Objective:To observe effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rate.Methods:A total of 75 SD rate were randomly divided into A,B,C,D,E groups with 15 in each g...Objective:To observe effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rate.Methods:A total of 75 SD rate were randomly divided into A,B,C,D,E groups with 15 in each group.Rats in group A served as the control group received just only but tissue separation without modeling operation,while model of unilateral ureteral obstruction(UUO) was established in B,C,D,E groups.Rats in A,B group were given saline lavage placebo treatment,while rats in C,D,E groups were given dianunonium glycyrrhizinate and alprostadil injection.Five rats were sacrificed 1,2,3 weeks after modeling,serum creatinine level of femoral venous blood was determined.Transforming growth factor- β1(TCF- β1) and concentration of connective tissue growth factor(CTGF) were also detected by using ELISA.Line renal interstitial tissue was taken after HE staining,renal interstitial TGF- β1 and CTGF expression were detected by using immunohistochemical method.Results:Serum creatinine levels of B,C,D,E group at different time points in were significantly higher than that of group A(P<0.05);serum creatinine levels in group B were significantly higher than that of C,D,E group at each time point(P<0.05).Serum creatinine level of Croup E was significantly lower than C,D group after 2,3 weeks(P<0.05).Rate in A group at each time point showed no significant changes in TGF- β1 and CREA concentration in serum and kidney tissues(P>0.05);while serum and kidney tissue TGF- β1,concentration of CREA.expression of rats in B,C,D,E groups showed a gradual increasing trend over time.TCF- β1 and CREF of Group B in serum and kidney tissues at each time point were significantly higher than that of the other groups(P<0.05).TCF- β1 and CREF of Group E in serum and kidney tissues at each time point were significantly lower than that of B,C,D group at all time points in serum and kidney tissues(P<0.05).Conclusions:Alprostadil combined with diammonium glycyrrhizinate can significantly lower the expression of TGF- β1 and CTGF in serum and tissues of SD rat with renal interstitial fibrosis,thus inhibit rat renal interstitial fibrosis process.It has synergy protective effect.展开更多
BACKGROUND Acute kidney injury(AKI)is a sudden or rapid decline in the filtration function of the kidneys which is marked by increased serum creatinine or blood urea nitrogen.AIM To examine the value of alprostadil-as...BACKGROUND Acute kidney injury(AKI)is a sudden or rapid decline in the filtration function of the kidneys which is marked by increased serum creatinine or blood urea nitrogen.AIM To examine the value of alprostadil-assisted continuous venous-venous hemofiltration(CVVH)in the treatment of severe AKI in severely ill patients.METHODS This was a retrospective study and the inclusion criteria were as follows:(1)Age of patients(≥18 years);(2)Admission to intensive care unit due to non-renal primary disease,APACHE II score(≥18 points);(3)The diagnostic criteria of AKI guidelines were formulated with reference to the Global Organization for the Improvement of Prognosis in Kidney Diseases,with AKI grades of II-III;(4)All patients were treated with CVVH;and(5)Complete basic data were obtained for all patients.RESULTS The clinical effect of alprostadil administered in the treatment group was better than that observed in the control group(P<0.05).The urine output of patients in the alprostadil group returned to normal time(9.1±2.0 d)and was lower than that in the control group(10.6±2.5 d),the difference was statistically significant(P<0.05);adverse reactions occurred in the alprostadil group compared with the control group,but the difference was not statistically significant(P>0.05).CONCLUSION Alprostadil-assisted CVVH in the treatment of severely ill patients with AKI can effectively improve the renal resistance index and partial pressure of urine oxygen,and has a positive effect on improving renal function.展开更多
Aim: To evaluate the efficacy and safety of transurethral application of alprostadil (MUSE^(R) ) for the treatment oferectile dysfunction in Indonesians. Methods: Twenty erectile dysfunction patients aged between 32-7...Aim: To evaluate the efficacy and safety of transurethral application of alprostadil (MUSE^(R) ) for the treatment oferectile dysfunction in Indonesians. Methods: Twenty erectile dysfunction patients aged between 32-74 years oldwere recruited in this study. The inclusion criteria were as follows: 1) adult males 18 years or older with a subjectivecomplaint or erectile dysfunction, 2) to provide written informed consent, 3) to agree not to use other forms of treat-ment for erectile dysfunction, 4) fulfill the screening laboratory values. Part Ⅰ, eligible patients were titrated in theclinic starting with a dose of 250μg and proceed in a stepwise manner to 500 μg and 1000 μg on separate clinic visitsuntil they identified a dose that produced a satisfactory response. The interval between each in-clinic titration was 2-3days. Each in-clinic titration dose was evaluated at 15 rain intervals over a one hour period for erection assessment,blood pressure and pulse. Part 2, patients used MUSE at home for three months at the dose identified during the in-clinic titration. Monthly interim visits were required for patient follow-up and drug distribution. At the end of thestudy, patients had another laboratory (except testosterone, only assayed in screening procedure) and physical examina-tion. Results: The etiology of erectile dysfunction was psychological in 5 patients and organic in 15 patients. The65% of the patients achieved the erection scale of 4 or 5 either in the clinic or at home, 10% achieved the scale of 4at home, but not in the clinic, and 25% only achieved the scale of 2 or 3 with the highest dose of 1000 μg either in theclinic or at home. No significant differences were found in biochemical examination before and after the study. The60% of the patients who achieved erection scale 4 or 5 continued to use MUSE until the end of the study, while 40%of them complained of pain at the time of MUSE application, during erection and/or during intercourse. They withdrewfrom the study. Conclusion: Transurethral application of alprostadil (MUSE) is effective and safe to produce erec-tion sufficient for intercourse in erectile dysfunction of various etiologies. Pain during application, erection and inter-course is a common side effect and a cause of withdrawal.展开更多
