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
Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphism...Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.展开更多
目的扁桃体切除术治疗IgA肾病(IgAN)的疗效目前仍存在争议,这项meta分析旨在评价其作为辅助或独立治疗的疗效,为其在临床中的应用提供更充分的循证学依据。方法计算机检索建库至2022年11月1日在Pubmed、Embase、ScienceDirect、Cochrane...目的扁桃体切除术治疗IgA肾病(IgAN)的疗效目前仍存在争议,这项meta分析旨在评价其作为辅助或独立治疗的疗效,为其在临床中的应用提供更充分的循证学依据。方法计算机检索建库至2022年11月1日在Pubmed、Embase、ScienceDirect、Cochrane library、Web of Science、中国知网(CNKI)、维普网(VIP)、中国生物医学文献数据库(CBM)和万方数据库公开发表的关于扁桃体切除术治疗IgAN的文献,以蛋白尿、血尿、完全缓解率及终末期肾病(ESRD)发生率作为观察点,使用Stata 12.0软件进行统计学分析。结果共纳入36篇文献,涉及5797名原发性IgAN患者。Meta分析结果显示,扁桃体切除术作为辅助或独立治疗手段与单纯药物治疗相比,蛋白尿缓解率显著增加(OR=4.44,95%CI:3.14~6.27),血尿缓解率显著增加(OR=5.11,95%CI:2.92~8.93),完全缓解率显著增加(OR=3.32,95%CI:2.79~3.96),而ESRD发生率显著降低(OR=0.24,95%CI:0.17~0.33)。结论扁桃体切除术作为辅助或独立治疗手段,有助于诱导临床缓解并抑制终末期肾病的进展,临床上应更加重视其应用价值。展开更多
Background The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains uncertain.Aims To investigate the association between dietary thiamine intake...Background The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains uncertain.Aims To investigate the association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals.Methods The study included a total of 3106 participants capable of completing repeated cognitive function tests.Dietary nutrient intake information was collected through 3-day dietary recalls and using a 3-day food-weighed method to assess cooking oil and condiment consumption.Cognitive decline was defined as the 5-year decline rate in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified.Results The median follow-up duration was 5.9 years.There was a J-shaped relationship between dietary thiamine intake and the 5-year decline rate in global and composite cognitive scores,with an inflection point of 0.68 mg/day(95%confidence interval(Cl):0.56 to 0.80)and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.Before the inflection point,thiamine intake was not significantly associated with cognitive decline.Beyond the inflection point,each unit increase in thiamine intake(mg/day)was associated with a significant decrease of 4.24(95%Cl:2.22 to 6.27)points in the global score and 0.49(95%Cl:0.23 to 0.76)standard units in the composite score within 5 years.A stronger positive association between thiamine intake and cognitive decline was observed in those with hypertension,obesity and those who were non-smokers(all p<0.05).Conclusions This study revealed a J-shaped association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals,with an inflection point at 0.68 mg/day and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.展开更多
AIM： To determine the temporal expression and pattern of Rel/nuclear factor （NF）-κB proteins in renal tissue in polycystic kidney disease （PKD）. METHODS： The renal expression of Rel/NF-κB proteins was determin...AIM： To determine the temporal expression and pattern of Rel/nuclear factor （NF）-κB proteins in renal tissue in polycystic kidney disease （PKD）. METHODS： The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofuorescence and immunoblot analysis in Lewis polycystic kidney rats （LPK, a genetic ortholog of human nephronopthsis-9） from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes （TNFa and CCL2） were determined. NF-κB was also histologically assessed in human PKD tissue.RESULTS： Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation （peaking at weeks 3 and 10 respectively）, and progressive interstitial fibrosis （with a smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards）. Rel/NF-κB proteins （phosphorylated-p105, p65, p50, c-Rel and RelB） were expressed in cystic epithelial cells （CECs） of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBa protein levels, and TNFa and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identifed in the CECs of LPK and human polycystic kidneys. CONCLUSION： Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases.展开更多
