Objective:To investigate the trajectory of frailty in elderly patients on maintenance hemodialysis(MHD)following SARS-CoV-2 infection and its associated risk factors.Methods:This prospective cohort study focused on elderly patients who underwent baseline frailty assessment(T0)during hemodialysis treatment at Beijing Friendship Hospital for over 3 months between December 1st, 2022, and December 31th, 2022, and were diagnosed with SARS-CoV-2 infection.The Fried Frailty Phenotype was evaluated at 1 month(T1), 3 months(T2), and 6 months(T3)post-infection.Frailty trajectory after infection was analyzed using repeated measurement ANOVA.Patients were divided into stable/improvement or exacerbation groups based on their frailty status at T0 and T3, with logistic regression analysis employed to identify risk factors for different frailty trajectories.Results:A total of 130 elderly maintenance hemodialysis patients, with a median age of 66 years(range: 63-71 years)and 62 males(47.7%), were included in the study.Six months after the infection, a majority of surviving patients saw their frailty scores return to baseline levels.Specifically, 72 patients(55.4%)either maintained or improved to robust or pre-frail states, while 9 patients(6.9%)progressed to a pre-frail state, 18 patients(13.8%)progressed to a frail state, and 31 patients(23.8%)remained in a frail state.Results from multivariate logistic regression analysis indicated that low grip strength( OR: 6.30, 95% CI: 1.48-26.73)and all-cause hospitalization( OR: 5.01, 95% CI: 1.19-21.03)were identified as risk factors for non-frail patients transitioning to frailty( P<0.05). Conclusions:The majority of elderly maintenance hemodialysis patients who survived SARS-CoV-2 infection returned to their baseline level of frailty or showed improvement within 6 months.Non-frail patients with low grip strength or those who were hospitalized were more likely to deteriorate towards frailty.

Objective:To investigate the predictive value of the Japanese nutritional risk index(NRI)for one-year all-cause mortality risk among elderly maintenance hemodialysis (MHD)patients.Additionally, it seeks to compare the predictive abilities of NRI with those of the geriatric nutritional risk index (GNRI)and the mini nutritional assessment short-form(MNA-SF).Methods:This research was conducted as a prospective cohort study.Elderly patients(aged ≥60 years)who underwent hemodialysis treatment at Beijing Friendship Hospital of Capital Medical University for more than three months between July and October 2019 were selected for inclusion.The NRI score was utilized to evaluate the nutritional status of the participants, with the maximum point of the Jordan index designated as the cut-off value, thereby categorizing patients into high-risk and low-risk groups.The follow-up period concluded in August 2020, with all-cause mortality serving as the primary outcome measure.Kaplan-Meier methods were employed to construct survival curves, and the Cox proportional hazards model was applied to analyze the association between NRI and all-cause mortality.Furthermore, area under the curve(AUC) of receiver operating characteristic(ROC)curves were utilized to compare the predictive values of the three nutritional assessment methods(NRI, GNRI, and MNA-SF)regarding mortality risk.Results:A total of 150 patients were included in the study, with a median age of 69(64.75) years.The cohort comprised 73 males(48.7%)and 77 females(51.3%). Based on the NRI, patients were categorized into a low-risk group(NRI<5; n=81, 54.0%)and a high-risk group(NRI ≥ 5; n=69, 46.0%). Of the 150 patients, 147 completed the follow-up.During the follow-up period, 15 patients died, with 13 from the high-risk group and 2 from the low-risk group.The Kaplan-Meier survival curve indicated that the 1-year cumulative survival rate for patients in the high-risk group was significantly lower than the low-risk group (log-rank χ2=11.71, P<0.001). Furthermore, multivariate Cox regression analysis revealed a significant association between NRI and 1-year all-cause mortality in elderly patients undergoing MHD ( HR=3.779, 95% CI: 1.036-13.783, P=0.044). Additionally, NRI demonstrated a high predictive value for 1-year all-cause mortality risk in elderly MHD patients, with an AUC of 0.755(95% CI: 0.654-0.855), a sensitivity of 86.7%, and a specificity of 59.1%.Its predictive capability was slightly superior to that of the GNRI(AUC=0.691, 95% CI: 0.548-0.835)and the MNA-SF(AUC=0.634, 95% CI: 0.475-0.793), although no statistically significant differences were observed( Z=0.880, 1.177, P=0.379, 0.239). Conclusions:The NRI score demonstrates effective predictive capability for one-year all-cause mortality risk in elderly MHD patients and may serve as a more suitable nutritional assessment method for this population.

