BACKGROUND Bile cast nephropathy(BCN)is suspected in the setting of liver disease and hyperbilirubinemia and is characterized by the formation of tubular bile casts and acute tubular injury.While postmortem studies re...BACKGROUND Bile cast nephropathy(BCN)is suspected in the setting of liver disease and hyperbilirubinemia and is characterized by the formation of tubular bile casts and acute tubular injury.While postmortem studies reveal a high prevalence of BCN,little is known about this orphan acute kidney injury syndrome.AIM To address this knowledge gap,we performed a systematic review of case reports and case series of BCN,focusing on risk factors,diagnostic criteria,clinical presentation,kidney biopsy findings,severity,treatment approaches,and outcomes.METHODS Electronic databases were searched to identify eligible studies of patients with possible,probable,or definite BCN,using pre-established criteria.Relevant variables were extracted and analyzed.We explored the impact of serum total bilirubin levels and alcoholic liver disease on BCN severity and outcomes by stratifying cases into total bilirubin tertiles and alcoholic vs non-alcoholic liver disease.Univariate and multivariable logistic regression analyses were used to examine factors associated with the composite outcome of dialysis requirement or death.RESULTS Sixty-seven case reports and six case series(involving 2 patients each)met the inclusion criteria,totaling 79 cases of BCN.The mean age was 48.3 years,and 83.5%were men.The most common cause of liver disease was drug-induced injury(30.4%),followed by infection(18.9%)and alcoholism(12.7%).BCN diagnosis was deemed definite,probable,and possible in 65.8%,32.9%,and 1.3%of cases,respectively.Levels of serum creatinine,dialysis requirement,and renal recovery did not differ among the total bilirubin tertile groups.However,both initial and peak serum creatinine were significantly higher in the alcoholic liver disease group compared to the non-alcoholic group(P=0.011 and P=0.012,respectively).There was also a non-significant trend toward a higher incidence of dialysis requirement or death in the alcoholic liver disease group(80%vs 52%,P=0.098).Finally,higher initial serum creatinine(per 1 mg/dL increase)was independently associated with dialysis requirement or death(adjusted odds ratio 1.291,95%confidence interval:1.032-1.615,P=0.025).CONCLUSION BCN is a common and potentially serious cause of acute kidney injury in patients with liver disease.The degree of hyperbilirubinemia does not appear to correlate with BCN severity or outcomes.However,in alcoholic liver disease,BCN is associated with a greater rise in serum creatinine and a trend toward worse outcomes compared to non-alcoholic liver disease.Serum creatinine may be a valuable predictor of BCN prognosis.Further studies are needed to develop non-invasive diagnostic tools and establish effective treatments for BCN.展开更多
Background and aim:Cholestasis-associated renal injury or cholemic nephropathy(CN)is a serious clinical problem.Previous studies mentioned that oxidative stress and mitochondrial impairment play a role in CN.There is ...Background and aim:Cholestasis-associated renal injury or cholemic nephropathy(CN)is a serious clinical problem.Previous studies mentioned that oxidative stress and mitochondrial impairment play a role in CN.There is no specific pharmacological intervention for CN.Metformin is an anti-diabetic drug administered for decades.On the other hand,novel pharmacological properties have emerged for this drug.The effect of metformin on oxidative stress parameters has been well-recognized in different experimental models.It has also been found that metformin positively affected mitochondrial function.The current study aimed to evaluate the effects of metformin in an animal model of CN.Methods:Rats underwent bile duct ligation(BDL)and were treated with metformin(250 and 500 mg/kg)for 14 consecutive days.Two weeks after the BDL operations,urine,serum,and kidney samples were collected and analyzed.Results:Markers of oxidative stress,including reactive oxygen species(ROS)formation,lipid peroxida-tion,protein carbonylation,depleted antioxidant capacity,and decreased glutathione(GSH)levels were detected in BDL animals.Moreover,mitochondrial indices,including adenosine triphosphate(ATP)level,dehydrogenase activity,mitochondrial membrane potential,and mitochondrial permeability,were impaired in the kidney of cholestatic rats.Renal histopathological alterations in cholestatic animals included tubular degeneration and interstitial inflammation,cast formation,and fibrosis.It was found that metformin significantly alleviated oxidative stress and improved mitochondrial indices in the kidney of cholestatic rats.Tissue histopathological alterations were also mitigated in metformin-treated groups.Conclusions:Metformin could be a candidate for managing CN.The nephroprotective role of metformin is primarily associated with its effects on oxidative stress parameters and mitochondrial function.展开更多
