Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole ...Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context.In the absence of established heart disease,cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease.It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities.Despite the clinical description of these potential cardiac-related complications of the liver,the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS.Yet from a physiological sense,temporality(prior onset)of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients.In this review,we discuss current concepts surrounding how the heart may influence the development and progression of HRS,and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting.The temporality of heart and kidney dysfunction in HRS will be discussed.For a subgroup of patients who receive portosystemic shunting,the dynamics of cardiorenal interactions following treatment is reviewed.Continued research to determine the unknowns in this topic is anticipated,hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.展开更多
BACKGROUND Hypertension is commonly observed in patients living with chronic kidney disease(CKD).Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship b...BACKGROUND Hypertension is commonly observed in patients living with chronic kidney disease(CKD).Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD.There remains variability in antihypertensive treatment practices.AIM To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD patients.METHODS The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since 2002.All patients are followed up annually,and their medical records including the list of medications are updated until they reach study endpoints[starting on renal replacement therapy or reaching estimated glomerular filtration rate(eGFR)expressed as mL/min/1.73 m2≤10 mL/min/1.73 m2,or the last follow-up date,or data lock on December 31,2021,or death].Data on antihypertensive prescription practices in correspondence to baseline eGFR,urine albumin-creatinine ratio,primary CKD aetiology,and cardiovascular disease were evaluated.Associations between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression analysis.Kaplan-Meier analysis demonstrated differences in survival probabilities.RESULTS Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were included.The median age was 65 years.A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages(53%of eGFR≤15 mL/min/1.73 m2 vs 26%of eGFR≥60 mL/min/1.73 m2,P<0.001).An increased number of patients receiving more classes of antihypertensive agents was observed as the urine albumin-creatinine ratio category increased(category A3:62%vs category A1:40%,P<0.001),with the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system blockers.The prescription of three or more antihypertensive agents was associated with all-cause mortality,independent of blood pressure control(hazard ratio:1.15;95%confidence interval:1.04-1.27,P=0.006).Kaplan-Meier analysis illustrated significant differences in survival outcomes between patients with three or more and those with less than three antihypertensive agents prescribed(log-rank,P<0.001).CONCLUSION Antihypertensive prescribing patterns in the Salford Kidney Study based on CKD stage were consistent with expectations from the current United Kingdom National Institute of Health and Care Excellence guideline algorithm.Outcomes were poorer in patients with poor blood pressure control despite being on multiple antihypertensive agents.Continued research is required to bridge remaining variations in hypertension treatment practices worldwide.展开更多
BACKGROUND Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)can result in clinically significant multi-system disease including involvement in the kidney.The underlying histopathological processes were unkno...BACKGROUND Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)can result in clinically significant multi-system disease including involvement in the kidney.The underlying histopathological processes were unknown at the start of the pandemic.As case reports and series have been published describing the underlying renal histopathology from kidney biopsies,we have started to gain an insight into the renal manifestations of this novel disease.AIM To provide an overview of the current literature on the renal histopathological features and mechanistic insights described in association with coronavirus disease 2019(COVID-19)infection.METHODS A systematic review was performed by conducting a literature search in the following websites-‘PubMed’,‘Web of Science’,‘Embase’and‘Medline-ProQuest’with the following search terms-“COVID-19 AND kidney biopsy”,“COVID-19 AND renal biopsy”,“SARS-CoV-2 AND kidney biopsy”and“SARS-CoV-2 AND renal biopsy”.We have included published data up until February 15,2021,which includes kidney biopsies(native,transplant and postmortem)from patients with COVID-19.Data on clinical presentation,histopathological features,management and outcome was extracted from the reported studies.RESULTS The total number of biopsies reported on here is 288,of which 189 are postmortem,84 native and 15 transplants.The results are varied and show underlying pathologies ranging from collapsing glomerulopathy and acute tubular injury(ATI)to anti-nuclear cytoplasmic antibody associated vasculitis and pigment nephropathy.There was variation in the specific treatment used for the various renal conditions,which included steroids,hydroxychloroquine,eculizumab,convalescent plasma,rituximab,anakinra,cyclophosphamide and renal replacement therapy,amongst others.The pathological process which occurs in the kidney following COVID-19 infection and leads to the described biopsy findings has been hypothesized in some conditions but not others(for example,sepsis related hypoperfusion for ATI).It is important to note that this represents a very small minority of the total number of cases of COVID-19 related kidney disease,and as such there may be inherent selection bias in the results described.Further work will be required to determine the pathogenetic link,if any,between COVID-19 and the other renal pathologies.CONCLUSION This report has clinical relevance as certain renal pathologies have specific management,with the implication that kidney biopsy in the setting of renal disease and COVID-19 should be an early consideration,dependent upon the clinical presentation.展开更多
Coronavirus disease 2019(COVID-19)is a highly infectious disease which emerged into a global pandemic.Although it primarily causes respiratory symptoms for affected patients,COVID-19 was shown to have multi-organ mani...Coronavirus disease 2019(COVID-19)is a highly infectious disease which emerged into a global pandemic.Although it primarily causes respiratory symptoms for affected patients,COVID-19 was shown to have multi-organ manifestations.Elevated liver enzymes appear to be commonly observed during the course of COVID-19,and there have been numerous reports of liver injury secondary to COVID-19 infection.It has been established that patients with pre-existing chronic liver disease(CLD)are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD.Co-morbidities such as diabetes,hypertension,obesity,cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD,and a substantial population may also live with some degree of frailty.The mechanisms of how COVID-19 induces liver injury have been postulated.Hepatorenal syndrome(HRS)is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause,and is usually a marker of severe decompensated liver disease.Select reports of HRS following acute COVID-19 infection have been presented,although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data.Evidence discussing the management of HRS in highdependency care and intensive care contexts is only emerging.In this article,we provide an overview on the speculative pathophysiological me-chanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.展开更多
文摘Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context.In the absence of established heart disease,cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease.It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities.Despite the clinical description of these potential cardiac-related complications of the liver,the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS.Yet from a physiological sense,temporality(prior onset)of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients.In this review,we discuss current concepts surrounding how the heart may influence the development and progression of HRS,and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting.The temporality of heart and kidney dysfunction in HRS will be discussed.For a subgroup of patients who receive portosystemic shunting,the dynamics of cardiorenal interactions following treatment is reviewed.Continued research to determine the unknowns in this topic is anticipated,hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.
