Youhua Zhu

Second Military Medical University, Shanghai, Shanghai, Shanghai Shi, China

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Publications (10)17.42 Total impact

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    ABSTRACT: Background Hypertonic citrate adenine (HC-A) solution, containing citrate and adenine, has become the most widely used preservation solution in isolated kidney preservation in China. More than 30 years of clinical application has demonstrated that HC-A is safe and effective. With higher requirement for kidney preservation and less tolerance of preservation-related graft dysfunction, a new solution, HC-A II, for kidney preservation was developed by Shanghai Changzheng Hospital. Material and Methods Upon approval from the State Food and Drug Administration of China (SFDA), a multi-center randomized controlled trial was performed to study the efficacy and safety of HC-A II in kidney preservation from 2008 to 2012, using histidine-tryptophan-ketoglutarate solution (HTK) as control (HC-A, n=137, and HTK, n=140). There were no differences with regard to donor and recipient demographics or cold ischemia. Results The trial results showed no significant difference in DGF rate, or patient or graft survival between the 2 groups. No significant difference between the 2 groups was found in the percentage of patients whose serum creatinine (SCr) test results returned to normal within 28 days (P>0.05), nor were there a significant difference in safety evaluation (P>0.05). Conclusions HC-A II and HTK appear to have similar efficacy in isolated kidney preservation.
    Annals of transplantation: quarterly of the Polish Transplantation Society 11/2014; 19:614-20. DOI:10.12659/AOT.892250 · 1.43 Impact Factor
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    ABSTRACT: The organ donation system in China has far lagged behind international levels. Transformation of this situation began in July 2005. A complete organ donation system that ensures fairness, impartiality, transparency and respect for life has now been developed. This system is composed of regulations and policies, an organizational structure, operational guidelines, organ procurement organizations, registration of donors and recipients, and an organ allocation system. Since March 2010, pilot trials on donation after circulatory death (DCD) have been carried out. In four years, organ donation has started in 25 out of 32 provinces in the country. From 2010 to 2013, the ratio of DCD liver transplantation to total case numbers in China rose from 1.38% to 26.1%, as for kidney the ratio were 0.59% and 24.6%, respectively. The total number of DCD in China has accumulated to 1,564 cases and 4,243 organs were transplanted. In order to alleviate the further difficulties of donation, establishment of professional organ procurement organizations in transplant hospitals, legislation of brain death, and promulgation of legal guidelines on DCD will be the main targets of organ donation development in China.This article is protected by copyright. All rights reserved.
    Transplant International 09/2014; 28(4). DOI:10.1111/tri.12467 · 3.16 Impact Factor
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    ABSTRACT: Kidney transplantation is the most cost-effective option for the treatment of end-stage renal disease, but the financial aspects of kidney transplantation have not yet been fully investigated. The purpose of this study was to determine the hospital cost of living donor kidney transplantation in China and to identify factors associated with the high cost. Demographic and clinical data of 103 consecutive patients who underwent living donor kidney transplantation from January 2007 to January 2011 at our center were reviewed, and detailed hospital cost of initial admission for kidney transplantation was analyzed. A stepwise multiple regression analysis was computed to determine predictors affecting the total hospital cost. The median total hospital cost was US $10,531, of which 69.2% was for medications, 13.2% for surgical procedures, 11.4% for para clinics, 3.7% for accommodations, 0.5% for nursing care, and 2.0% for other miscellaneous medical services. A multivariate stepwise logistic regression model for overall cost of transplantation revealed that the length of hospital stay, induction therapy, steroid-resistant rejection, maintenance therapy, infection status and body weight were independent predictors affecting the total hospitalization cost. Although the cost of living donor kidney transplantation in China is much lower than that in developed countries, it is a heavy burden for both the government and the patients. As medications formed the greater proportion of the total hospitalization cost, efforts to reduce the cost of drugs should be addressed.
