Impact of acute kidney injury in donors on renal graft survival: a systematic review and Meta-Analysis.

The acute kidney injury (AKI) of deceased donors was an important strategy to address donor shortage. This meta-analysis was conducted to explore the clinical effect of kidney transplantation from donors with AKI. PubMed, Embase, and Cochrane Library were searched through July 2017. Fourteen cohort studies, involving a total of 15,345 donors, were included. Studies were pooled, and the hazard ratio (HR), relative risk (RR), weighted mean difference (WMD), and their corresponding 95% confidence interval (CI) were calculated. The present meta-analysis showed no significant difference in allograft survival between the AKI and non-AKI groups (HR = 1.16, 95% CI = 0.99-1.37, Pheterogeneity = 0.238, I2 = 21.6%) from 12 months to 120 months after kidney transplantation. However, the time of hospital stay was significantly longer (WMD = 2.49, 95% CI = 1.06-3.92, Pheterogeneity = 0.458, I2 = 0%) and the incidence of delayed graft function (DGF) was significantly higher (RR = 1.76, 95% CI = 1.52-2.04, Pheterogeneity < 0.001, I2 = 71.2%) in the AKI group than in the non-AKI group. We concluded that even though hospital stay time was longer and the incidence of DGF was significantly higher in the AKI group, there is no significant difference in allograft survival between the two groups.

Up-Regulation of HMGB1 Exacerbates Renal Ischemia-Reperfusion Injury by Stimulating Inflammatory and Immune Responses through the TLR4 Signaling Pathway in Mice.

BACKGROUND/AIMS: The aim of this study was to elucidate how high-mobility group box 1 (HMGB1) exacerbates renal ischemic-reperfusion injury (IRI) by inflammatory and immune responses through the toll-like receptor 4 (TLR4) signaling pathway. METHODS: A total of 30 wild-type (WT) mice and 30 TLR4 knockout (TLR4-/-) mice were selected and then randomly assigned to the Sham, I/R or HMGB1 groups. The serum and kidney tissues of all mice were collected 24 h after the perfusion. The fully automatic biochemical detector and ELISA were applied to determine the blood urea nitrogen (BUN) and serum creatinine (Scr) levels, and TNF-α, IL-1ß, IL-6, IFN-γ and IL-10 levels, respectively. HE staining was used to evaluate kidney tissue damage, immunofluorescence and immunohistochemical staining were performed to observe CD68 and MPO cell infiltration, and flow cytometry was applied to detect immune cells. qRT-PCR and Western blotting were used to detect the expressions of TLR signaling pathway-related genes and proteins, respectively. RESULTS: Compared with the Sham group, the levels of BUN, Scr, TNF-α, IL-1ß, IL-6, IFN-γ and IL-10, kidney tissue damage score, CD68 and MPO cell infiltration, the numbers of immune cells, and the expressions of TLR signaling pathway-related genes and proteins in the I/R and HMGB1 groups were significantly up-regulated. In the I/R and HMGB1 groups, the levels of BUN and Scr, TNF-α, IL-1ß, IL-6 and IFN-γ, kidney tissue damage score, CD68 and MPO cell infiltration, immune cell numbers, and TLR signaling pathway-related gene and protein expressions in the WT mice were all higher than those in the TLR4-/- mice, but IL-10 level was significantly lower. Similarly, all aforementioned indexes but IL-10 level in the WT and TLR4-/- mice were higher in the HMGB1 group than in the I/R group. CONCLUSION: Our study indicated that the up-regulation of HMGB1 could exacerbate renal IRI by stimulating inflammatory and immune responses through the TLR4 signaling pathway.c.

A simplified multivisceral transplantation procedure for patients with combined end-stage liver disease and type 2 diabetes mellitus.

In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end-stage liver disease and concurrent type 2 DM. Forty-four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end-stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD.

Kidney transplantation from donors with rhabdomyolysis and acute renal failure.

