Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prio...Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prion protein.These diseases can be spontaneous,heritable,anthropogenic/iatrogenic,or in some cases horizontally transmissible,and include such notable TSEs as bovine spongiform encephalopathy(BSE)of cattle and chronic wasting disease(CWD)of cervids.Although they are both unequivocally protein misfolding disorders,they differ markedly in their pathogenesis,transmissibility,and zoonotic potential.While the BSE epidemic has largely abated over the past three decades following global feed bans on ruminant meat and bone meal,CWD,which is readily transmitted through various forms of excreta,has rapidly expanded from its original endemic zone to encompass much of North America,along with recently identified foci in Scandinavia.Most importantly,although the classical form of BSE has proven transmissible to humans consuming contaminated beef or beef products,so far there have been no conclusive reports on the zoonotic transmission of cWD to humans.The underlying basis for these differences-whether host or agent directed-are not well understood,though may be due to inherent differences in the three-dimensional structure of the misfolded BSE or CWD prion proteins or the expression levels and tissue distribution of respective cellular prion proteins.With the uncontrolled geographic spread of CWD,it is imperative that we improve our understanding of the factors governing prion disease pathogenesis,transmission,and zoonotic potential.展开更多
This treatise of chronic kidney disease (CKD) describes association of hypertension, diabetes and congestive heart failure (CHF) with CKD. CKD is defined by estimated glomerular filtration rate (eGFR) of less than 60 ...This treatise of chronic kidney disease (CKD) describes association of hypertension, diabetes and congestive heart failure (CHF) with CKD. CKD is defined by estimated glomerular filtration rate (eGFR) of less than 60 ml/min for three months or more. CKD is generally irreversible but not necessarily progressive. Thus progression of CKD into end stage renal disease (ESRD) is the concern here and what can be done to reduce the progression of CKD. Exact data of CKD with progression are unavailable but high incidence of ESRD (dialysis) eleven times more in 2011 than in 1980 accordingly to United States (US) Renal Data System is a testimonial to progression of CKD in patients with diabetes, hypertension, CHF and other renal diseases. US Renal Data System reveals that ESRD has soared in parallel with marketing of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) drugs, providing strong indirect evidence that these drugs are someway instrumental in the progression of CKD into ESRD. These drugs produce acute renal failure which is an independent risk factor for CKD. Thus shift in therapy with enthusiastic use of ACEI/ARB drugs has led to dialysis bonanza throughout the world benefiting the professionals and corporations at the expense of vegetative life of the patients associated with family and societal burdens. The ways to turn the pendulum is to treat diabetes with insulin and hypertension with beta blocker, calcium channel blocker and diuretic therapy, and avoid the use of ACEI/ARB drugs. It is important to understand that diuretic orally, by intravenous boluses or by continuous infusion, is the cornerstone of therapy for CHF, whereas ACEI/ARB drugs markedly impair the efficacy of diuretics by lowering the blood pressure to a very low level thereby reducing renal perfusion. An evidence for that is marked elevation of BUN with comparatively slight increase of serum creatinine. Thus with the approaches stated above, CKD is less likely to progress;hence rate of ESRD is likely to decrease.展开更多
