Does kidney transplantation onto the external iliac artery affect the haemodynamic parameters of
kidney transplant
Donor treatment with a PHD-inhibitor activating HIFs prevents graft injury and prolongs survival in an allogenic kidney transplant modelW.M.Bernhardt a,1,2,U.Gottmann b,1,F.Doyon b ,B.Buchholz a ,V.Campean c ,J.Scho¨del a ,A.Reisenbuechler b ,S.Klaus d ,M.Arend d ,L.Flippin d ,C.Willam a ,M.S.Wiesener a ,B.Yard b ,C.Warnecke a ,and K.-U.Eckardt aa Departmentof Nephrology and Hypertension,Friedrich–Alexander University,Erlangen–Nuremberg,Germany;b V Department of Medicine(Nephrology/Endocrinology/Rheumatology),University Hospital Mannheim,Mannheim,Germany;c Institute for Pathology,Friedrich–Alexander University,Erlangen–Nuremberg,Germany;and d FibroGen,Inc.,South San Francisco,CAEdited by Gregg L.Semenza,Johns Hopkins University School of Medicine,Baltimore,MD,and approved October 12,2009(received for review May 5,2009)Long-term survival of renal allografts depends on the chronic immune response and is probably influenced by the initial injury caused by ischemia and reperfusion.Hypoxia-inducible transcrip-tion factors (HIFs)are essential for adaptation to low oxygen.Normoxic inactivation of HIFs is regulated by oxygen-dependent hydroxylation of specific prolyl-residues by prolyl-hydroxylases (PHDs).Pharmacological inhibition of PHDs results in HIF accumu-lation with subsequent activation of tissue-protective genes.We examined the effect of donor treatment with a specific PHD inhibitor (FG-4497)on graft function in the Fisher–Lewis rat model of allogenic kidney transplantation (KTx).Orthotopic transplanta-tion of the left donor kidney was performed after 24h of cold storage.The right kidney was removed at the time of KTx (acute model)or at day 10(chronic model).Donor animals received a single dose of FG-4497(40mg/kg i.v.)or vehicle 6h before donor nephrectomy.Recipients were followed up for 10days (acute model)or 24weeks (chronic model).Donor preconditioning with FG-4497resulted in HIF accumulation and induction of HIF target genes,which persisted beyond cold storage.It reduced acute renal injury (serum creatinine at day 10:0.66؎0.20vs.1.49؎1.36mg/dL;P <0.05)and early mortality in the acute model and improved long-term survival of recipient animals in the chronic model (mortality at 24weeks:3of 16vs.7of 13vehicle-treated animals;P <0.05).In conclusion,pretreatment of organ donors with FG-4497improves short-and long-term outcomes after allo-genic KTx.Inhibition of PHDs appears to be an attractive strategy for organ preservation that deserves clinical evaluation.hypoxia-inducible transcription factors ͉kidney injury ͉protection ͉transplantationIn patients suffering from end-stage renal disease,kidney transplantation (KTx)offers the best form of renal replace-ment therapy,leading to improved quality of life and survival in comparison to dialysis (1).However,organ shortage significantly limits the opportunities for transplantation.Moreover,despite improvements in immunosuppressive therapy leading to a de-creased incidence of acute rejection episodes,there has been little improvement in long-term graft survival.The mean half-life of renal allografts from cadaveric donors is Ϸ8years (2).Accordingly,chronic allograft nephropathy contributes signifi-cantly to the need for initiation of regular dialysis (3).Reducing the risk for late graft loss therefore remains a major challenge in KTx.The mechanisms of chronic allograft failure reflect a complex interplay between immune and nonimmune mechanisms (4).Acute kidney injury immediately after transplantation,which is induced by the sequence of cold ischemia,warm ischemia,and reperfusion,in conjunction with an early immune response,not only impairs early graft function but is associated with reduced long-term graft survival (5,6).Although causality of this link has not been proven,it is tempting to assume that minimizing earlygraft injury improves long-term outcome.At the same time,the need to extend donor criteria in light of organ shortage further increases the risk for delayed graft function.Several approaches have already been taken to reduce early graft dysfunction,including optimization of the perfusion fluid (7,8)and the use of pharmaceuticals that interact with single steps in the patho-genesis of ischemia reperfusion injury (9).We reasoned that an effective way to improve early and possibly late graft function could be the induction of an array of endogenous protective mechanisms before the initiation of the acute injury associated with transplantation.Moreover,we hypothesized that the induc-tion of genes that have become inducible by hypoxia during evolution could confer such protection.Testing this hypothesis has become possible