Background Patients with unstable angina pectoris and diabetes mellitus are very common. When they receive interventional therapy, contrast agentscan causerenal injuryand platelet activation. Alprostadil has been show...Background Patients with unstable angina pectoris and diabetes mellitus are very common. When they receive interventional therapy, contrast agentscan causerenal injuryand platelet activation. Alprostadil has been shown to decrease inflammation and microvascular resistance. There is no any report on the protection effects of alprostadilon renal injuryand the platelet activation during cardiac interventional therapy. Methods A total of 57 patients were divided into two groups, alprostadil group （n=35） and normal group n=22）. BUN （blood urea ni- trogen） and SCr （serum creatine） were measured as the renal function parameters. GFR （glomerular filtration rate） was calculated by the MDRD formula. Platelet parameters： PLT （platelet count, 109）, PDW （platelet distribu- tion width, fL）, MPV （mean platelet volume, fL）, PLCR （large platelet scale ratio, %） were measured as the platelet activationindex. T test and Chi-square test were used as statistical methods, and P〈0.05 was considered statistically significant. Results In the alprostadil group, SCr was 71.1±13.8 μmoFL and 65.9±12.6 ＆tool/L, before and after interventional therapy （P〈0.05）. BUN was 5.68±1.79 mmol/L and 3.86±1.19 mmol/L （P〈0.001）, before and after interventional therapy. I n the platelet tests, MPV was seemed to be the only useful platelet parameter, before and after interventional therapy （11.8±1.8 fL and ll.l±1.2fL, P〈0.05）, while the PLT （109/L）, PDW （fl）, PLCR （%） didn＇ t show any significant difference. In the normal group, all these tests＇ results didn＇ t significantly change after interventional therapy. Conclusions The patients with the unstable angina pectoris and diabetes mellitus have on the risk of renal function damage and platelet activation when undertaking cardiac interventional therapy. Alprostadil protects renal function and alleviates olatelet activation.展开更多
ObjectiveTo investigate the effects of alprostadil combined with lipoic acid on clinical efficacy,hemodynamics,fibronectin and plasma D-dimer in elderly patients with type 2 diabetic foot.Methods Ninety-six elderly pa...ObjectiveTo investigate the effects of alprostadil combined with lipoic acid on clinical efficacy,hemodynamics,fibronectin and plasma D-dimer in elderly patients with type 2 diabetic foot.Methods Ninety-six elderly patients with type 2 diabetic foot hospitalized in Department of Endocrinology,Xining First People's Hospital from January 2017 to June 2019 were selected as the study subjects.They were divided into control group(48 cases)and case group(48 cases)by random number table method.The control group was treated with lipoic acid,and the case group was treated with Alprostadil for injection on the basis of the control group.The clinical efficacy,clinical symptom score,ulcer healing,hemodynamics of dorsal artery of foot,fibronectin and plasma D-two dimer in two groups were observed.Results The total effective rate of the case group was 95.83%,which was significantly higher than that of the control group(83.33%).The difference was statistically significant(P<0.05).After treatment,the pain,swelling,claudication,numbness score,ulcer area,wound PH value,plasma D-dimer level of the two groups were lower than those before treatment,and the oxygen partial pressure,blood flow velocity,vascular diameter,Resistance index(RI),pulsation index(PI)and fibronectin levels of the two groups were higher than those before treatment,the difference was statistically significant(P<0.05).The improvement of clinical efficacy,ulcer healing,dorsal pedal artery hemodynamics,fibronectin and plasma D-dimer levels in the case group were significantly better than those in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).ConclusionsAlprostadil combined with lipoic acid has significant clinical effect on elderly patients with type 2 diabetic foot.It can correct the abnormal hemodynamics of dorsal pedal artery,promote the healing of foot ulcer,increase the content of fibronectin ulcer tissue,reduce the level of plasma D-dimer and improve the high coagulation state.It has high efficiency and safety.It is worthy of clinical application.Further promotion.展开更多
Objective:To investigate the clinical efficacy and safety of alprostadil combined with Bailing Capsule in the treatment of chronic renal failure,and the influence of alprostadil combined with Bailing Capsule on residu...Objective:To investigate the clinical efficacy and safety of alprostadil combined with Bailing Capsule in the treatment of chronic renal failure,and the influence of alprostadil combined with Bailing Capsule on residual renal function,renal hemodynamics,immune indexes and nutritional status.Methods 86 patients with chronic renal failure(CRF)hospitalized in Wuhan integrated traditional Chinese and Western Medicine Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology from January 2018 to June 2019 were selected as the study objects.They were randomly divided into control group and case group with 43 cases in each group.Two groups were given peritoneal dialysis treatment,the control group was given bailing capsule,the case group was given alprostadil injection on the basis of the control group.To observe the clinical effect of the two groups before and after treatment,and the changes of residual renal function,renal hemodynamics,immune index and nutritional status.Results The total effective rate of the case group was 97.68%,higher than 83.73%of the control group,the difference was statistically significant(P<0.05).After treatment,the levels of bun,SCR,GFR,24h urinary protein quantity,resistance index,CRP,IL-6,TNF,CD8+and SGA in the two groups were lower than those before treatment;the levels of renal blood flow,RRF,CD3+,CD4+,ALB,PA,TRF and Hb were higher than those before treatment;moreover,the improvement of serum inflammatory cytokines,residual renal function and renal hemodynamic indexes,immune indexes and nutritional status in the case group were significant The difference was statistically significant(P<0.05).The incidence of adverse reactions in the control group was 16.28%,higher than 6.98%in the case group,with no significant difference(P>0.05).Conclusion Alprostadil combined with Bailing capsule can significantly improve the residual renal function,hemodynamics,immune index,reduce the degree of inflammatory response in patients with chronic renal failure.展开更多