Chronic infammation and nutritional imbalance are impor-tant comorbid conditions that correlate with poor clinical outcomes in children with chronic kidney disease （CKD）. Nutritional disorders such as cachexia/prote...Chronic infammation and nutritional imbalance are impor-tant comorbid conditions that correlate with poor clinical outcomes in children with chronic kidney disease （CKD）. Nutritional disorders such as cachexia/protein energy wasting, obesity and growth retardation negatively impact the quality of life and disease progression in children with CKD. Inadequate nutrition has been asso-ciated with growth disturbances in children with CKD. On the other hand, over-nutrition and obesity are associated with poor outcomes in children with CKD. The exact mechanisms leading to these unfavorable conditions are not fully elucidated and are most likely multifactorial. In this review, we focus on the pathophysiology of nutrition disorders and infammation and their impact on clinical outcomes in children with CKD.展开更多
Haematuria was known as a benign hallmark of some glomerular diseases, but over the last decade, new evidences pointed its negative implications on kidneydisease progression. Cytotoxic effects of oxidative stress indu...Haematuria was known as a benign hallmark of some glomerular diseases, but over the last decade, new evidences pointed its negative implications on kidneydisease progression. Cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells may account for the tubular injury observed in human biopsy specimens. However, the precise mechanisms responsible for haematuria remain unclear. The presence of red blood cells （RBCs） with irregular contours and shape in the urine indicates RBCs egression from the glomerular capillary into the urinary space. Therefore glomerular haematuria may be a marker of glomerular filtration barrier dysfunction or damage. In this review we describe some key issues regarding epidemiology and pathogenesis of haematuric diseases as well as their renal morphological fndings.展开更多
Protein energy wasting (PEW) is a major challenge in CKD. Objective: To assess PEW in predialysis patients on their first visit to a nephrologist. Methods: Three day dietary intake of 484 CKD stage 3 patients was take...Protein energy wasting (PEW) is a major challenge in CKD. Objective: To assess PEW in predialysis patients on their first visit to a nephrologist. Methods: Three day dietary intake of 484 CKD stage 3 patients was taken. Appetite was assessed with ADAT. Patients were divided into groups based on appetite and BMI. Results: Male and female parameters are serum albumin 3.7 ± 0.84/3.68.8 ± 0.81 g/dL, total protein 7.02 ± 1.27/6.94 ± 1.26 g/dL, creatinine 4.68 ± 4.19/3.74 ± 3.36 mg% creatinine clearance 33.22 ± 30.48/37.55 ± 33.87 ml/minute, BMI 22.60 ± 4.29/23.43 ± 4.77kg/m2 energy/kg 16.97 ± 0.65/16.8 ± 0.64, protein g/kg 0.65 ± 0.28/0.64 ± 0.30, carbohydrate g/kg 2.98 ± 1.54/2.98 ± 0.1.36, fat g/kg 2.98 ± 0.23/2.79 ± 0.22, respectively. As appetite decreased, dietary protein and energy intake decreased significantly. Appetite in males and females: Average 14.46%, 4.13%, poor 9.7%, 18.18%, anorexic 13.2%, 7.4%. Income had strong correlation with BMI (p 0.000), dietary protein (p 0.000), energy (p 0.000) and carbohydrate (p 0.000). Appetite correlated with creatinine (p 0.019), dietary energy, protein, carbohydrate and fat (p 0.000) intake. BMI correlated (p 0.000) with fat, carbohydrate, energy and creatinine clearance. ANOVA showed significant difference within and between appetite groups in energy, protein, fat, carbohydrate, creatinine clearance (p 0.000) and serum albumin (p 0.025). There was significant difference in protein (p 0.026), energy intake (p 0.000) and creatinine clearance (p 0.038) within and between BMI groups. Based on income, there was significant difference among groups in BMI (p 0.000), energy (p 0.019), protein (p 0.031) and albumin (0.001).展开更多