Rhabdomyolysis in deceased donors usually causes acute renal failure (ARF), which may be considered a contraindication for kidney transplantation. From January 2012 to December 2016, 30 kidneys from 15 deceased donors with severe rhabdomyolysis and ARF were accepted for transplantation at our center. The peak serum creatinine (SCr) kinase, myoglobin, and SCr of the these donors were 15 569±8597 U/L, 37 092±42 100 µg/L, and 422±167 µmol/L, respectively. Two donors received continuous renal replacement therapy due to anuria. Six kidneys exhibited a discolored appearance (from brown to glossy black) due to myoglobin casts. The kidney transplant results from the donors with rhabdomyolysis donors were compared with those of 90 renal grafts from standard criteria donors (SCD). The estimated glomerular filtration rate at 2 years was similar between kidney transplants from donors with rhabdomyolysis and SCD (70.3±14.6 mL/min/1.73 m2 vs 72.3±15.1 mL/min/1.73 m2 ). We conclude that excellent graft function can be achieved from kidneys donors with ARF caused by rhabdomyolysis.

miR-26a regulates mouse hepatocyte proliferation via directly targeting the 3' untranslated region of CCND2 and CCNE2.

BACKGROUND: The deficiency of liver regeneration needs to be addressed in the fields of liver surgery, split liver transplantation and living donor liver transplantation. Researches of microRNAs would broaden our understandings on the mechanisms of various diseases. Our previous research confirmed that miR-26a regulated liver regeneration in mice; however, the relationship between miR-26a and its target, directly or indirectly, remains unclear. Therefore, the present study further investigated the mechanism of miR-26a in regulating mouse hepatocyte proliferation. METHODS: An established mouse liver cell line, Nctc-1469, was transfected with Ad5-miR-26a-EGFP, Ad5-anti-miR-26a-EGFP or Ad5-EGFP vector. Cell proliferation was assessed by MTS, cell apoptosis and cell cycle by flow cytometry, and gene expression by Western blotting and quantitative real-time PCR. Dual-luciferase reporter assays were used to test targets of miR-26a. RESULTS: Compared with the Ad5-EGFP group, Ad5-anti-miR-26a-EGFP down-regulated miR-26a and increased proliferation of hepatocytes, with more cells entering the G1 phase of cell cycle (82.70%+/-1.45% vs 75.80%+/-3.92%), and decreased apoptosis (5.50%+/-0.35% vs 6.73%+/-0.42%). CCND2 and CCNE2 were the direct targeted genes of miR-26a. miR-26a down-regulation up-regulated CCND2 and CCNE2 expressions and down-regulated p53 expression in Nctc-1469 cells. On the contrary, miR-26a over-expression showed the opposite results. CONCLUSIONS: miR-26a regulated mouse hepatocyte proliferation by directly targeting the 3' untranslated regions of cyclin D2/cyclin E2; miR-26a also regulated p53-mediated apoptosis. Our data suggested that miR-26a may be a promising regulator in liver regeneration.

Liver transplantation using organs from deceased organ donors: a single organ transplant center experience.

BACKGROUND: In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program. METHODS: From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively. RESULTS: Among the 29 donors, 24 were China Category II donors (organ donation after cardiac death), and five were China Category III donors (organ donation after brain death followed by cardiac death). The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422 (2-696) days. Among the five mortalities during the follow-up, three died of tumor recurrence. In terms of post-transplant complications, 9 recipients (34.6%) experienced early allograft dysfunction, 1 (3.8%) had non-anastomotic biliary stricture, and 1 (3.8%) was complicated with hepatic arterial thrombosis. None of these complications resulted in patient death. Notably, primary non-function was not observed in any of the grafts. CONCLUSION: With careful donor selection, liver transplant from deceased donors can be performed safely and plays a critical role in overcoming the extreme organ shortage in China.

Effects of ligustrazine on ureteral obstruction-induced renal tubulointerstitial fibrosis.