Objective: To explore the role of bone morphorgenetic protein-7 （BMP-7） in the renal tubulo-interstitial lesions induced by unilateral ureteral obstruction （UUO）. Methods: Sixty Wistar rats were equally and random...Objective: To explore the role of bone morphorgenetic protein-7 （BMP-7） in the renal tubulo-interstitial lesions induced by unilateral ureteral obstruction （UUO）. Methods: Sixty Wistar rats were equally and randomly divided into normal control, sham operation and UUO groups, and respectively sacrificed on the 1st, 3rd, 7th, 14th day after the time of UUO operation. The mRNA levels of BMP-7 and TGF-β1 in the renal tissues were examined by RT-PCR. The expression sites and levels of BMP-7 and TGF-β1 proteins were detected by immunohistochemistry staining. Results:Compared to control groups, the level of BMP-7 mRNA was significantly decreased, but that of TGF-β1 mRNA was significantly increased in UUO rats. Immunohistochemistry staining indicated that BMP-7 mainly expressed in the renal tubules and interstitum, rarely in the glomeruli. In UUO rats, the expression of BMP-7 protein was decreased, but that of TGF-β1 was increased in an obstruction dependent manner. Conclusion:The down- regulation of BMP-7 is observed in the early phase of fibrotic process of the renal interstitium, suggesting it may be involved in the formation and development of the tubulo-interstitial lesions.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
The study was designed to investigate the use of two sorbents namely(i) Fe3O4 nanoparticles immobilized in sodium alginate matrix(FNPSA) and(ii) Fe3O4 nanoparticles and saponified orange peel residue immobilized in so...The study was designed to investigate the use of two sorbents namely(i) Fe3O4 nanoparticles immobilized in sodium alginate matrix(FNPSA) and(ii) Fe3O4 nanoparticles and saponified orange peel residue immobilized in sodium alginate matrix(FNPSOPR) as sorbents for fluoride removal from contaminated water. The synthesized nanoparticles were analyzed and characterized by dynamic light scattering, X-ray diffraction, vibrating sample magnetometry, and scanning electron microscopy with energy dispersive X-ray spectroscopy and Fourier transform-infrared spectrometry. The sorbent matrices were prepared in the form of beads and surface functionalized to enable enhanced sorption of fluoride ions. Batch sorption studies were carried out and the sorption isotherm and reaction kinetics were analyzed. Both the sorbents followed Langmuir model of isotherm and fitted well with Pseudo first order reaction. The maximum sorption capacity exhibited by FNPSA and FNPSOPR was58.24 mg·g-1and 80.33 mg·g-1respectively. Five sorption–desorption cycles exhibited 100%, 97.56%, 94.53%,83.21%, and 76.53% of regeneration of FNPSOPR. Accordingly, it is demonstrated that FNSOPR could be used as a promising sorbent for easy and efficient removal of fluoride from contaminated water with good reusability.The current work suggests a simple and effective method to remove fluoride from contaminated water.展开更多
Matrix metalloproteinases(MMPs) are members of the neutral proteinase family. They were previously thought to be anti-fibrotic because of their ability to degrade and remodel of extracellular matrix. However, recent s...Matrix metalloproteinases(MMPs) are members of the neutral proteinase family. They were previously thought to be anti-fibrotic because of their ability to degrade and remodel of extracellular matrix. However, recent studies have shown that MMPs are implicated in initiation and progression of kidney fibrosis through tubular cell epithelial–mesenchymal transition(EMT) as well as activation of resident fibroblasts, endothelial-mesenchymal transition(Endo MT) and pericyte-myofibroblast transdifferentiation. Interstitial macrophage infiltration has also been shown to correlate with the severity of kidney fibrosis in various chronic kidney diseases. MMPs secreted by macrophages, especially MMP-9, hasbeen shown by us to be profibrotic by induction of tubular cells EMT. EMT is mainly induced by transforming growth factor-β(TGF-β). However, MMP-9 was found by us and others to be up-regulated by TGF-β1 in kidney tubular epithelial cells and secreted by activated macrophages, resulting in EMT and ultimately kidney fibrosis. Therefore, MMP-9 may serve as a potential therapeutic target to prevent kidney fibrosis in chronic kidney disease. This review, by a particular focus on EMT, seeks to provide a comprehensive understanding of MMPs, especially MMP-9, in kidney fibrosis.展开更多