[目的]为中医药防治慢性肾脏病(chronic kidney disease,CKD)并发蛋白质能量消耗(protein energy wasting,PEW)提供新的思路与方法。[方法]从中医脾肾两脏分析讨论CKD并发PEW的病因病机,提出"祛瘀生新"和"脾主肌肉"...[目的]为中医药防治慢性肾脏病(chronic kidney disease,CKD)并发蛋白质能量消耗(protein energy wasting,PEW)提供新的思路与方法。[方法]从中医脾肾两脏分析讨论CKD并发PEW的病因病机,提出"祛瘀生新"和"脾主肌肉"的论治依据,据此运用益气健脾消瘀泄浊方治疗CKD并发PEW,并佐以一则医案加以验证。[结果]CKD并发PEW患者以脾肾亏虚、浊瘀壅滞为基本病因病机,此时先天之本已然衰败,治疗应以培补后天之本为重,并贯穿疾病治疗始终,同时还应兼顾随证而生的浊瘀之邪,将生新与祛瘀结合,以益气健脾消瘀泄浊方通畅肾络,健脾治痿。所举医案中患者诊断为慢性肾脏病4期并蛋白质能量消耗,中医辨为尿浊,属脾肾亏虚、浊瘀壅滞之证,治以益气健脾、消瘀泄浊,以益气健脾消瘀泄浊方为主方治疗,复建脾运,祛除肾中瘀浊,使气血津液化生运行如初,以后天脾气固补先天肾气,顽疾复有转机。[结论]从脾肾亏虚、浊瘀壅滞的基本病机出发,运用益气健脾、消瘀泄浊法治疗CKD并发PEW,可有效改善患者临床症状,稳定肾功能,临床疗效肯定,值得推广。展开更多
Background An accelerated muscle wasting was the pivotal factor for protein-energy wasting in end stage renal disease. However, very few researches have examined the skeletal muscle quantity and quality in clinical pa...Background An accelerated muscle wasting was the pivotal factor for protein-energy wasting in end stage renal disease. However, very few researches have examined the skeletal muscle quantity and quality in clinical patients. This study investigated the muscle morphologic changes by magnetic resonance imaging （MRI） and analyzed the related factors in hemodialysis patients. Methods Fifty-eight patients receiving maintenance hemodialysis （HD） were investigated and 28 healthy adults with gender and age matched were used as controls （Control）. Anthropometry, cytokine factors, and laboratory data were measured. The muscle and intermuscular adipose tissues （IMAT） were analyzed via a Thigh MRI. The bicep samples were observed after HE staining. Homeostatic model assessment of insulin resistance （HOMA-IR） was measured and their association with muscle wasting was analyzed. Results HD patients tended to have a lower protein diet, anthropometry data, and serum albumin, but the C reactive protein and interleukin-6 increased significantly. The MRI showed that HD patients had less muscle mass and a lower muscle/total ratio, but the fat/muscle and IMAT was higher when compared to the Control group. The muscle fiber showed atrophy and fat accumulation in the biceps samples come from the HD patients. Moreover, we found that the HD patients presented with a high level of plasma fasting insulin and increased HOMA-IR which negatively correlated with the muscle/ total ratio, but positively with the fat/muscle ratio. Conclusions Muscle wasting presented early before an obvious malnutrition condition emerged in HD patients. The main morphological change was muscle atrophy along with intermuscular lipid accumulation. Insulin resistance was associated with muscle wasting in dialysis patients.展开更多
基金funded in part by the Center on Emerging and Zoonotic Infectious Diseases(CEZID)of the National Institutes of General Medical Sciences underaward number P20GM130448.
文摘Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prion protein.These diseases can be spontaneous,heritable,anthropogenic/iatrogenic,or in some cases horizontally transmissible,and include such notable TSEs as bovine spongiform encephalopathy(BSE)of cattle and chronic wasting disease(CWD)of cervids.Although they are both unequivocally protein misfolding disorders,they differ markedly in their pathogenesis,transmissibility,and zoonotic potential.While the BSE epidemic has largely abated over the past three decades following global feed bans on ruminant meat and bone meal,CWD,which is readily transmitted through various forms of excreta,has rapidly expanded from its original endemic zone to encompass much of North America,along with recently identified foci in Scandinavia.Most importantly,although the classical form of BSE has proven transmissible to humans consuming contaminated beef or beef products,so far there have been no conclusive reports on the zoonotic transmission of cWD to humans.The underlying basis for these differences-whether host or agent directed-are not well understood,though may be due to inherent differences in the three-dimensional structure of the misfolded BSE or CWD prion proteins or the expression levels and tissue distribution of respective cellular prion proteins.With the uncontrolled geographic spread of CWD,it is imperative that we improve our understanding of the factors governing prion disease pathogenesis,transmission,and zoonotic potential.