because of recent progress in understanding the mechanisms by which hypoxia influences gene expression through activation of hypoxia-inducible transcription factors (HIFs).HIFs are heterodimers of a constitutive -subunit (HIF-)and one of two alternative oxygen-regulated ␣-subunits,HIF-1␣or HIF-2␣.Under normoxia,HIF ␣is rapidly degraded via the ubiquitin–proteasome pathway.To target HIF-␣for degradation,two specific prolyl residues are hydroxylated by HIF-prolyl hydroxylases [prolyl hydroxylation domain (PHD)proteins]that require dioxygen and 2-oxoglutarate as cosub-strates (10,11).Oxoglutarate analogues therefore act as com-petitive inhibitors of PHDs (PHD-I)and HIF stabilizers.To date,far more than 100HIF target genes have been identified,including erythropoietin (EPO),VEGF,glucose transporters,and heme oxygenase-1(HO-1),which have the potential to confer nephroprotection under different conditions (12).We and others have previously shown that the application of PHD-Inhibitor stabilizes HIF in the kidney (13,14)and confers protection against prolonged warm renal ischemia (14,15)and toxic renal injury (16).Here,we have used a small molecule PHD-I (FG-4497)to test the hypothesis that stabilization of HIF in organ donors prevents early graft dysfunction in an allogenic rat kidney transplant model and that this effect translates into a long-term improvement of allograft function.ResultsFG-4497Stabilizes HIF-␣and Induces HIF Target Genes in Human Proximal Tubular Cells.FG-4497(FibroGen,Inc.)was identifiedfrom a PHD-I library for its capacity to activate the HIF pathwayAuthor contributions:W.M.B.and K.-U.E.designed research;W.M.B.,U.G.,F.D.,B.B.,J.S.,A.R.,B.Y.,and C.Warnecke performed research;S.K.,M.A.,and L.F.contributed new reagents;W.M.B.,U.G.,F.D.,B.B.,V.C.,J.S.,C.Willam,and C.Warnecke analyzed data;and W.M.B.,M.S.W.,and K.-U.E.wrote the paper.Conflict of interest statement:S.K.,M.A.,and L.F.are employees of FibroGen.This article is a PNAS Direct Submission.1W.M.B.and U.G.contributed equally to this work.2Towhom correspondence should be addressed.E-mail:wanja.bernhardt@uk-erlangen.de.This article contains supporting information online at /cgi/content/full/0903978106/DCSupplemental .21276–21281͉PNAS ͉December 15,2009͉vol.106͉no.50 ͞cgi ͞doi ͞10.1073͞pnas.0903978106in vitro(17).It has previously been demonstrated that4–6h after treatment of rats with FG-4497,EPO production is induced (18)and protection occurs against ex vivo ischemic injury in isolated perfused kidneys(19).Moreover,FG-4497was found to protect mucosal cells in a murine colitis model(18)and neuronal cells(20).To test its ability to inhibit HIF degradation in kidney cells,increasing concentrations of FG-4497were applied in vitro. Immunoblotting of protein extracts of HKC-8cells(immortal-ized human tubular cells)showed stabilization of both HIF-␣isoforms(HIF-1␣and HIF-2␣)after treatment with dipyridyl (positive control)or FG-4497(0.5–100M)for6h(Fig.1A). Analysis of the time course of HIF induction by FG-4497revealed very rapid stabilization of HIF-␣(15min)and stable HIF protein levels for up to6h(Fig.1B).To test the time course of HIF target gene expression,mRNA levels of angiopoietin-like 4(AngPTL4),glucose transporter-1(Glut-1),and VEGF were determined for up to6h.Expression levels of the genes were initially elevated after2h and increased further up to6h.FG-4497Stabilizes HIF-␣in Rat Kidneys,and HIF Remains Stable After Cold Ischemia.Next,we injected FG-4497into rats to test the time course of HIF stabilization in the kidney in vivo.Both HIF-␣isoforms were detectable in rat kidneys1,4,and6h after i.v. injection of FG-4497at a dose of40mg/kg,which was found to stimulate HIF in prior dose-finding experiments(Methods;Fig. 2A).There was no apparent difference between the extent of HIF accumulation between1and6h.Based on these results,the time course of target gene expression(Fig.1C),and published data(14,18–21),we chose a6-h interval between injection and kidney explantation for cold preservation.To determine whether HIF-␣is still detectable after cold ischemia,kidneys were removed,perfused with University of Wisconsin solution, and maintained in this solution for24h at4°C following prior treatment with FG-4497.Immunohistochemistry revealed strong intranuclear accumulation of HIF-␣after FG-4497treatment, whereas cold ischemia did not induce HIF-␣in vehicle(Veh)-treated rats(Fig.2B).The expression pattern of the two HIF-␣isoforms stabilized by FG4497resembles physiological activa-tion under systemic hypoxia(22);HIF-1␣was expressed in tubular epithelial cells[Fig.2A(Upper)and B(Left)],and HIF-2␣was expressed in interstitial,glomerular,and endothelial cells[Fig.2A(Lower)and B(Right)].FG-4497Transactivates HIF Target Genes in Vivo.To