Background:Diabetic kidney disease is now the principal cause of end-stage renal failure worldwide.Alprostadil combined with tripterygium glycosides tablet is a new method for diabetic kidney disease treatment.However...Background:Diabetic kidney disease is now the principal cause of end-stage renal failure worldwide.Alprostadil combined with tripterygium glycosides tablet is a new method for diabetic kidney disease treatment.However,there are currently few systematic reviews on treatment for alprostadil combined with tripterygium glycosides tablet.Therefore,a systematic review and meta-analysis was conducted to analyze the function of alprostadil combined with tripterygium glycosides tablet in the treatment of diabetic kidney disease.Methods:We searched Pubmed,Embase,the Cochrane Library,Chinese databases,and clinical trial for randomized controlled trials of alprostadil combined with tripterygium glycosides tablet in the treatment of diabetic kidney disease,including results from the foundation of database until August 5,2020.Two reviewers have independently performed literature screening,data extraction,and quality evaluation.This meta-analysis has been carried out by RevMan5.4 software.Results:Ten randomized controlled trials with 724 patients were involved.Compared with alprostadil alone,the combination of alprostadil and tripterygium glycosides tablet in treatment of diabetic kidney disease could reduce the level of 24-hour urine protein(95%CI(–2.05,–0.22),P=0.01),serum creatinine(95%CI(–5.01,–0.20),P=0.03),level of interleukin-6(95%CI(−4.57,−2.37),P<0.00001),tumor necrosis factor-α(95%CI(−4.57,−2.37),P<0.00001).The combined treatment could also improve the clinical efficacy(95%CI(1.09,1.25),P<0.0001),and reduce the occurrence of serious adverse events(95%CI(0.26,0.94),P=0.03).However,there is no association of two treatments in blood urea nitrogen(95%CI(–4.17,2.11),P=0.52),albumin(95%CI(–1.10,0.97),P=0.90),triglyceride(95%CI(−1.44,1.50),P=0.97).Conclusion:Alprostadil combined with tripterygium glycosides tablet contributes to protecting renal function,inhibiting inflammation,and reducing the occurrence of adverse events,which could be considered as a feasible therapy for diabetic kidney disease patients.However,some clinical variables did not accurately conclude due to the low quality of methodology and small sample sizes.More rigorous and more extensive trials are essential to validate our results.Trial registration:Systematic review registration:(CRD42020203725).展开更多
Objective: To evaluate whether the combination of Uremic clearance granule with Alprostadil is superior to Alprostadil alone for CRF. Methods: Relevant RCTs were searched through March 2019. Data were analyzed by Stat...Objective: To evaluate whether the combination of Uremic clearance granule with Alprostadil is superior to Alprostadil alone for CRF. Methods: Relevant RCTs were searched through March 2019. Data were analyzed by Stata 15.0. Results: Nine articles involving 726 patients were enrolled in this study. Meta-analysis showed that the total effective rate [OR = 3.68 (2.44, 5.55), P < 0.001], Scr [SMD =-2.34 (-3.49,-1.19), P < 0.001], BUN [SMD =-1.80 (-2.73,-0.87), P < 0.001], Ccr [SMD = 0.71 (0.44, 0.97), P < 0.001] were better in the experimental group. But there were no significant difference in UA, CysC, 24h-Upro and incidence of adverse reactions (all P > 0.05) between two groups. No serious adverse reactions were found. Conclusions: The effect of the integrated medicine on CRF was better than Alprostadil alone. Uremic clearance granule is safe and has no obvious adverse reactions.展开更多
Objective: To research the effect of calcium dobesilate combinated with alprostadil on the changes of vascular endothelium function in patients with t diabetic nephropathy (DN), and assess the clinical effect and reco...Objective: To research the effect of calcium dobesilate combinated with alprostadil on the changes of vascular endothelium function in patients with t diabetic nephropathy (DN), and assess the clinical effect and record the untoward effect. Method: A totoal of 120 patients with DN, then they were randomly divided into control group (n=60) and observation group(n=60). Two groups were given hypoglycemic (melbinum)+improving circulatory (calcium dobesilate), and observation group were given alprostadil on the basic, they were treated 30 days. After treatment, we observed the changes of fasting plasma glucose (FBG), 2-hour postprandial blood glucose (2hPBG), the factot of vasomotion angiokinesis (nitrogen oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF)), diastolic function of vascular endothelium (flow mediated dilation (FMD), nitroglycerin mediated dilation (NMD)), renal function index (glomerular filtration rate (GFR), creatinine (Cr), blood urea nitrogen (BUN), albumin excrete rate (AER), urinary albumin creatinine ratio (UACR), urinary albumin evacuate ratio (UAER)), and record the untoward effect. Results: After treatment, the FBG, 2hPBG were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the FBG, 2hPBG in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the ET-1, VEGF were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the ET-1, VEGF in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the NO, FDM, NDM were higher than before treatment in both groups, the difference had statistical significance (P<0.05), and the NO, FDM, NDM in the observation group were higher than the control group, and the difference had statistical significance (P<0.05). After treatment, the GFR, Cr, BUN, AER, UACR, and UAER were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the GFR, Cr, BUN, UACR, and UAER in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). Conclusions: Treatment of the patients with DN before improving the cardiovascular system and hypoglycemic, giving the alprostadil can improve the function of vascular endothelium, rasing the clinical effect and safety.展开更多
Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV...Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection.Methods: 136 patients with decompensated cirrhosis of HBV infection who were hospitalized in Linxi Hospital of Kailuan General Hospital, Tangshan Infectious Disease Hospital and North China University of Technology Hospital from January to February 2018, 2017 were selected. All patients were divided into control group and case group by random number table method, 68 cases in each group. The control group was treated with routine liver protection and antiviral therapy, while the case group was treated with alprostadil on the basis of the control group. The changes of liver function, liver fibrosis, liver and spleen imaging indexes, anti-virus related indexes and inflammatory factors were observed before and after treatment in the two groups.Results: The total effective rate of the case group was 97.06%, which was significantly higher than that of the control group (85.29%), and the difference was statistically significant. The ALT, AST, TBIL, LN, HA, PCIII, CIV, portal vein diameter, spleen vein diameter, spleen thickness, IL-6, hs-CRP, TNF-α and TGF-β1 were significantly lower in the case group than in the control group. ALB, HBV DNA conversion rate, HBsAg negative rate, and HBeAg negative rate were significantly higher than the control group, the difference was statistically significant. Conclusion: Alprostadil combined with nucleoside antiviral drugs can significantly improve the decompensation of HBV infection Liver function in patients with cirrhosis, reduce the degree of liver fibrosis, inhibit the production of serum inflammatory factors, and can effectively inhibit HBV replication, clinical efficacy is significant, with certain clinical application value.展开更多