    Annals of transplantation: quarterly of the Polish Transplantation Society 06/2012; 17(2):5-10. · 1.43 Impact Factor
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    ABSTRACT: Oxidative stress due to excessive production of reactive oxygen species (ROS) and subsequent lipid peroxidation plays a critical role in renal ischemia/reperfusion (IR) injury. The purpose of current study is to demonstrate the effect of antecedent ethanol exposure on IR-induced renal injury by modulation of oxidative stress. Bilateral renal warm IR was induced in male C57BL/6 mice after ethanol or saline administration. Blood ethanol concentration, kidney function, histological damage, inflammatory infiltration, cytokine production, oxidative stress, antioxidant capacity and Aldehyde dehydrogenase (ALDH) enzymatic activity were assessed to evaluate the impact of antecedent ethanol exposure on IR-induced renal injury. After bilateral kidney ischemia, mice preconditioned with physiological levels of ethanol displayed significantly preserved renal function along with less histological tubular damage as manifested by the reduced inflammatory infiltration and cytokine production. Mechanistic studies revealed that precondition of mice with physiological levels of ethanol 3 h before IR induction enhanced antioxidant capacity characterized by significantly higher superoxidase dismutase (SOD) activities. Our studies further demonstrated that ethanol pretreatment specifically increased ALDH2 activity, which then suppressed lipid peroxidation by promoting the detoxification of Malondialdehyde (MDA) and 4-hydroxynonenal (HNE). Our results provide first line of evidence indicating that antecedent ethanol exposure can provide protection for kidneys against IR-induced injury by enhancing antioxidant capacity and preventing lipid peroxidation. Therefore, ethanol precondition and ectopic ALDH2 activation could be potential therapeutic approaches to prevent renal IR injury relevant to various clinical conditions.
    PLoS ONE 10/2011; 6(10):e25811. DOI:10.1371/journal.pone.0025811 · 3.53 Impact Factor
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    ABSTRACT: We sought to evaluate the outcomes of a single kidney transplant from pediatric donors into adult recipients after controlled circulatory death. A retrospective, single-center review of all adult recipients who received a single pediatric kidney from controlled-cardiac deceased-donors (aged, < 9 years old) between January 2006 and March 2008 was performed. Eleven adult recipients (aged, 16-41 years) used single renal grafts from the controlled-cardiac deceased-donors (median donor age, 74 months; range, 49-106 months; median donor weight, 20.95 kg; range, 16.6-37.8 kg). The median recipient age was 27 years (range, 16-41 years; median recipient weight, 47 kg; range 39.5-53.6 kg). The patient's serum creatinine level gradually decreased, and the estimated glomerular filtration rate increased stably more than 2 times during follow-up. The graft length increased significantly the first week after transplant compared with that recorded immediately after reperfusion (P < .001) and grew slightly thereafter. Acute rejection occurred in 1 patient. Nine patients had high renal artery blood flow velocity index at 1 to 2 cm. Beside the anastomosis (167-321 cm/s), only 1 patient developed hypertension and slightly increased serum creatinine at 14 weeks after transplant. The 1-year patient/graft survival was 100%. Use of single kidneys from pediatric donors after controlled cardiac death could expand the donor pool without compromising recipient outcomes.
    06/2011; 9(3):165-9.
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    ABSTRACT: Nutcracker syndrome (NCS) is caused by a compression of the left renal vein between the aorta and the superior mesenteric artery (SMA). It results in left renal venous hypertension, and the subsequent development of venous varicosities of the renal pelvis, ureter, and gonadal vein. A 21-year-old Chinese woman was admitted with a seven-month history of unilateral severe hematuria. On admission, she was identified as having nutcracker syndrome. The patient was treated with retroperitoneal laparoscopic donor nephrectomy and renal autotransplantation. The patient underwent retroperitoneal laparoscopic donor nephrectomy using a retroperitoneal three-port technique with ex vitro autograft repair and subsequent renal autotransplantation into the iliac fossa. In order to shorten the hot ischemia time and improve the patient's cosmetic outcome, a minor oblique incision in the left, lower quadrant was prepared in advance of the laparoscopic donor nephrectomy for use as a site for the autograft to be procured through the retroperitoneal space and as a transplant site for the autograft. Two days after the operation, the patient's symptoms subsided. Serum creatinine before and after the operation were 53 mmol/L and 55 mmol/L, respectively. The patient had normal renal function during a follow-up three months after the operation. The treatment of nutcracker syndrome by retroperitoneal laparoscopic nephrectomy with ex vitro repair and autotransplantation is a simpler and less invasive procedure than open surgery. Moreover, a minor incision on the left hypogastrium can shorten the autograft's hot ischemic time and improve patients' cosmetic outcomes, especially in young women.
