Icosapent ethyl (IPE), a highly purified ethyl ester of eicosapentaenoic acid (EPA), was evaluated for its effect on coronary atherosclerotic plaque progression in patients with elevated triglycerides on statin therapy. In a randomized controlled trial of 80 patients, IPE 4g/day resulted in significant regression of low attenuation plaque volume compared to placebo after 18 months. IPE also reduced total, non-calcified, fibrofatty and fibrous plaque volumes but not calcified plaque volume. No significant differences in lipid levels were observed between groups.
Presented during Surgical Grand Round in Clonmel Hospital in 2011. The purpose of this presentation is to educate junior doctors on appendicitis.
This presentation was presented in 2011. So the content may be outdated. So please keep yourself updated.
WanYusof Wan Jeffery
zenslides.com [Eng]
presentasipukau.com [Malay]
This document describes the development and validation of a new clinical scoring system called the Appendicitis Inflammatory Response Score (AIRS) to aid in the diagnosis of acute appendicitis. The AIRS was constructed using data from 545 patients prospectively admitted for suspected appendicitis. Eight clinical and laboratory variables were identified via logistic regression as having independent diagnostic value and were used to create the scoring system. When validated on 229 additional patients, the AIRS demonstrated superior diagnostic accuracy compared to the existing Alvarado score, with an area under the ROC curve of 0.97 for advanced appendicitis versus 0.92 for the Alvarado score. The AIRS is able to correctly classify the majority of
This randomized trial compared a double dose versus standard dose of clopidogrel and a high dose versus low dose of aspirin in over 25,000 patients undergoing percutaneous coronary intervention. It found that a 7-day double dose of clopidogrel was more effective at preventing cardiovascular death, heart attack, or stroke compared to the standard dose, with no increase in fatal or intracranial bleeding. However, high-dose aspirin did not provide additional benefits over low-dose aspirin for preventing these outcomes.
Clinical prediction rules use combinations of clinical findings to predict the probability of a specific condition or outcome. This document summarizes several clinical prediction rules for orthopedic conditions seen in outpatient settings, including rules for ankle injuries, knee injuries, patellofemoral pain, hip osteoarthritis, and low back pain. It provides details on the clinical findings and validation levels for each rule. The document concludes by describing where to find more information on clinical prediction rules and validation studies.
Clinical Practice Guideline on management of patients with diabetes and chron...Ahmed Albeyaly
This document provides a summary of a clinical practice guideline on managing patients with diabetes and chronic kidney disease (CKD) stage 3b or higher. It outlines the composition of the guideline development group, which included nephrologists, endocrinologists, and epidemiologists from several European countries. The group aimed to provide guidance on evidence-based approaches to improve care for this patient population. The guideline's target audience is healthcare professionals treating adults with both diabetes and reduced kidney function (eGFR <45 mL/min). It focuses on developing standards of care for managing this complex patient group.
Bariatric surgery, especially malabsorptive procedures like Roux-en-Y gastric bypass, significantly increases the risk of kidney stones compared to obese controls. The risk is highest with malabsorptive procedures and correlates with the degree of fat malabsorption and enteric hyperoxaluria. However, bariatric surgery does not appear to increase the risk of chronic kidney disease. Further research is still needed to fully understand the mechanisms by which bariatric surgery leads to hyperoxaluria and kidney stone formation.
Icosapent ethyl (IPE), a highly purified ethyl ester of eicosapentaenoic acid (EPA), was evaluated for its effect on coronary atherosclerotic plaque progression in patients with elevated triglycerides on statin therapy. In a randomized controlled trial of 80 patients, IPE 4g/day resulted in significant regression of low attenuation plaque volume compared to placebo after 18 months. IPE also reduced total, non-calcified, fibrofatty and fibrous plaque volumes but not calcified plaque volume. No significant differences in lipid levels were observed between groups.
Presented during Surgical Grand Round in Clonmel Hospital in 2011. The purpose of this presentation is to educate junior doctors on appendicitis.
This presentation was presented in 2011. So the content may be outdated. So please keep yourself updated.
WanYusof Wan Jeffery
zenslides.com [Eng]
presentasipukau.com [Malay]
This document describes the development and validation of a new clinical scoring system called the Appendicitis Inflammatory Response Score (AIRS) to aid in the diagnosis of acute appendicitis. The AIRS was constructed using data from 545 patients prospectively admitted for suspected appendicitis. Eight clinical and laboratory variables were identified via logistic regression as having independent diagnostic value and were used to create the scoring system. When validated on 229 additional patients, the AIRS demonstrated superior diagnostic accuracy compared to the existing Alvarado score, with an area under the ROC curve of 0.97 for advanced appendicitis versus 0.92 for the Alvarado score. The AIRS is able to correctly classify the majority of
This randomized trial compared a double dose versus standard dose of clopidogrel and a high dose versus low dose of aspirin in over 25,000 patients undergoing percutaneous coronary intervention. It found that a 7-day double dose of clopidogrel was more effective at preventing cardiovascular death, heart attack, or stroke compared to the standard dose, with no increase in fatal or intracranial bleeding. However, high-dose aspirin did not provide additional benefits over low-dose aspirin for preventing these outcomes.
Clinical prediction rules use combinations of clinical findings to predict the probability of a specific condition or outcome. This document summarizes several clinical prediction rules for orthopedic conditions seen in outpatient settings, including rules for ankle injuries, knee injuries, patellofemoral pain, hip osteoarthritis, and low back pain. It provides details on the clinical findings and validation levels for each rule. The document concludes by describing where to find more information on clinical prediction rules and validation studies.
Clinical Practice Guideline on management of patients with diabetes and chron...Ahmed Albeyaly
This document provides a summary of a clinical practice guideline on managing patients with diabetes and chronic kidney disease (CKD) stage 3b or higher. It outlines the composition of the guideline development group, which included nephrologists, endocrinologists, and epidemiologists from several European countries. The group aimed to provide guidance on evidence-based approaches to improve care for this patient population. The guideline's target audience is healthcare professionals treating adults with both diabetes and reduced kidney function (eGFR <45 mL/min). It focuses on developing standards of care for managing this complex patient group.
Bariatric surgery, especially malabsorptive procedures like Roux-en-Y gastric bypass, significantly increases the risk of kidney stones compared to obese controls. The risk is highest with malabsorptive procedures and correlates with the degree of fat malabsorption and enteric hyperoxaluria. However, bariatric surgery does not appear to increase the risk of chronic kidney disease. Further research is still needed to fully understand the mechanisms by which bariatric surgery leads to hyperoxaluria and kidney stone formation.
This document discusses antiplatelet treatment strategies in diabetic patients with acute coronary syndrome (ACS). It summarizes several clinical trials comparing different P2Y12 inhibitors in this population. The key points are:
1. Diabetic patients with ACS have higher mortality and morbidity than non-diabetic patients. Clopidogrel response is more variable in diabetics, with higher rates of non-response.
2. A head-to-head trial found ticagrelor reduced platelet reactivity more than prasugrel in diabetic ACS patients after loading doses, with fewer patients having high on-treatment platelet reactivity.
3. Clinical trials showed ticagrelor and prasug
This document provides an overview of several ICU scoring systems used to evaluate severity of illness and predict outcomes in critically ill patients. It describes the components and scoring of systems such as APACHE, SAPS, SOFA, MODS, and LODS. APACHE uses physiological variables and chronic health factors to calculate mortality risk. SAPS and SAPS II similarly assess physiology but also include age and admission type. SOFA evaluates degree of organ dysfunction in six organ systems. MODS and LODS also score dysfunction across multiple organ systems based on laboratory and clinical findings.
