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Wenjun Z Martini - One of the best experts on this subject based on the ideXlab platform.
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Hypercoagulation and HyperMetabolism of Fibrinogen in Severely Burned Adults.
Journal of burn care & research : official publication of the American Burn Association, 2020Co-Authors: Wenjun Z Martini, John B. Holcomb, Anthony E. Pusateri, Steven E. Wolf, Leopoldo C. Cancio, Michael A DubickAbstract:This study investigated changes in plasma Fibrinogen Metabolism and changes in coagulation in severely burned adults. Ten patients (27 ± 3 years; 91 ± 6 kg) with 51 ± 3% TBSA were consented and enrolled into an institutional review board-approved prospective study. On the study day, stable isotope infusion of 1-13C-phenylalanine and d5-phenylalanine was performed to quantify Fibrinogen production and consumption. During the infusion, vital signs were recorded and blood samples were drawn every hour. Coagulation was measured by thromboelastograph (TEG). Ten normal healthy volunteers (37 ± 7 years; 74 ± 4 kg) were included as the control group. Burned adults had elevated heart rates (120 ± 2 vs 73 ± 5 [control] beats/minute), respiration rates (23 ± 2 vs 15 ± 1 breaths/minute), plasma glucose (127 ± 10 vs 89 ± 2 mg/dl), and Fibrinogen levels (613 ± 35 vs 239 ± 17 mg/dl); and decreased albumin (1.3 ± 0.2 vs 3.7 ± 0.1 g/dl) and total protein (4.4 ± 0.2 vs 6.8 ± 0.1 g/dl, all P < .05). Fibrinogen breakdown was elevated in the burn group (2.3 ± 0.4 vs. 1.0 ± 0.3 µmol/kg/minute); and Fibrinogen synthesis was further enhanced in the burn group (4.4 ± 0.7 vs 0.7 ± 0.2 µmol/kg/minute, both P < .05). Clotting speed (TEG-alpha) and clot strength (TEG-MA) were increased in the burn group (62 ± 4 vs 50 ± 4°, and 76 ± 2 vs 56 ± 2 mm, respectively, both P < .05). Fibrinolysis of TEG-LY60 was accelerated in the burn group (16 ± 6 vs 3 ± 1) and so was the increase in D-dimer level in the burn group (4.5 ± 0.4 vs 1.9 ± 0.3 mg/l, both P < .05). The hypercoagulable state postburn is in part a result of increased Fibrinogen synthesis, over and above increased Fibrinogen breakdown.
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Daily profiles of Fibrinogen Metabolism for 5 days following hemorrhage and lactated ringer's resuscitation in pigs.
Shock (Augusta Ga.), 2012Co-Authors: Wenjun Z Martini, Michael A Dubick, Kevin K. Chung, Lorne H. BlackbourneAbstract:This study's objective was to investigate the daily dynamics of Fibrinogen Metabolism and coagulation function for 5 days after hemorrhagic shock in pigs. Sixteen pigs were randomized into the control (C) and the hemorrhage (H) groups. On day 1, hemorrhage was induced in H by bleeding 35% of the estimated total blood volume, followed by resuscitation with lactated Ringer's solution at three times the bled volume. Then, a primed constant infusion of stable isotopes was performed in both groups daily for 5 days to measure changes in Fibrinogen Metabolism, together with changes in hemodynamics and coagulation function. Hemorrhage caused a decrease in mean arterial pressure and an increase in heart rate. Fluid resuscitation corrected these changes. Compared with baseline day 1, Fibrinogen levels in H were decreased to 76% ± 6% by hemorrhage and resuscitation on day 1, increased to 217% ± 16% on day 2, and remained elevated afterward; clot strength in H was decreased by hemorrhage on day 1 and returned to baseline values on day 2 and afterward. Compared with day 1 control value (1.3 ± 0.1 mg/kg per hour), Fibrinogen synthesis in H was increased to 3.6 ± 0.1, 5.1 ± 0.5, 2.6 ± 0.4, 2.7 ± 0.5, and 2.3 ± 0.3 mg/kg per hour on days 1 through 5 (all P < 0.05); Fibrinogen breakdown in H was elevated on days 1 and 2 but returned to control values afterward. Hemorrhage caused acute decreases in Fibrinogen concentration and clot strength, followed by an increase in Fibrinogen concentration and recovery of clot strength. The increase in Fibrinogen appeared primarily due to a sustained increase in Fibrinogen synthesis.