    Journal of Medical Case Reports 10/2009; 3:82. DOI:10.1186/1752-1947-3-82
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    ABSTRACT: To assess the activity of baclofen, a potent gamma-aminobutyric acid-ergic agonist, against dysfunctional voiding (DV) and lower urinary tract symptoms (LUTS) in a clinical trial, as DV is a leading cause of LUTS in women, but there is no effective treatment. We conducted a randomized double-blind placebo-controlled crossover trial in 60 women with DV and LUTS between January 2003 and January 2006; patients were randomly assigned either baclofen 10 mg three times daily, then matching placebo for 4 weeks, or matching placebo then baclofen 10 mg three times daily for 4 weeks, separated by a 2-week washout period. Voiding diaries and multichannel urodynamics (at baseline, 4 and 10 weeks) were used to record the changes of voids/24 h and urodynamic variables. The primary efficacy endpoint was the change in voids/24 h, and the TL value (log[T/L]), a new electromyographic variables showing the extent of DV. Efficacy outcomes at 4 and 10 weeks were compared with the baseline data, using a crossover-designed analysis of variance model. The efficacy analysis of the treatment showed that baclofen was associated with significantly fewer voids/24 h than placebo (mean difference from baseline 5.53 vs 2.70; P = 0.001) and a significant increase in TL (mean difference from baseline -1.78 vs 0.01, P = 0.001). No significant adverse events were reported. A 4-week course of baclofen significantly reduced the number of voids/24 h and increased the TL value in women with DV confirmed by transdermal perineal electromyography. These encouraging results suggest that baclofen could be used for treating DV in women.
    BJU International 10/2007; 100(3):588-92. DOI:10.1111/j.1464-410X.2007.06987.x · 3.13 Impact Factor
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    ABSTRACT: To analyze the epidemiographic features of urological malignancy in renal allograft recipients (RAR) in a single center A retrospective analysis was made on 3150 patients who received renal allografts from June 1978 until the autumn of 2006 and anti-rejection treatment for at least 3 months. Of the 3150 recipients, 33 (1.05%) developed malignancies, including 12 patients (0.38%; eight males and four females) with urological tumors and 21 patients with skin carcinoma, right liver lobular cystic adenocarcinoma, hepatocellular carcinoma, gastric cancer, colorectal carcinoma, ileocecal adenoma, lip cancer, nasopharyngeal carcinoma, Kaposi's Sarcoma, pulmonary lymphoma, and breast cancer. The 12 cases of urological malignancies included one case of renal cell carcinoma, one case of transplanted kidney carcinoma, two cases of bilateral pelvic transitional cell carcinoma (TCC), three cases of unilateral pelvic TCC, one case of bilateral ureter TCC, one case of unilateral ureter TCC, and three cases of bladder TCC. The age at which the diagnosis was made ranged from 48 to 66 years with a mean of 58.3 +/- 4.6 years, and the mean course of immunosuppressive therapy ranged from 26 to 120 months with a mean of 62 +/- 18 months. Of the 12 patients who developed urological malignancies, six had been on a Oyclosporine A + Azaithioprine + Prednisone (OsA + Aza + Pred) protocol; five on a Oyclosporine A + Mycophenolate Mofetil + Prednisone (OsA + MMF + Pred) protocol; and one on a Tacrolimus + Mycophenolate Mofetil + Prednisone (FK506 + MMF + Pred) protocol. One of the 12 patients died soon after the diagnosis was made, and the remaining 11 patients received surgical resection. Of them, 10 patients survived well, and the other one died from cerebral hemorrhage soon after operation. Urological malignancies, especially TCC, are an important complication in renal transplanatation found in this center. The incidence of urological malignancy in renal allograft recipients (RAR) is about 10 times that found in the general population of Shanghai versus two times for other malignancies. The occurrence of the malignancies in PAR seems to be closely related to the use of immunosuppressive agents. lmmunosuppression results in the weakening of immnuologic surveillance function, leading to mutation, aberration, and carcinogenesis. The immunological status of patients after renal transplantation should be assessed regularly. Painless macroscopic hematuria should be considered a significant sign in assessing the potential occurrence of urological malignancy in RAR. Treatment includes early diagnosis, timely surgical resection, and reduction of immunosuppressive agents.
