Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight ...Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.展开更多
Nocardiosis manifests as an opportunistic infection,primarily affecting individuals who are immunocompromised and susceptible to the infection.We present a case study of one patient with nephrotic syndrome and membran...Nocardiosis manifests as an opportunistic infection,primarily affecting individuals who are immunocompromised and susceptible to the infection.We present a case study of one patient with nephrotic syndrome and membranous nephropathy,who underwent treatment with prednisone and cyclosporine in 2016.In early 2017,the patient was diagnosed with a"fungal infection"and discontinued the use of cyclosporine.After one month of anti-infection therapy,a cranial magnetic resonance imaging scan showed multiple abscesses in the right temporal region.The diagnosis of nocardiosis was confirmed based on the presence of metastatic abscess masses,multiple lung and brain lesions,and a positive culture of Nocardia in the drainage.We changed the anti-infection therapy to a combination of trimethoprim-sulfamethoxazole(TMP-SMX),minocycline,and voriconazole.However,the patient experienced a sudden cardiac arrest and subsequently recovered after cardiopulmonary resuscitation.During the five-month follow-up period following the discharge,the patient displayed an enhanced nutritional status and stable renal function.The focal infection ultimately resolved during the subsequent three years.Neuro-infection caused by Nocardia should be considered in immunocompromised patients,and TMP-SMX is the preferred initial therapy;however,because of the high mortality rate,a long-term combination therapy with imipenem,cefotaxime,amikacin,and TMP-SMX is suggested.展开更多
This was a rare case, in which clinical manifestation was a thymus area tumor accompanied by proteinuria, kidney dysfunction and kidney enlargement. Tumor biopsy and bone marrow examination failed to clarify its diagn...This was a rare case, in which clinical manifestation was a thymus area tumor accompanied by proteinuria, kidney dysfunction and kidney enlargement. Tumor biopsy and bone marrow examination failed to clarify its diagnosis. Renal biopsy revealed diffuse infiltration by atypical lymphoid cells in renal interstitium. Immunoperoxidase studies demonstrated this case was non-Hodgkin ＇ s lymphoma （NHL） of the B cell type through the renal biopsy.展开更多
Background:This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection(recombinant human erythropoietin injection,rHuEPO)for the treatment of anemia associ...Background:This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection(recombinant human erythropoietin injection,rHuEPO)for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method:This study was a multicenter,randomized,open-label,intergroup parallel control phase III noninferiority trial from April 19,2013 to September 9,2014 at 25 sites.In this study,the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks.The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week.All subjects underwent epoetin alfa administration during the 8-week baseline period.After that,subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group.The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period(noninferiority threshold:-1.0 g/dl)was tested between the two treatments.The time-dependent hemoglobin(Hb)concentration and the maintenance rate of the target Hb concentration(the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl)were also evaluated.Iron metabolism,including changes in the serum iron,total iron-binding capacity,ferritin,transferrin saturation,and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further.Adverse events(AEs)were also observed and compared,and the safety was analyzed between the two treatment groups.The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:Four hundred and sixty-six patients were enrolled in this study,and ultimately 384 cases were analyzed for safety,including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group.There were 211 cases in the per-protocol set,including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group.The changes in the average Hb concentrations from the baseline to the end of the evaluation period were-0.07 and-0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively.The difference between the two groups was 0.08 g/dl(95%confidence interval[CI]:-0.22 to 0.39),and the lower limit of the 95%CI was-0.22>-1.0 g/dl.The average Hb concentrations of the two groups were 10.88-11.43 g/dl(darbepoetin alfa)and 10.91-11.38 g/dl(epoetin alfa)during the study period of Weeks 0-28,with the maintenance rates of the target Hb concentration ranging within 71%-87%and 78%-95%in the darbepoetin alfa group and epoetin alfa group respectively.During the period of comparison between the two groups,the incidence of AEs in the darbepoetin alfa group was 61.42%,while in the epoetin alfa group it was 56.41%.All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion:The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.展开更多