Ligustrazine (LIG) is a purified and chemically identified component of the Chinese herb Ligusticum wallichii Franchat. It is a potent blocker of vasoconstriction and has strong scavenger of oxygen free radicals. We investigated the effect of LIG on renal tubulointerstitial fibrosis using a rat model of unilateral ureteral obstruction. Ligustrazine treatment significantly reduced the scores of interstitial collagen deposition, amounts of hydroxyproline, the density of myofibroblasts and macrophages, and amounts of transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF) compared with their level in a saline-treated control group. Using quantitative polymerase chain reaction we found that LIG treatment significantly reduced the mRNA expression of TGF-ß1, CTGF, monocyte chemoattractant protein-1 and osteopontin. Moreover, the mRNA expression of hepatocyte growth factor and bone morphogenetic protein-7 were significantly increased by LIG. In vitro, LIG inhibited the TGF-ß1-induced loss of cytokeratin-18 expression and de novo increase of the expression of α-smooth muscle actin of HK-2 cells in a dose-dependent manner, which suggested that LIG could restrain the process of epithelial-myofibroblast transition of tubular epithelial cells. This study indicates that LIG can attenuate renal tubulointerstitial fibrosis. It might be useful as a potential candidate in the treatment of chronic renal diseases.

Kidney transplantation in diabetic recipients with iliac atherosclerosis: arterial anastomosis with Nakayama's ring pin stapler after endarterectomy.

OBJECTIVES: To report our experience of arterial anastomosis with Nakayama's ring pin staplers (titanium staplers) after an endarterectomy in kidney transplantation of diabetic recipients with iliac atherosclerosis. METHODS: In a series of 2126 kidney transplantations carried out between January 1998 and December 2008, 62 recipients received an endarterectomy during transplantation before renal arterial anastomoses as a result of severe iliac atherosclerosis. The renal arteries were anatomosed to hypogastric arteries through titanium staplers in 32 patients (group 1), or to external/common iliac arteries with conventional suturing in 30 patients (group 2). Perioperative outcomes of the two groups have been compared. RESULTS: The mean artery anastomosis time in group 1 was considerably shorter than in the group 2 (6.4 min vs 17.3 min, P < 0.001). Group 1 showed a lower rate of delayed graft function (4.8% vs 27.5%, P = 0.004). No difference in Kaplan-Meier patient survival rate was found between group 1 and group 2 after follow up of 67 ± 28 months (P = 0.58). Graft survival rate (patient deaths included) was higher in group 1 than in group 2 (P = 0.04). CONCLUSIONS: Arterial anastomosis with a titanium stapler is more rapid than conventional suture. It can diminish the rate of delayed graft function and improve the graft survival rate in diabetic recipients with severe iliac atherosclerosis.

Triptolide attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction.

AIM: Extracts of Tripterygium wilfordii Hook F. have been used to treat glomerulonephritis for more than 30 years in China. Most of the anti-inflammatory and immunosuppressive activities of these extracts can be attributed to triptolide (Trip). The present study was to investigate the effect of Trip on renal interstitial fibrosis in a model of unilateral ureteral obstruction (UUO). METHODS: UUO or sham-operated rats were randomly assigned to receive mycophenolate mofetil (MMF), Trip or vehicle and were killed on days 7 and 14 after UUO or sham operation. Kidney specimens were fixed for immunohistochemistry for myofibroblasts (α-smooth muscle actin, α-SMA), macrophages (ED-1), monocyte chemoattractant protein-1 (MCP-1) and osteopontin. Interstitial collagen deposition and amounts of transforming growth factor-ß1 (TGF-ß1) were determined by Sirius red staining and enzyme-linked immunosorbent assay, respectively. The mRNA expression of TGF-ß1, connective tissue growth factor (CTGF), MCP-1 and osteopontin were measured by real-time polymerase chain reaction analysis. RESULTS: The scores for the density of α-SMA- and ED-1-positive cells, the staining of MCP-1 and osteopontin, interstitial collagen deposition and amounts of TGF-ß1 were significantly reduced by MMF or Trip. MMF or Trip significantly reduced the mRNA expression of TGF-ß1, CTGF, MCP-1 and osteopontin. CONCLUSION: Trip significantly attenuated tubulointerstitial fibrosis in a rat UUO model and the effect of Trip on renal fibrosis was similar to that of MMF. Trip may be useful as a potential candidate in the treatment of renal fibrosis.

Renal Transplantation Using Stone-bearing Deceased Donor Kidneys-Experience of a Transplant Center in China.