OBJECTIVE: To observe the effect of Shuxuening Injection combined with alprostadil on healing of diabetic foot ulcers and hemodynamic indexes of dorsal artery of foot. METHODS: A total of 84 cases of diabetic foot pat...OBJECTIVE: To observe the effect of Shuxuening Injection combined with alprostadil on healing of diabetic foot ulcers and hemodynamic indexes of dorsal artery of foot. METHODS: A total of 84 cases of diabetic foot patients treated in Wuhan Red Cross Hospital(from February 2016 to April 2017) were divided into treatment group(42 cases) and control group(42 cases) by the random digital table. The control group was given basic clinical treatment while the treatment group was given Shuxuening Injection combined with alprostadil on the basis of the treatment in control group. After 2 weeks of treatment, the improvement of TCM symptom scores(pain, numbness, swelling, claudication), conditions of foot ulcer healing(ulcer area, wound oxygen pressure, wound pH), the hemodynamics of the dorsum pedis artery(the blood flow velocity of the dorsum pedis artery, the blood vessel diameter, resistance index(RI), pulsation index(PI)) of both groups were compared, and the clinical efficacy of 2 groups were statistically analyzed. RESULTS: The scores of pain, numbness, swelling and claudication were significantly reduced in 2 groups after the treatment(P < 0.05), and the improvement of the above symptom scores in the treatment group were all significantly better than that in the control group(P < 0.05). The area of ulcer and the p H of the wounds in the 2 groups were significantly decreased after the treatment(P < 0.05), and the oxygen partial pressure in the wound was significantly increased(P < 0.05), and the improvements of the wound healing outcomes in the treatment group were significantly better than that in the control group(P < 0.05). The blood flow velocity of the foot, the blood vessel diameter, the level of RI and PI after treatment in both groups were significantly increased after the treatment(P < 0.05), and the improvement of the hemodynamic index of the foot back after treatment in the treatment group was significantly better than that in the control group(P < 0.05). The total effective rate of the treatment group was significantly higher than that of the control group(P < 0.05). CONCLUSION: The application of Shuxuening Injection combined with alprostadil can quickly improve the clinical symptoms of the patients, correct the abnormal hemodynamics of the dorsum pedis artery and promote the healing of foot ulcers, and the combination of the two medicines has a synergistic effect.展开更多
Objective: To investigate the effects of alprostadil on respiratory parameters and hemodynamics of newborns with persistent pulmonary hypertension. Methods: According to random data table method, 80 newborns of pulmon...Objective: To investigate the effects of alprostadil on respiratory parameters and hemodynamics of newborns with persistent pulmonary hypertension. Methods: According to random data table method, 80 newborns of pulmonary hypertension were randomly divided into the control group (n=40) and observation group (n=40), patients in the control group were given normal frequency ventilation, on the basis of the treatment of the control group, the observation group received alprostadil. The changes of respiratory parameters and hemodynamics were compared between the two groups before and after treatment. Results:The levels of respiratory parameters (SaO2, PaO2, PaCO2) and hemodynamics (PA, PVR, SVR) in the two groups before treatment were not statistically significant. After treatment, The levels of SaO2, PaO2in the two groups were significantly higher than those in the same group before treatment, and the observation group levels were (90.71±8.92)%, (85.27±8.23) mmHg, which were significantly higher than those in the control group after treatment;The levels of PaCO2, PA, PVR and SVR in the two groups after treatment were significantly lower than those in the same group before treatment, and the observation group were (35.22±3.46) mmHg, (26.95±3.78) mmHg, (725.71±108.82) dyns/cm5, (1 125.27±152.23) dyns/cm5, which were significantly lower than that of the control group. Conclusion: Adding alprostadil based on conventional frequent ventilation thraphy can effectively improve blood pressure and oxygen saturation, and improve hemodynamics of newborns with persistent pulmonary hypertension, which has important clinical value.展开更多
Objective:To analyze the renal function and oxidative stress after alprostadil combined with valsartan treatment of early diabetic nephropathy.Methods:A total of 230 patients with early diabetic nephropathy who were t...Objective:To analyze the renal function and oxidative stress after alprostadil combined with valsartan treatment of early diabetic nephropathy.Methods:A total of 230 patients with early diabetic nephropathy who were treated in our hospital between December 2011 and December 2015 were divided into control group (n=115) and observation group (n=115) according to random number table. Control group received valsartan treatment, observation group received alprostadil combined with valsartan treatment, and both lasted for one month. After treatment, renal blood flow parameters were evaluated by ultrasound contrast technique, renal function index levels in peripheral blood and urine were measured, and serum levels of oxidative stress indexes were detected.Results:After 1 month of treatment, area under curve (AUC) and time to peak (TTP) levels under ultrasound contrast of observation group were lower than those of control group while derived peak intensity (DPI) level was higher than that of control group;peripheral blood urea nitrogen (BUN) and serum creatinine (Scr) levels of observation group were lower than those of control group, albumin (Alb) level was higher than that of control group, and urine red blood cell (RBC) level was lower than that of control group;serum oxidative stress indexes malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels of observation group were lower than those of control group while superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) levels were higher than those of control group.Conclusion: Alprostadil combined with valsartan can optimize renal function and reduce systemic oxidative stress in patients with early diabetic nephropathy.展开更多