文摘BACKGROUND Bile cast nephropathy(BCN)is suspected in the setting of liver disease and hyperbilirubinemia and is characterized by the formation of tubular bile casts and acute tubular injury.While postmortem studies reveal a high prevalence of BCN,little is known about this orphan acute kidney injury syndrome.AIM To address this knowledge gap,we performed a systematic review of case reports and case series of BCN,focusing on risk factors,diagnostic criteria,clinical presentation,kidney biopsy findings,severity,treatment approaches,and outcomes.METHODS Electronic databases were searched to identify eligible studies of patients with possible,probable,or definite BCN,using pre-established criteria.Relevant variables were extracted and analyzed.We explored the impact of serum total bilirubin levels and alcoholic liver disease on BCN severity and outcomes by stratifying cases into total bilirubin tertiles and alcoholic vs non-alcoholic liver disease.Univariate and multivariable logistic regression analyses were used to examine factors associated with the composite outcome of dialysis requirement or death.RESULTS Sixty-seven case reports and six case series(involving 2 patients each)met the inclusion criteria,totaling 79 cases of BCN.The mean age was 48.3 years,and 83.5%were men.The most common cause of liver disease was drug-induced injury(30.4%),followed by infection(18.9%)and alcoholism(12.7%).BCN diagnosis was deemed definite,probable,and possible in 65.8%,32.9%,and 1.3%of cases,respectively.Levels of serum creatinine,dialysis requirement,and renal recovery did not differ among the total bilirubin tertile groups.However,both initial and peak serum creatinine were significantly higher in the alcoholic liver disease group compared to the non-alcoholic group(P=0.011 and P=0.012,respectively).There was also a non-significant trend toward a higher incidence of dialysis requirement or death in the alcoholic liver disease group(80%vs 52%,P=0.098).Finally,higher initial serum creatinine(per 1 mg/dL increase)was independently associated with dialysis requirement or death(adjusted odds ratio 1.291,95%confidence interval:1.032-1.615,P=0.025).CONCLUSION BCN is a common and potentially serious cause of acute kidney injury in patients with liver disease.The degree of hyperbilirubinemia does not appear to correlate with BCN severity or outcomes.However,in alcoholic liver disease,BCN is associated with a greater rise in serum creatinine and a trend toward worse outcomes compared to non-alcoholic liver disease.Serum creatinine may be a valuable predictor of BCN prognosis.Further studies are needed to develop non-invasive diagnostic tools and establish effective treatments for BCN.
基金This work was financially supported by the Vice-Chancellor of Research Affairs of Shiraz University of Medical Sciences,Shiraz,Iran(Grant No.19444).
文摘Background and aim:Cholestasis-associated renal injury or cholemic nephropathy(CN)is a serious clinical problem.Previous studies mentioned that oxidative stress and mitochondrial impairment play a role in CN.There is no specific pharmacological intervention for CN.Metformin is an anti-diabetic drug administered for decades.On the other hand,novel pharmacological properties have emerged for this drug.The effect of metformin on oxidative stress parameters has been well-recognized in different experimental models.It has also been found that metformin positively affected mitochondrial function.The current study aimed to evaluate the effects of metformin in an animal model of CN.Methods:Rats underwent bile duct ligation(BDL)and were treated with metformin(250 and 500 mg/kg)for 14 consecutive days.Two weeks after the BDL operations,urine,serum,and kidney samples were collected and analyzed.Results:Markers of oxidative stress,including reactive oxygen species(ROS)formation,lipid peroxida-tion,protein carbonylation,depleted antioxidant capacity,and decreased glutathione(GSH)levels were detected in BDL animals.Moreover,mitochondrial indices,including adenosine triphosphate(ATP)level,dehydrogenase activity,mitochondrial membrane potential,and mitochondrial permeability,were impaired in the kidney of cholestatic rats.Renal histopathological alterations in cholestatic animals included tubular degeneration and interstitial inflammation,cast formation,and fibrosis.It was found that metformin significantly alleviated oxidative stress and improved mitochondrial indices in the kidney of cholestatic rats.Tissue histopathological alterations were also mitigated in metformin-treated groups.Conclusions:Metformin could be a candidate for managing CN.The nephroprotective role of metformin is primarily associated with its effects on oxidative stress parameters and mitochondrial function.