OBJECTIVE: To evaluate the outcomes of transplantation of deceased donor stone-bearing kidneys. METHODS: A total of 32 patients who received renal transplantation at our center from July 2011 to June 2016 were included. Eight recipients received kidneys with incidental renal stone(s) (stone group). Twenty-four recipients received kidneys without renal stones (non-stone group). The transplantation outcomes of the 2 groups were compared. RESULTS: There was 1 case of postoperative urinary tract infection in the stone group, and 2 cases in the non-stone group. No ureteral obstruction or hydronephrosis occurred in either group. No significant difference was found in the incidence of complications, serum creatinine level, and estimated glomerular filtration rate between the groups (all, P >.05). No deaths occurred in either group during the follow-up period. One recipient had postoperative calculi recurrence, and 4 recipients had residual calculi before transplantation. However, these patients had no symptomatic nephrolithiasis or obstruction, and their renal functions were normal. CONCLUSION: Transplantation of deceased donor stone-bearing kidneys can achieve comparable outcomes of deceased donor non-stone-bearing kidneys.

MicroRNA-423-5p facilitates hypoxia/reoxygenation-induced apoptosis in renal proximal tubular epithelial cells by targeting GSTM1 via endoplasmic reticulum stress.

It has been reported that microRNAs (miRs) can regulate renal response to acute injury and members of them are believed to be important in maintenance of renal function and development of renal injury. We investigated the actions of microRNA-423-5p (miR-423-5p) and glutathione-S-transferase (GST) M1 after acute kidney injury. MiR-423-5p was up-regulated and GSTM1 was down-regulated in human kidney (HK-2) cells subjected to hypoxia/reoxygenation (H/R) and in rat kidneys subjected to ischemia/reperfusion (I/R) injury. Dual luciferase assays revealed miR-423-5p binding to the 3' untranslated region of GSTM1. Proliferation was lower and apoptosis, ER stress and oxidative stress were all higher in H/R-treated HK-2 cells transfected with or without miR-423-5p mimics and GSTM1 siRNA than in the same cells transfected with miR-423-5p inhibitors and a GSTM1 expression vector. Increased miR-423-5p and decreased GSTM1 mRNA and protein levels were observed in rat kidneys on days 1, 2 and 7 after I/R. Levels had normalized by days 14 and 21. On day 3 after treatment, rats receiving I/R or I/R plus miR-423-5p mimics exhibited higher serum creatinine and urea nitrogen levels than rats receiving I/R plus a miR-423-5p inhibitor. MiR-423-5p and lower GSTM1 mRNA and protein levels were higher in the I/R and I/R plus miR-423-5p mimic groups than in the I/R plus miR-423-5p inhibitors group. These findings demonstrate that after acute kidney injury, miR-423-5p induces ER stress and oxidative stress by inhibiting GSTM1and suppresses repair.

MicroRNA-34a regulates liver regeneration and the development of liver cancer in rats by targeting Notch signaling pathway.

OBJECTIVE: This study aimed to investigate the role of microRNA-34a (miR-34a) in regulating liver regeneration (LR) and the development of liver cancer in rats by targeting Notch signaling pathway. METHODS: Thirty male Sprague-Dawley (SD) rats were randomly assigned into partial hepatectomy (PH) group and sham hepatectomy (SH) group. Hematoxylin and eosin (HE) staining was used to observe the histological change in liver tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels. Dual-luciferase reporter gene assay was performed to examine whether miR-34a targeted Notch1 gene. Human liver cancer Huh7 cells were transfected and divided into blank, negative control (NC), miR-34a mimics and miR-34a inhibitors groups. MTT and flow cytometry were used to detect cell growth, and cell cycle and apoptosis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied detect to the expressions of miR-34a and Notch receptor mRNA. Western blotting was performed to detect the protein expressions of Notch receptors, P21, Bax, Bcl-2 and Bcl-xL. Tumor xenograft in nude mice was done to observe tumor formation in different groups. RESULTS: Compared to the SH group, miR-34a expression in liver tissues in the PH group decreased first and then increased to the normal level during LR. In early stage of LR, the expressions of Notch receptors and miR-34a were negatively correlated. Compared to the blank and NC groups, the cell growth was inhibited, cell cycle was mainly arrested in the G2/M phase and cell apoptosis rate increased in the miR-34a mimics group. Moreover, the expressions of miR-34a, P21 and Bax were up-regulated, while the expressions of Notch receptors, and Bcl-2 and Bcl-xL were down-regulated in this group. Additionally, the tumor growth in the miR-34a mimics group was reduced. The miR-34a inhibitors group showed contrary tendencies. CONCLUSION: Our study demonstrates that miR-34a regulated LR and the development of liver cancer by inhibiting Notch signaling pathway.