Objective:To study the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy.Methods:90 patients with early diabetic nephropathy...Objective:To study the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy.Methods:90 patients with early diabetic nephropathy treated in our hospital between June 2011 and November 2015 were collected and divided into observation group and control group (n=45) according to the single-blind randomized control method. Observation group received epalrestat combined with alprostadil treatment, control group received alprostadil treatment alone, and the treatment of both groups lasted for 3 months. Before treatment and after 3 months of treatment, turbidimetric immunoassay was used to detect the renal function indexes in peripheral blood, rate method was used to detect the renal function indexes in urine, and ELISA method was used to detect the levels of peroxidation indexes and inflammation indexes.Results:Before treatment, differences in renal function, peroxidation damage and inflammatory damage indexes were not statistically significant between two groups of patients (P>0.05). After 3 months of treatment, creatinine (Scr), cystatin C (CysC),β2 microglobulin (β2-MG), N-acetyl-β-D-glucosaminidase (NAG), reactive oxygen species (ROS), advanced protein oxidation products (AOPPs), interleukin-8 (IL-8), interleukin-27 (IL-27) and procalcitonin (PCT) levels of observation group were lower than those of control group while catalase (CAT), total superoxide dismutase (TSOD), interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13) levels were higher than those of control group (P<0.05). Conclusions:Epalrestat combined with alprostadil can protect the renal function and inhibit the peroxidation damage and inflammatory injury in patients with early diabetic nephropathy.展开更多
基金supported by Yantai Science and Technology Development Projects(2008142-19)
文摘Objective:To observe effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rate.Methods:A total of 75 SD rate were randomly divided into A,B,C,D,E groups with 15 in each group.Rats in group A served as the control group received just only but tissue separation without modeling operation,while model of unilateral ureteral obstruction(UUO) was established in B,C,D,E groups.Rats in A,B group were given saline lavage placebo treatment,while rats in C,D,E groups were given dianunonium glycyrrhizinate and alprostadil injection.Five rats were sacrificed 1,2,3 weeks after modeling,serum creatinine level of femoral venous blood was determined.Transforming growth factor- β1(TCF- β1) and concentration of connective tissue growth factor(CTGF) were also detected by using ELISA.Line renal interstitial tissue was taken after HE staining,renal interstitial TGF- β1 and CTGF expression were detected by using immunohistochemical method.Results:Serum creatinine levels of B,C,D,E group at different time points in were significantly higher than that of group A(P<0.05);serum creatinine levels in group B were significantly higher than that of C,D,E group at each time point(P<0.05).Serum creatinine level of Croup E was significantly lower than C,D group after 2,3 weeks(P<0.05).Rate in A group at each time point showed no significant changes in TGF- β1 and CREA concentration in serum and kidney tissues(P>0.05);while serum and kidney tissue TGF- β1,concentration of CREA.expression of rats in B,C,D,E groups showed a gradual increasing trend over time.TCF- β1 and CREF of Group B in serum and kidney tissues at each time point were significantly higher than that of the other groups(P<0.05).TCF- β1 and CREF of Group E in serum and kidney tissues at each time point were significantly lower than that of B,C,D group at all time points in serum and kidney tissues(P<0.05).Conclusions:Alprostadil combined with diammonium glycyrrhizinate can significantly lower the expression of TGF- β1 and CTGF in serum and tissues of SD rat with renal interstitial fibrosis,thus inhibit rat renal interstitial fibrosis process.It has synergy protective effect.
文摘BACKGROUND Acute kidney injury(AKI)is a sudden or rapid decline in the filtration function of the kidneys which is marked by increased serum creatinine or blood urea nitrogen.AIM To examine the value of alprostadil-assisted continuous venous-venous hemofiltration(CVVH)in the treatment of severe AKI in severely ill patients.METHODS This was a retrospective study and the inclusion criteria were as follows:(1)Age of patients(≥18 years);(2)Admission to intensive care unit due to non-renal primary disease,APACHE II score(≥18 points);(3)The diagnostic criteria of AKI guidelines were formulated with reference to the Global Organization for the Improvement of Prognosis in Kidney Diseases,with AKI grades of II-III;(4)All patients were treated with CVVH;and(5)Complete basic data were obtained for all patients.RESULTS The clinical effect of alprostadil administered in the treatment group was better than that observed in the control group(P<0.05).The urine output of patients in the alprostadil group returned to normal time(9.1±2.0 d)and was lower than that in the control group(10.6±2.5 d),the difference was statistically significant(P<0.05);adverse reactions occurred in the alprostadil group compared with the control group,but the difference was not statistically significant(P>0.05).CONCLUSION Alprostadil-assisted CVVH in the treatment of severely ill patients with AKI can effectively improve the renal resistance index and partial pressure of urine oxygen,and has a positive effect on improving renal function.
文摘Aim: To evaluate the efficacy and safety of transurethral application of alprostadil (MUSE^(R) ) for the treatment oferectile dysfunction in Indonesians. Methods: Twenty erectile dysfunction patients aged between 32-74 years oldwere recruited in this study. The inclusion criteria were as follows: 1) adult males 18 years or older with a subjectivecomplaint or erectile dysfunction, 2) to provide written informed consent, 3) to agree not to use other forms of treat-ment for erectile dysfunction, 4) fulfill the screening laboratory values. Part Ⅰ, eligible patients were titrated in theclinic starting with a dose of 250μg and proceed in a stepwise manner to 500 μg and 1000 μg on separate clinic visitsuntil they identified a dose that produced a satisfactory response. The interval between each in-clinic titration was 2-3days. Each in-clinic titration dose was evaluated at 15 rain intervals over a one hour period for erection assessment,blood pressure and pulse. Part 2, patients used MUSE at home for three months at the dose identified during the in-clinic titration. Monthly interim visits were required for patient follow-up and drug distribution. At the end of thestudy, patients had another laboratory (except testosterone, only assayed in screening procedure) and physical examina-tion. Results: The etiology of erectile dysfunction was psychological in 5 patients and organic in 15 patients. The65% of the patients achieved the erection scale of 4 or 5 either in the clinic or at home, 10% achieved the scale of 4at home, but not in the clinic, and 25% only achieved the scale of 2 or 3 with the highest dose of 1000 μg either in theclinic or at home. No significant differences were found in biochemical examination before and after the study. The60% of the patients who achieved erection scale 4 or 5 continued to use MUSE until the end of the study, while 40%of them complained of pain at the time of MUSE application, during erection and/or during intercourse. They withdrewfrom the study. Conclusion: Transurethral application of alprostadil (MUSE) is effective and safe to produce erec-tion sufficient for intercourse in erectile dysfunction of various etiologies. Pain during application, erection and inter-course is a common side effect and a cause of withdrawal.