examine the activation of HIF target genes6h after i.v.injection of FG-4497 (40mg/kg)with and without subsequent cold storage for24h, we performed real-time PCR for selected known HIF target genes,which may be of particular relevance for a potential nephroprotective effect.FG-4497was found to increase HO-1 and EPO4–5-fold and more than200-fold,respectively,inde-pendent of cold storage(Fig.3).In addition,HIF target genes involved in glucose metabolism,such as Glut-1or hexokinase, were increased(Fig.S1A).Given their potential pathophysio-logical relevance,we also tested the expression of inflammatory cytokines known to be inducible by HIF and found that IL-1was induced approximately2-fold by FG-4497[0h,of cold ischemia(c.i.):2.27Ϯ0.19;24h of c.i.:2.23Ϯ0.49].To identify additional genes that may be involved in mediating the protective effect,we performed an oligonucleotide microarray analysis of whole kidney extracts.Table S1shows additional genes that were more than2.0-fold up-regulated in whole kidney extracts6h after application of FG-4497.The change of mRNA in renal cortical extract may underestimate the change in expression level of the respective gene in specific cell populations that contribute only a proportion to total kidney mRNA.The microarray revealed that FG-4497up-regulated known HIF target genes and additional genes not previously identified as HIF target genes. The activation of all these genes remained stable over24h of cold storage.Change in expression of the2most strongly up-and down-regulated genes(Rarres2,Lox,and IGFBP3,Id2,respec-tively)was confirmed by Real Time-PCR(Fig.S1B and C). Single genes,such as the sodium channel Scnn1a,were induced by cold ischemia only but not by FG-4497.Taken together, FG-4497stabilizes HIF and transactivates HIF target genes in rat kidneys,and this effect remains stable during cold ischemia, which is a prerequisite for a potentially protective effect during reperfusion.We then tested the effect of donor pretreatment with FG-4497in a rat model of allograft KTx.Fig.1.Induction of HIF-␣and HIF target genes by FG-4497in human proximal tubular cells.(A)HKC-8cells were exposed to dipyridyl(DP,positive control)or FG-4497(0.5,1,5,10,25,50,and100M)for6h.Immunoblotting for HIF-␣protein shows dose-dependent accumulation of HIF-1␣and HIF-2␣by FG-4497,with a maximal level of HIF-␣stabilization at concentrations above10M.(B)Fifteen minutes after FG-4497treatment(150M),HIF-1␣and HIF-2␣were stabilized and remained stable over the observation period of6h.(C)With a delay of approximately2h,the mRNA(real-time PCR)of the HIF target genes AngPTL4,Glut-1,and VEGF was significantly up-regulated compared with baseline(set as‘‘1’’)and further increased up to6h after treatment with FG-4497.Normoxic untreated cells(N)served as a negative control.Bernhardt et al.PNAS͉December15,2009͉vol.106͉no.50͉21277M E D I C A L S C I E N C ESDonor Treatment with FG-4497Ameliorates Renal Function in the Acute Phase of Allograft KTx.To test the effect of FG-4497on earlygraft function,the left kidney from a donor animal (Fisher strain)treated with FG-4497or Veh was transplanted ortho-topically into a recipient animal (Lewis strain)following 24h of cold storage,with a warm ischemia period of Ϸ30min.Imme-diately after transplantation,the right kidney of the recipient was removed so that survival became graft-dependent and the occurrence of delayed graft function predictably resulted in thedeath of the recipient animal after 2–5days.Animals were not treated with immunosuppressants so as not to blunt the devel-opment of allograft injury.In control experiments,the same procedure was performed in isogenic animals (Lewis–Lewis strain).In the allogenic constellation,kidney injury was severe,resulting in survival of only 6(23.1%)of 26animals in the Veh-treated group.FG-4497pretreatment significantly reduced mortality,with 8(53.3%)of 15animals surviving (P ϭ0.019;Fig.4A ).In addition,among animals surviving for 10days,those receiving a kidney from a donor pretreated with FG-4497(n ϭ8)had significantly lower serum creatinine levels as compared with animals receiving a transplant from a Veh-treated donor (n ϭ6)(Fig.4B ).This functional improvement was paralleled by reduced structural damage,as reflected by an acute tubular necrosis score (Fig.4C ).In contrast,animals subjected to isogenic transplantation all survived (Fig.4A )and showed only a very moderate increase in serum creatinine,with no difference between animals receiving kidneys from donors pretreated with FG-4497or Veh (Fig.4B ).However,renal morphology was significantly better preserved in kidneys from FG-4497-pretreated donors (Fig.4C ),indicating an effect of FG-4497on ischemic injury that was independent of immunological mis-match.The