文摘This treatise of chronic kidney disease (CKD) describes association of hypertension, diabetes and congestive heart failure (CHF) with CKD. CKD is defined by estimated glomerular filtration rate (eGFR) of less than 60 ml/min for three months or more. CKD is generally irreversible but not necessarily progressive. Thus progression of CKD into end stage renal disease (ESRD) is the concern here and what can be done to reduce the progression of CKD. Exact data of CKD with progression are unavailable but high incidence of ESRD (dialysis) eleven times more in 2011 than in 1980 accordingly to United States (US) Renal Data System is a testimonial to progression of CKD in patients with diabetes, hypertension, CHF and other renal diseases. US Renal Data System reveals that ESRD has soared in parallel with marketing of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) drugs, providing strong indirect evidence that these drugs are someway instrumental in the progression of CKD into ESRD. These drugs produce acute renal failure which is an independent risk factor for CKD. Thus shift in therapy with enthusiastic use of ACEI/ARB drugs has led to dialysis bonanza throughout the world benefiting the professionals and corporations at the expense of vegetative life of the patients associated with family and societal burdens. The ways to turn the pendulum is to treat diabetes with insulin and hypertension with beta blocker, calcium channel blocker and diuretic therapy, and avoid the use of ACEI/ARB drugs. It is important to understand that diuretic orally, by intravenous boluses or by continuous infusion, is the cornerstone of therapy for CHF, whereas ACEI/ARB drugs markedly impair the efficacy of diuretics by lowering the blood pressure to a very low level thereby reducing renal perfusion. An evidence for that is marked elevation of BUN with comparatively slight increase of serum creatinine. Thus with the approaches stated above, CKD is less likely to progress;hence rate of ESRD is likely to decrease.
基金Supported by The Capital Health Research and Development of Special Research Fund 2014-4-2102(to Juan Tu)
文摘Chronic infammation and nutritional imbalance are impor-tant comorbid conditions that correlate with poor clinical outcomes in children with chronic kidney disease （CKD）. Nutritional disorders such as cachexia/protein energy wasting, obesity and growth retardation negatively impact the quality of life and disease progression in children with CKD. Inadequate nutrition has been asso-ciated with growth disturbances in children with CKD. On the other hand, over-nutrition and obesity are associated with poor outcomes in children with CKD. The exact mechanisms leading to these unfavorable conditions are not fully elucidated and are most likely multifactorial. In this review, we focus on the pathophysiology of nutrition disorders and infammation and their impact on clinical outcomes in children with CKD.
基金Supported by Grants from FIS (Programa Miguel Servet:CP10/00479,PI13/00802 and PI14/00883)Spanish Society of Nephrology to Moreno JAInstitute of Research Queen Sophia,FRIAT and ISCIII fund PI10/00072 to Egido J.
文摘Haematuria was known as a benign hallmark of some glomerular diseases, but over the last decade, new evidences pointed its negative implications on kidneydisease progression. Cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells may account for the tubular injury observed in human biopsy specimens. However, the precise mechanisms responsible for haematuria remain unclear. The presence of red blood cells （RBCs） with irregular contours and shape in the urine indicates RBCs egression from the glomerular capillary into the urinary space. Therefore glomerular haematuria may be a marker of glomerular filtration barrier dysfunction or damage. In this review we describe some key issues regarding epidemiology and pathogenesis of haematuric diseases as well as their renal morphological fndings.