基金supported by the National Natural Science Foundation of China(No.81170276)
文摘Background Patients with unstable angina pectoris and diabetes mellitus are very common. When they receive interventional therapy, contrast agentscan causerenal injuryand platelet activation. Alprostadil has been shown to decrease inflammation and microvascular resistance. There is no any report on the protection effects of alprostadilon renal injuryand the platelet activation during cardiac interventional therapy. Methods A total of 57 patients were divided into two groups, alprostadil group （n=35） and normal group n=22）. BUN （blood urea ni- trogen） and SCr （serum creatine） were measured as the renal function parameters. GFR （glomerular filtration rate） was calculated by the MDRD formula. Platelet parameters： PLT （platelet count, 109）, PDW （platelet distribu- tion width, fL）, MPV （mean platelet volume, fL）, PLCR （large platelet scale ratio, %） were measured as the platelet activationindex. T test and Chi-square test were used as statistical methods, and P〈0.05 was considered statistically significant. Results In the alprostadil group, SCr was 71.1±13.8 μmoFL and 65.9±12.6 ＆tool/L, before and after interventional therapy （P〈0.05）. BUN was 5.68±1.79 mmol/L and 3.86±1.19 mmol/L （P〈0.001）, before and after interventional therapy. I n the platelet tests, MPV was seemed to be the only useful platelet parameter, before and after interventional therapy （11.8±1.8 fL and ll.l±1.2fL, P〈0.05）, while the PLT （109/L）, PDW （fl）, PLCR （%） didn＇ t show any significant difference. In the normal group, all these tests＇ results didn＇ t significantly change after interventional therapy. Conclusions The patients with the unstable angina pectoris and diabetes mellitus have on the risk of renal function damage and platelet activation when undertaking cardiac interventional therapy. Alprostadil protects renal function and alleviates olatelet activation.
基金National Natural Science Foundation of China(81870544)National Natural Science Foundation of China(81673661).
文摘ObjectiveTo investigate the effects of alprostadil combined with lipoic acid on clinical efficacy,hemodynamics,fibronectin and plasma D-dimer in elderly patients with type 2 diabetic foot.Methods Ninety-six elderly patients with type 2 diabetic foot hospitalized in Department of Endocrinology,Xining First People's Hospital from January 2017 to June 2019 were selected as the study subjects.They were divided into control group(48 cases)and case group(48 cases)by random number table method.The control group was treated with lipoic acid,and the case group was treated with Alprostadil for injection on the basis of the control group.The clinical efficacy,clinical symptom score,ulcer healing,hemodynamics of dorsal artery of foot,fibronectin and plasma D-two dimer in two groups were observed.Results The total effective rate of the case group was 95.83%,which was significantly higher than that of the control group(83.33%).The difference was statistically significant(P<0.05).After treatment,the pain,swelling,claudication,numbness score,ulcer area,wound PH value,plasma D-dimer level of the two groups were lower than those before treatment,and the oxygen partial pressure,blood flow velocity,vascular diameter,Resistance index(RI),pulsation index(PI)and fibronectin levels of the two groups were higher than those before treatment,the difference was statistically significant(P<0.05).The improvement of clinical efficacy,ulcer healing,dorsal pedal artery hemodynamics,fibronectin and plasma D-dimer levels in the case group were significantly better than those in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).ConclusionsAlprostadil combined with lipoic acid has significant clinical effect on elderly patients with type 2 diabetic foot.It can correct the abnormal hemodynamics of dorsal pedal artery,promote the healing of foot ulcer,increase the content of fibronectin ulcer tissue,reduce the level of plasma D-dimer and improve the high coagulation state.It has high efficiency and safety.It is worthy of clinical application.Further promotion.
基金National Natural Science Foundation of China(No.81770679)
文摘Objective:To investigate the clinical efficacy and safety of alprostadil combined with Bailing Capsule in the treatment of chronic renal failure,and the influence of alprostadil combined with Bailing Capsule on residual renal function,renal hemodynamics,immune indexes and nutritional status.Methods 86 patients with chronic renal failure(CRF)hospitalized in Wuhan integrated traditional Chinese and Western Medicine Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology from January 2018 to June 2019 were selected as the study objects.They were randomly divided into control group and case group with 43 cases in each group.Two groups were given peritoneal dialysis treatment,the control group was given bailing capsule,the case group was given alprostadil injection on the basis of the control group.To observe the clinical effect of the two groups before and after treatment,and the changes of residual renal function,renal hemodynamics,immune index and nutritional status.Results The total effective rate of the case group was 97.68%,higher than 83.73%of the control group,the difference was statistically significant(P<0.05).After treatment,the levels of bun,SCR,GFR,24h urinary protein quantity,resistance index,CRP,IL-6,TNF,CD8+and SGA in the two groups were lower than those before treatment;the levels of renal blood flow,RRF,CD3+,CD4+,ALB,PA,TRF and Hb were higher than those before treatment;moreover,the improvement of serum inflammatory cytokines,residual renal function and renal hemodynamic indexes,immune indexes and nutritional status in the case group were significant The difference was statistically significant(P<0.05).The incidence of adverse reactions in the control group was 16.28%,higher than 6.98%in the case group,with no significant difference(P>0.05).Conclusion Alprostadil combined with Bailing capsule can significantly improve the residual renal function,hemodynamics,immune index,reduce the degree of inflammatory response in patients with chronic renal failure.
基金This work was supported by grants from the National Natural Science Foundation of China(81703968 and 81403333)Scientific Research Subject of Traditional Chinese Medicine/Integrative Chinese and Western Medicine of Health Commission of Tianjin(2017098).