kidney leukocyte infiltrate as assessed according to the Banff 97classification (23)(Table S2)and the number of T lymphocytes (CD3ϩcells)(Fig.S2)did not reveal differences between Veh-and FG-4497-treated groups.Donor Treatment with FG-4497Significantly Improves Long-Term Graft Survival.To investigate the long-term consequences ofprotection against early graft dysfunction induced by donor pretreatment with FG-4497,an additional group of animals was studied in which nephrectomy of the right kidney of the recipient animal was delayed until day 10after transplantation.This allowed animals to survive periods of early severe graft dysfunc-tion and assessment of the effect of the intervention on chronic graft failure by studying survival rates.As in the acute setting,we chose not to treat rats with immunosuppressants to accelerate chronic allograft nephropathy.Fig.5illustrates thatdonorFig.2.Kinetics of HIF accumulation after FG-4497treatment in the kidneys of Fisher (F-344)rats before and after cold ischemia.b.w.,body weight.(A )At 1,4,and 6h after i.v.injection of FG-4497,HIF-1␣was immunohistochemically detectable in tubular epithelial cells of rat kidneys and HIF-2␣was detectable in interstitial,endothelial,and glomerular cells.(B )After FG-4497and cold ischemia of 24h,HIF-␣was still detectable to a comparable degree as before cold ischemia.Veh treatment with or without cold ischemia did not lead to detectable HIF-␣accumulation.Fig.3.Effect of FG-4497on the expression of HIF target genes.Single potentially protective HIF target genes were quantified by real-time PCR 6h after FG-4497treatment without cold ischemia (c.i.)or after an additional 24-h period of cold ischemia.The nephroprotective genes HO-1and EPO were strongly up-regulated after FG-4497treatment irrespective of cold ischemia (*,P Ͻ0.05).21278͉ ͞cgi ͞doi ͞10.1073͞pnas.0903978106Bernhardt etal.treatment with FG-4497markedly prolonged graft-dependent survival in recipient animals by more than 50%.Two weeks after transplantation,when all animals in both groups were still alive,recipients of FG-4497-treated donors already showed a tendency toward lower serum creatinine concentrations (1.45Ϯ0.66mg/dL vs.2.75Ϯ1.55mg/dL;P ϭ0.07).Isogenically trans-planted control animals showed no mortality within the obser-vation period.FG-4497Treatment Protects Human Proximal Tubular Cells from Apoptosis.To test whether HIF accumulation induced by FG-4497protects cells under in vitro conditions mimicking ischemia reperfusion injury,we used an in vitro model of cell injury induced by oxygen–glucose deprivation and subsequent reoxy-genation.After 24h of exposure to 1Vol%O 2in a glucose-free medium,cells were reoxygenated (21Vol%O 2)in glucose-containing medium for another 24h.At the end of the exper-iment,the apoptosis rate was determined.Pretreatment for 6h with FG-4497significantly reduced the rate of apoptosis by about 30%in the HKC-8cell line and in primary human tubular cells (Fig.S3A ).In vivo,however,there was no detectable difference in the number of apoptotic cells at day 10after KTx (Fig.S3B )between surviving recipients of Veh-and FG-4497-treated donors as assessed by Tunel staining.FG-4497Has No Influence on NF-B Signaling.Hydroxylation ofaspargyl-residues of ankyrin repeats by factor-inhibiting HIF (FIH)has been shown to influence signaling pathways in addi-tion to HIF signaling,such as Notch (24,25)or NF-B signaling (26).Therefore,we examined NF-B expression after ing a luciferase assay and electrophoretic mobility shift assay we found no influence of FG-4497on NF-B induc-tion (Fig.S4A and C )or on protein levels of its regulatory subunit I B (Fig.S4B ).DiscussionThis study translates recent knowledge on the molecular mech-anisms of hypoxia-inducible gene expression into a widely accepted animal model of allograft nephropathy.Donor pre-treatment using a single dose of a small molecule inhibitor of HIF PHDs,FG-4497,which stabilizes HIF and activates HIF target genes in the kidney,significantly reduced the frequency of delayed graft function and markedly improved long-term out-come,suggesting opportunities for improvement of kidney func-tion after transplantation.Previous experimental data suggest that short periods of ischemia/reperfusion can protect against subsequent ischemic injury (27–29).However,the clinical application of this so-called ‘‘ischemic preconditioning’’is limited by (i )obvious difficulties to induce controlled ischemia in vivo,(ii )sensitivity of the protective effect to changes in the duration and sequence of ischemia and reperfusion episodes,and (iii )the failure to identify unequivocally the molecular mediators.In contrast,the approach used in this study relies on mimicking the response to hypoxia through inhibition of the enzymes that degrade the transcription factor HIF.The analysis of mRNAexpressionFig.4.Effect of FG-4497on early graft function and renal morphology.In the acute setting,FG-4497significantly improved survival within the initial days after KTx (A ),indicating a lower incidence of delayed graft function.In addition,in surviving animals,FG-4497donor pretreatment resulted in an earlier and more pronounced decrease in serum creatinine from days 3–10after allogenic transplantation (Allo)when compared with donor pretreat-ment with Veh only (B ).In isogenic KTx,there was no measurable difference in serum creatinine and survival between FG-4497and Veh.