ABSTRACT
Angiotensin II (AT II) is thought to be associated with the development of renal interstitial fibrosis. However, the molecular mechanisms of the interstitial fibrosis have not been extensively studied. We have examined the role of mitogen-activated protein kinases (MAPKs) on fibronectin (FN) accumulation in cultured normal rat kidney interstitial fibroblasts (NRK 49F cell line). AT II caused dose-dependent increases in FN accumulation and FN mRNA in these cells. AT II also activated the extracellular signal-regulated kinase (ERK) and p38 MAPK in the presence of AT II. These increases in FN accumulation and activation of MAPKs were inhibited with AT I receptor antagonist (ARB; CV-11974) in renal interstitial fibroblasts. The inhibitors against ERK (PD98059) and p38 MAPK (SB203580) significantly inhibited AT II-induced increases in FN mRNA. These findings suggest that the MAPKs play an important role in AT II-mediated renal interstitial fibrosis and that ARB may be useful for preventing renal interstitial fibrosis.
Subject(s)
Angiotensin II/metabolism , Fibroblasts/metabolism , Fibronectins/biosynthesis , JNK Mitogen-Activated Protein Kinases , Mitogen-Activated Protein Kinases/metabolism , Angiotensin II/pharmacology , Animals , Cell Line , Dose-Response Relationship, Drug , Extracellular Matrix Proteins/biosynthesis , Extracellular Space/drug effects , Extracellular Space/metabolism , Fibroblasts/drug effects , Kidney/drug effects , Kidney/metabolism , MAP Kinase Kinase 4 , Mitogen-Activated Protein Kinase Kinases/drug effects , Mitogen-Activated Protein Kinase Kinases/metabolism , Mitogen-Activated Protein Kinases/drug effects , Rats , p38 Mitogen-Activated Protein KinasesABSTRACT
OBJECTIVE: The present study was undertaken to evaluate clinical application of serum cystatin C as a new marker of glomerular filtration rate (GFR) in patients with various renal diseases. PATIENTS AND METHODS: A total of 140 patients were enrolled in the study. We measured the serum cystatin C levels and compared them with creatinine clearance (Ccr) and inulin clearance (Cin) as an indicator of GFR. RESULTS: There was a significant positive correlation between serum cystatin C and creatinine levels (r=0.928). Serum cystatin C was inversely correlated with creatinine clearance. Moreover, the reciprocal serum cystatin C level was positively correlated with Cin (r=0.882). The receiver-operating characteristic curve of serum cystatin C and creatinine demonstrated that the diagnostic accuracy of the serum cystatin C level is superior to that of creatinine in identifying individuals with reduced GFR. CONCLUSION: These results indicated that measurement of serum cystatin C is useful to estimate GFR, and in particular, to detect a mild reduction of GFR in patients with renal diseases.
Subject(s)
Cystatins/blood , Glomerular Filtration Rate , Kidney Diseases/blood , Kidney Diseases/physiopathology , Adult , Aged , Biomarkers/blood , Creatinine/blood , Cystatin C , Female , Humans , Male , Middle AgedABSTRACT
We report a rare case of nephrotic syndrome in an elderly woman with positive antineutrophil cytoplasmic antibody(ANCA). The patient was 81 years of age and had a history of interstitial pneumonia. She was diagnosed rheumatoid arthritis(RA) at admission. Rapidly progressing renal damage was found with mild microscopic hematuria and positive ANCA. The renal biopsy findings indicated membranous nephropathy. Neither gold nor anti-rheumatic drugs had been previously administered. She may have had an RA-specific membranous nephropathy. Crescentic formation was not clear. With hematuria, the leukocyte infiltration in the capillary lumen and the change in epithelial cells of Bowman's capsules would be histological findings suggesting ANCA-associated nephritis. This is a rare report on membranous nephropathy in an RA patient with ANCA-associated nephritis.