World Kidney Day on March 8th 2012 provides a chance to reflect on the success of kidney transplantation as a therapy for end stage kidney disease that surpasses dialysis treatments both for the quality and quantity o...World Kidney Day on March 8th 2012 provides a chance to reflect on the success of kidney transplantation as a therapy for end stage kidney disease that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness.Anything that is both cheaper and better,but is not actually the dominant therapy,must have other drawbacks that prevent replacement of all dialysis treatment by transplantation.The barriers to universal transplantation as the therapy for end stage kidney disease include the economic limitations which,in some countries place transplantation,appropriately,at a lower priority than public health fundamentals such as clean water,sanitation and vaccination.Even in high income countries the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients,but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical,surgical and nursing workforces with the required expertise.These problems have solutions which involve the full range of societal,professional,governmental and political environments.World Kidney Day is a call to deliver transplantation therapy to the one million people a year who have a right to benefit.展开更多
AIM： To determine whether complement membrane attack complex （C5b-9） has a pathogenic role in tubuloin-terstitial injury in a renal disease model characterized by acute highly selective proteinuria. METHODS： Prote...AIM： To determine whether complement membrane attack complex （C5b-9） has a pathogenic role in tubuloin-terstitial injury in a renal disease model characterized by acute highly selective proteinuria. METHODS： Protein-overload nephropathy （PON） was induced in adult female Piebald-Viral-Glaxo rats with or without complement C6 defciency （C6- and C6＋） by daily intraperitoneal injections of bovine serum albumin （BSA, 2 g/d）, and examined on days 2, 4 and 8.RESULTS： Groups with PON developed equivalent levels of heavy proteinuria within 24 h of BSA injection. In C6＋ rats with PON, the tubulointerstitial expression of C5b-9 was increased and localized predominantly to the basolateral surface of tubular epithelial cells （TECs）, whereas it was undetectable in C6- animals. TEC proliferation （as assessed by the number of BrdU＋cells） increased by more than 50-fold in PON, peaking on day 2 and declining on days 4 to 8. There was a trend for a reduction in the number of BrdU＋ TECs on day 4 in the C6- PON group （ P = 0.10 compared to C6＋） but not at any other time-point. Kidney enlargement, TEC apoptosis （TUNEL＋ cells） and markers of tubular injury （tubule dilatation, loss of TEC height, protein cast formation） were not altered by C6 deficiency in PON. Interstitial monocyte （ED-1＋ cell） accumulation was partially reduced in C6- animals with PON on day 4 （ P = 0.01） but there was no change in myofbroblast accumulation. CONCLUSION： These data suggest that C5b-9 does not mediate tubulointerstitial injury in acute glomerular diseases characterized by selective proteinuria.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supported by the General Project of Henan Natural Science Foundation(No.232300420034)the National Natural Science Foundation of China for the Youth(No.81600555)the General Project of China Postdoctoral Science Foundation(No.2018M640684)。
文摘Objective Glucocorticoid(GC)-induced adverse reactions(ARs)have been extensively studied due to their potential impact on patients’health.This study aimed to examine the potential correlation between two polymorphisms[adenosine triphosphate-binding cassette B1(ABCB1)C3435T and plasminogen activator inhibitor-1(PAI-1)4G/5G]and various GC-induced ARs in nephrotic syndrome(NS)patients.Methods In this study,513 NS patients who underwent GC treatment were enrolled.Then,the patients were divided into two groups based on ABCB1 C3435T and PAI-14G/5G genotyping,and intergroup comparisons of clinicopathological data and GC-induced ARs were performed.Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs,and a nomogram was subsequently established and validated via the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head(SANFH)(OR:2.191,95%CI:1.258–3.813,P=0.006)but not as a risk factor for the occurrence of steroid diabetes mellitus(S-DM).On the other hand,PAI-14G/5G was identified as an independent risk factor for the development of both SANFH(OR:2.198,95%CI:1.267–3.812,P=0.005)and S-DM(OR:2.080,95%CI:1.166–3.711,P=0.013).Notably,no significant correlation was found between the two gene polymorphisms and other GC-induced ARs.In addition,two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.Conclusion Assessing ABCB1 C3435T and PAI-14G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.