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Coagulopathy by Hypothermia and Acidosis: Mechanisms of Thrombin Generation and Fibrinogen Availability
The Journal of trauma, 2009Co-Authors: Wenjun Z MartiniAbstract:Although the lethal triad of hypothermia, acidosis, and coagulopathy has been recognized for a decade, the underlying mechanisms related to the development of coagulopathy are not fully understood. Consequently, current strategy in treating trauma patients with coagulopathy is limited to "staying out of the trouble" instead of "getting out of trouble." A better understanding of the underlying mechanisms will facilitate the search for effective therapeutic approaches when this lethal triad cannot be avoided. Reviewing recent studies that explored alterations of thrombin generation and Fibrinogen availability caused by hypothermia and acidosis. Hypothermia and acidosis compromise thrombin-generation kinetics via different mechanisms. Hypothermia primarily inhibits the initiation phase, whereas acidosis severely inhibits the propagation phase of thrombin generation. Similarly, hypothermia and acidosis affect Fibrinogen Metabolism differently. Hypothermia inhibits Fibrinogen synthesis, whereas acidosis accelerates Fibrinogen degradation, leading to a potential deficit in Fibrinogen availability. In addition, coagulation complications caused by acidosis cannot be immediately corrected by pH neutralization alone. Hypothermia and acidosis impair thrombin generation and Fibrinogen availability via different mechanisms. Current data indicate that pH correction alone cannot immediately correct acidosis-induced coagulation impairments. Future studies are warranted to test the effects of pH neutralization in conjunction with Fibrinogen supplementation in normalizing acidosis-induced clotting complications.
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Acidosis and coagulopathy: the differential effects on Fibrinogen synthesis and breakdown in pigs.
Annals of surgery, 2007Co-Authors: Wenjun Z Martini, John B. HolcombAbstract:Objective:Uncontrolled bleeding from coagulopathy signals imminent death in severely injured patients. Acidosis is an important predictor of coagulopathy, but the underlying contributing mechanisms are unclear. This study was designed to investigate the effects of acidosis on Fibrinogen Metabolism a
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effects of hemorrhage and lactated ringer s resuscitation on coagulation and Fibrinogen Metabolism in swine
Shock, 2006Co-Authors: Wenjun Z Martini, David L Chinkes, Jill L Sondeen, Michael A DubickAbstract:ABSTRACTHemorrhagic coagulopathy is a significant complication after traumatic injury, and much of the underlying mechanism remains unclear. We investigated the changes in Fibrinogen Metabolism and coagulation after a moderate hemorrhage and resuscitation. Pigs of either sex (weight, 40.9 ± 0.8 kg)
Pietro Castellino - One of the best experts on this subject based on the ideXlab platform.
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Effects of dietary protein restriction on Fibrinogen and albumin Metabolism in nephrotic patients
Kidney international, 2001Co-Authors: Mauro Giordano, Pierpaolo De Feo, Paola Lucidi, Emanuela Depascale, Gelsomina Giordano, Domenico Cirillo, Giuseppe Dardo, Salvatore Santo Signorelli, Pietro CastellinoAbstract:Effects of dietary protein restriction on Fibrinogen and albumin Metabolism in nephrotic patients. Background Nephrotic syndrome (NS) is characterized by profound changes in albumin and Fibrinogen levels. Dietary protein restriction has been advocated in the treatment of patients with NS, but its effects on albumin and Fibrinogen Metabolism have not been fully elucidated. Methods We evaluated the effects of dietary protein restriction on endogenous leucine flux (ELF), Fibrinogen and albumin Metabolism in seven patients with NS who consumed either a normal protein diet (NPD; 1.20 ± 0.06 g/kg/day), or a low protein diet (LPS; 0.66 ± 0.04 g/kg/day) for four weeks. Seven normal subjects served as controls. The postabsorptive ELF value, fractional synthesis rate (FSR) and absolute synthesis rate (ASR) of both albumin and Fibrinogen were evaluated during the last 120 minutes of a five-hour 5,5,5-D3- L -leucine infusion. Results During the NPD regimen. ELF was increased, serum albumin was reduced, plasma Fibrinogen was increased, albumin FSR and ASR were both increased, Fibrinogen FSR was normal, and Fibrinogen ASR was greater in patients with NS compared to controls. In patients with NS the LPD regimen reduced proteinuria, ELF, albumin FSR and ASR, plasma Fibrinogen levels, Fibrinogen ASR, and increased serum ulbumin levels. Dietary-induced changes in albumin and Fibrinogen synthesis were significantly correlated ( r = 0.719, P Conclusions Patients with NS treated with LPD show: ( 1 ) a reduction of proteinuria, albumin ASR and FSR, with an increase in serum albumin levels and its intravascular pool; ( 2 ) a decrease of Fibrinogen ASR, with a reduction in both plasma Fibrinogen levels and intravascular pool; and ( 3 ) a reduced rate of whole body proteolysis.
