[Serum level and urinary excretion of RANTES in patients with primary glomerulonephritis].
Proteinuria plays a central role in the progression of glomerular disease, and there is growing evidence suggesting that it may determine tubular cell activation with release of proinflammatory chemokines and fibrogenic factors, leading to interstitial inflammatory reaction. Chemokines are proteins that contribute to the migration of leukocytes to sites of tissue injury. C-C chemokine receptor 5 is receptor for the C-C chemokine RANTES, which is expressed in inflammatory kidney diseases. To better understand the role of RANTES in various types of human glomerular diseases, we studied 53 patients with primary glomerular diseases (5 minimal change--MC; 4 focal glomerulosclerosis--FS; 4 membranous nephropathy--MN; 12--mesangial proliferative GN--MesPGN; 18 IgA nephropathy--IgAN; 6 membranoproliferative GN-MPGN, and 4 extracapillary GN-ExGN) and 10 healthy person. Renal biopsies were evaluated by light and immunofluorescence microscopy. RANTES concentrations in serum and urine were measured by ELISA (BIOSOURCE international kits). The treatment of patients consisted of 3 to 5 i.v. methylprednisolone pulses (1.0 g per single dose, average total 1.0 g/20 kg given alternate days) followed by oral prednisone 20 to 25 mg/day and six monthly i.v. cyclophosphamide 0.6 g/l m2/month. The study groups (except FS) showed a significantly higher concentration of RANTES in their sera compared with the control. The increase of urinary excretion for RANTES was 2-fold in patients with MN, and 8-fold in patients with ExGN but in patients with FS a significant decrease in urinary RANTES excretion was found. There was no significant differences in the urinary excretion of RANTES in other groups compared to a control group. In patient groups serum Cr showed significant correlations with interstitial volume in renal biopsy. No significant correlation was found between serum concentration of RANTES and their urinary excretion and other parameters considered (serum creatinine, urinary protein, serum protein concentration, and interstitial volume in renal biopsy). In patients with renal insufficiency (Cr > 1.3 mg%) and reduction of proteinuria > 50% after 1 year of treatment, the serum concentration and urinary secretion of RANTES was higher before treatment than in patients with protein reduction < 50%, and in patients with renal sufficiency. These results showed that patients with glomerular diseases who showed renal insufficiency and reduction of urinary protein after 1 year of immunosuppressive treatment revealed high levels of serum and urinary excretion of RANTES. It was thus suggested that the measurement of serum and urinary excretion of RANTES is useful in evaluating the degree of renal injury in patients with glomerular diseases after immunosuppressive treatment.
Kacprzyk
Feliks
F
Klinika Nefrologiczna Instytutu Medycyny Wewnetrznej AM w Łodzi.
D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood* / Q000652:urine*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007262:Infusions, Intravenous; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D018946:Chemokine CCL5; D007166:Immunosuppressive Agents; D011241:Prednisone; D008775:Methylprednisolone