(C )Blinded scoring for acute tubular necrosis revealed better preservation of renal morphology after FG-4497compared with Veh independent of the immunological con-stellation (*,P Ͻ0.05).Fig.5.Effect of FG-4497on long-term graft survival.Kaplan-Meier curves after allograft KTx in animals with and without pretreatment of the donor with FG-4497.Animals that received a renal transplant from an FG-4497-treated donor had significantly better survival rates (black line)than animals transplanted with a kidney from a Veh-treated donor (dotted gray line).None of the isogenic control animals died (dashed gray line).(*,P Ͻ0.05).Bernhardt et al.PNAS ͉December 15,2009͉vol.106͉no.50͉21279M E D I C A L S C I E N C ESconfirmed that a number of genes previously identified as HIF-dependent are inducible in the kidney,including EPO,which has previously been demonstrated to be nephroprotective in renal ischemia-reperfusion models (30–33),and HO-1,which has also been shown to improve short-and long-term graft function in the same rat model (34,35).In addition,HIF activation facilitates cellular anaerobic metabolism by inducing Glut-1or enzymes involved in glycolysis.Although it is possible that among the large number of genes induced by HIF,single genes like EPO and HO-1are of particular importance,identi-fication of their relative contribution is of theoretical rather than practical relevance,because the concerted activation is likely to be superior to single gene induction.In terms of target gene specificity,the parallel activation of HIF-1␣and HIF-2␣is possibly of particular relevance.Although HIF-2␣transactivates EPO (36,37),HIF-1␣is the subunit stabilized in tubular cells,and target genes involved in glucose metabolism are predomi-nantly HIF-1␣-dependent (38).The design of this study sheds further light on the dependence of long-term graft function on early graft injury.Although an association between the occurrence of early graft dysfunction and long-term graft failure has been clearly demonstrated (39–41),causality of this link has not been proven to date.It is thus noteworthy that donor pretreatment limiting early graft dysfunction had a significant impact on long-term graft survival.The HIF system responds primarily to reduced availability of molecular oxygen,but changes in cellular function induced by HIF apparently also confer protection against more complex types of cellular injury,including those induced by the sequence of ischemia and reperfusion in vivo (14,42,43)and partially mimicked by oxygen–glucose deprivation in vitro.HIF activation by FG-4497reduced apoptosis in vitro and tubular necrosis in ing Tunel staining,we did not observe reduced apoptosis rates in vivo after 10days,but this may be attributable to survival bias,because only animals not developing early graft failure survived until this time point.We also observed no effects of HIF stabilization on lymphocyte counts in allogenic animals at day 10after KTx,which might suggest that the observed protection is most likely attributable to reduction of the ischemic injury rather than to a modulation of immunological factors.Nevertheless,the far better outcome of transplantation between isogenic animals indicates that the interplay between ischemia reperfusion injury and immunological factors is of crucial importance both for early and late graft dysfunction.HIF has recently been shown to influence several aspects of the innate and adaptive immune response (44–46),but donor treatment limits such effects toimmune cells residing in the graft.Although HIF may stimulate dendritic cells (47),any potential adverse effects of such stim-ulation are obviously offset by inhibition of ischemia reperfusion injury.FIH has also been shown to hydroxylate defined residues of ankyrin repeats,thereby possibly affecting the regulation of other signaling pathways,including Notch (24,25)and NF-B (26).Although we found no evidence that FG-4497influences NF-B or I B-signaling,non-HIF-dependent effects of hydrox-ylase inhibition cannot be definitively ruled out.Although current management of organ donors is largely