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Effects of dietary protein restriction on Fibrinogen and albumin Metabolism in nephrotic patients
Kidney international, 2001Co-Authors: Mauro Giordano, Pierpaolo De Feo, Paola Lucidi, Emanuela Depascale, Gelsomina Giordano, Domenico Cirillo, Giuseppe Dardo, Salvatore Santo Signorelli, Pietro CastellinoAbstract:Nephrotic syndrome (NS) is characterized by profound changes in albumin and Fibrinogen levels. Dietary protein restriction has been advocated in the treatment of patients with NS, but its effects on albumin and Fibrinogen Metabolism have not been fully elucidated. We evaluated the effects of dietary protein restriction on endogenous leucine flux (ELF), Fibrinogen and albumin Metabolism in seven patients with NS who consumed either a normal protein diet (NPD; 1.20 +/- 0.06 g/kg/day), or a low protein diet (LPS; 0.66 +/- 0.04 g/kg/day) for four weeks. Seven normal subjects served as controls. The postabsorptive ELF value, fractional synthesis rate (FSR) and absolute synthesis rate (ASR) of both albumin and Fibrinogen were evaluated during the last 120 minutes of a five-hour 5,5,5-D3-L-leucine infusion. During the NPD regimen. ELF was increased, serum albumin was reduced, plasma Fibrinogen was increased, albumin FSR and ASR were both increased, Fibrinogen FSR was normal, and Fibrinogen ASR was greater in patients with NS compared to controls. In patients with NS the LPD regimen reduced proteinuria, ELF, albumin FSR and ASR, plasma Fibrinogen levels, Fibrinogen ASR, and increased serum ulbumin levels. Dietary-induced changes in albumin and Fibrinogen synthesis were significantly correlated (r = 0.719, P < 0.05). Patients with NS treated with LPD show: (1) a reduction of proteinuria, albumin ASR and FSR, with an increase in serum albumin levels and its intravascular pool; (2) a decrease of Fibrinogen ASR, with a reduction in both plasma Fibrinogen levels and intravascular pool; and (3) a reduced rate of whole body proteolysis.
John B. Holcomb - One of the best experts on this subject based on the ideXlab platform.
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Hypercoagulation and HyperMetabolism of Fibrinogen in Severely Burned Adults.
Journal of burn care & research : official publication of the American Burn Association, 2020Co-Authors: Wenjun Z Martini, John B. Holcomb, Anthony E. Pusateri, Steven E. Wolf, Leopoldo C. Cancio, Michael A DubickAbstract:This study investigated changes in plasma Fibrinogen Metabolism and changes in coagulation in severely burned adults. Ten patients (27 ± 3 years; 91 ± 6 kg) with 51 ± 3% TBSA were consented and enrolled into an institutional review board-approved prospective study. On the study day, stable isotope infusion of 1-13C-phenylalanine and d5-phenylalanine was performed to quantify Fibrinogen production and consumption. During the infusion, vital signs were recorded and blood samples were drawn every hour. Coagulation was measured by thromboelastograph (TEG). Ten normal healthy volunteers (37 ± 7 years; 74 ± 4 kg) were included as the control group. Burned adults had elevated heart rates (120 ± 2 vs 73 ± 5 [control] beats/minute), respiration rates (23 ± 2 vs 15 ± 1 breaths/minute), plasma glucose (127 ± 10 vs 89 ± 2 mg/dl), and Fibrinogen levels (613 ± 35 vs 239 ± 17 mg/dl); and decreased albumin (1.3 ± 0.2 vs 3.7 ± 0.1 g/dl) and total protein (4.4 ± 0.2 vs 6.8 ± 0.1 g/dl, all P < .05). Fibrinogen breakdown was elevated in the burn group (2.3 ± 0.4 vs. 1.0 ± 0.3 µmol/kg/minute); and Fibrinogen synthesis was further enhanced in the burn group (4.4 ± 0.7 vs 0.7 ± 0.2 µmol/kg/minute, both P < .05). Clotting speed (TEG-alpha) and clot strength (TEG-MA) were increased in the burn group (62 ± 4 vs 50 ± 4°, and 76 ± 2 vs 56 ± 2 mm, respectively, both P < .05). Fibrinolysis of TEG-LY60 was accelerated in the burn group (16 ± 6 vs 3 ± 1) and so was the increase in D-dimer level in the burn group (4.5 ± 0.4 vs 1.9 ± 0.3 mg/l, both P < .05). The hypercoagulable state postburn is in part a result of increased Fibrinogen synthesis, over and above increased Fibrinogen breakdown.
