Elevated urinary plasmin activity resistant to alpha2-antiplasmin in acute poststreptococcal glomerulonephritis.

Abstract

BACKGROUND:

A pathogenic role of intraglomerular plasmin bound to nephritogenic antigen (nephritis-associated plasmin receptor, NAPlr) and resistant to physiologic inhibitors such as alpha(2)-antiplasmin (alpha(2)-AP) has recently been proposed in acute poststreptococcal glomerulonephritis (APSGN). To confirm this concept, we analysed the urinary profile of plasmin cascade in APSGN patients.

METHODS:

Urine samples from 10 patients with APSGN, 12 patients with IgA nephropathy (IgAN), 10 patients with streptococcal infection without nephritis (SI) and 10 healthy control subjects were analysed. The alpha(2)-AP-resistant plasmin activity was assessed by a chromogenic assay after alpha(2)-AP was added to each urine sample. Urinary plasminogen activator (PA) and plasmin were further analysed by polyacrylamide gel zymography. Urinary NAPlr was assessed by western blot analysis in selected samples.

RESULTS:

Urinary alpha(2)-AP-resistant plasmin activity corrected for creatinine concentration (units/g x creatinine) was significantly higher in patients with APSGN (2.99 +/- 0.63) than in patients with IgAN (1.02 +/- 0.20, P < 0.01), SI (0.79 +/- 0.17, P < 0.01), or in healthy control subjects (0.73 +/- 0.18, P < 0.01). This tendency was confirmed by casein gel zymography. However urinary PA activity assessed by plasminogen-casein gel zymography did not differ between groups. NAPlr was detected in the urine of APSGN patients.

CONCLUSIONS:

We found elevated urinary plasmin activity resistant to alpha(2)-AP, which may be due to urinary excretion of NAPlr in patients with APSGN. This result supports the pathogenic role of the NAPlr-plasmin complex in the development of APSGN. Furthermore, alpha(2)-AP-resistant urinary plasmin activity may be useful as a diagnostic marker for APSGN.

• Authors: Takashi Oda, Kikuko Tamura, Nobuyuki Yoshizawa, Tetsuzo Sugisaki, Koichi Matsumoto, Motoshi Hattori, Toshihiro Sawai, Tamehachi Namikoshi, Muneharu Yamada, Yuichi Kikuchi, Shigenobu Suzuki, Soichiro Miura
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 23 Issue 7 Pg. 2254-9 (Jul 2008) ISSN: 1460-2385 [Electronic] England
• PMID: 18223261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Receptors, Peptide
• alpha-2-Antiplasmin
• plasmin receptor
• Creatinine
• Fibrinolysin

Topics

• Acute Disease
• Adolescent
• Adult
• Biomarkers (urine)
• Case-Control Studies
• Child
• Child, Preschool
• Creatinine (urine)
• Fibrinolysin (drug effects, urine)
• Glomerulonephritis (diagnosis, microbiology, urine)
• Glomerulonephritis, IGA (urine)
• Humans
• Middle Aged
• Receptors, Peptide (metabolism)
• Streptococcal Infections (complications, diagnosis, urine)
• alpha-2-Antiplasmin (pharmacology)