Background:Erythropoietin is a glycoprotein that mainly regulates erythropoiesis.In patients with chronic renal failure with anemia,darbepoetin alfa can stimulate erythropoiesis,correct anemia,and maintain hemoglobin ...Background:Erythropoietin is a glycoprotein that mainly regulates erythropoiesis.In patients with chronic renal failure with anemia,darbepoetin alfa can stimulate erythropoiesis,correct anemia,and maintain hemoglobin levels.This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections(Recombinant Human Erythropoietin injection,rHuEPO)when maintaining hemoglobin(Hb)levels within the target range(10.0-12.0 g/dL)for the treatment of renal anemia.Methods:Ninety-five patients were enrolled in this study from April 15,2013 to April 10,2014 at 25 sites.In this study,patients(n=95)aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group(n=56)and a twice or three times per week intravenous epoetin alfa group(n=39)for 28 weeks,who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease(CKD)and were undergoing hemodialysis or hemofiltration with ESA-naive(erythropoiesis stimulating agent-naive).The primary efficacy profile was the mean Hb level(the non-inferiority margin was-1.0 g/dL,week 21-28);the secondary efficacy profiles were the Hb increase rate(week 0-4),the target Hb achievement cumulative rate and time,the change trends of the Hb levels,and the target Hb maintenance ratio.Adverse events(AEs)were observed and compared,and the efficacy and safety were analyzed between the two treatment groups.Additionally,the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group,respectively;the difference of the lower limits of the 95%confidence intervals(CI)between the two groups was 0.1 g/dL(>-1.0 g/dL),and non-inferiority was proven;the Hb levels started to increase in the first four weeks at a similar increase rate;no obvious differences were observed between the groups in the target Hb achievement cumulative rates,and the Hb levels as well as the target Hb level maintenance rate changed over time.The incidence of AEs was 62.5%in the darbepoetin alfa group and 76.9%in the epoetin alfa group.All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion:Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well,which makes it not inferior to epoetin alfa intravenously twice or three times per week.Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.展开更多
Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progr...Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progressive skin ischemia,large areas of painful malodorous ulcers,and mummified legs.Because of the worsening symptoms and signs refractory to conventional therapies,treatment with human amnion-derived mesenchymal stem cells(hAMSCs)was approved.Preclinical release inspections of hAMSCs,efficacy,and safety assessment,including cytokine secretory ability,immunocompetence,tumorigenicity,and genetics analysis in vitro,were introduced.We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats,abnormal immune response tests in C57BL/6 mice,and tumorigenicity tests in neonatal Balbc-nu nude mice.After the preclinical research,the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers.When followed up to 15 months,the blood-based markers of bone and mineral metabolism improved,with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells.Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis,and 20 months later,the re-epithelialization restored the integrity of the damaged site.No infusion or local treatment-related adverse events occurred.Thus,this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,anti-inflammatory and immune modulation,multidifferentiation,re-epithelialization,and restoration of integrity.展开更多
基金funded by the National Natural Science Foundation of China(Grant No.82470766 to H.M.)the Jiangsu Provincial Medical Key Discipline(Laboratory)Cultivation Unit(Grant No.JSDW202206 to C.X.)the First Affiliated Hospital of Nanjing Medical University Clinical Capacity Enhancement Project(Grant No.JSPH-MC-2022-18 to C.X.).
文摘Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.
基金funded by grants from the National Natural Science Foundation of China(Grant No.81570666)International Society of Nephrology Clinical Research Program(Grant No.18-01-0247)+3 种基金Program of Jiangsu Clinical Research Center(Grant No.BL2014084)Jiangsu Province Key Medical Personnel Project(Grant No.ZDRCA2016002)CKD Anemia Research Foundation from China International Medical Foundation(Grant No.Z-2017-24-2037)Outstanding Young and Middle-aged Talents Support Program of the First Affiliated Hospital of Nanjing Medical University(Jiangsu Province Hospital).
文摘Nocardiosis manifests as an opportunistic infection,primarily affecting individuals who are immunocompromised and susceptible to the infection.We present a case study of one patient with nephrotic syndrome and membranous nephropathy,who underwent treatment with prednisone and cyclosporine in 2016.In early 2017,the patient was diagnosed with a"fungal infection"and discontinued the use of cyclosporine.After one month of anti-infection therapy,a cranial magnetic resonance imaging scan showed multiple abscesses in the right temporal region.The diagnosis of nocardiosis was confirmed based on the presence of metastatic abscess masses,multiple lung and brain lesions,and a positive culture of Nocardia in the drainage.We changed the anti-infection therapy to a combination of trimethoprim-sulfamethoxazole(TMP-SMX),minocycline,and voriconazole.However,the patient experienced a sudden cardiac arrest and subsequently recovered after cardiopulmonary resuscitation.During the five-month follow-up period following the discharge,the patient displayed an enhanced nutritional status and stable renal function.The focal infection ultimately resolved during the subsequent three years.Neuro-infection caused by Nocardia should be considered in immunocompromised patients,and TMP-SMX is the preferred initial therapy;however,because of the high mortality rate,a long-term combination therapy with imipenem,cefotaxime,amikacin,and TMP-SMX is suggested.
文摘This was a rare case, in which clinical manifestation was a thymus area tumor accompanied by proteinuria, kidney dysfunction and kidney enlargement. Tumor biopsy and bone marrow examination failed to clarify its diagnosis. Renal biopsy revealed diffuse infiltration by atypical lymphoid cells in renal interstitium. Immunoperoxidase studies demonstrated this case was non-Hodgkin ＇ s lymphoma （NHL） of the B cell type through the renal biopsy.