Induction chemotherapy followed by concurrent chemoradiation and nimotuzumab for locoregionally advanced nasopharyngeal carcinoma: preliminary results from a phase II clinical trial.

Overexpression of epidermal growth factor receptor can be found in more than 80% of patients with locoregionally advanced nasopharyngeal carcinoma and is associated with shorter survival. In this work, we evaluated the feasibility of adding nimotuzumab to chemoradiation in locoregionally advanced nasopharyngeal carcinoma. Twenty-three patients with clinically staged T3-4 or any node-positive disease were enrolled. They were scheduled to receive one cycle of induction chemotherapy followed by intensity-modulated radiotherapy, weekly administration of nimotuzumab and concurrent chemotherapy. Results showed that all patients received a full course of radiotherapy, 19(82.6%)patients completed the scheduled neoadjuvant and concurrent chemotherapy, and 22(95.7%) patients received ≥6 weeks of nimotuzumab. During the period of concurrent chemoradiation and nimotuzumab, grade 3-4 toxicities occurred in 14(60.9%) patients: 8 (34.8%) had grade 3-4 oral mucositis, 6(26.1%) had grade 3 neutropenia, and 1(4.3%) had grade 3 dermatitis. No acne-like rash was observed. With a median follow-up of 24.1 months, the 2-year progression-free survival and overall survival were 83.5% and 95.0%, respectively. In conclusion, concurrent administration of chemoradiation and nimotuzumab was well-tolerated with good compliance. Preliminary clinical outcome data appear encouraging with favorable normal tissue toxicity results comparing with historical data of concurrent chemoradiation plus cetuximab.

Effect and safety of Tripterygium Hypoglaucum (Lévl.) hutch in treating proteinuria of kidney transplant recipients.

OBJECTIVE: To investigate the therapeutic and adverse effects of Tripterygium hypoglaucum (Lévl.) Hutch (THH) in treating proteinuria of renal transplant recipients. METHODS: Thirty patients with proteinuria greater than 1 g/24 h were enrolled to be treated with one tablet preparation of THH extract (360 mg, 3 times daily, equivalent to triptolide 30 µg/d) for 6 months. The proteinuria, serum creatinine, sex hormones, semen analysis and erectile function in male were determined at entry, 3 and 6 months. Incidence of adverse events was evaluated. RESULTS: THH treatment significantly improved proteinuria (from 2.52±1.87 g/d at baseline to 1.11±0.96 g/d at 3 months, and to 1.04±1.09 g/d at 6 months). No significant changes were observed in serum creatinine, liver enzymes or complete blood count. In female (15 cases), THH treatment induced a significant increase in follicle stimulating hormone and luteinizing hormone levels, and a significant decrease in estradiol and progesterone levels, and the main adverse effects were reversible menstrual irregularities (73.3% at 6 months). In male (15 cases), the sperm concentration and viability were markedly decreased by THH treatment, but the sex hormone levels and erectile function did not change significantly by treatment. CONCLUSIONS: THH is effective and safe for the treatment of proteinuria in renal transplant recipients. Its primary adverse effect is reversible toxicity to reproductive organs. Further controlled clinical trials are warranted to determine the true clinical benefit of THH.

One center's experiences of 101 cases of kidney transplants from cardiac death donors.