    Clinical transplants 02/2006;
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    ABSTRACT: Dendritic cells (DC) not only initiate T cell responses, but are also involved in the induction of tolerance. The functional properties of DC are strictly dependent on their state of maturation. It has been shown that immature DC can induce immune tolerance and prolong allograft survival. Interleukin-10 (IL-10) is an important immunosuppressive cytokine which inhibits maturation and function of DC. In order to improve the tolerogenicity of DC, we and others showed that adenovirus vectors can effectively mediate IL-10 genetic modification of DC, and IL-10 genetic modification can inhibit MHC II, B7.2, and CD40 expression, IL-12 secretion and the T cell stimulatory capacity of DC. The primary aim of this study is to examine the in vivo effects of this approach on allograft survival in a murine cardiac allograft transplantation model. To our surprise,we observed that infusion of immature DC genetically modified to express IL-10 (DC-IL-10) via the tail vein could not prolong allograft survival in the recipients, but shortened their survival. More interestingly, portal venous infusion of DC-IL-10 markedly prolonged allograft survival. The diverse effects of DC-IL-10 infusion through different routes may be due to the different immune responses to alloantigens in recipients that received DC-IL-10 via either the portal or the tail vein. Decreased cytotoxicity, polarization of Th2 response, poor T cell stimulating activity of liver DC and enhanced incidence of donor DC in the recipients may contribute to the more efficient prolongation of allograft survival observed after portal venous infusion of DC-IL-10. These results suggest that portal venous infusion may be an effective approach for immature DC to induce immune tolerance or hyporesponsiveness against donor antigens, and prolong allograft survival.
    Journal of Molecular Medicine 05/2004; 82(4):240-9. DOI:10.1007/s00109-003-0521-0 · 4.74 Impact Factor
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    ABSTRACT: To review kidney transplantation in the center and analyze the risk factors affecting long-term allograft survival. Thirty-two relative variables were analyzed with SAS statistical software. Using Log-rank method, we investigated influence of these variables on short-and long-term survival of grafts. Kaplan-Meier analysis was used to estimate the 1-, 3-, 5-, 10-years graft survival rates and half-life. Proportional hazards regression analysis (Cox model) was used to assess and rank the relative risk of potential variables. The 1-, 3-, 5-, 10-years graft survival rates were 83%, 75%, 66% and 48%. After excluding the patients died with functioning grafts, the 1-, 3-, 5-, 10 years grafts survival rate increased to 89%, 82%, 75% and 69%, respectively. The mean half-life was 8.78 +/- 0.14 and 14.09 +/- 0.20 years, respectively. By Log-rank analysis, factors affecting short- and long-term graft survival were identified as: renal function, duration of graft function became normal, cold-ischemia time, presence of acute rejection, delayed graft function, immunosuppressive regimen, complication, infection, anti-rejection therapy. Cox model multivariate analysis showed that there were 18 factors affecting graft survival. New immunosuppressive agents not only significantly increase short-term graft survival, but also have the better long-term outcome tendency. Making assurance to get high quality donor organ and minimizing the death with graft function may be the most feasible way to prolong graft survival at present.
    Zhonghua wai ke za zhi [Chinese journal of surgery] 05/2002; 40(4):241-7.