Clinical Impact of New NAFLD/NASH Data From EASL 2018hivlifeinfo
This document summarizes data presented at the 2018 International Liver Congress on noninvasive screening and clinical outcomes in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). New algorithms using blood tests and imaging were shown to improve detection of NASH and fibrosis without liver biopsy. Studies found patients with NAFLD/NASH and cirrhosis had high mortality, healthcare costs that increased substantially after cirrhosis diagnosis, and a significant economic burden on healthcare systems.
This document discusses relative blood volume (RBV) monitoring and its potential applications in dialysis. It provides an overview of RBV monitoring principles, compartmental fluid shifts, and RBV profiles in relation to intradialytic hypotension. While RBV monitoring shows promise for fluid management and blood pressure control, evidence from studies is mixed. The largest study to date found RBV monitoring increased mortality and hospitalizations. Further research is still needed to fully understand the clinical utility and appropriate applications of RBV monitoring.
Perioperative n acetylcysteine for patients undergoing living donor orthotopichanaa
This study evaluated the efficacy of perioperative intravenous N-acetylcysteine (NAC) in reducing acute kidney injury (AKI) and improving liver graft function in patients undergoing living donor orthotopic liver transplantation. 100 patients undergoing transplantation were randomly assigned to receive either intravenous NAC or saline as control. The results showed NAC decreased the incidence of postoperative AKI, primary graft non-function, and reduced hospital and ICU stay compared to the control group. However, NAC had no effect on the number of ventilator days or mortality.
Gpc manejo de enfermedades glomerulares-kdigo-2021WilliamBarrera34
This document provides clinical practice guidelines for the management of glomerular diseases published by KDIGO (Kidney Disease: Improving Global Outcomes) in 2021. It includes 11 chapters covering various glomerular diseases and recommendations for their evaluation and treatment. Key recommendations are presented in figures and tables throughout. Evaluation of evidence and grading of recommendations follows standardized processes. The guidelines aim to provide an evidence-based framework to guide clinical decision-making for glomerular diseases.
Safety and Efficacy of Low Dose versus Standard Dose of Alteplase for Stroke Thrombolysis in Hospital Sultanah Nur Zahirah (HSNZ)
Presentation Slides by Ms Mahfuzah Ishak, presented on the 14th National Conference for Clinical Research (NCCR) 2021 Dr Wu Lien Teh Youth Investigator Awards (YIA) on 19th August 2021
Following are the links for this presentation on Zenodo Repository:
Presentation Slides: https://zenodo.org/record/5348496
E-Poster: https://zenodo.org/record/5348723
A limited presentation about a) age related renal functional changes b) management of CKD, including advance care planning and transplantation referral c) management of potentially risky drugs in the elderly with CKD (NOACs)
1) The document discusses a Phase 3 clinical trial investigating the effects of the ASK1 inhibitor selonsertib (SEL) in patients with diabetic kidney disease (DKD).
2) The trial did not meet its primary endpoint of a 50% improvement in eGFR from baseline to week 48. However, exploratory analyses found SEL induced acute but reversible eGFR declines followed by stabilization or improvement in eGFR slope over time.
3) Adverse events including acute kidney injury and fluid overload were similar between SEL and placebo groups. The study was limited by its short duration and data issues from two sites.
This study compared outcomes of steroid withdrawal versus continued steroid therapy in kidney and heart transplant recipients. Over 1500 patients were enrolled from 1994-2002 and followed for 5-6 years on average. Results showed that steroid withdrawal led to superior patient and graft survival rates compared to controls continuing steroids. Steroid withdrawal also reduced risks of complications like osteoporosis and cataracts. However, it was associated with a small increased risk of acute rejection episodes. Overall, the study suggests that steroid withdrawal after 6 months is safe and effective for transplant recipients.
This document summarizes a study on gastric artery embolization via radial artery access for the treatment of obesity. The study included 7 obese patients with BMI over 40 and obesity-related conditions. Through selective cannulation and embolization of gastric arteries using PVA particles, the procedure achieved 100% technical success. At 1 month, patients lost an average of 5.6 pounds. No major complications occurred. While more data is needed, gastric artery embolization shows promise as a minimally invasive treatment for obesity.
The document discusses several medical topics:
1. New guidelines from the Endocrine Society on the management of primary aldosteronism, including case detection criteria, confirmation testing, subtype classification testing, and treatment recommendations.
2. Pros and cons of the National Bone Health Alliance's diagnostic criteria for osteoporosis, which expands the definition to include factors like fracture risk assessment (FRAX) scores in addition to bone mineral density testing.
3. Updated clinical practice guidelines from the American Association of Clinical Endocrinologists and American College of Endocrinology for developing comprehensive care plans for patients with diabetes mellitus.
Clinical Impact of New NAFLD/NASH Data From San Francisco 2018hivlifeinfo
Expert faculty summarize key NAFLD/NASH studies from this important annual conference. Use these slides to review data on noninvasive screening, clinical outcomes, emerging treatments.
Ira M. Jacobson, MD
Philip N. Newsome, PhD, FRCPE
Format: Microsoft PowerPoint (.ppt)
File Size: 421 KB
Released: December 3, 2018
Associated Factors of Stroke Severity Among Young Adult Stroke Patients in Malaysia from National Neurology Registry 2014 - 2018
Presentation Slides by Ms Fara Waheda Jusoh, presented on the 14th National Conference for Clinical Research (NCCR) 2021 Dr Wu Lien Teh Youth Investigator Awards (YIA) on 19th August 2021
Following are the links for this presentation on Zenodo Repository:
Presentation Slides: https://zenodo.org/record/5348488
E-Poster: https://zenodo.org/record/5348580
Results: NWO subjects (n = 283) demonstrated metabolic dysregulation compared to NWL individuals (n = 1795). After
adjusting for age, sex, and smoking, NWO individuals showed higher PWV values than NWL individuals (1474.0 ± 275.4 vs.
1380.7 ± 234.3 cm/s, p = 0.006 by ANCOVA). Compared with NWL subjects, NWO subjects had a higher prevalence of soft
plaques even after age, sex, and smoking adjustment (21.6 % vs. 14.5 %, p = 0.039 by ANCOVA). The PWV value and the
log{(number of segments with plaque) + 1} showed a positive correlation with numerous parameters such as age, systolic
blood pressure, visceral fat, fasting glucose level, serum triglyceride level, and C-reactive protein (CRP) in contrast to the
negative correlation with high-density lipoprotein-cholesterol level. The visceral fat was an independent determinant of
log{(number of segments with plaque) + 1} (ß = 0.027, SE = 0.011, p = 0.016) even after adjustment for other significant
factors. Most importantly, NWO was an independent risk factor for the presence of soft plaques (odds ratio 1.460, 95 %
confidence interval 1.027–2.074, p = 0.035) even after further adjustment for multiple factors associated with atherosclerosis
(blood pressure, blood glucose, lipid level, CRP, medication, smoking status, physical activity).
Normal-Weight Obesity Is Associated With
Increased Risk of Subclinical Atherosclerosis.
Conclusions: NWO individuals carry a higher incidence of subclinical atherosclerosis compared with NWL individuals,
regardless of other clinical risk factors for atherosclerosis.
New Approaches To The Treatment Of Hyperphosphataemia (CRF)Andre Garcia
The document discusses new approaches to treating hyperphosphataemia in patients with kidney disease. It summarizes findings from several studies that show disorders of mineral metabolism like hyperphosphatemia are associated with increased risks of cardiovascular disease and mortality in dialysis patients. One study found that treatment with the phosphate binder lanthanum carbonate was more effective at controlling serum phosphate levels and reducing the calcium-phosphate product compared to calcium-based binders, with fewer hypercalcemia side effects.