OBJECTIVES: In 2011, a pilot program of organ donation after cardiac death was begun at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, where we hosted one of the largest donation after cardiac death organ transplant programs in the country. We report our initial single-center experiences of kidney transplant from donation after cardiac deaths. MATERIALS AND METHODS: From January 2011 to July 2013 at our center, 101 kidney transplants from donation after cardiac death donors were performed. The results of kidney transplants from donation after cardiac death donors were compared with those of 50 kidney transplants from donation after brain death performed during the same time. RESULTS: Delayed graft function occurred more frequently in donation after cardiac death than donation after brain death kidneys (16.8% vs 4.0%; P = .035). There was no difference in the incidence of acute rejection between donation after cardiac death and donation after brain death kidneys (10.9% vs 6.0%). Actual 1-year graft survival rate was similar (donation after cardiac death 94.4% vs donation after brain death 96.2%). Estimated glomerular filtration rate at 12 months was similar between donation after cardiac death and donation after brain death kidneys (73.8 ± 20.0 vs 77.8 ± 22.7 mL/min/1.73 m2). CONCLUSIONS: Kidney transplants from donation after cardiac death donors have comparable short-term outcomes to kidney transplants from donation after brain death donors. Donation after cardiac death can play a crucial role in overcoming the organ shortage in China.

[Characterization of specific monoclonal antibodies to Aspergillus conidia by flow cytometry].

OBJECTIVE: To characterize the specific monoclonal antibodies to Aspergillus conidia. METHODS: Flow cytometry was used to examine the reactivity of the specific monoclonal antibodies to Aspergillus conidia. RESULTS: Both the monoclonal antibodies MA3 and Con2 showed specific reactivity to Aspergillus conidia suspensions. MA3 was capable of binding to the conidia of A.fumigatus, A.flavus, A.niger and A.terreus, while Con2 was reactive only to the conidia of A.fumigatus. CONCLUSION: Two specific monoclonal antibodies (MA3 and Con2) to Aspergillus conidia have been obtained.

Kidney transplant in highly sensitized patients after desensitization with plasmapheresis and low-dose intravenous immunoglobulin.

OBJECTIVES: This study sought to evaluate the efficacy of plasmapheresis plus low-dose intravenous immunoglobulin in highly sensitized patients waiting for a deceased-donor renal transplant. MATERIALS AND METHODS: Thirty-five highly sensitized patients (HLA class I panel reactive antibody > 50%) received plasmapheresis, plus low-dose intravenous immunoglobulin treatment. In 25 patients (group 1), a positive T- and/or B-cell cytotoxicity crossmatch was rendered negative by plasmapheresis plus low-dose intravenous immunoglobulin treatment. Two patients did not receive renal transplants owing to persistent positive crossmatch. Eight patients already had a negative crossmatch before desensitization. During the same time, 32 highly sensitized patients (group 2), without desensitization, had a negative crossmatch and received deceased-donor renal transplants. RESULTS: Group 1 showed a numerically higher rate of acute rejection (32.0% vs 21.9%; P = .6) and antibody-mediated rejection (20.0% vs 9.4%; P = .3), but the difference was not statistically significant. Four of 5 cases of antibody-mediated rejection in group 1 had a peak donor specific antibody titer = 1:8. Comparable mean serum creatinine levels at 24 months were observed (group 1: 130 +/- 38 micromol/L vs group 2: 123 +/- 41 micromol/L; P = .5). No difference in Kaplan-Meier graft survival was found between group 1 and group 2 after follow-up of 52 +/- 26 months (P = .7). CONCLUSIONS: Desensitization with plasmapheresis, plus low-dose intravenous immunoglobulin enables successful deceased-donor renal transplant in highly sensitized patients with a positive crossmatch. Antibody-mediated rejection occurred predominantly in recipients with donor-specific antibodies of high titers.

Protection against Helicobacter pylori infection by a trivalent fusion vaccine based on a fragment of urease B-UreB414.

A multivalent fusion vaccine is a promising option for protection against Helicobacter pylori infection. In this study, UreB414 was identified as an antigenic fragment of urease B subunit (UreB) and it induced an antibody inhibiting urease activity. Immunization with UreB414 partially protected mice from H. pylori infection. Furthermore, a trivalent fusion vaccine was constructed by genetically linking heat shock protein A (HspA), H. pylori adhesin A (HpaA), and UreB414, resulting in recombinant HspA-HpaA-UreB414 (rHHU). Its protective effect against H. pylori infection was tested in BALB/c mice. Oral administration of rHHU significantly protected mice from H. pylori infection, which was associated with H. pylori-specific antibody production and Th1/Th2-type immune responses. The results show that a trivalent fusion vaccine efficiently combats H. pylori infection, and that an antigenic fragment of the protein can be used instead of the whole protein to construct a multivalent vaccine.