文摘Background:This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection(recombinant human erythropoietin injection,rHuEPO)for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method:This study was a multicenter,randomized,open-label,intergroup parallel control phase III noninferiority trial from April 19,2013 to September 9,2014 at 25 sites.In this study,the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks.The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week.All subjects underwent epoetin alfa administration during the 8-week baseline period.After that,subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group.The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period(noninferiority threshold:-1.0 g/dl)was tested between the two treatments.The time-dependent hemoglobin(Hb)concentration and the maintenance rate of the target Hb concentration(the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl)were also evaluated.Iron metabolism,including changes in the serum iron,total iron-binding capacity,ferritin,transferrin saturation,and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further.Adverse events(AEs)were also observed and compared,and the safety was analyzed between the two treatment groups.The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:Four hundred and sixty-six patients were enrolled in this study,and ultimately 384 cases were analyzed for safety,including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group.There were 211 cases in the per-protocol set,including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group.The changes in the average Hb concentrations from the baseline to the end of the evaluation period were-0.07 and-0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively.The difference between the two groups was 0.08 g/dl(95%confidence interval[CI]:-0.22 to 0.39),and the lower limit of the 95%CI was-0.22>-1.0 g/dl.The average Hb concentrations of the two groups were 10.88-11.43 g/dl(darbepoetin alfa)and 10.91-11.38 g/dl(epoetin alfa)during the study period of Weeks 0-28,with the maintenance rates of the target Hb concentration ranging within 71%-87%and 78%-95%in the darbepoetin alfa group and epoetin alfa group respectively.During the period of comparison between the two groups,the incidence of AEs in the darbepoetin alfa group was 61.42%,while in the epoetin alfa group it was 56.41%.All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion:The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.
文摘Background:Erythropoietin is a glycoprotein that mainly regulates erythropoiesis.In patients with chronic renal failure with anemia,darbepoetin alfa can stimulate erythropoiesis,correct anemia,and maintain hemoglobin levels.This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections(Recombinant Human Erythropoietin injection,rHuEPO)when maintaining hemoglobin(Hb)levels within the target range(10.0-12.0 g/dL)for the treatment of renal anemia.Methods:Ninety-five patients were enrolled in this study from April 15,2013 to April 10,2014 at 25 sites.In this study,patients(n=95)aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group(n=56)and a twice or three times per week intravenous epoetin alfa group(n=39)for 28 weeks,who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease(CKD)and were undergoing hemodialysis or hemofiltration with ESA-naive(erythropoiesis stimulating agent-naive).The primary efficacy profile was the mean Hb level(the non-inferiority margin was-1.0 g/dL,week 21-28);the secondary efficacy profiles were the Hb increase rate(week 0-4),the target Hb achievement cumulative rate and time,the change trends of the Hb levels,and the target Hb maintenance ratio.Adverse events(AEs)were observed and compared,and the efficacy and safety were analyzed between the two treatment groups.Additionally,the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group,respectively;the difference of the lower limits of the 95%confidence intervals(CI)between the two groups was 0.1 g/dL(>-1.0 g/dL),and non-inferiority was proven;the Hb levels started to increase in the first four weeks at a similar increase rate;no obvious differences were observed between the groups in the target Hb achievement cumulative rates,and the Hb levels as well as the target Hb level maintenance rate changed over time.The incidence of AEs was 62.5%in the darbepoetin alfa group and 76.9%in the epoetin alfa group.All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion:Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well,which makes it not inferior to epoetin alfa intravenously twice or three times per week.Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.
基金funded by the National Natural Science Foundation of China(81270408,81570666,81730041,and 81671447)the International Society of Nephrology(ISN)Clinical Research Program(18-01-0247)+7 种基金Construction Program of Jiangsu Provincial Clinical Research Center Support System(BL2014084)Jiangsu Province Key Medical Personnel Project(ZDRCA2016002)CKD Anemia Research Foundation from China International Medical Foundation(Z-2017-24-2037)Outstanding Young and Middle-Aged Talents Support Program of The First Affiliated Hospital of Nanjing Medical University(Jiangsu Province Hospital)the National Key Research and Development Program of China(2017YFC1001303)the Program of Jiangsu Province Clinical Medical Center(YXZXB2016001,BL2012009)the State Key Laboratory of Reproductive Medicine Program(SKLRM-GC201803)the Program of Jiangsu Commission of Health(H201605).
文摘Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progressive skin ischemia,large areas of painful malodorous ulcers,and mummified legs.Because of the worsening symptoms and signs refractory to conventional therapies,treatment with human amnion-derived mesenchymal stem cells(hAMSCs)was approved.Preclinical release inspections of hAMSCs,efficacy,and safety assessment,including cytokine secretory ability,immunocompetence,tumorigenicity,and genetics analysis in vitro,were introduced.We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats,abnormal immune response tests in C57BL/6 mice,and tumorigenicity tests in neonatal Balbc-nu nude mice.After the preclinical research,the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers.When followed up to 15 months,the blood-based markers of bone and mineral metabolism improved,with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells.Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis,and 20 months later,the re-epithelialization restored the integrity of the damaged site.No infusion or local treatment-related adverse events occurred.Thus,this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,anti-inflammatory and immune modulation,multidifferentiation,re-epithelialization,and restoration of integrity.