文摘Background:Diabetic kidney disease is now the principal cause of end-stage renal failure worldwide.Alprostadil combined with tripterygium glycosides tablet is a new method for diabetic kidney disease treatment.However,there are currently few systematic reviews on treatment for alprostadil combined with tripterygium glycosides tablet.Therefore,a systematic review and meta-analysis was conducted to analyze the function of alprostadil combined with tripterygium glycosides tablet in the treatment of diabetic kidney disease.Methods:We searched Pubmed,Embase,the Cochrane Library,Chinese databases,and clinical trial for randomized controlled trials of alprostadil combined with tripterygium glycosides tablet in the treatment of diabetic kidney disease,including results from the foundation of database until August 5,2020.Two reviewers have independently performed literature screening,data extraction,and quality evaluation.This meta-analysis has been carried out by RevMan5.4 software.Results:Ten randomized controlled trials with 724 patients were involved.Compared with alprostadil alone,the combination of alprostadil and tripterygium glycosides tablet in treatment of diabetic kidney disease could reduce the level of 24-hour urine protein(95%CI(–2.05,–0.22),P=0.01),serum creatinine(95%CI(–5.01,–0.20),P=0.03),level of interleukin-6(95%CI(−4.57,−2.37),P<0.00001),tumor necrosis factor-α(95%CI(−4.57,−2.37),P<0.00001).The combined treatment could also improve the clinical efficacy(95%CI(1.09,1.25),P<0.0001),and reduce the occurrence of serious adverse events(95%CI(0.26,0.94),P=0.03).However,there is no association of two treatments in blood urea nitrogen(95%CI(–4.17,2.11),P=0.52),albumin(95%CI(–1.10,0.97),P=0.90),triglyceride(95%CI(−1.44,1.50),P=0.97).Conclusion:Alprostadil combined with tripterygium glycosides tablet contributes to protecting renal function,inhibiting inflammation,and reducing the occurrence of adverse events,which could be considered as a feasible therapy for diabetic kidney disease patients.However,some clinical variables did not accurately conclude due to the low quality of methodology and small sample sizes.More rigorous and more extensive trials are essential to validate our results.Trial registration:Systematic review registration:(CRD42020203725).
文摘Objective: To evaluate whether the combination of Uremic clearance granule with Alprostadil is superior to Alprostadil alone for CRF. Methods: Relevant RCTs were searched through March 2019. Data were analyzed by Stata 15.0. Results: Nine articles involving 726 patients were enrolled in this study. Meta-analysis showed that the total effective rate [OR = 3.68 (2.44, 5.55), P < 0.001], Scr [SMD =-2.34 (-3.49,-1.19), P < 0.001], BUN [SMD =-1.80 (-2.73,-0.87), P < 0.001], Ccr [SMD = 0.71 (0.44, 0.97), P < 0.001] were better in the experimental group. But there were no significant difference in UA, CysC, 24h-Upro and incidence of adverse reactions (all P > 0.05) between two groups. No serious adverse reactions were found. Conclusions: The effect of the integrated medicine on CRF was better than Alprostadil alone. Uremic clearance granule is safe and has no obvious adverse reactions.
文摘Objective: To research the effect of calcium dobesilate combinated with alprostadil on the changes of vascular endothelium function in patients with t diabetic nephropathy (DN), and assess the clinical effect and record the untoward effect. Method: A totoal of 120 patients with DN, then they were randomly divided into control group (n=60) and observation group(n=60). Two groups were given hypoglycemic (melbinum)+improving circulatory (calcium dobesilate), and observation group were given alprostadil on the basic, they were treated 30 days. After treatment, we observed the changes of fasting plasma glucose (FBG), 2-hour postprandial blood glucose (2hPBG), the factot of vasomotion angiokinesis (nitrogen oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF)), diastolic function of vascular endothelium (flow mediated dilation (FMD), nitroglycerin mediated dilation (NMD)), renal function index (glomerular filtration rate (GFR), creatinine (Cr), blood urea nitrogen (BUN), albumin excrete rate (AER), urinary albumin creatinine ratio (UACR), urinary albumin evacuate ratio (UAER)), and record the untoward effect. Results: After treatment, the FBG, 2hPBG were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the FBG, 2hPBG in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the ET-1, VEGF were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the ET-1, VEGF in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the NO, FDM, NDM were higher than before treatment in both groups, the difference had statistical significance (P<0.05), and the NO, FDM, NDM in the observation group were higher than the control group, and the difference had statistical significance (P<0.05). After treatment, the GFR, Cr, BUN, AER, UACR, and UAER were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the GFR, Cr, BUN, UACR, and UAER in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). Conclusions: Treatment of the patients with DN before improving the cardiovascular system and hypoglycemic, giving the alprostadil can improve the function of vascular endothelium, rasing the clinical effect and safety.
文摘Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection.Methods: 136 patients with decompensated cirrhosis of HBV infection who were hospitalized in Linxi Hospital of Kailuan General Hospital, Tangshan Infectious Disease Hospital and North China University of Technology Hospital from January to February 2018, 2017 were selected. All patients were divided into control group and case group by random number table method, 68 cases in each group. The control group was treated with routine liver protection and antiviral therapy, while the case group was treated with alprostadil on the basis of the control group. The changes of liver function, liver fibrosis, liver and spleen imaging indexes, anti-virus related indexes and inflammatory factors were observed before and after treatment in the two groups.Results: The total effective rate of the case group was 97.06%, which was significantly higher than that of the control group (85.29%), and the difference was statistically significant. The ALT, AST, TBIL, LN, HA, PCIII, CIV, portal vein diameter, spleen vein diameter, spleen thickness, IL-6, hs-CRP, TNF-α and TGF-β1 were significantly lower in the case group than in the control group. ALB, HBV DNA conversion rate, HBsAg negative rate, and HBeAg negative rate were significantly higher than the control group, the difference was statistically significant. Conclusion: Alprostadil combined with nucleoside antiviral drugs can significantly improve the decompensation of HBV infection Liver function in patients with cirrhosis, reduce the degree of liver fibrosis, inhibit the production of serum inflammatory factors, and can effectively inhibit HBV replication, clinical efficacy is significant, with certain clinical application value.