Objective To study the influencing factors of intradialytic hypotension(IDH)in diabetic maintenance hemodialysis(MHD)patients,and to provide references for clinical prevention of IDH quality control.Methods A total of 200 diabetic patients from four hemodialysis centers in Beijing from March 2022 to September 2022 were collected as the research objects.According to the definition of IDH[systolic blood pressure during hemodialysis≤90 mmHg(1 mmHg=0.133 kPa)or systolic blood pressure reduction during dialysis≥30 mmHg],the patients were divided into IDH group(frequency of hypotension events during dialysis≥30%during 7 months of follow-up)and non-IDH group.Univariate analysis and multivariate Logistic regression were used to analyze the influencing factors of IDH.receive operating characteristic curve(ROC)curve analysis was used to evaluate the predictive value of each influencing factor for IDH.Results Univariate analysis showed that compared with non-IDH group,IDH group had higher systolic blood pressure,higher blood glucose and lower serum albumin before dialysis(P<0.05).There were more patients with orthostatic hypotension in the IDH group than in the non-IDH group(P<0.05).Multivariate Logistic regression analysis showed that pre-dialysis systolic blood pressure,orthostatic hypotension and serum albumin were the influencing factors of IDH(P<0.05).ROC curve was used to evaluate the diagnostic accuracy of pre-hemodialysis systolic blood pressure for IDH.The area under the ROC curve was 0.787(95%CI:0.720-0.854,P<0.001),the threshold of IDH predicted by the Jorden index was 153 mmHg,the sensitivity was 75.5%,and the specificity was 75.4%.Conclusion Pre-hemodialysis systolic blood pressure,blood albumin and postural hypotension are independent factors of IDH in diabetic patients.In order to predict the occurrence of IDH,the pre-hemodialysis systolic blood pressure threshold was 153 mmHg.

Objective To study the influencing factors of intradialytic hypotension(IDH)in diabetic maintenance hemodialysis(MHD)patients,and to provide references for clinical prevention of IDH quality control.Methods A total of 200 diabetic patients from four hemodialysis centers in Beijing from March 2022 to September 2022 were collected as the research objects.According to the definition of IDH[systolic blood pressure during hemodialysis≤90 mmHg(1 mmHg=0.133 kPa)or systolic blood pressure reduction during dialysis≥30 mmHg],the patients were divided into IDH group(frequency of hypotension events during dialysis≥30%during 7 months of follow-up)and non-IDH group.Univariate analysis and multivariate Logistic regression were used to analyze the influencing factors of IDH.receive operating characteristic curve(ROC)curve analysis was used to evaluate the predictive value of each influencing factor for IDH.Results Univariate analysis showed that compared with non-IDH group,IDH group had higher systolic blood pressure,higher blood glucose and lower serum albumin before dialysis(P<0.05).There were more patients with orthostatic hypotension in the IDH group than in the non-IDH group(P<0.05).Multivariate Logistic regression analysis showed that pre-dialysis systolic blood pressure,orthostatic hypotension and serum albumin were the influencing factors of IDH(P<0.05).ROC curve was used to evaluate the diagnostic accuracy of pre-hemodialysis systolic blood pressure for IDH.The area under the ROC curve was 0.787(95%CI:0.720-0.854,P<0.001),the threshold of IDH predicted by the Jorden index was 153 mmHg,the sensitivity was 75.5%,and the specificity was 75.4%.Conclusion Pre-hemodialysis systolic blood pressure,blood albumin and postural hypotension are independent factors of IDH in diabetic patients.In order to predict the occurrence of IDH,the pre-hemodialysis systolic blood pressure threshold was 153 mmHg.

