Makoto Nishina

Glomerular expression of connective tissue growth factor mRNA in various renal diseases.

SUMMARY:  Connective tissue growth factor (CTGF) is a cysteine‐rich member of a new family of growth regulators. It is an important factor in the pathogenesis of mesangial matrix accumulation and progressive glomerulosclerosis. The present study was designed to elucidate the role of CTGF in diabetic nephropathy (DN), immunoglobulin A nephropathy (IgA‐N), membranous nephropathy (MN), and minimal change nephrotic syndrome (MCNS). We evaluated the expression and localization of CTGF mRNA in surgically excised renal tissue samples from 10 patients with DN, 10 with IgA‐N, 10 with MN, 10 with MCNS, and 10 normal human kidney (NHK) tissue samples, by using high‐resolution in situ hybridization with digoxigenin‐labelled oligonucleotide. To quantify CTGF mRNA expression, we counted all nuclei, and nuclei surrounded by CTGF‐positive cytoplasm, in at least 10 randomly selected cross‐sections of non‐sclerotic glomeruli, and expressed the results as a percentage of total glomerular cells. In all glomeruli, CTGF mRNA was expressed mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells and some cells of Bowmans capsule. The percentage of cells positive for CTGF mRNA was significantly higher in DN and IgA‐N than in MN, MCNS and NHK. However, there was no significant difference in the percentage of CTGF mRNA‐positive cells between DN and IgA‐N. Our study indicates that CTGF may play an important role in the development and progression of glomerulosclerosis in DN and IgA‐N, which are both accompanied by mesangial matrix expansion and comprise two major causes of end‐stage renal failure.

Neutral-pH peritoneal dialysis solution improves peritoneal function and decreases matrix metalloproteinase-2 (MMP-2) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD)

BackgroundConventional lactate-buffered peritoneal dialysis (PD) solutions have several bioincompatible characteristics, including acidic pH, lactate buffer, and the presence of glucose degradation products (GDPs), and these characteristics contribute to membrane dysfunction in PD patients. The formation of GDPs can be reduced by separating the glucose component of the solution from the lactate component during sterilization. This study was carried out to evaluate the clinical effect of dual-chambered neutral-pH PD solution in patients on continuous ambulatory peritoneal dialysis (CAPD).MethodsThirteen CAPD patients using conventional PD solution were enrolled in this study. The fast peritoneal equilibration test (fast PET) was performed periodically before and after treatment with neutral PD solution. The concentration of matrix metalloproteinase-2 (MMP-2) in dialysate effluent was measured using 4-h dwelling 2.5% glucose dialysis solution. The patients were categorized into two groups, according to the value of the initial dialysate/plasma (D/P) creatinine ratio: i.e., lower transporters (group L, D/PCr < 0.65) and higher transporters (group H, D/PCr ≥ 0.65).ResultsThe mean D/P creatinine ratio measured by fast PET, was significantly decreased (0.72 ± 0.09 to 0.60 ± 0.06; P < 0.03) after treatment with neutral PD solution in group H. The mean glucose level in 4-h dwelling dialysate effluent was elevated (824.6 ± 195.9 mg/dl to 942.6 ± 147.8 mg/dl; P < 0.022) in all subjects. In group H, a significant decrease of MMP-2 in the dialysate effluent was recognized from 15 months after the beginning of treatment with the neutral PD solution (141.4 ± 52.5 ng/ml to 91.3 ± 15.1 ng/ml; P < 0.05), with the lowest value being shown at 21 months (80.0 ± 31.8 ng/ml; P < 0.03).ConclusionsNeutral-pH peritoneal dialysis solution decreased the MMP-2 level in dialysate and improved peritoneal function in high-transporter patients with CAPD treatment.