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Acidosis and coagulopathy: the differential effects on Fibrinogen synthesis and breakdown in pigs.
Annals of surgery, 2007Co-Authors: Wenjun Z Martini, John B. HolcombAbstract:Objective:Uncontrolled bleeding from coagulopathy signals imminent death in severely injured patients. Acidosis is an important predictor of coagulopathy, but the underlying contributing mechanisms are unclear. This study was designed to investigate the effects of acidosis on Fibrinogen Metabolism a
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Acute changes in Fibrinogen Metabolism and coagulation after hemorrhage in pigs.
American journal of physiology. Endocrinology and metabolism, 2005Co-Authors: Wenjun Z Martini, David L Chinkes, John B. Holcomb, Anthony E. Pusateri, Xiao-jun Zhang, Robert R. WolfeAbstract:Hemorrhagic coagulopathy is involved in the morbidity and mortality of trauma patients. Nonetheless, many aspects of the mechanisms underlying this disorder are poorly understood. We have therefore...
Michael A Dubick - One of the best experts on this subject based on the ideXlab platform.
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Hypercoagulation and HyperMetabolism of Fibrinogen in Severely Burned Adults.
Journal of burn care & research : official publication of the American Burn Association, 2020Co-Authors: Wenjun Z Martini, John B. Holcomb, Anthony E. Pusateri, Steven E. Wolf, Leopoldo C. Cancio, Michael A DubickAbstract:This study investigated changes in plasma Fibrinogen Metabolism and changes in coagulation in severely burned adults. Ten patients (27 ± 3 years; 91 ± 6 kg) with 51 ± 3% TBSA were consented and enrolled into an institutional review board-approved prospective study. On the study day, stable isotope infusion of 1-13C-phenylalanine and d5-phenylalanine was performed to quantify Fibrinogen production and consumption. During the infusion, vital signs were recorded and blood samples were drawn every hour. Coagulation was measured by thromboelastograph (TEG). Ten normal healthy volunteers (37 ± 7 years; 74 ± 4 kg) were included as the control group. Burned adults had elevated heart rates (120 ± 2 vs 73 ± 5 [control] beats/minute), respiration rates (23 ± 2 vs 15 ± 1 breaths/minute), plasma glucose (127 ± 10 vs 89 ± 2 mg/dl), and Fibrinogen levels (613 ± 35 vs 239 ± 17 mg/dl); and decreased albumin (1.3 ± 0.2 vs 3.7 ± 0.1 g/dl) and total protein (4.4 ± 0.2 vs 6.8 ± 0.1 g/dl, all P < .05). Fibrinogen breakdown was elevated in the burn group (2.3 ± 0.4 vs. 1.0 ± 0.3 µmol/kg/minute); and Fibrinogen synthesis was further enhanced in the burn group (4.4 ± 0.7 vs 0.7 ± 0.2 µmol/kg/minute, both P < .05). Clotting speed (TEG-alpha) and clot strength (TEG-MA) were increased in the burn group (62 ± 4 vs 50 ± 4°, and 76 ± 2 vs 56 ± 2 mm, respectively, both P < .05). Fibrinolysis of TEG-LY60 was accelerated in the burn group (16 ± 6 vs 3 ± 1) and so was the increase in D-dimer level in the burn group (4.5 ± 0.4 vs 1.9 ± 0.3 mg/l, both P < .05). The hypercoagulable state postburn is in part a result of increased Fibrinogen synthesis, over and above increased Fibrinogen breakdown.