Objective To investigate the mechanism by which apelin inhibits the transition from acute kidney injury(AKI)to chronic kidney disease(CKD).Methods Human proximal tubular epithelial cells were cultured in vitro and divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 siRNA,and apelin groups.Cells were transfected with Sirt3 siRNA and incubated with a medium containing cisplatin(10 μmol/L)and/or apelin-13(1 μmol/L).Mitochondrial morphology was observed using MitoTracker? probes;mito-chondrial membrane potential was detected using the JC-1 assay kit;and the expression of the fibrogenic cytokine,transforming growth factor β1(TGF-β1)was measured by Western blotting.Forty 10-week-old male C57BL/6J mice were divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 knockdown,and empty adenovirus groups,with eight mice per group.Except for the control and empty adenovirus groups,all the other groups were intraperitoneally injected with cisplatin(20 mg/kg)to establish the AKI model.The cis-platin+apelin group was intraperitoneally injected with apelin-13(0.1 μg·kg-1·d-1);the control group was injected with an equal volume of saline;the cisplatin+apelin+Sirt3 knockdown group was injected with Sirt3 knockdown adenovirus(2 × 109 pfu/mL)via the tail vein and intraperitoneal injection of apelin-13(0.1 μg·kg-1·d-1);and the empty adenovirus group was injected with adenovirus(2 × 109 pfu/mL)via the tail vein.The mice were sacrificed after 2 weeks.Kidney fibrosis was assessed by Masson's trichome staining.Type Ⅰ collagen(Col-Ⅰ)expression was observed by immunohistochemical staining.Plasma creatinine(Cr)and blood urea nitrogen(BUN)levels were measured by ELISA.Results In vitro experiments showed that,compared with the control group,the cisplatin group exhibited reduced mitochondrial fluorescence staining,decreased mitochondrial membrane potential,and increased TGF-β1 expression(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed increased fluorescence staining,elevated mitochondrial membrane potential,and reduced TGF-β1 expression(all P＜0.05);however,these effects were counteracted after Sirt3 siRNA transfection.In vivo experiments showed that,compared with the control group,the cisplatin group exhibited significant renal tubular atrophy and interstitial fibrosis,increased Col-Ⅰ positive expression,and elevated plasma Cr and BUN levels(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed a significant improvement in all the above indicators(all P＜0.05).Compared with the cisplatin+apelin group,the cisplatin+apelin+Sirt3 knockdown group showed a significant reduction in the renal protective effects of apelin.Conclusion The polypeptide apelin inhibits the transition from AKI to CKD by regulating Sirt3 expression to maintain mitochondrial structure and function,which can reduce renal fibrosis and improve renal function.

Tubulointerstitial renal fibrosis is an essential feature of diabetic nephropathy (DN). Pericytes play a critical role in microvascular diseases and renal fibrogenesis. However, the role of pericytes in DN remains unclear. Herein, we aimed to explore the properties and possible mechanisms of pericytes in renal fibrosis in DN. Methods: We used multiplex immunofluorescence staining to evaluate the location and expression of activated pericytes and to assess capillary dilation and interstitial fibrosis in the kidneys of db/db mice. Pericytes were co-stained for alpha-smooth muscle actin (α-SMA) to determine which ones differentiate into myofibroblasts in db/db mice. Expression of CD34 and platelet-derived growth factor receptor beta (PDGFR-β) was assessed in kidney tissue from patients with DN by immunohistochemical staining. Results: We found that cell staining for nerve/glial antigen 2 (NG2)+ and PDGFR-β+ was greater in the kidneys of db/db mice than in those of db/m mice. There was impaired pericyte coverage of blood vessels and capillary dilation in the renal interstitium. These changes were accompanied by increased collagen I staining and an increase in the number of pericytes with profibrotic phenotypes, as identified by increased NG2+/PDGFR-β+/α-SMA+ and decreased NG2+/PDGFR-β+/α-SMA– staining. In DN patients, expression of PDGFR-β was stronger and there was loss of CD34 compared with the findings in control patients with minor glomerular lesions. Conclusion: In this study, we demonstrated that pericyte activation accompanied by peritubular capillary dysfunction and pericytemyofibroblast transition is associated with renal fibrosis in DN.