This document provides guidelines for the evaluation and management of chronic kidney disease (CKD) developed by the Kidney Disease: Improving Global Outcomes (KDIGO) organization. It defines CKD and staging systems based on glomerular filtration rate and albuminuria levels. The guidelines provide recommendations on screening and diagnosis of CKD, predicting progression, managing risk factors and complications, and referral to specialists. CKD is a major global public health problem, and these evidence-based guidelines aim to aid healthcare providers in delivering optimal care to patients with CKD.
The ACT Trial was a large pragmatic randomized controlled trial that evaluated the effectiveness of acetylcysteine in preventing contrast-induced nephropathy in over 2,300 high-risk patients undergoing coronary angiography. The trial found no significant difference in the rates of contrast-induced nephropathy or other clinical outcomes like mortality between patients who received acetylcysteine or placebo. Subgroup and meta-analysis of previous trials confirmed these results. The conclusions indicate that acetylcysteine is not effective in reducing short-term renal or clinical risks in high-risk patients undergoing angiography.
This document discusses hepatorenal syndrome (HRS), an acute kidney injury that can occur in patients with cirrhosis and liver failure. It provides updates on diagnostic criteria and classifications of HRS subtypes. The pathophysiology of HRS involves increased blood flow to the gut, decreased central blood volume, and kidney vasoconstriction. Risk factors include advanced cirrhosis and bacterial translocation. Terlipressin with albumin is the standard treatment and can reverse HRS, though noradrenaline is also effective with fewer side effects. The timing of renal replacement therapy and role of liver transplantation in HRS are also reviewed.
This document summarizes research on acute kidney injury (AKI) in critical care. It discusses changing incidence and mortality rates of AKI over time. It defines AKI and classifies its stages of severity. It also analyzes risk factors for AKI, evaluates the use of crystalloids versus colloids for fluid resuscitation, and discusses prevention and management of AKI.
This document discusses antiplatelet treatment strategies in diabetic patients with acute coronary syndrome (ACS). It summarizes several clinical trials comparing different P2Y12 inhibitors in this population. The key points are:
1. Diabetic patients with ACS have higher mortality and morbidity than non-diabetic patients. Clopidogrel response is more variable in diabetics, with higher rates of non-response.
2. A head-to-head trial found ticagrelor reduced platelet reactivity more than prasugrel in diabetic ACS patients after loading doses, with fewer patients having high on-treatment platelet reactivity.
3. Clinical trials showed ticagrelor and prasug
This document provides an overview of several ICU scoring systems used to evaluate severity of illness and predict outcomes in critically ill patients. It describes the components and scoring of systems such as APACHE, SAPS, SOFA, MODS, and LODS. APACHE uses physiological variables and chronic health factors to calculate mortality risk. SAPS and SAPS II similarly assess physiology but also include age and admission type. SOFA evaluates degree of organ dysfunction in six organ systems. MODS and LODS also score dysfunction across multiple organ systems based on laboratory and clinical findings.
Clinical Impact of New NAFLD/NASH Data From EASL 2018hivlifeinfo
This document summarizes data presented at the 2018 International Liver Congress on noninvasive screening and clinical outcomes in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). New algorithms using blood tests and imaging were shown to improve detection of NASH and fibrosis without liver biopsy. Studies found patients with NAFLD/NASH and cirrhosis had high mortality, healthcare costs that increased substantially after cirrhosis diagnosis, and a significant economic burden on healthcare systems.
This document discusses relative blood volume (RBV) monitoring and its potential applications in dialysis. It provides an overview of RBV monitoring principles, compartmental fluid shifts, and RBV profiles in relation to intradialytic hypotension. While RBV monitoring shows promise for fluid management and blood pressure control, evidence from studies is mixed. The largest study to date found RBV monitoring increased mortality and hospitalizations. Further research is still needed to fully understand the clinical utility and appropriate applications of RBV monitoring.
Perioperative n acetylcysteine for patients undergoing living donor orthotopichanaa
This study evaluated the efficacy of perioperative intravenous N-acetylcysteine (NAC) in reducing acute kidney injury (AKI) and improving liver graft function in patients undergoing living donor orthotopic liver transplantation. 100 patients undergoing transplantation were randomly assigned to receive either intravenous NAC or saline as control. The results showed NAC decreased the incidence of postoperative AKI, primary graft non-function, and reduced hospital and ICU stay compared to the control group. However, NAC had no effect on the number of ventilator days or mortality.
Gpc manejo de enfermedades glomerulares-kdigo-2021WilliamBarrera34
This document provides clinical practice guidelines for the management of glomerular diseases published by KDIGO (Kidney Disease: Improving Global Outcomes) in 2021. It includes 11 chapters covering various glomerular diseases and recommendations for their evaluation and treatment. Key recommendations are presented in figures and tables throughout. Evaluation of evidence and grading of recommendations follows standardized processes. The guidelines aim to provide an evidence-based framework to guide clinical decision-making for glomerular diseases.
Safety and Efficacy of Low Dose versus Standard Dose of Alteplase for Stroke Thrombolysis in Hospital Sultanah Nur Zahirah (HSNZ)
Presentation Slides by Ms Mahfuzah Ishak, presented on the 14th National Conference for Clinical Research (NCCR) 2021 Dr Wu Lien Teh Youth Investigator Awards (YIA) on 19th August 2021
Following are the links for this presentation on Zenodo Repository:
Presentation Slides: https://zenodo.org/record/5348496
E-Poster: https://zenodo.org/record/5348723
A limited presentation about a) age related renal functional changes b) management of CKD, including advance care planning and transplantation referral c) management of potentially risky drugs in the elderly with CKD (NOACs)
1) The document discusses a Phase 3 clinical trial investigating the effects of the ASK1 inhibitor selonsertib (SEL) in patients with diabetic kidney disease (DKD).
2) The trial did not meet its primary endpoint of a 50% improvement in eGFR from baseline to week 48. However, exploratory analyses found SEL induced acute but reversible eGFR declines followed by stabilization or improvement in eGFR slope over time.
3) Adverse events including acute kidney injury and fluid overload were similar between SEL and placebo groups. The study was limited by its short duration and data issues from two sites.
This study compared outcomes of steroid withdrawal versus continued steroid therapy in kidney and heart transplant recipients. Over 1500 patients were enrolled from 1994-2002 and followed for 5-6 years on average. Results showed that steroid withdrawal led to superior patient and graft survival rates compared to controls continuing steroids. Steroid withdrawal also reduced risks of complications like osteoporosis and cataracts. However, it was associated with a small increased risk of acute rejection episodes. Overall, the study suggests that steroid withdrawal after 6 months is safe and effective for transplant recipients.
This document summarizes a study on gastric artery embolization via radial artery access for the treatment of obesity. The study included 7 obese patients with BMI over 40 and obesity-related conditions. Through selective cannulation and embolization of gastric arteries using PVA particles, the procedure achieved 100% technical success. At 1 month, patients lost an average of 5.6 pounds. No major complications occurred. While more data is needed, gastric artery embolization shows promise as a minimally invasive treatment for obesity.
The document discusses several medical topics:
1. New guidelines from the Endocrine Society on the management of primary aldosteronism, including case detection criteria, confirmation testing, subtype classification testing, and treatment recommendations.
2. Pros and cons of the National Bone Health Alliance's diagnostic criteria for osteoporosis, which expands the definition to include factors like fracture risk assessment (FRAX) scores in addition to bone mineral density testing.