文摘目的扁桃体切除术治疗IgA肾病(IgAN)的疗效目前仍存在争议,这项meta分析旨在评价其作为辅助或独立治疗的疗效,为其在临床中的应用提供更充分的循证学依据。方法计算机检索建库至2022年11月1日在Pubmed、Embase、ScienceDirect、Cochrane library、Web of Science、中国知网(CNKI)、维普网(VIP)、中国生物医学文献数据库(CBM)和万方数据库公开发表的关于扁桃体切除术治疗IgAN的文献,以蛋白尿、血尿、完全缓解率及终末期肾病(ESRD)发生率作为观察点,使用Stata 12.0软件进行统计学分析。结果共纳入36篇文献,涉及5797名原发性IgAN患者。Meta分析结果显示,扁桃体切除术作为辅助或独立治疗手段与单纯药物治疗相比,蛋白尿缓解率显著增加(OR=4.44,95%CI:3.14~6.27),血尿缓解率显著增加(OR=5.11,95%CI:2.92~8.93),完全缓解率显著增加(OR=3.32,95%CI:2.79~3.96),而ESRD发生率显著降低(OR=0.24,95%CI:0.17~0.33)。结论扁桃体切除术作为辅助或独立治疗手段,有助于诱导临床缓解并抑制终末期肾病的进展,临床上应更加重视其应用价值。
基金National Key Research and Development Program of China(2022YFC2009600,2022YFC2009605)National Natural Science Foundation of China(81973133)。
文摘Background The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains uncertain.Aims To investigate the association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals.Methods The study included a total of 3106 participants capable of completing repeated cognitive function tests.Dietary nutrient intake information was collected through 3-day dietary recalls and using a 3-day food-weighed method to assess cooking oil and condiment consumption.Cognitive decline was defined as the 5-year decline rate in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified.Results The median follow-up duration was 5.9 years.There was a J-shaped relationship between dietary thiamine intake and the 5-year decline rate in global and composite cognitive scores,with an inflection point of 0.68 mg/day(95%confidence interval(Cl):0.56 to 0.80)and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.Before the inflection point,thiamine intake was not significantly associated with cognitive decline.Beyond the inflection point,each unit increase in thiamine intake(mg/day)was associated with a significant decrease of 4.24(95%Cl:2.22 to 6.27)points in the global score and 0.49(95%Cl:0.23 to 0.76)standard units in the composite score within 5 years.A stronger positive association between thiamine intake and cognitive decline was observed in those with hypertension,obesity and those who were non-smokers(all p<0.05).Conclusions This study revealed a J-shaped association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals,with an inflection point at 0.68 mg/day and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.