Objective:To investigate the trajectory of frailty in elderly patients on maintenance hemodialysis(MHD)following SARS-CoV-2 infection and its associated risk factors.Methods:This prospective cohort study focused on elderly patients who underwent baseline frailty assessment(T0)during hemodialysis treatment at Beijing Friendship Hospital for over 3 months between December 1st, 2022, and December 31th, 2022, and were diagnosed with SARS-CoV-2 infection.The Fried Frailty Phenotype was evaluated at 1 month(T1), 3 months(T2), and 6 months(T3)post-infection.Frailty trajectory after infection was analyzed using repeated measurement ANOVA.Patients were divided into stable/improvement or exacerbation groups based on their frailty status at T0 and T3, with logistic regression analysis employed to identify risk factors for different frailty trajectories.Results:A total of 130 elderly maintenance hemodialysis patients, with a median age of 66 years(range: 63-71 years)and 62 males(47.7%), were included in the study.Six months after the infection, a majority of surviving patients saw their frailty scores return to baseline levels.Specifically, 72 patients(55.4%)either maintained or improved to robust or pre-frail states, while 9 patients(6.9%)progressed to a pre-frail state, 18 patients(13.8%)progressed to a frail state, and 31 patients(23.8%)remained in a frail state.Results from multivariate logistic regression analysis indicated that low grip strength( OR: 6.30, 95% CI: 1.48-26.73)and all-cause hospitalization( OR: 5.01, 95% CI: 1.19-21.03)were identified as risk factors for non-frail patients transitioning to frailty( P<0.05). Conclusions:The majority of elderly maintenance hemodialysis patients who survived SARS-CoV-2 infection returned to their baseline level of frailty or showed improvement within 6 months.Non-frail patients with low grip strength or those who were hospitalized were more likely to deteriorate towards frailty.

Objective To investigate the mechanism by which apelin inhibits the transition from acute kidney injury(AKI)to chronic kidney disease(CKD).Methods Human proximal tubular epithelial cells were cultured in vitro and divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 siRNA,and apelin groups.Cells were transfected with Sirt3 siRNA and incubated with a medium containing cisplatin(10 μmol/L)and/or apelin-13(1 μmol/L).Mitochondrial morphology was observed using MitoTracker? probes;mito-chondrial membrane potential was detected using the JC-1 assay kit;and the expression of the fibrogenic cytokine,transforming growth factor β1(TGF-β1)was measured by Western blotting.Forty 10-week-old male C57BL/6J mice were divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 knockdown,and empty adenovirus groups,with eight mice per group.Except for the control and empty adenovirus groups,all the other groups were intraperitoneally injected with cisplatin(20 mg/kg)to establish the AKI model.The cis-platin+apelin group was intraperitoneally injected with apelin-13(0.1 μg·kg-1·d-1);the control group was injected with an equal volume of saline;the cisplatin+apelin+Sirt3 knockdown group was injected with Sirt3 knockdown adenovirus(2 × 109 pfu/mL)via the tail vein and intraperitoneal injection of apelin-13(0.1 μg·kg-1·d-1);and the empty adenovirus group was injected with adenovirus(2 × 109 pfu/mL)via the tail vein.The mice were sacrificed after 2 weeks.Kidney fibrosis was assessed by Masson's trichome staining.Type Ⅰ collagen(Col-Ⅰ)expression was observed by immunohistochemical staining.Plasma creatinine(Cr)and blood urea nitrogen(BUN)levels were measured by ELISA.Results In vitro experiments showed that,compared with the control group,the cisplatin group exhibited reduced mitochondrial fluorescence staining,decreased mitochondrial membrane potential,and increased TGF-β1 expression(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed increased fluorescence staining,elevated mitochondrial membrane potential,and reduced TGF-β1 expression(all P＜0.05);however,these effects were counteracted after Sirt3 siRNA transfection.In vivo experiments showed that,compared with the control group,the cisplatin group exhibited significant renal tubular atrophy and interstitial fibrosis,increased Col-Ⅰ positive expression,and elevated plasma Cr and BUN levels(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed a significant improvement in all the above indicators(all P＜0.05).Compared with the cisplatin+apelin group,the cisplatin+apelin+Sirt3 knockdown group showed a significant reduction in the renal protective effects of apelin.Conclusion The polypeptide apelin inhibits the transition from AKI to CKD by regulating Sirt3 expression to maintain mitochondrial structure and function,which can reduce renal fibrosis and improve renal function.