3. Updated clinical practice guidelines from the American Association of Clinical Endocrinologists and American College of Endocrinology for developing comprehensive care plans for patients with diabetes mellitus.
Clinical Impact of New NAFLD/NASH Data From San Francisco 2018hivlifeinfo
Expert faculty summarize key NAFLD/NASH studies from this important annual conference. Use these slides to review data on noninvasive screening, clinical outcomes, emerging treatments.
Ira M. Jacobson, MD
Philip N. Newsome, PhD, FRCPE
Format: Microsoft PowerPoint (.ppt)
File Size: 421 KB
Released: December 3, 2018
Associated Factors of Stroke Severity Among Young Adult Stroke Patients in Malaysia from National Neurology Registry 2014 - 2018
Presentation Slides by Ms Fara Waheda Jusoh, presented on the 14th National Conference for Clinical Research (NCCR) 2021 Dr Wu Lien Teh Youth Investigator Awards (YIA) on 19th August 2021
Following are the links for this presentation on Zenodo Repository:
Presentation Slides: https://zenodo.org/record/5348488
E-Poster: https://zenodo.org/record/5348580
Results: NWO subjects (n = 283) demonstrated metabolic dysregulation compared to NWL individuals (n = 1795). After
adjusting for age, sex, and smoking, NWO individuals showed higher PWV values than NWL individuals (1474.0 ± 275.4 vs.
1380.7 ± 234.3 cm/s, p = 0.006 by ANCOVA). Compared with NWL subjects, NWO subjects had a higher prevalence of soft
plaques even after age, sex, and smoking adjustment (21.6 % vs. 14.5 %, p = 0.039 by ANCOVA). The PWV value and the
log{(number of segments with plaque) + 1} showed a positive correlation with numerous parameters such as age, systolic
blood pressure, visceral fat, fasting glucose level, serum triglyceride level, and C-reactive protein (CRP) in contrast to the
negative correlation with high-density lipoprotein-cholesterol level. The visceral fat was an independent determinant of
log{(number of segments with plaque) + 1} (ß = 0.027, SE = 0.011, p = 0.016) even after adjustment for other significant
factors. Most importantly, NWO was an independent risk factor for the presence of soft plaques (odds ratio 1.460, 95 %
confidence interval 1.027–2.074, p = 0.035) even after further adjustment for multiple factors associated with atherosclerosis
(blood pressure, blood glucose, lipid level, CRP, medication, smoking status, physical activity).
Normal-Weight Obesity Is Associated With
Increased Risk of Subclinical Atherosclerosis.
Conclusions: NWO individuals carry a higher incidence of subclinical atherosclerosis compared with NWL individuals,
regardless of other clinical risk factors for atherosclerosis.
New Approaches To The Treatment Of Hyperphosphataemia (CRF)Andre Garcia
The document discusses new approaches to treating hyperphosphataemia in patients with kidney disease. It summarizes findings from several studies that show disorders of mineral metabolism like hyperphosphatemia are associated with increased risks of cardiovascular disease and mortality in dialysis patients. One study found that treatment with the phosphate binder lanthanum carbonate was more effective at controlling serum phosphate levels and reducing the calcium-phosphate product compared to calcium-based binders, with fewer hypercalcemia side effects.
This document provides guidelines for the evaluation and management of chronic kidney disease (CKD) developed by the Kidney Disease: Improving Global Outcomes (KDIGO) organization. It defines CKD and staging systems based on glomerular filtration rate and albuminuria levels. The guidelines provide recommendations on screening and diagnosis of CKD, predicting progression, managing risk factors and complications, and referral to specialists. CKD is a major global public health problem, and these evidence-based guidelines aim to aid healthcare providers in delivering optimal care to patients with CKD.
The ACT Trial was a large pragmatic randomized controlled trial that evaluated the effectiveness of acetylcysteine in preventing contrast-induced nephropathy in over 2,300 high-risk patients undergoing coronary angiography. The trial found no significant difference in the rates of contrast-induced nephropathy or other clinical outcomes like mortality between patients who received acetylcysteine or placebo. Subgroup and meta-analysis of previous trials confirmed these results. The conclusions indicate that acetylcysteine is not effective in reducing short-term renal or clinical risks in high-risk patients undergoing angiography.
This document discusses hepatorenal syndrome (HRS), an acute kidney injury that can occur in patients with cirrhosis and liver failure. It provides updates on diagnostic criteria and classifications of HRS subtypes. The pathophysiology of HRS involves increased blood flow to the gut, decreased central blood volume, and kidney vasoconstriction. Risk factors include advanced cirrhosis and bacterial translocation. Terlipressin with albumin is the standard treatment and can reverse HRS, though noradrenaline is also effective with fewer side effects. The timing of renal replacement therapy and role of liver transplantation in HRS are also reviewed.
This document summarizes research on acute kidney injury (AKI) in critical care. It discusses changing incidence and mortality rates of AKI over time. It defines AKI and classifies its stages of severity. It also analyzes risk factors for AKI, evaluates the use of crystalloids versus colloids for fluid resuscitation, and discusses prevention and management of AKI.
This document discusses predicting postoperative outcomes for patients undergoing surgery for hepatocellular carcinoma (HCC). It finds that acceptable postoperative mortality in cirrhotic patients is less than 5%. Pre-operative parameters like liver stiffness measurement, hepatic venous pressure gradient, and indocyanine green clearance can help predict outcomes. Laparoscopic surgery and modulating portal flow may help improve outcomes compared to open surgery for cirrhotic patients undergoing liver resection. Direct assessment of liver function and parenchyma quality are important to predict postoperative liver decompensation risk, especially for patients with a MELD score greater than 8 undergoing minor hepatectomy.
<SUMMARY>
The document provides an overview of acute kidney injury (AKI), including definitions, classification, epidemiology, etiology, diagnosis, management, and prevention strategies. It defines AKI according to the KDIGO criteria and discusses the RIFLE and AKIN classification systems. Prerenal, intrinsic, and postrenal causes of AKI are outlined. Diagnosis involves establishing baseline kidney function, identifying potential causes, and evaluating volume status, laboratory tests, and imaging studies. Management focuses on treating the underlying cause, optimizing hemodynamics, and preventing complications. Prevention emphasizes recognizing risk factors and avoiding nephrotoxic exposures.
</SUMMARY>
This document discusses intra-abdominal hypertension and the relationship between fluids and intra-abdominal pressure. It defines key terms like intra-abdominal pressure, intra-abdominal hypertension, and abdominal compartment syndrome. It then summarizes research showing that factors like obesity, sepsis, surgery, and large-volume crystalloid resuscitation can increase the risk of elevated intra-abdominal pressure. The document advocates limiting crystalloid use and explores strategies for removing excess fluids like using colloids, diuretics, ultrafiltration, and plasma resuscitation. It concludes that fluid management is critical for preventing secondary intra-abdominal hypertension and its associated poor outcomes.
This document discusses the diagnosis and management of acute kidney injury (AKI) in the intensive care unit (ICU). It defines AKI and outlines biomarkers that can help identify it earlier than creatinine. Common causes of AKI in the ICU include sepsis, major surgery, low cardiac output, and medications. The document reviews risk factors for developing AKI and strategies for preventing it, such as fluid management and avoiding nephrotoxins. It discusses general management of established AKI including nutrition, anticoagulation, and dialysis. The impact of renal replacement therapy on outcomes is also addressed.