focused on maintenance of physical homeostasis,this study suggests that there is significant potential to improve the results of organ transplantation by inducing protective biological mech-anisms before organ explantation.A recent analysis of human kidney graft biopsies obtained immediately after engraftment revealed significant variability in the extent of baseline HIF expression (48),consistent with animal experiments showing that ischemia reperfusion injury,per se,is only a weak stimulus for HIF activation (22).Interestingly,however,renal allografts with higher baseline HIF expression tended to have better functional outcomes (48),suggesting that the current experi-mental strategy of pharmacological HIF induction is potentially suitable for translation into clinical practice.The 6-h time interval between drug dosing and nephrectomies used in this study would be achievable in human organ donors,and future studies will have to address whether shorter pretreatment peri-ods are sufficient to induce protection,even though HIF-dependent gene expression is not yet maximal.The potential applicability of our approach to humans is underscored by the fact that a small molecule inhibitor of PHDs was used,and other members of this class of drugs are already being developed for the treatment of anemia through stimulation of endogenous EPO production (49).MethodsDetails for cell culture,HIF,and I B ␣protein extraction and immunoblotting,animal experiments/transplantation protocol,functional studies,tissue prep-aration,immunohistochemistry,morphological analysis,real-time PCR,oxy-gen–glucose deprivation,caspase 3/7assay,oligonucleotide microarray anal-ysis,luciferase reporter assays,electrophoretic mobility shift assay,and statistics are given in SI Materials and Methods .ACKNOWLEDGMENTS.We thank B.Teschemacher,H.Fees,and A.Kosel for excellent technical assistance.The work was supported by the Collaborative Research Center of the Deutsche Forschungsgemeinschaft (Grant SFB 423)‘‘Kidney Injury:Pathogenesis and Regenerative Mechanisms’’(TP A14).B.B.was the recipient of a grant from the Interdisciplinary Centre for Clinical Research at the University of Erlangen–Nuremberg.1.Wolfe RA,et al.(1999)Comparison of mortality in all patients on dialysis,patients on dialysis awaiting transplantation,and recipients of a first cadaveric transplant.N Engl J Med 341:1725–1730.2.Meier-Kriesche HU,Schold JD,Kaplan B (2004)Long-term renal allograft survival:Have we made significant progress or is it time to rethink our analytic and therapeutic strategies?Am J Transplant 4:1289–1295.3.Vadivel N,Tullius SG,Chandraker A (2007)Chronic allograft nephropathy.Semin Nephrol 27(4):414–429.4.Kaplan B (2006)Overcoming barriers to long-term graft survival.Am J Kidney Dis 47(4suppl.2):S52–S64.5.Baid-Agrawal S,Frei UA (2007)Living donor renal transplantation:Recent develop-ments and perspectives.Nat Clin Pract Nephrol 3:31–41.6.Cecka JM (2000)The UNOS Scientific Renal Transplant Registry—2000.Clin Transpl 2000:1–18.7.Faenza A,et al.(2001)Kidney preservation with University of Wisconsin and Celsior solution:A prospective multicenter randomized study.Transplantation 72:1274–1277.8.Hauet T,et al.(2003)A modified University of Wisconsin preservation solution with high-NA ϩlow-K ϩcontent reduces reperfusion injury of the pig kidney graft.Trans-plantation 76:18–27.9.Cugini D,et al.(2005)Inhibition of the chemokine receptor CXCR2prevents kidney graft function deterioration due to ischemia/reperfusion.Kidney Int 67:1753–1761.10.Semenza GL (2004)Hydroxylation of HIF-1:Oxygen sensing at the molecular level.Physiology (Bethesda)19:176–182.11.Kaelin WG,Jr,Ratcliffe PJ (2008)Oxygen sensing by metazoans:The central role of theHIF hydroxylase pathway.Mol Cell 30:393–402.12.Bernhardt WM,et al.(2007)Organ protection by hypoxia and hypoxia-induciblefactors.Methods Enzymol 435:221–245.13.Warnecke C,et al.(2003)Activation of the hypoxia-inducible factor-pathway andstimulation of angiogenesis by application of prolyl hydroxylase inhibitors.FASEB J 17:1186–1188.14.Bernhardt WM,et al.(2006)Preconditional activation of hypoxia-inducible factorsameliorates ischemic acute renal failure.J Am Soc Nephrol 17:1970–1978.15.Hill P,et al.(2008)Inhibition of hypoxia inducible factor hydroxylases protects againstrenal ischemia-reperfusion injury.J Am Soc Nephrol 19:39–46.16.Weidemann A,et al.(2008)HIF activation protects from acute kidney injury.J Am SocNephrol 19:486–494.17.Norman LO (1983)US Patent 4,379,752.18.Robinson A,et al.(2008)Mucosal protection by hypoxia-inducible factor prolyl hy-droxylase inhibition.Gastroenterology 134:145–155.19.Rosenberger C,et al.(2008)Activation of hypoxia-inducible factors ameliorates hy-poxic distal tubular injury in the isolated perfused rat kidney.Nephrol Dial Transplant 23:3472–3478.osevic J,et al.(2009)Non-hypoxic stabilization of hypoxia-inducible factor alpha(HIF-␣):Relevance in neural progenitor/stem cells.Neurotox Res 15:367–380.21.Schneider C,et al.(2009)Short-term effects of pharmacologic HIF stabilization onvasoactive and cytotrophic factors in developing mouse brain.Brain Res 1280:43–51.22.Rosenberger C,et al.(2002)Expression of hypoxia-inducible factor-1␣and -2␣inhypoxic and ischemic rat kidneys.J Am Soc Nephrol 13:1721–1732.23.Racusen LC,et al.(1999)The Banff 97working classification of renal allograft pathol-ogy.Kidney Int 55(2):713–723.21280͉ ͞cgi ͞doi ͞10.1073͞pnas.0903978106Bernhardt etal.。