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Daily profiles of Fibrinogen Metabolism for 5 days following hemorrhage and lactated ringer's resuscitation in pigs.
Shock (Augusta Ga.), 2012Co-Authors: Wenjun Z Martini, Michael A Dubick, Kevin K. Chung, Lorne H. BlackbourneAbstract:This study's objective was to investigate the daily dynamics of Fibrinogen Metabolism and coagulation function for 5 days after hemorrhagic shock in pigs. Sixteen pigs were randomized into the control (C) and the hemorrhage (H) groups. On day 1, hemorrhage was induced in H by bleeding 35% of the estimated total blood volume, followed by resuscitation with lactated Ringer's solution at three times the bled volume. Then, a primed constant infusion of stable isotopes was performed in both groups daily for 5 days to measure changes in Fibrinogen Metabolism, together with changes in hemodynamics and coagulation function. Hemorrhage caused a decrease in mean arterial pressure and an increase in heart rate. Fluid resuscitation corrected these changes. Compared with baseline day 1, Fibrinogen levels in H were decreased to 76% ± 6% by hemorrhage and resuscitation on day 1, increased to 217% ± 16% on day 2, and remained elevated afterward; clot strength in H was decreased by hemorrhage on day 1 and returned to baseline values on day 2 and afterward. Compared with day 1 control value (1.3 ± 0.1 mg/kg per hour), Fibrinogen synthesis in H was increased to 3.6 ± 0.1, 5.1 ± 0.5, 2.6 ± 0.4, 2.7 ± 0.5, and 2.3 ± 0.3 mg/kg per hour on days 1 through 5 (all P < 0.05); Fibrinogen breakdown in H was elevated on days 1 and 2 but returned to control values afterward. Hemorrhage caused acute decreases in Fibrinogen concentration and clot strength, followed by an increase in Fibrinogen concentration and recovery of clot strength. The increase in Fibrinogen appeared primarily due to a sustained increase in Fibrinogen synthesis.
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effects of hemorrhage and lactated ringer s resuscitation on coagulation and Fibrinogen Metabolism in swine
Shock, 2006Co-Authors: Wenjun Z Martini, David L Chinkes, Jill L Sondeen, Michael A DubickAbstract:ABSTRACTHemorrhagic coagulopathy is a significant complication after traumatic injury, and much of the underlying mechanism remains unclear. We investigated the changes in Fibrinogen Metabolism and coagulation after a moderate hemorrhage and resuscitation. Pigs of either sex (weight, 40.9 ± 0.8 kg)
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Effects of hemorrhage and lactated Ringer's resuscitation on coagulation and Fibrinogen Metabolism in swine.
Shock (Augusta Ga.), 2006Co-Authors: Wenjun Z Martini, David L Chinkes, Jill L Sondeen, Michael A DubickAbstract:Hemorrhagic coagulopathy is a significant complication after traumatic injury, and much of the underlying mechanism remains unclear. We investigated the changes in Fibrinogen Metabolism and coagulation after a moderate hemorrhage and resuscitation. Pigs of either sex (weight, 40.9+/-0.8 kg) were anesthetized and instrumented with arterial and venous catheters and a thermodilution cardiac output catheter. Pigs were randomized into control (C; n=6), hemorrhage (H; n=6), and hemorrhage and resuscitation (H-LR; n=6) groups. Hemorrhage was induced by bleeding 35% of total blood volume for 30 min in H and H-LR groups. Resuscitation in H-LR group was performed using lactated Ringer's solution (LR) at 3 times the bled volume for 30 min. Fibrinogen Metabolism was quantified using a primed constant infusion of 1-13C-phenylalanine (6 h) and d5-phenylalanine (4 h) and subsequent analysis by gas chromatograph-mass spectrometry, together with measurements of hemodynamics (hourly) and coagulation by thromboelastography (at baseline and 4 h after hemorrhage and resuscitation). Hemorrhage caused decreases in arterial pH and base excess, and an increase in arterial lactate content. Fluid resuscitation corrected these changes toward normal levels. Fibrinogen level was unchanged in C and decreased to 76%+/-4% in H and to 73%+/-3% in H-LR (both P
Mauro Giordano - One of the best experts on this subject based on the ideXlab platform.