This trial describes the use of Aspirin or Clopidogrel as a monotherapy after percutaneous coronary intervention in myocardial infarction patients. Though the guidelines have not said anything strictly but trials have shown Clopidogrel to be better than Aspirin.
This document provides information about acute kidney injury in liver disease. It begins with definitions of acute kidney injury and hepatorenal syndrome. It then discusses the types, epidemiology, pathophysiology, diagnosis, treatment and prevention. For diagnosis it outlines the criteria for hepatorenal syndrome from the International Club of Ascites. It discusses treatment approaches including vasoconstrictor therapy with terlipressin and noradrenaline. Trials comparing terlipressin to placebo or noradrenaline show terlipressin can induce reversal of hepatorenal syndrome in around 30-40% of patients.
Contrast-induced nephropathy (CIN) is a type of acute kidney injury caused by iodinated contrast media used in medical imaging procedures. The document defines CIN and discusses its risk factors, pathophysiology, prevention, and management. It summarizes that CIN risk increases with reduced kidney function, diabetes, and other comorbidities. Prevention focuses on identifying at-risk patients, using lower contrast volumes and iso-osmolar agents when possible, and intravenous fluid administration before and after the procedure. Sodium bicarbonate and N-acetylcysteine may provide additional protective effects. For higher risk patients, alternative imaging should be considered to avoid CIN.
Dr. Paul Sabbatini: Recurrent Ovarian Cancer: Now What? (SHARE Program)bkling
On May 22, 2013, SHARE presented "Recurrent Ovarian Cancer: Now What?" The program featured Dr. Ginger Gardner and Dr. Paul Sabbatini of Memorial Sloan-Kettering Cancer Center discussing treatment strategies, as well as new approaches and agents, for managing an ovarian cancer recurrence. Listen to the audio here http://www.sharecancersupport.org/sabbatini.
The information in this presentation is not intended to be a substitute for professional medical advice, diagnosis or treatment.
Based on the clinical information provided:
- Metastatic pancreatic cancer being treated with chemotherapy
- New onset nephrotic range proteinuria, hematuria, hypertension, edema
- Dysmorphic RBCs and granular casts on urine microscopy
The most likely histological finding on renal biopsy would be:
Amyloidosis. This constellation of findings is classic for amyloidosis-associated nephrotic syndrome in the setting of an underlying plasma cell dyscrasia or malignancy. Cellular crescents and endocapillary proliferation would be unusual in this case. Mesangial hypercellularity alone is nonspecific and does not fit with the clinical picture.
- The addition of selective internal radiation therapy (SIRT) to sorafenib (SOR) did not significantly improve overall survival compared to SOR alone in patients with advanced hepatocellular carcinoma based on two randomized controlled trials.
- Subgroup analyses found potential clinical benefits for younger patients, those with non-alcoholic disease etiology, and those without cirrhosis.
- Regorafenib, a multi-kinase inhibitor, significantly improved progression-free survival, overall survival, and disease control compared to placebo in patients with hepatocellular carcinoma progressing on sorafenib.
- Lenvatinib, an oral multi-kinase inhibitor, demonstrated non-inferior
This document discusses the prevention and treatment of acute kidney injury (AKI) in intensive care units. It covers the pathophysiology and risk factors for AKI, current diagnostic criteria and biomarkers for early detection, and strategies for prevention including maintaining renal perfusion and avoiding nephrotoxins. The document also reviews renal replacement therapy modalities for AKI treatment, such as intermittent hemodialysis, slow low efficiency dialysis, hemofiltration and hemodiafiltration, and their definitions and comparisons. It concludes that prevention of AKI is better than treatment and emphasizes maintaining renal perfusion status and prompt treatment of sepsis.
This document provides definitions and diagnostic criteria for acute kidney injury (AKI) according to the Acute Kidney Injury Network and RIFLE criteria. It discusses causes of AKI including prerenal azotemia, intrinsic renal disease, and postrenal obstruction. It also reviews biomarkers for early AKI detection and outcomes associated with AKI. Treatment is largely supportive though some promising pharmacologic approaches are discussed.
This document discusses acute kidney injury (AKI), including:
1) Definitions and diagnostic criteria for AKI based on increases in serum creatinine and decreases in urine output.
2) New biomarkers for detecting AKI such as NGAL, IL-18, and KIM-1.
3) Causes of AKI including prerenal, intrinsic renal, and postrenal etiologies. Prerenal and acute tubular necrosis are most common.
4) Supportive treatment is typically used while research investigates potential pharmacologic therapies like dopamine, ANP, and fenoldopam.
- Acute Kidney Injury (AKI) is defined as an abrupt loss of kidney function, resulting in the retention of waste products and dysregulation of fluids and electrolytes.
- Definitions and criteria for AKI have evolved over time from RIFLE to AKIN to KDIGO, focusing on increases in creatinine and decreases in urine output.
- AKI has many causes including decreased blood flow, nephrotoxins, and inflammation. It is associated with increased mortality, costs, and long term kidney problems in survivors. Early identification and preventive measures are important.
The document discusses the cardio-renal syndrome, which refers to the bidirectional relationship between heart and kidney dysfunction. It provides several key points:
1) The cardio-renal axis is an important but often underestimated player in cardiovascular disease, as the heart and kidneys regulate many of the same processes and their dysfunction can exacerbate each other.
2) There are different types and definitions of cardio-renal syndrome depending on whether heart or kidney disease initiated or occurred secondarily.
3) Worsening renal function in heart failure is associated with higher mortality and morbidity, though it may simply indicate more severe heart failure rather than having a direct causal relationship.
4) Several studies demonstrate the link
This document discusses emerging biomarkers for the early detection of acute kidney injury (AKI). It notes that AKI affects many hospitalized and ICU patients and is currently diagnosed too late using increases in serum creatinine. Novel biomarkers like neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and kidney injury molecule 1 (KIM-1) can predict and diagnose AKI earlier. NGAL levels measured 2 hours after cardiac surgery or in the emergency department can distinguish AKI and predict outcomes like dialysis need and mortality. Biomarkers may help identify injury location and severity, differentiate AKI from other kidney conditions, and help monitor AKI treatment response. Their early detection of
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L’insufficienza renale nel cirrotico - Gastrolearning®
1. Acute renal failure in patients with cirrhosis
“Gastrolearning”
Padova 8 Aprile 2013
P. Angeli
Unit of Hepatic Emergencies and Liver Transplantation
Dept. of Medicine
University of Padova, Italy
pangeli@unipd.it
2. • Diagnosis of AKI/HRS
• Pharmacological treatment of HRS
Hepatorenal syndrome (HRS)
Topics
4. Phenotypes of renal dysfunction in patients with cirrhosis
AKI in cirrhosis
G. Garcia-Tsao et al. Hepatology 2008 ; 48 : 2064—2077 (modified).
Definition of ARF/AKI = a rapid reduction in kidney function
currently defined as a percentage increase in serum creatinine of more
or equal to 50 % (1.5-fold from baseline) to a final value equal or
higher than 1.5 mg/dl.
Hospitalized patients with cirrhosis
ARF/AKI
(19%)
CKD
(1%)
5. Definition and staging of Acute Kidney Injury (AKI) according to AKIN
criteria
R.L. Mehta et al. Crit. Care 2007 ; 11 : R31.
Definition of AKI = an abrupt (within 48 hours) reduction in kidney function
currently defined as an absolute increase in serum creatinine of more than or
equal to 0.3 mg/dl (≥ 26.4 μmol/l), or a percentage increase in serum
creatinine of more or equal to 50 % (1.5-fold from baseline).