供者来源性细胞游离DNA在肾移植诊疗中的研究进展与应用
第１３卷 第４期２０２２年７月Ｖｏｌ． １３ Ｎｏ．４Ｊｕｌ． ２０２２器官移植Ｏｒｇａｎ Ｔｒａｎｓｐｌａｎｔａｔｉｏｎ【摘要】 肾移植术后排斥反应的早期诊断及治疗对于减少移植物损伤至关重要。
供者来源性细胞游离DNA （dd-cfDNA ）检测是基于二代测序等技术，通过浓度法及绝对定量法检测循环体液中源于坏死、凋亡的供肾组织DNA 片段含量，具有监测同种异体移植物损伤的临床应用潜力。
相比传统血清肌酐等检测指标，dd-cfDNA 检测可提前数周至数月监测到移植物损伤，为临床治疗和延缓移植物失功提供了“时间窗”。
随着近年来对dd-cfDNA 研究的不断深入，dd-cfDNA 因其兼具无创性、灵敏度高和能够对治疗效果进行实时评估等特点受到广泛关注。
本文综述了目前有关dd-cfDNA 检测在肾移植诊疗中多维度应用的研究证据与结论，并讨论了dd-cfDNA 未来的研究和临床应用方向，旨在为dd-cfDNA 检测广泛应用于我国的临床实践提供参考依据。
【关键词】 肾移植；供者来源性细胞游离DNA （dd-cfDNA ）；排斥反应；生物标志物；移植物损伤；抗体介导的排斥反应（AMR ）；T 细胞介导的排斥反应（TCMR ）；BK 病毒相关性肾病（BKV AN ）【中图分类号】 R617，R692 【文献标志码】A 【文章编号】 1674-7445（2022）04-0007-08供者来源性细胞游离DNA 在肾移植诊疗中的研究进展与应用杨洋 张健 林俊·专家论坛·【Abstract 】 Early diagnosis and treatment of rejection after kidney transplantation play a critical role in alleviating allograft injury. Detection of donor-derived cell-free DNA (dd-cfDNA) could be performed based on the next-generation sequencing and other techniques. The content of DNA fragments derived from necrotic and apoptotic donor kidney tissues in circulating body fluids could be determined by concentration and absolute quantitative methods, which has application potential in monitoring allograft injury in clinical practice. Compared with traditional serum creatinine and other indicators, dd-cfDNA detection may monitor allograft injury from several weeks to months in advance, providing a “time window ” for clinical treatment and delaying graft failure. Along with deepening research of dd-cfDNA in recent years, dd-cfDNA has captivated widespread attention due to its non-invasiveness, high sensitivity and real-time evaluation of therapeutic effect. In this article, current study evidence and conclusions related to multidimensional application of dd-cfDNA detection in diagnosis and treatment of kidney transplantation were reviewed, and the future research and clinical application direction of dd-cfDNA were discussed, aiming to provide reference for widespread application of dd-cfDNA detection in clinical practice in China.【Key words 】 Kidney transplantation; Donor-derived cell-free DNA (dd-cfDNA); Rejection; Biomarker; Allograft injury; Antibody-mediated rejection (AMR); T-cell mediated rejection (TCMR); BK virus-associated nephropathy (BKV AN)Research progress and application of donor-derived cell-free DNA in diagnosis and treatment of kidney transplantation Yang Yang, Zhang Jian, Lin Jun. Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China Corresponding author: Lin Jun, Email : *********************DOI: 10.3969/j.issn.1674-7445.2022.04.007基金项目 ： 国家自然科学基金（82000717）；北京市自然科学基金（7192043、7194250）；北京市医院管理中心“青苗计划”（QML20190106）作者单位：100050 北京，首都医科大学附属北京友谊医院泌尿外科作者简介：杨洋，男，1990年生，博士，医师，研究方向为肾移植，Email ：*****************通信作者：林俊，Email ：*********************·４５６·第１３卷器官移植肾移植是终末期肾病的最佳治疗方法，与透析相比，肾移植能提高患者生存率，改善生活质量[1]。
亲属肾移植手续和流程
亲属肾移植手续和流程英文回答：Kidney Transplantation from a Living Donor: Procedures and Processes.Kidney transplantation from a living donor is a surgical procedure in which a healthy kidney is removed from a living person and transplanted into a person with kidney failure. The recipient of the kidney is typically someone who has been on dialysis for a long period of time and is in need of a new kidney to survive.The process of kidney transplantation from a living donor involves several steps:1. Evaluation of the Potential Donor: The potential donor must undergo a thorough medical evaluation to ensure that they are healthy enough to donate a kidney. This evaluation includes a physical exam, blood tests, andimaging studies.2. Matching the Donor and Recipient: Once the potential donor has been evaluated, they are matched with a recipient based on their blood type and tissue compatibility.3. Surgery: The kidney transplantation surgery is typically performed laparoscopically, which involves making small incisions in the abdomen. The surgeon removes the kidney from the donor and transplants it into the recipient.4. Recovery: After surgery, both the donor and the recipient will need to recover in the hospital. The donorwill typically stay in the hospital for a