AIM： To determine whether complement membrane attack complex （C5b-9） has a pathogenic role in tubuloin-terstitial injury in a renal disease model characterized by acute highly selective proteinuria. METHODS： Prote...AIM： To determine whether complement membrane attack complex （C5b-9） has a pathogenic role in tubuloin-terstitial injury in a renal disease model characterized by acute highly selective proteinuria. METHODS： Protein-overload nephropathy （PON） was induced in adult female Piebald-Viral-Glaxo rats with or without complement C6 defciency （C6- and C6＋） by daily intraperitoneal injections of bovine serum albumin （BSA, 2 g/d）, and examined on days 2, 4 and 8.RESULTS： Groups with PON developed equivalent levels of heavy proteinuria within 24 h of BSA injection. In C6＋ rats with PON, the tubulointerstitial expression of C5b-9 was increased and localized predominantly to the basolateral surface of tubular epithelial cells （TECs）, whereas it was undetectable in C6- animals. TEC proliferation （as assessed by the number of BrdU＋cells） increased by more than 50-fold in PON, peaking on day 2 and declining on days 4 to 8. There was a trend for a reduction in the number of BrdU＋ TECs on day 4 in the C6- PON group （ P = 0.10 compared to C6＋） but not at any other time-point. Kidney enlargement, TEC apoptosis （TUNEL＋ cells） and markers of tubular injury （tubule dilatation, loss of TEC height, protein cast formation） were not altered by C6 deficiency in PON. Interstitial monocyte （ED-1＋ cell） accumulation was partially reduced in C6- animals with PON on day 4 （ P = 0.01） but there was no change in myofbroblast accumulation. CONCLUSION： These data suggest that C5b-9 does not mediate tubulointerstitial injury in acute glomerular diseases characterized by selective proteinuria.展开更多
AIM: To study complement activation in 46 patients with alcoholic cirrhosis and ascites but no spontaneous bacterial peritonitis (SBP) and 10 healthy controls. METHODS: Complement activation was determined by the meas...AIM: To study complement activation in 46 patients with alcoholic cirrhosis and ascites but no spontaneous bacterial peritonitis (SBP) and 10 healthy controls. METHODS: Complement activation was determined by the measurement of soluble membrane attack complex (sMAC) concentrations in ascites and plasma. In patients, metabolic liver function was determined by the galactose elimination capacity and the clinical status assessed by the Model of End-Stage Liver Disease and Child-Pugh scores. RESULTS: Ascites sMAC levels were markedly higherthan in the corresponding plasma sample (median (range): 596 (170 - 1519) vs 160 (77 - 848) μg/L; P < 0.01). Ascites sMAC levels correlated positively with liver status. There was no relationship between ascites sMAC and leukocyte count. No relationship between ascites sMAC and blood C-reactive protein, albumin or neutrophile count was found. Plasma sMAC concentrations were slightly higher in patients than in controls [130 μg/L (70 - 204); P = 0.04]. Neither sMAC in ascites nor plasma was related to mortality. CONCLUSION: The increased sMAC concentration in ascites and plasma indicate an activation of the complement system in cirrhosis even in the absence of SBP. This was particularly evident in the peritoneal fluid and most marked in patients with preserved liver status. The high ascites sMAC levels may reflect transudation of membrane attack complexes from the liver. Whether this complement activation has any clinical implications remains to be clarified.展开更多
基金Supported by The United States National Institutes of Health(Nos.DK34198 and DK07467)to Dr.CouserThe Don Jacquot Fellowship(Australian and New Zealand Society of Nephrology Travelling Fellowship)+3 种基金The BJ Amos Travelling Fellowships(Westmead Hospital)The Medical Research Fund of Western AustraliaThe Fremantle Hospital Medical Research FoundationThe National Health and Medical Research Council(No.230500)to Dr.Rangan
文摘AIM： To determine whether complement membrane attack complex （C5b-9） has a pathogenic role in tubuloin-terstitial injury in a renal disease model characterized by acute highly selective proteinuria. METHODS： Protein-overload nephropathy （PON） was induced in adult female Piebald-Viral-Glaxo rats with or without complement C6 defciency （C6- and C6＋） by daily intraperitoneal injections of bovine serum albumin （BSA, 2 g/d）, and examined on days 2, 4 and 8.RESULTS： Groups with PON developed equivalent levels of heavy proteinuria within 24 h of BSA injection. In C6＋ rats with PON, the tubulointerstitial expression of C5b-9 was increased and localized predominantly to the basolateral surface of tubular epithelial cells （TECs）, whereas it was undetectable in C6- animals. TEC proliferation （as assessed by the number of BrdU＋cells） increased by more than 50-fold in PON, peaking on day 2 and declining on days 4 to 8. There was a trend for a reduction in the number of BrdU＋ TECs on day 4 in the C6- PON group （ P = 0.10 compared to C6＋） but not at any other time-point. Kidney enlargement, TEC apoptosis （TUNEL＋ cells） and markers of tubular injury （tubule dilatation, loss of TEC height, protein cast formation） were not altered by C6 deficiency in PON. Interstitial monocyte （ED-1＋ cell） accumulation was partially reduced in C6- animals with PON on day 4 （ P = 0.01） but there was no change in myofbroblast accumulation. CONCLUSION： These data suggest that C5b-9 does not mediate tubulointerstitial injury in acute glomerular diseases characterized by selective proteinuria.
基金Supported by grants from the Danish Medical Research Council
文摘AIM: To study complement activation in 46 patients with alcoholic cirrhosis and ascites but no spontaneous bacterial peritonitis (SBP) and 10 healthy controls. METHODS: Complement activation was determined by the measurement of soluble membrane attack complex (sMAC) concentrations in ascites and plasma. In patients, metabolic liver function was determined by the galactose elimination capacity and the clinical status assessed by the Model of End-Stage Liver Disease and Child-Pugh scores. RESULTS: Ascites sMAC levels were markedly higherthan in the corresponding plasma sample (median (range): 596 (170 - 1519) vs 160 (77 - 848) μg/L; P < 0.01). Ascites sMAC levels correlated positively with liver status. There was no relationship between ascites sMAC and leukocyte count. No relationship between ascites sMAC and blood C-reactive protein, albumin or neutrophile count was found. Plasma sMAC concentrations were slightly higher in patients than in controls [130 μg/L (70 - 204); P = 0.04]. Neither sMAC in ascites nor plasma was related to mortality. CONCLUSION: The increased sMAC concentration in ascites and plasma indicate an activation of the complement system in cirrhosis even in the absence of SBP. This was particularly evident in the peritoneal fluid and most marked in patients with preserved liver status. The high ascites sMAC levels may reflect transudation of membrane attack complexes from the liver. Whether this complement activation has any clinical implications remains to be clarified.