Stage Serum creatinine criteria
1°
Increase in serum creatinine equal or less than 200 % (≤ 2-fold ) from
baseline
2°
Increase in serum creatinine to more than 200% to 300% (> 2- to 3-fold)
from baseline
3°
Increase in serum creatinine to more than 300 % (> 3-fold) from baseline
or serum creatinine of more or equal to 4.0 mg/dl (≥ 354 μmol/l) with an
acute increase of at least 0.5 mg/dl (44 μmol/l) or need for renal
replacement therapy
AKI in cirrhosis
6. Definition
AKI in cirrhosis
Further and larger prospective studies are needed to assess
the ability of new criteria versus the conventional criteria of
renal dysfunction in the prediction of survival in patients
with cirrhosis.
P. Angeli et al. Liver Int. 2012 (Epub ahead of print)
7. Criteria Sensibility
95 % CI
Specificity
95% CI
PPV
95% CI
NPV
95% CI
LR+
95% CI
LR-
95% CI
Conventional criterion 0.5152
(0.33 - 0.69)
0.9450
(0.90 - 0.97)
0.6071
(0.40 - 0.78)
0.9220
(0.87 - 0.95)
9.3664
(4.8 - 18.17)
0.5131
(0.36 - 0.73)
AKIN criteria 0.6667
(0.48 - 0.82)
0.8100
(0.74 - 0.86)
0.3667
(0.24 - 0.50)
0.9364
(0.88 - 0.96)
3.5088
(2.41 - 5.10)
0.4115
( 0.25 - 0.66)
Accuracy of conventional criterion vs AKIN criteria in the precition of
in-hospital mortality in a series of 233 patients with cirrhosis and ascites
S. Piano et al. (J. Hepatol. 2013 ; in press)
Renal failure in cirrhosis
8. Patient survival with the acute kidney injury (AKI) and
non-AKI groups
AKI in cirrhosis
CD. Tsien et al. Gut 2013 ; 62 : 131-137
9. 0
20
40
60
80
100
No AKIN AKI stage 1 AKI stage 2 AKI stage 3
P<0.001
P<0.0001
P<0.0001
P=N.S.
P<0.025
P<0.01
Initial acute Kidney Injury Network (AKIN) stage (panel A) and in-hospital mortality
S. Piano et al. (J. Hepatol. 2013 ; in press)
Serum creatinine < 1.5 mg/dl
Renal failure in cirrhosis
10. Initial Stage 1 (72.1%) Initial Stage 2 (14.8%) Initial Stage 3 (13.1%)
Dynamics of AKI stage after initially fullfilling AKIN criteria (1)
Peak Stage 1 (52.5%)
72.7 %
65.6 %
Peak Stage 2 (16.4%)
11.4 %
Peak Stage 3 (31.2%)
15.9 % 44.4 %
S. Piano et al. (J. Hepatol. 2013 ; in press)
Renal failure in cirrhosis
11. Criteria Sensibility
95 % CI
Specificity
95% CI
PPV
95% CI
NPV
95% CI
LR+
95% CI
LR-
95% CI
Conventional criterion 0.5152
(0.33 - 0.69)
0.9450
(0.90 - 0.97)
0.6071
(0.40 - 0.78)
0.9220
(0.87 - 0.95)
9.3664
(4.8 - 18.17)
0.5131
(0.36 - 0.73)
AKIN criteria 0.6667
(0.48 - 0.82)
0.8100
(0.74 - 0.86)
0.3667
(0.24 - 0.50)
0.9364
(0.88 - 0.96)
3.5088
(2.41 - 5.10)
0.4115
( 0.25 - 0.66)
AKIN with
Progression
0.5455
(0.36 - 0.71)
0.9450
(0.90 - 0.97)
0.6207
(0.42 - 0.79)
0.9265
(0.88 - 0.95)
9.9174
(5.15 - 19.06)
0.4810
(0.33 - 0.70)
Accuracy of conventional criterion vs AKIN criteria in the precition of
in-hospital mortality in a series of 233 patients with cirrhosis and ascites
S. Piano et al. (J. Hepatol. 2013 ; in press)
Renal failure in cirrhosis
12. Non-progressors
(n° = 37)
Progressors
(n° = 16)
P
Age (years) – mean (SD) 67.4 (10.6) 70.4 (7) 0.3707
Gender M/F – n° (%) 20 (54%) / 17 (46%) 8 (50%) / 8 (50%) 1.00
Child Pugh score – median (min-max) 10 (5-14) 10.5 (5-14) 0.9286
MELD score – median (min-max) 19 (9-38) 21 (11-37) 0.5540
Albumin (g/dl) – median (min-max) 2.7 (1.9-4.3) 2.7 (1.8-4.5) 0.8824
Bilirubin (µmol/L) – median (min-max) 63.3 (7.9-477.8) 85.3(8.9-631) 0.5571
Protrombin time (%) – mean (SD) 45.3 (13.9) 48.4 (16.0) 0.3563
Baseline sCr (mg/dl) – median (min-max) 1.1 (0.48-3.0) 1.2 (0.7-2.9) 0.3090
Baseline sCr ≥ 1.5 mg/dl – n (%) 14 (37.8) 5 (31.3) 0.7363
19 (51.4) 15 (93.7)
Bacterial infections – n (%) 24 (64.9) 11 (68.8) 1.000
Leukocyte counts el/µl – median (min-max) 6,500 (1,240-18,480)
6,170 (2,750-
13,570)
0.9764
Characteristics of patients with and without progression of initial stage of Acute
Kidney Injury (AKI) according to the Acute Kidney Injury Network criteria
(AKIN)
S. Piano et al. (J. Hepatol. 2013 ; in press)
0.0041sCr ≥ 1.5 mg/dl at diagnosis of AKI –n (%)
Renal failure in cirrhosis
13. %
0
20
40
60
80
100
sCr < 1.5 mg/dl sCr > 1.5 mg/dl-
Probability of AKIN stage progression according to the cut off
of 1.5 of serum creatinine (sCr)
S. Piano et al. (J. Hepatol. 2013 ; in press)
p < 0.01
Renal failure in cirrhosis
14. Initial Stage 1 (72.1%) Initial Stage 2 (14.8%) Initial Stage 3 (13.1%)
Dynamics of AKI stage after initially fullfilling AKIN criteria (2)
Peak Stage 1 (52.5%)
72.7 % 65.6 %
Peak Stage 2 (16.4%)
11.4 %
Peak Stage 3 (31.2%)
15.9 % 44.4 %
S. Piano et al. (J. Hepatol. 2013 ; in press)
Resolution
62.5 % 36.8 %40 %
Renal failure in cirrhosis
15. %
0
20
40
60
80
100
sCr < 1.5 mg/dl sCr > 1.5 mg/dl-
Probability of AKIN 1 stage regression accordind to the cut off
of 1.5 of serum creatinine (sCr)
S. Piano et al. (J. Hepatol. 2013 ; in press)
p < 0.01
Renal failure in cirrhosis
16. Proposal of an algorithm for AKI management
Withdrawal of diuretics (if not
yet applied) and volume
expansion with albumin
(1g/kg) for 2 days
Initial AKI# stage 1 and sCr ≥ 1.5
mg/dl° or initial AKI# stage > 1
Initial AKI# stage 1 and sCr < 1.5
mg/dl°
° = sCr at the first fulfilling of AKIN crieria
#= AKI at the first fulfilling of AKIN crieria
* Treatment of SBP includes albumin infusion
Close monitoring
Remove risk factors (withdrawal of nephrotoxic
drugs, vasodilators and NSADs, taper/withdraw
diuretics treat infections*when diagnosed)
Progression ?
