Elevated urinary plasmin activity resistant to alpha2-antiplasmin in acute poststreptococcal glomerulonephritis.
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.
Oda
Takashi
T
Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa-shi, Saitama 359-8513, Japan. takashio@ndmc.ac.jp
Tamura
Kikuko
K
Yoshizawa
Nobuyuki
N
Sugisaki
Tetsuzo
T
Matsumoto
Koichi
K
Hattori
Motoshi
M
Sawai
Toshihiro
T
Namikoshi
Tamehachi
T
Yamada
Muneharu
M
Kikuchi
Yuichi
Y
Suzuki
Shigenobu
S
Miura
Soichiro
S
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D005341:Fibrinolysin / Q000187:drug effects* / Q000652:urine*; D005921:Glomerulonephritis / Q000175:diagnosis / Q000382:microbiology* / Q000652:urine*; D005922:Glomerulonephritis, IGA / Q000652:urine; D006801:Humans; D008875:Middle Aged; D018000:Receptors, Peptide / Q000378:metabolism; D013290:Streptococcal Infections / Q000150:complications* / Q000175:diagnosis / Q000652:urine*; D000979:alpha-2-Antiplasmin / Q000494:pharmacology*
D015415:Biomarkers; D018000:Receptors, Peptide; D000979:alpha-2-Antiplasmin; C065181:plasmin receptor; D003404:Creatinine; D005341:Fibrinolysin