Objective:To investigate the predictive value of the Japanese nutritional risk index(NRI)for one-year all-cause mortality risk among elderly maintenance hemodialysis (MHD)patients.Additionally, it seeks to compare the predictive abilities of NRI with those of the geriatric nutritional risk index (GNRI)and the mini nutritional assessment short-form(MNA-SF).Methods:This research was conducted as a prospective cohort study.Elderly patients(aged ≥60 years)who underwent hemodialysis treatment at Beijing Friendship Hospital of Capital Medical University for more than three months between July and October 2019 were selected for inclusion.The NRI score was utilized to evaluate the nutritional status of the participants, with the maximum point of the Jordan index designated as the cut-off value, thereby categorizing patients into high-risk and low-risk groups.The follow-up period concluded in August 2020, with all-cause mortality serving as the primary outcome measure.Kaplan-Meier methods were employed to construct survival curves, and the Cox proportional hazards model was applied to analyze the association between NRI and all-cause mortality.Furthermore, area under the curve(AUC) of receiver operating characteristic(ROC)curves were utilized to compare the predictive values of the three nutritional assessment methods(NRI, GNRI, and MNA-SF)regarding mortality risk.Results:A total of 150 patients were included in the study, with a median age of 69(64.75) years.The cohort comprised 73 males(48.7%)and 77 females(51.3%). Based on the NRI, patients were categorized into a low-risk group(NRI<5; n=81, 54.0%)and a high-risk group(NRI ≥ 5; n=69, 46.0%). Of the 150 patients, 147 completed the follow-up.During the follow-up period, 15 patients died, with 13 from the high-risk group and 2 from the low-risk group.The Kaplan-Meier survival curve indicated that the 1-year cumulative survival rate for patients in the high-risk group was significantly lower than the low-risk group (log-rank χ2=11.71, P<0.001). Furthermore, multivariate Cox regression analysis revealed a significant association between NRI and 1-year all-cause mortality in elderly patients undergoing MHD ( HR=3.779, 95% CI: 1.036-13.783, P=0.044). Additionally, NRI demonstrated a high predictive value for 1-year all-cause mortality risk in elderly MHD patients, with an AUC of 0.755(95% CI: 0.654-0.855), a sensitivity of 86.7%, and a specificity of 59.1%.Its predictive capability was slightly superior to that of the GNRI(AUC=0.691, 95% CI: 0.548-0.835)and the MNA-SF(AUC=0.634, 95% CI: 0.475-0.793), although no statistically significant differences were observed( Z=0.880, 1.177, P=0.379, 0.239). Conclusions:The NRI score demonstrates effective predictive capability for one-year all-cause mortality risk in elderly MHD patients and may serve as a more suitable nutritional assessment method for this population.

Objective To explore the protective effect of polypeptide Apelin on podocyte mitochondria in diabetic nephropathy and underling mechanisms.Methods Human renal podocytes were divided into four experimental groups:control group,high glucose(HG)group(glucose 25 mmol/L,48 h),Apelin intervention HG group(Ape-lin-13 1 μmol/L,48 h)and Apelin group(Apelin-13 1 μmol/L,48 h).The podocyte apoptosis was observed by TUNEL staining,the expression of mitochondrial membrane protein FUNDC1 was detected by Western blot,and the binding of mitochondrial fission protein DRP1 to FUNDC1 was examined by immunoprecipitation.The 8-week-old male mice were divided into three experimental groups:control group,diabetes group(intraperito-neal injection of streptozotocin 150 mg/kg,only one time)and Apelin intervention DM group(intraperitoneal injection of Apelin-13 0.3 μmol/kg,daily).The morphology of renal was observed by PAS staining and trans-mission electron microscopy.Plasma creatinine(Cr),urea nitrogen,urinary albumin and creatinine were de-tected by ELISA kit.The level of creatinine clearance rate(Ccr)and urinary albumin/creatinine(ACR)was calculated.Results Compared with the control group,the podocyte apoptosis and expression of FUNDC1 in the HG group increased significantly(P＜0.05),and the combination of mitochondrial fission division protein DRP1 to FUNDC1 raised.Meanwhile,compared with the HG group,the number of apoptosis,the expression of FUNDC1(P＜0.05),and the combination of DRP1 to FUNDC1 all reduced in Apelin intervention HG group.Animal experiments showed that the kidney structure of the control group was intact.In the DM group,the num-ber of podocytes decreased significantly,the foot processes were fused and dropped off.In the Apelin intervention DM group,podocyte lesions were less severe than those in the DM group.Compared with the control group,the level of plasma Cr,BUN and urine ACR in the DM group increased,while the level of Ccr decreased significantly(P＜0.05).However,compared with the DM group,the level of above biomarkers in the Apelin intervention DM group was improved(P＜0.05).Conclusions Apelin keeps mitochondrial homeostasis and reduces podocyte ap-optosis by inhibiting the expression of mitochondrial membrane protein FUNDC1,which may contribute to allevia-tion of diabetic nephropathy.