NO
Close follow up
YES
Response ?
YES NO
Does AKI Meet criteria of HRS ?
Specific treatment for
other AKI phenotypes
NO
Terlipressin and
albumin
YES
S. Piano et al. (J. Hepatol. 2013 ; in press)
Renal failure in cirrhosis
17. • The acceptance of the main point that derived from the
application of AKIN criteria that is to focus attention on and
to manage promptly even small increases in sCr.
• A clear dinstinction between AKI and hepatorenal
syndrome (which is only one of the possible phenotypes of
AKI)
• A more rationale application of the therapeutic resources
(avoiding of potentially dangerous consequences of an
overtreatment of AKI as a consequence of an uncritical
application of the AKIN criteria)
• The definitive removal of any cut off of serum creatinine
from the criteria for diagnosis of HRS
Clinical consequences of our proposal of an algorithm
for AKI management
S. Piano et al. (J. Hepatol. 2013 ; in press)
Renal failure in cirrhosis
18. Proposal of an algorithm for AKI management
Withdrawal of diuretics (if not
yet applied) and volume
expansion with albumin
(1g/kg) for 2 days
Initial AKI# stage 1 and sCr ≥ 1.5
mg/dl° or initial AKI# stage > 1
Initial AKI# stage 1 and sCr < 1.5
mg/dl°
° = sCr at the first fulfilling of AKIN crieria
#= AKI at the first fulfilling of AKIN crieria
* Treatment of SBP includes albumin infusion
Close monitoring
Remove risk factors (withdrawal of nephrotoxic
drugs, vasodilators and NSADs, taper/withdraw
diuretics treat infections*when diagnosed)
Progression ?
NO
Close follow up
YES
Response ?
YES NO
Does AKI Meet criteria of HRS ?
Specific treatment for
other AKI phenotypes
NO
Terlipressin and
albumin
YES
S. Piano et al. (J. Hepatol. 2013 ; in press)
Renal failure in cirrhosis
22. Hepatorenal syndrome (HRS)
Cumulative probability of survival during therapy of patients treated
with noradrenaline and terlipressin
V. Singh et al. J. Hepatol. 2012 ; 56 : 1293–1298
24. Patients with response to treatment
Hepatorenal syndrome (HRS)
0
20
40
60
80
100
Group A (Terlipressin) Group B (Midodrine + Octreotide)
All responders Full responders
% P < 0.01
75.0
25.0
P < 0.01
54.2
8.3
M. Cavallin et. al. (manuscript in preparation)
25. Pharmacologic therapy for HRS
• Albumin (20-40 g/day intravenously)
• Terlipressin (0.5-2 mg/4-6hr intravenously)
J. Uriz et al. J. Hepatol. 2000 ; 33 : 43-48.
Hepatorenal syndrome (HRS)
26. The facts
• Vasoconstrictors and albumin are effective in
less of 50 % of patients with type 1 HRS.
• Vasoconstrictor and albumin improve survival
slightly.
• Vasoconsctrictors and albumin can not be
used in all patients with type 1 HRS.
• In up to 25 % of patients the treatment should
be discontinued for adverse effects.
• High cost of treatment.
Hepatorenal syndrome (HRS)
P. Angeli et al. Liver Int. 2012 (Epub ahead of print)
28. HRS is a functional renal failure caused by intrarenal
vasoconstriction which occurs in patients with end stage liver
disease as well as in patients with acute liver failure or alcoholic
hepatitis.
HRS is characterized by impaired renal function, marked
alterations in cardiovascular function, and overactivity in the
endogenous vasoactive systems.
Hepatorenal syndrome (HRS)
Definition of HRS
F. Salerno et al. Gut 2007 ; 56 : 1310-1318.
29. CKD AKI
Serum creatinine > 1.5 mg/dl for ≥ 3 months
/type 2 HRS* /type 1 HRS*
* Proteinuria < 0.5 g/l and no hematuria
Hepatorenal syndrome (HRS)
JM. Trawale et al. Liver Int. 2010 ; 30 : 725-732.
32. 0
100
200
300
400
no HRS HRS
NGAL urinary levels in patients with cirrhosis and
ascites according to the diagnosis of type 1 HRS
M. Cavallin at al. AASLD 2011
P < 0.025
(ng/ml)
Hepatorenal syndrome (HRS)
Instrinsic AKI
*
*
*
*
** *
*
*
*
*
*
*
*
*
*
*
*
**
*
** *
E. Singer et al. Kidney Int. 2011 ; 80 : 405-414
33. 0
100
200
300
400
500
Full responders Partial or non responders
p < 0.0025
M. Cavallin. et. al. AASLD 2011
NGAL urinary levels in patients with type 1 HRS
according to the response to terlipressin and albumin
(ng/ml)
Hepatorenal syndrome (HRS)
34. The ratio of urinary excretion of γ-glutamyltranspeptidase
to glomerular filtration rate in patients with type 1 HRS
treated with vasonsctrictors and albumin
0
100
200
300
400
500
* = P < 0.05 ; ** = P < 0.025
*
**
*
B D5 D10 B D5 D10
Nonresponders Responders
D20
P. Angeli et al. Hepatology 1999 ; 29 : 1690-1697.
Normal range
Hepatorenal syndrome (HRS)
35. Peripheral arterial vasodilation “hypothesis”
Portal hypertension/liver failure
Reduction of effective circulating volume
Severe renal arterial vasoconstriction
Maximal activation of
endogenous vasocontrictor systems
RW. Schrier, et al. Hepatology 1988 ; 8 : 1151-1157 (revised)
Increased release of NO, CO
and other vasodilators
Splanchnic arterial vasodilationTerlipressin
Albumin
Hepatorenal syndrome (HRS)
36. Hepatorenal syndrome (HRS)
HRS after SBP
resolution
No HRS after SBP
resolution
P
MAP (mm Hg) 73±8 83±8 < 0.025
SVR (dyn sec/cm ) 1268±320 968±226 N.S.
Plasma NE (pg/ml) 1290.5±415.3 317.±195.3 <.025
CO (l/min) 4.6±0.7 6.8±2.0 < 0.01
RAP (mm Hg) 4.6±2.7 4.1±1.7 N.S.
PCWP (mm Hg) 7.4 ±2.6 7.0±2.3 N.S.
HR (bpm) 87±9 79±16 N.S.
5
Systemic heamodynamics before and after the onset of HRS after the
resolution of SBP
L. Ruiz-del-Arbol et. al. Hepatology 2003 ; 38 : 1210-1218
37. Baseline
At the diagnosis of
HRS
P
MAP (mm Hg) 80±9
75±7
< 0.001
HVPG (mm Hg) 19.5±3.0
20.0±4.0
< 0.005
SVR (dyn sec/cm ) 1158±285 1096±327 N.S.
CO (l/min) 6.0±1.2 5.4±1.3 < 0.001
RAP (mm Hg) 6.9±2.6
5.7±2.2
< 0.05
PCWP (mm Hg) 9.2 ±2.6
7.5±2.6
< 0.001
Systemic heamodynamics before and after the onset of type 1 HRS in
patients with cirrhosis and ascites without a precipitating factor
L. Ruiz-del-Arbol et. al. Hepatology 2005 ; 62 : 439-447.
5
Hepatorenal syndrome (HRS)
38. Peripheral arterial vasodilation “hypothesis” (revised)
Portal hypertension/liver failure
Reduction of effective circulating volume
Severe renal arterial vasoconstriction
Maximal activation of
endogenous vasocontrictor systems
RW. Schrier et al. Hepatology 1988 ; 8 : 1151-1157 (revised)
Increased release of NO, CO
and other vasodilators
Splanchnic arterial vasodilation Reduced cardiac output
?