基金Supported by Funding from the National Health and Medical Research Council of Australia,Nos.457575 and 632647 to Rangan GKthe Baltimore Polycystic Kidney Disease Research and Clinical Core Center,No.P30DK090868+2 种基金DK095036 to Watnick Tsupported by an Australian Postgraduate Award(University of Sydney)the Michael Stern Polycystic Kidney Disease Research Fellowship
文摘AIM： To determine the temporal expression and pattern of Rel/nuclear factor （NF）-κB proteins in renal tissue in polycystic kidney disease （PKD）. METHODS： The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofuorescence and immunoblot analysis in Lewis polycystic kidney rats （LPK, a genetic ortholog of human nephronopthsis-9） from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes （TNFa and CCL2） were determined. NF-κB was also histologically assessed in human PKD tissue.RESULTS： Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation （peaking at weeks 3 and 10 respectively）, and progressive interstitial fibrosis （with a smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards）. Rel/NF-κB proteins （phosphorylated-p105, p65, p50, c-Rel and RelB） were expressed in cystic epithelial cells （CECs） of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBa protein levels, and TNFa and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identifed in the CECs of LPK and human polycystic kidneys. CONCLUSION： Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases.
文摘Objective: To explore the role of bone morphorgenetic protein-7 （BMP-7） in the renal tubulo-interstitial lesions induced by unilateral ureteral obstruction （UUO）. Methods: Sixty Wistar rats were equally and randomly divided into normal control, sham operation and UUO groups, and respectively sacrificed on the 1st, 3rd, 7th, 14th day after the time of UUO operation. The mRNA levels of BMP-7 and TGF-β1 in the renal tissues were examined by RT-PCR. The expression sites and levels of BMP-7 and TGF-β1 proteins were detected by immunohistochemistry staining. Results:Compared to control groups, the level of BMP-7 mRNA was significantly decreased, but that of TGF-β1 mRNA was significantly increased in UUO rats. Immunohistochemistry staining indicated that BMP-7 mainly expressed in the renal tubules and interstitum, rarely in the glomeruli. In UUO rats, the expression of BMP-7 protein was decreased, but that of TGF-β1 was increased in an obstruction dependent manner. Conclusion:The down- regulation of BMP-7 is observed in the early phase of fibrotic process of the renal interstitium, suggesting it may be involved in the formation and development of the tubulo-interstitial lesions.
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.
基金the management of VIT University for their support in research and Defence Metallurgical Research Laboratory, DRDO, Hyderabad for helping in VSM analysis
文摘The study was designed to investigate the use of two sorbents namely(i) Fe3O4 nanoparticles immobilized in sodium alginate matrix(FNPSA) and(ii) Fe3O4 nanoparticles and saponified orange peel residue immobilized in sodium alginate matrix(FNPSOPR) as sorbents for fluoride removal from contaminated water. The synthesized nanoparticles were analyzed and characterized by dynamic light scattering, X-ray diffraction, vibrating sample magnetometry, and scanning electron microscopy with energy dispersive X-ray spectroscopy and Fourier transform-infrared spectrometry. The sorbent matrices were prepared in the form of beads and surface functionalized to enable enhanced sorption of fluoride ions. Batch sorption studies were carried out and the sorption isotherm and reaction kinetics were analyzed. Both the sorbents followed Langmuir model of isotherm and fitted well with Pseudo first order reaction. The maximum sorption capacity exhibited by FNPSA and FNPSOPR was58.24 mg·g-1and 80.33 mg·g-1respectively. Five sorption–desorption cycles exhibited 100%, 97.56%, 94.53%,83.21%, and 76.53% of regeneration of FNPSOPR. Accordingly, it is demonstrated that FNSOPR could be used as a promising sorbent for easy and efficient removal of fluoride from contaminated water with good reusability.The current work suggests a simple and effective method to remove fluoride from contaminated water.