文摘Protein energy wasting (PEW) is a major challenge in CKD. Objective: To assess PEW in predialysis patients on their first visit to a nephrologist. Methods: Three day dietary intake of 484 CKD stage 3 patients was taken. Appetite was assessed with ADAT. Patients were divided into groups based on appetite and BMI. Results: Male and female parameters are serum albumin 3.7 ± 0.84/3.68.8 ± 0.81 g/dL, total protein 7.02 ± 1.27/6.94 ± 1.26 g/dL, creatinine 4.68 ± 4.19/3.74 ± 3.36 mg% creatinine clearance 33.22 ± 30.48/37.55 ± 33.87 ml/minute, BMI 22.60 ± 4.29/23.43 ± 4.77kg/m2 energy/kg 16.97 ± 0.65/16.8 ± 0.64, protein g/kg 0.65 ± 0.28/0.64 ± 0.30, carbohydrate g/kg 2.98 ± 1.54/2.98 ± 0.1.36, fat g/kg 2.98 ± 0.23/2.79 ± 0.22, respectively. As appetite decreased, dietary protein and energy intake decreased significantly. Appetite in males and females: Average 14.46%, 4.13%, poor 9.7%, 18.18%, anorexic 13.2%, 7.4%. Income had strong correlation with BMI (p 0.000), dietary protein (p 0.000), energy (p 0.000) and carbohydrate (p 0.000). Appetite correlated with creatinine (p 0.019), dietary energy, protein, carbohydrate and fat (p 0.000) intake. BMI correlated (p 0.000) with fat, carbohydrate, energy and creatinine clearance. ANOVA showed significant difference within and between appetite groups in energy, protein, fat, carbohydrate, creatinine clearance (p 0.000) and serum albumin (p 0.025). There was significant difference in protein (p 0.026), energy intake (p 0.000) and creatinine clearance (p 0.038) within and between BMI groups. Based on income, there was significant difference among groups in BMI (p 0.000), energy (p 0.019), protein (p 0.031) and albumin (0.001).
文摘[目的]为中医药防治慢性肾脏病(chronic kidney disease,CKD)并发蛋白质能量消耗(protein energy wasting,PEW)提供新的思路与方法。[方法]从中医脾肾两脏分析讨论CKD并发PEW的病因病机,提出"祛瘀生新"和"脾主肌肉"的论治依据,据此运用益气健脾消瘀泄浊方治疗CKD并发PEW,并佐以一则医案加以验证。[结果]CKD并发PEW患者以脾肾亏虚、浊瘀壅滞为基本病因病机,此时先天之本已然衰败,治疗应以培补后天之本为重,并贯穿疾病治疗始终,同时还应兼顾随证而生的浊瘀之邪,将生新与祛瘀结合,以益气健脾消瘀泄浊方通畅肾络,健脾治痿。所举医案中患者诊断为慢性肾脏病4期并蛋白质能量消耗,中医辨为尿浊,属脾肾亏虚、浊瘀壅滞之证,治以益气健脾、消瘀泄浊,以益气健脾消瘀泄浊方为主方治疗,复建脾运,祛除肾中瘀浊,使气血津液化生运行如初,以后天脾气固补先天肾气,顽疾复有转机。[结论]从脾肾亏虚、浊瘀壅滞的基本病机出发,运用益气健脾、消瘀泄浊法治疗CKD并发PEW,可有效改善患者临床症状,稳定肾功能,临床疗效肯定,值得推广。
文摘Background An accelerated muscle wasting was the pivotal factor for protein-energy wasting in end stage renal disease. However, very few researches have examined the skeletal muscle quantity and quality in clinical patients. This study investigated the muscle morphologic changes by magnetic resonance imaging （MRI） and analyzed the related factors in hemodialysis patients. Methods Fifty-eight patients receiving maintenance hemodialysis （HD） were investigated and 28 healthy adults with gender and age matched were used as controls （Control）. Anthropometry, cytokine factors, and laboratory data were measured. The muscle and intermuscular adipose tissues （IMAT） were analyzed via a Thigh MRI. The bicep samples were observed after HE staining. Homeostatic model assessment of insulin resistance （HOMA-IR） was measured and their association with muscle wasting was analyzed. Results HD patients tended to have a lower protein diet, anthropometry data, and serum albumin, but the C reactive protein and interleukin-6 increased significantly. The MRI showed that HD patients had less muscle mass and a lower muscle/total ratio, but the fat/muscle and IMAT was higher when compared to the Control group. The muscle fiber showed atrophy and fat accumulation in the biceps samples come from the HD patients. Moreover, we found that the HD patients presented with a high level of plasma fasting insulin and increased HOMA-IR which negatively correlated with the muscle/ total ratio, but positively with the fat/muscle ratio. Conclusions Muscle wasting presented early before an obvious malnutrition condition emerged in HD patients. The main morphological change was muscle atrophy along with intermuscular lipid accumulation. Insulin resistance was associated with muscle wasting in dialysis patients.