Hepatorenal syndrome (HRS)
39. Hepatorenal syndrome (HRS)
Y. Narahara et al. J. Gastroenterol. Hepatol. 2009 ; 24 : 1791-1797
Parameter Baseline
After
terlipressin
P
Heart rate (bpm) 83 ± 16 72 ± 16 < 0.005
Mean arterial pressure (mm Hg) 89 ± 11 105 ± 14 < 0.005
Systemic vascular resistance (dynes/s · cm5
) 1295 ±293 1653 ± 465 < 0.005
Cardiac output (l/min) 5.2 ± 1.0 4.9 ± 1.1 < 0.05
Pulmunary capillary wedged pressure
(mm Hg)
9.6 ± 3.1 12.3 ± 2.6 < 0.005
Systemic hemodynamics at baseline and 30 min. after terlipressin in patients
with cirrhosis and ascites
40. Hepatorenal syndrome (HRS)
Parameter
Contrl
subjects
(n° = 46)
Patients with
cirrhosis and
without
ascites (n° =
36)
Patients with
cirrhosis and
responsive
ascites
(n° = 31)
Patients with
cirrhosis and
refractory
ascites
(n° = 46)
Heart rate (beat/min) 67±10 70±10 68±11 78±13*#
Mean arterial pressure
(mm Hg)
97±7 99±10 96±11 87±9*##
Systemic vasciular
resistance (din s/cm5
m2
)
3371±648 2925±641*** 2860±776*** 2439±573***#
Stroke volume (ml/beat) 64±10 75±12** 77±11** 73±17**
Cardiac output (L/min) 4.27±0.80 5.28±1.11*** 5.29±1.42*** 5.60±1.50***
Systemic hemaodynamics according to the stage of cirrhosis
* = p < 0.01 ; ** = p < 0.001 ; *** = p < 0.001 versus control subjects ; # = p < 0.05 ; ## = < 0.001 versus
other groups of patients with cirrhosis
M. Cesari et al. (manuscript submitted)
41. Cardiac output in cirrhotic patients according to the Child-
Pugh-Turcotte class
3000
6000
9000
12000
15000
Class A Class B Class C
Basal After i.v. albumin (40 g)
K. Brinch et al. J. Hepatol. 2003 ; 39 : 24-31
* = P < 0.025
* *
(ml/min)
* ** * = P < 0.01
Hepatorenal syndrome (HRS)
42. 0
5
10
15
20
P < 0.005
Overall transvascular transport of albumin in
cirrhosis
J. H. Henriksen et al. J. Hepatol. 2001 ; 34 : 53-60.
Controls Cirrhotics
with ascites
Cirrhotics
with refractory ascites
P < 0.01
(% IVM • h )-1
Hepatorenal syndrome (HRS)
43. Effects of albumin on cardiac contractility in cirrhotic rats
-10.0 -9.5 -9.0 -8.5 -8.0
0
5
10
15
20
25
∆LVDP(mmHg)
Control
Cirrhotic
Log . Isoproterenol
Cirrhotic + albumin
* = P < 0.01
*
*
Cirrhotic + starch
Hepatorenal syndrome (HRS)
A. Bortoluzzi et al. Hepatology 2013 ; 57 : 266-276
46. 0
0,5
1
1,5
2
control rats treated with V control rats treated with A
rats with cirrhosis treated with V rats with cirrhosis treated with A
Membrane/cytosolratio
(foldofincrease)
*p <0.05 vs controls ; # = p <0.05 vs rats with cirrhosis
treated with V
*
#
p47-phox Rac-1
*
#
Effects of albumin on the NADH/NADPH oxidase in the cardiac
tissue according to treatment with saline (V) or albumin (A)
Hepatorenal syndrome (HRS)
A. Bortoluzzi et al. Hepatology 2013 ; 57 : 266-276
48. 0
0,2
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
Control rats treated
with V
Control rats treated
with A
Rats with cirrhosis
treated with V
Rats with cirrhosis
treated with A
Foldofincrease
*
#
* p<0.05 vs control rats # p<0.05 vs rats with cirrhosis treated with V
Levels of NF-kB traslocation in the cardiac tissue according to
treatment with saline (V) or with albumin (A)
Hepatorenal syndrome (HRS)
A. Bortoluzzi et al. Hepatology 2013 ; 57 : 266-276
49. Proteinexpression
(foldofincrease)
*
#
* p<0.05 vs controls
Effects of albumin on TNF-α protein expression in the cardiac
tissue according to treatment with saline (S) or albumin (A)
# p<0.05 vs rats with cirrhosis treated with A
0
0,5
1
1,5
2
2,5
Control rats treated
with S
Control rats treated
with A
Rats with cirrhosis
treated with S
Rats with cirrhosis
treated with A
Hepatorenal syndrome (HRS)
A. Bortoluzzi et al. Hepatology 2013 ; 57 : 266-276
50. Proteinexpression
(foldofincrease)
*
#
* p<0.05 vs controls
Effects of albumin on iNos protein expression in the cardiac
tissue according to treatment with saline (S) or albumin (A)
# p<0.05 vs rats with cirrhosis treated with A
0
0,5
1
1,5
2
2,5
Control rats treated
with S
Control rats treated
with A
Rats with cirrhosis
treated with S
Rats with cirrhosis
treated with A
Hepatorenal syndrome (HRS)
A. Bortoluzzi et al. Hepatology 2013 ; 57 : 266-276
53. * = p < 0.01 vs controll
Effects of albumin on β-adgrenergic signaling in cardiac tissue according to
treatement with saline (V) or albumin (A)
0
0,5
1
1,5
2
2,5
β1 β2 Adcy3 Gαi2
control rats treated with V control rats treated with A
rats with cirrhosis treated with V rats with cirrhosis treated with A
*
*
*
*
# #
* p<0.05 vs controls ; # p<0.05 vs ascites with saline
Geneexpression
(Foldofincrease)
*
*
Hepatorenal syndrome (HRS)
A. Bortoluzzi et al. Hepatology 2013 ; 57 : 266-276
56. Response to tretament (%) according to the baseline serum
creatinine value
0
10
20
30
40
50
60
3.0 mg/dl < 3 - 5 mg/dl > 5.0 mg/dl
TD. Boyer et al. J. Hepatol. 2011 ; 55 ; 315-321.
%
MANAGEMENT OF RENAL DYSFUNCTION IN PATIENTS WITH CIRRHOSIS
57. Summary
• The application of conventional criterion is more accurate than a formal
application of AKIN criteria in the prediction of in-hospital mortality in
patients with cirrhosis and ascites.
• Nevertheless, the addition of either the progression of AKIN stage or the cut-
off of serum creatinine ≥1.5 mg/dl, to the AKIN improves their prognostic
accuracy in these patients .
• The potential effects of implementation of the conventional criterion with the
most innnovative aspects of AKIN criteria, should be tested by interventional
clinical trials in the next future.
• Terlipressin and albumin are effective in patients with type 1 HRS.
• Noradrenalin and albumin but not midodrine, octreotide and albumin can
represent an alternative in the treatment of type 1 HRS.
• Some of the limits of the treatment with terlipressin and albumin may be
related to the fact that HRS may not be completely functional in nature
and/or to the fact that the global effect of the treatment on cardiac output
may be negative in some patients.
Hepatorenal syndrome (HRS)
P. Angeli et al. Liver Int. 2013 ; 33 : 16-23