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Effects of dietary protein restriction on Fibrinogen and albumin Metabolism in nephrotic patients
Kidney international, 2001Co-Authors: Mauro Giordano, Pierpaolo De Feo, Paola Lucidi, Emanuela Depascale, Gelsomina Giordano, Domenico Cirillo, Giuseppe Dardo, Salvatore Santo Signorelli, Pietro CastellinoAbstract:Effects of dietary protein restriction on Fibrinogen and albumin Metabolism in nephrotic patients. Background Nephrotic syndrome (NS) is characterized by profound changes in albumin and Fibrinogen levels. Dietary protein restriction has been advocated in the treatment of patients with NS, but its effects on albumin and Fibrinogen Metabolism have not been fully elucidated. Methods We evaluated the effects of dietary protein restriction on endogenous leucine flux (ELF), Fibrinogen and albumin Metabolism in seven patients with NS who consumed either a normal protein diet (NPD; 1.20 ± 0.06 g/kg/day), or a low protein diet (LPS; 0.66 ± 0.04 g/kg/day) for four weeks. Seven normal subjects served as controls. The postabsorptive ELF value, fractional synthesis rate (FSR) and absolute synthesis rate (ASR) of both albumin and Fibrinogen were evaluated during the last 120 minutes of a five-hour 5,5,5-D3- L -leucine infusion. Results During the NPD regimen. ELF was increased, serum albumin was reduced, plasma Fibrinogen was increased, albumin FSR and ASR were both increased, Fibrinogen FSR was normal, and Fibrinogen ASR was greater in patients with NS compared to controls. In patients with NS the LPD regimen reduced proteinuria, ELF, albumin FSR and ASR, plasma Fibrinogen levels, Fibrinogen ASR, and increased serum ulbumin levels. Dietary-induced changes in albumin and Fibrinogen synthesis were significantly correlated ( r = 0.719, P Conclusions Patients with NS treated with LPD show: ( 1 ) a reduction of proteinuria, albumin ASR and FSR, with an increase in serum albumin levels and its intravascular pool; ( 2 ) a decrease of Fibrinogen ASR, with a reduction in both plasma Fibrinogen levels and intravascular pool; and ( 3 ) a reduced rate of whole body proteolysis.
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Effects of dietary protein restriction on Fibrinogen and albumin Metabolism in nephrotic patients
Kidney international, 2001Co-Authors: Mauro Giordano, Pierpaolo De Feo, Paola Lucidi, Emanuela Depascale, Gelsomina Giordano, Domenico Cirillo, Giuseppe Dardo, Salvatore Santo Signorelli, Pietro CastellinoAbstract:Nephrotic syndrome (NS) is characterized by profound changes in albumin and Fibrinogen levels. Dietary protein restriction has been advocated in the treatment of patients with NS, but its effects on albumin and Fibrinogen Metabolism have not been fully elucidated. We evaluated the effects of dietary protein restriction on endogenous leucine flux (ELF), Fibrinogen and albumin Metabolism in seven patients with NS who consumed either a normal protein diet (NPD; 1.20 +/- 0.06 g/kg/day), or a low protein diet (LPS; 0.66 +/- 0.04 g/kg/day) for four weeks. Seven normal subjects served as controls. The postabsorptive ELF value, fractional synthesis rate (FSR) and absolute synthesis rate (ASR) of both albumin and Fibrinogen were evaluated during the last 120 minutes of a five-hour 5,5,5-D3-L-leucine infusion. During the NPD regimen. ELF was increased, serum albumin was reduced, plasma Fibrinogen was increased, albumin FSR and ASR were both increased, Fibrinogen FSR was normal, and Fibrinogen ASR was greater in patients with NS compared to controls. In patients with NS the LPD regimen reduced proteinuria, ELF, albumin FSR and ASR, plasma Fibrinogen levels, Fibrinogen ASR, and increased serum ulbumin levels. Dietary-induced changes in albumin and Fibrinogen synthesis were significantly correlated (r = 0.719, P < 0.05). Patients with NS treated with LPD show: (1) a reduction of proteinuria, albumin ASR and FSR, with an increase in serum albumin levels and its intravascular pool; (2) a decrease of Fibrinogen ASR, with a reduction in both plasma Fibrinogen levels and intravascular pool; and (3) a reduced rate of whole body proteolysis.