文摘Matrix metalloproteinases(MMPs) are members of the neutral proteinase family. They were previously thought to be anti-fibrotic because of their ability to degrade and remodel of extracellular matrix. However, recent studies have shown that MMPs are implicated in initiation and progression of kidney fibrosis through tubular cell epithelial–mesenchymal transition(EMT) as well as activation of resident fibroblasts, endothelial-mesenchymal transition(Endo MT) and pericyte-myofibroblast transdifferentiation. Interstitial macrophage infiltration has also been shown to correlate with the severity of kidney fibrosis in various chronic kidney diseases. MMPs secreted by macrophages, especially MMP-9, hasbeen shown by us to be profibrotic by induction of tubular cells EMT. EMT is mainly induced by transforming growth factor-β(TGF-β). However, MMP-9 was found by us and others to be up-regulated by TGF-β1 in kidney tubular epithelial cells and secreted by activated macrophages, resulting in EMT and ultimately kidney fibrosis. Therefore, MMP-9 may serve as a potential therapeutic target to prevent kidney fibrosis in chronic kidney disease. This review, by a particular focus on EMT, seeks to provide a comprehensive understanding of MMPs, especially MMP-9, in kidney fibrosis.
基金This work was supported by the National Health and Medical Research Council of Australia Acknowledgements This work was supported by the National Health and Medical Research Council of Australia. A.P.C. is the recipient of an Australian Postgraduate Award at the University of Sydney.
文摘World Kidney Day on March 8th 2012 provides a chance to reflect on the success of kidney transplantation as a therapy for end stage kidney disease that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness.Anything that is both cheaper and better,but is not actually the dominant therapy,must have other drawbacks that prevent replacement of all dialysis treatment by transplantation.The barriers to universal transplantation as the therapy for end stage kidney disease include the economic limitations which,in some countries place transplantation,appropriately,at a lower priority than public health fundamentals such as clean water,sanitation and vaccination.Even in high income countries the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients,but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical,surgical and nursing workforces with the required expertise.These problems have solutions which involve the full range of societal,professional,governmental and political environments.World Kidney Day is a call to deliver transplantation therapy to the one million people a year who have a right to benefit.
基金Supported by The United States National Institutes of Health(Nos.DK34198 and DK07467)to Dr.CouserThe Don Jacquot Fellowship(Australian and New Zealand Society of Nephrology Travelling Fellowship)+3 种基金The BJ Amos Travelling Fellowships(Westmead Hospital)The Medical Research Fund of Western AustraliaThe Fremantle Hospital Medical Research FoundationThe National Health and Medical Research Council(No.230500)to Dr.Rangan
文摘AIM： To determine whether complement membrane attack complex （C5b-9） has a pathogenic role in tubuloin-terstitial injury in a renal disease model characterized by acute highly selective proteinuria. METHODS： Protein-overload nephropathy （PON） was induced in adult female Piebald-Viral-Glaxo rats with or without complement C6 defciency （C6- and C6＋） by daily intraperitoneal injections of bovine serum albumin （BSA, 2 g/d）, and examined on days 2, 4 and 8.RESULTS： Groups with PON developed equivalent levels of heavy proteinuria within 24 h of BSA injection. In C6＋ rats with PON, the tubulointerstitial expression of C5b-9 was increased and localized predominantly to the basolateral surface of tubular epithelial cells （TECs）, whereas it was undetectable in C6- animals. TEC proliferation （as assessed by the number of BrdU＋cells） increased by more than 50-fold in PON, peaking on day 2 and declining on days 4 to 8. There was a trend for a reduction in the number of BrdU＋ TECs on day 4 in the C6- PON group （ P = 0.10 compared to C6＋） but not at any other time-point. Kidney enlargement, TEC apoptosis （TUNEL＋ cells） and markers of tubular injury （tubule dilatation, loss of TEC height, protein cast formation） were not altered by C6 deficiency in PON. Interstitial monocyte （ED-1＋ cell） accumulation was partially reduced in C6- animals with PON on day 4 （ P = 0.01） but there was no change in myofbroblast accumulation. CONCLUSION： These data suggest that C5b-9 does not mediate tubulointerstitial injury in acute glomerular diseases characterized by selective proteinuria.
