabetics with superimposed IgA nephropathy (76.9%) than in diabetic glomerulosclerosis alone (31.4%) and diabetics with superimposed non-IgA nephropathy (25.0%). In conclusion, our findings indicate that high serum IgA level is a sign of the existence of IgA nephropathy superimposed on diabetes mellitus.

MATRIX METALLOPROTEINASE-2 AND MESANGIOLYSIS IN DIABETIC NEPHROPATHY

Accessible online at: http://BioMedNet.com/karger Dear Sir, Diabetic nephropathy is characterized by the accumulation or extracellular matrix (ECM) in the glomerular basement membrane and mesangium, which depends on the balance between its synthesis and degradation [1]. The role of matrix metalloproteinases (MMPs) in the development of diabetic nephropathy has been investigated, and it has been hypothesized that decreased degradation by MMPs may be responsible for the increase in ECM [2]. MMP-2 (gelatinase A), the 72-kD type IV collagenase, is a member of this family of enzymes which specifically degrades type IV collagen, fibronectin, laminin and proteoglycans [3]. Mesangiolysis, as dissolution or attenuation of the mesangial matrix and degeneration of mesangial cells, is the initial event in the remodeling of glomerular lesions and/or the process of nodular formation in diabetic nephropathy [4]. One hypothesis suggests that excess MMP-2 proteolytic activity causes ECM degradation resulting in mesangiolysis. We therefore investigated the relationship between the serum MMP-2 activity and the severity of glomerular lesions in type 2 diabetic patients. Thirty-nine type 2 diabetic patients (26 men and 13 women, 35–74 years of age, mean 57 B 10 years) were enrolled in this study after informed consent. Patients with any clinical and/or serologic evidence of chronic liver disease or underlying malignancy were excluded from the study. Serum MMP-2 activity was measured using a onestep sandwich enzyme immunoassay [5]. Tissue specimens obtained by percutaneous renal biopsy were processed for morphometric evaluation using light microscopy. The severity of glomerular lesions was graded as D1, D2, D3+4 using Gellman’s criteria [6]. Mesangiolysis was defined as light microscopic evidence of focal and segmental lesions consisting of loosening and disintegration of mesangial structures with associated cystic dilatation of the involved tuft and/or a fibrillar or reticular appearance or the mesangial matrix [7]. Relationship between serum MMP-2 activity and severity of glomerular lesions is shown in table 1. Mesangiolysis was observed in 3 patients with grade D2, and 5 patients with grade D3+4, glomerular lesions, but was not detected in patients with grade D1 lesions. In D3+4 group, the serum MMP-2 activity was significantly higher in patients with mesangiolysis than in patients without evidence of mesangiolysis. Human mesangial cells secrete both neutral metalloproteinase enzymes and a 68to 72-kD gelatinase [8]. MMP-2 is constitutively expressed by renal cells in culture, by mesangial cells in the normal kidney, and by macrophages that have infiltrated glomeruli [9]. The early decrease in glomerular MMP-2 gene expression has been demonstrated in renal biopsy specimens obtained from type 2 diabetic patients [10], and decreased degradation of matrix may contribute to mesangial matrix accumulation in the setting of Table 1. Serum MMP-2 activity (ng/ml) and mesangiolysis

Role of secreted protein acidic and rich in cysteine (SPARC) in patients with diabetic nephropathy

BackgroundA protein called “secreted protein acidic and rich in cysteine” (SPARC) may be important in the progression of diabetic nephropathy. Recent animal studies have shown a possible correlation between SPARC levels and diabetes-related kidney growth.MethodsWe measured serum levels of SPARC in patients with diabetic nephropathy and compared them to the severity of glomerular lesions as determined by renal biopsy. A total of 50 non-insulin-dependent diabetic patients were divided into 2 groups; patients with endstage diabetic nephropathy (ESDN, n=10) or without ESDN (DM, n=40). Renal biopsies were performed in all patients without ESDN. Serum levels of SPARC were measured by enzyme-linked immunosorbent assay (ELISA) in the 50 patients with diabetes, in 10 healthy controls, and in 10 patients with immunoglobulin (Ig) A nephropathy. Values for serum creatinine, creatinine clearance, β2-microglobulin, and hemoglobin A1C also were obtained.ResultsThe mean serum SPARC levels (ng/mL) were 29±12, 41±21, 43±20, and 85±28, for healthy controls, IgA nephropathy, DM, and ESDN patients, respectively. Serum SPARC levels showed a significant increase with an increase in severity of glomerular diffuse lesions. Serum levels of SPARC were significantly higher in the DM group than in controls, and significantly higher in the ESDN group than in the control, IgA nephropathy and DM groups.ConclusionThe findings suggest that SPARC may contribute to the progression of diabetic nephropathy.