文摘OBJECTIVE: To observe the effect of Shuxuening Injection combined with alprostadil on healing of diabetic foot ulcers and hemodynamic indexes of dorsal artery of foot. METHODS: A total of 84 cases of diabetic foot patients treated in Wuhan Red Cross Hospital(from February 2016 to April 2017) were divided into treatment group(42 cases) and control group(42 cases) by the random digital table. The control group was given basic clinical treatment while the treatment group was given Shuxuening Injection combined with alprostadil on the basis of the treatment in control group. After 2 weeks of treatment, the improvement of TCM symptom scores(pain, numbness, swelling, claudication), conditions of foot ulcer healing(ulcer area, wound oxygen pressure, wound pH), the hemodynamics of the dorsum pedis artery(the blood flow velocity of the dorsum pedis artery, the blood vessel diameter, resistance index(RI), pulsation index(PI)) of both groups were compared, and the clinical efficacy of 2 groups were statistically analyzed. RESULTS: The scores of pain, numbness, swelling and claudication were significantly reduced in 2 groups after the treatment(P < 0.05), and the improvement of the above symptom scores in the treatment group were all significantly better than that in the control group(P < 0.05). The area of ulcer and the p H of the wounds in the 2 groups were significantly decreased after the treatment(P < 0.05), and the oxygen partial pressure in the wound was significantly increased(P < 0.05), and the improvements of the wound healing outcomes in the treatment group were significantly better than that in the control group(P < 0.05). The blood flow velocity of the foot, the blood vessel diameter, the level of RI and PI after treatment in both groups were significantly increased after the treatment(P < 0.05), and the improvement of the hemodynamic index of the foot back after treatment in the treatment group was significantly better than that in the control group(P < 0.05). The total effective rate of the treatment group was significantly higher than that of the control group(P < 0.05). CONCLUSION: The application of Shuxuening Injection combined with alprostadil can quickly improve the clinical symptoms of the patients, correct the abnormal hemodynamics of the dorsum pedis artery and promote the healing of foot ulcers, and the combination of the two medicines has a synergistic effect.
文摘Objective: To investigate the effects of alprostadil on respiratory parameters and hemodynamics of newborns with persistent pulmonary hypertension. Methods: According to random data table method, 80 newborns of pulmonary hypertension were randomly divided into the control group (n=40) and observation group (n=40), patients in the control group were given normal frequency ventilation, on the basis of the treatment of the control group, the observation group received alprostadil. The changes of respiratory parameters and hemodynamics were compared between the two groups before and after treatment. Results:The levels of respiratory parameters (SaO2, PaO2, PaCO2) and hemodynamics (PA, PVR, SVR) in the two groups before treatment were not statistically significant. After treatment, The levels of SaO2, PaO2in the two groups were significantly higher than those in the same group before treatment, and the observation group levels were (90.71±8.92)%, (85.27±8.23) mmHg, which were significantly higher than those in the control group after treatment;The levels of PaCO2, PA, PVR and SVR in the two groups after treatment were significantly lower than those in the same group before treatment, and the observation group were (35.22±3.46) mmHg, (26.95±3.78) mmHg, (725.71±108.82) dyns/cm5, (1 125.27±152.23) dyns/cm5, which were significantly lower than that of the control group. Conclusion: Adding alprostadil based on conventional frequent ventilation thraphy can effectively improve blood pressure and oxygen saturation, and improve hemodynamics of newborns with persistent pulmonary hypertension, which has important clinical value.
文摘Objective:To analyze the renal function and oxidative stress after alprostadil combined with valsartan treatment of early diabetic nephropathy.Methods:A total of 230 patients with early diabetic nephropathy who were treated in our hospital between December 2011 and December 2015 were divided into control group (n=115) and observation group (n=115) according to random number table. Control group received valsartan treatment, observation group received alprostadil combined with valsartan treatment, and both lasted for one month. After treatment, renal blood flow parameters were evaluated by ultrasound contrast technique, renal function index levels in peripheral blood and urine were measured, and serum levels of oxidative stress indexes were detected.Results:After 1 month of treatment, area under curve (AUC) and time to peak (TTP) levels under ultrasound contrast of observation group were lower than those of control group while derived peak intensity (DPI) level was higher than that of control group;peripheral blood urea nitrogen (BUN) and serum creatinine (Scr) levels of observation group were lower than those of control group, albumin (Alb) level was higher than that of control group, and urine red blood cell (RBC) level was lower than that of control group;serum oxidative stress indexes malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels of observation group were lower than those of control group while superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) levels were higher than those of control group.Conclusion: Alprostadil combined with valsartan can optimize renal function and reduce systemic oxidative stress in patients with early diabetic nephropathy.
文摘Objective:To study the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy.Methods:90 patients with early diabetic nephropathy treated in our hospital between June 2011 and November 2015 were collected and divided into observation group and control group (n=45) according to the single-blind randomized control method. Observation group received epalrestat combined with alprostadil treatment, control group received alprostadil treatment alone, and the treatment of both groups lasted for 3 months. Before treatment and after 3 months of treatment, turbidimetric immunoassay was used to detect the renal function indexes in peripheral blood, rate method was used to detect the renal function indexes in urine, and ELISA method was used to detect the levels of peroxidation indexes and inflammation indexes.Results:Before treatment, differences in renal function, peroxidation damage and inflammatory damage indexes were not statistically significant between two groups of patients (P>0.05). After 3 months of treatment, creatinine (Scr), cystatin C (CysC),β2 microglobulin (β2-MG), N-acetyl-β-D-glucosaminidase (NAG), reactive oxygen species (ROS), advanced protein oxidation products (AOPPs), interleukin-8 (IL-8), interleukin-27 (IL-27) and procalcitonin (PCT) levels of observation group were lower than those of control group while catalase (CAT), total superoxide dismutase (TSOD), interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13) levels were higher than those of control group (P<0.05). Conclusions:Epalrestat combined with alprostadil can protect the renal function and inhibit the peroxidation damage and inflammatory injury in patients with early diabetic nephropathy.