基金the National Institute of Health Research Manchester Biomedical Research Centre for their funding support in the SKS(NIHR203308).
文摘BACKGROUND Hypertension is commonly observed in patients living with chronic kidney disease(CKD).Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD.There remains variability in antihypertensive treatment practices.AIM To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD patients.METHODS The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since 2002.All patients are followed up annually,and their medical records including the list of medications are updated until they reach study endpoints[starting on renal replacement therapy or reaching estimated glomerular filtration rate(eGFR)expressed as mL/min/1.73 m2≤10 mL/min/1.73 m2,or the last follow-up date,or data lock on December 31,2021,or death].Data on antihypertensive prescription practices in correspondence to baseline eGFR,urine albumin-creatinine ratio,primary CKD aetiology,and cardiovascular disease were evaluated.Associations between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression analysis.Kaplan-Meier analysis demonstrated differences in survival probabilities.RESULTS Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were included.The median age was 65 years.A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages(53%of eGFR≤15 mL/min/1.73 m2 vs 26%of eGFR≥60 mL/min/1.73 m2,P<0.001).An increased number of patients receiving more classes of antihypertensive agents was observed as the urine albumin-creatinine ratio category increased(category A3:62%vs category A1:40%,P<0.001),with the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system blockers.The prescription of three or more antihypertensive agents was associated with all-cause mortality,independent of blood pressure control(hazard ratio:1.15;95%confidence interval:1.04-1.27,P=0.006).Kaplan-Meier analysis illustrated significant differences in survival outcomes between patients with three or more and those with less than three antihypertensive agents prescribed(log-rank,P<0.001).CONCLUSION Antihypertensive prescribing patterns in the Salford Kidney Study based on CKD stage were consistent with expectations from the current United Kingdom National Institute of Health and Care Excellence guideline algorithm.Outcomes were poorer in patients with poor blood pressure control despite being on multiple antihypertensive agents.Continued research is required to bridge remaining variations in hypertension treatment practices worldwide.
文摘BACKGROUND Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)can result in clinically significant multi-system disease including involvement in the kidney.The underlying histopathological processes were unknown at the start of the pandemic.As case reports and series have been published describing the underlying renal histopathology from kidney biopsies,we have started to gain an insight into the renal manifestations of this novel disease.AIM To provide an overview of the current literature on the renal histopathological features and mechanistic insights described in association with coronavirus disease 2019(COVID-19)infection.METHODS A systematic review was performed by conducting a literature search in the following websites-‘PubMed’,‘Web of Science’,‘Embase’and‘Medline-ProQuest’with the following search terms-“COVID-19 AND kidney biopsy”,“COVID-19 AND renal biopsy”,“SARS-CoV-2 AND kidney biopsy”and“SARS-CoV-2 AND renal biopsy”.We have included published data up until February 15,2021,which includes kidney biopsies(native,transplant and postmortem)from patients with COVID-19.Data on clinical presentation,histopathological features,management and outcome was extracted from the reported studies.RESULTS The total number of biopsies reported on here is 288,of which 189 are postmortem,84 native and 15 transplants.The results are varied and show underlying pathologies ranging from collapsing glomerulopathy and acute tubular injury(ATI)to anti-nuclear cytoplasmic antibody associated vasculitis and pigment nephropathy.There was variation in the specific treatment used for the various renal conditions,which included steroids,hydroxychloroquine,eculizumab,convalescent plasma,rituximab,anakinra,cyclophosphamide and renal replacement therapy,amongst others.The pathological process which occurs in the kidney following COVID-19 infection and leads to the described biopsy findings has been hypothesized in some conditions but not others(for example,sepsis related hypoperfusion for ATI).It is important to note that this represents a very small minority of the total number of cases of COVID-19 related kidney disease,and as such there may be inherent selection bias in the results described.Further work will be required to determine the pathogenetic link,if any,between COVID-19 and the other renal pathologies.CONCLUSION This report has clinical relevance as certain renal pathologies have specific management,with the implication that kidney biopsy in the setting of renal disease and COVID-19 should be an early consideration,dependent upon the clinical presentation.
文摘Coronavirus disease 2019(COVID-19)is a highly infectious disease which emerged into a global pandemic.Although it primarily causes respiratory symptoms for affected patients,COVID-19 was shown to have multi-organ manifestations.Elevated liver enzymes appear to be commonly observed during the course of COVID-19,and there have been numerous reports of liver injury secondary to COVID-19 infection.It has been established that patients with pre-existing chronic liver disease(CLD)are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD.Co-morbidities such as diabetes,hypertension,obesity,cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD,and a substantial population may also live with some degree of frailty.The mechanisms of how COVID-19 induces liver injury have been postulated.Hepatorenal syndrome(HRS)is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause,and is usually a marker of severe decompensated liver disease.Select reports of HRS following acute COVID-19 infection have been presented,although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data.Evidence discussing the management of HRS in highdependency care and intensive care contexts is only emerging.In this article,we provide an overview on the speculative pathophysiological me-chanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.