few days, whilethe recipient may stay for a week or more.5. Follow-up Care: After surgery, both the donor andthe recipient will need to follow up with their doctors regularly to ensure that the kidney is functioning properly and that there are no complications.Advantages of Living Donor Kidney Transplantation:There are several advantages to receiving a kidney transplant from a living donor, including:Shorter waiting time for a kidney: Living donor kidney transplants typically have a shorter waiting time than deceased donor kidney transplants.Better chance of success: Living donor kidney transplants are more likely to be successful than deceased donor kidney transplants.Better quality of life: Living donor kidneytransplants can improve the quality of life for recipients by allowing them to live a more active and independent life.Risks of Living Donor Kidney Transplantation:There are also some risks associated with living donor kidney transplantation, including:Risks to the donor: The donor may experiencecomplications during surgery, such as bleeding, infection, or damage to other organs.Risks to the recipient: The recipient may experience complications after surgery, such as rejection of the kidney, infection, or blood clots.Alternatives to Living Donor Kidney Transplantation:If a living donor kidney transplant is not possible, there are other options for people with kidney failure, including:Deceased donor kidney transplantation: A deceased donor kidney transplant involves receiving a kidney from a person who has died.Dialysis: Dialysis is a treatment that helps to remove waste products from the blood when the kidneys are not working properly.中文回答：亲属肾移植手术和流程。
巨噬细胞在移植肾纤维化中的作用研究进展
· 综述·巨噬细胞在移植肾纤维化中的作用研究进展任滌非 王於尘 苗芸【摘要】 缺血-再灌注损伤、排斥反应、钙调磷酸酶抑制剂造成的肾毒性等因素会在肾移植术后使肾细胞外基质过度积聚，逐渐造成移植肾纤维化，最终导致肾衰竭。
近年来，巨噬细胞在移植肾纤维化中的作用机制逐渐受到关注，有研究表明哺乳动物雷帕霉素靶蛋白抑制剂等药物可以通过巨噬细胞途径减缓肾移植术后移植肾纤维化。
本文就移植肾纤维化的主要病因及病理生理学机制、不同巨噬细胞在移植肾纤维化进展中的作用、外周募集巨噬细胞和肾驻留巨噬细胞对肾损伤区域的浸润、巨噬细胞对肌成纤维细胞的诱导作用及巨噬细胞相关的移植肾纤维化潜在治疗方案进行综述，以期为巨噬细胞在移植肾纤维化中的研究提供参考。
【关键词】 纤维化；肾移植；巨噬细胞；肌成纤维细胞；缺血-再灌注损伤；钙调磷酸酶抑制剂；炎症反应；排斥反应【中图分类号】 R617, R329.2 【文献标志码】 A 【文章编号】 1674-7445（2023）05-0013-07Research progress on the role of macrophages in renal allograft fibrosis Ren Difei *, Wang Yuchen, Miao Yun. *Department of Organ Transplantation , Nanfang Hospital of Southern Medical University , Guangzhou 510515, China Corresponding author: Miao Yun, Email: *******************【Abstract 】 Ischemia-reperfusion injury, rejection, nephrotoxicity caused by calcineurin inhibitors and other factors cause excessive accumulation of renal extracellular matrix after kidney transplantation, which gradually induce renal fibrosis and eventually lead to renal failure. In recent years, the mechanism of macrophages in renal allograft fibrosis has gradually captivated widespread attention. Studies have shown that some drugs like mammalian target of rapamycin inhibitors may mitigate renal allograft fibrosis through the macrophage. In this article, the main pathogenesis and pathophysiological mechanism of renal allograft fibrosis, the role of different macrophages in the progression of renal allograft fibrosis, the infiltration of peripherally-recruited macrophages and renal resident macrophages into renal injury areas, the induction of myofibroblasts by macrophages and potential treatment regimens of macrophage-associated renal allograft fibrosis were reviewed, aiming to provide reference for investigating the role of macrophages in renal allograft fibrosis.【Key words 】 Fibrosis; Kidney transplantation; Macrophage; Myofibroblasts; Ischemia-reperfusion injury;Calcineurin inhibitor; Inflammation; Rejection纤维化本质上是组织损伤后的过度修复，多种与炎症相关的损伤机制导致器官中实质细胞数量减少，而间充质细胞及其产生的细胞外基质过度增加，使器官生理功能逐渐减退。
南京军区总院肾移植 流程
南京军区总院肾移植流程I think the process of kidney transplantation at the Nanjing Military Region General Hospital is quite complex and requires a lot of careful planning and coordination. 我认为南京军区总院的肾移植程序是相当复杂的，需要大量仔细的规划和协调。
First, the patient needs to undergo a series of thorough medical evaluations to determine if they are a suitable candidate for a kidney transplant. 首先，患者需要接受一系列彻底的医学评估，以确定他们是否适合接受肾移植。
The next step is to find a suitable donor, whether it be a living donor or a deceased donor. 接下来的步骤是找到一个合适的捐赠者，无论是活体捐赠者还是死亡捐赠者。
If a living donor is available, they will need to undergo a thorough evaluation to ensure they are healthy enough to undergo the surgery. 如果有活体捐赠者，他们需要接受彻底评估，以确保他们足够健康进行手术。
Once a suitable donor has been found and all evaluations have been completed, the transplant surgery can be scheduled. 一旦找到合适的捐赠者并完成所有评估，移植手术就可以安排了。
基于加权基因共表达网络鉴定肾移植术后排斥反应中巨噬细胞M1亚型相关基因
第14卷 第1期2023年1月Vol. 14 No.1Jan. 2023器官移植Organ Transplantation ·论著·基于加权基因共表达网络鉴定肾移植术后排斥反应中巨噬细胞M1亚型相关基因董博清 李杨 石玉婷 张静 冯新顺 郑瑾 李潇 丁小明 薛武军【摘要】 目的 鉴定肾移植术后排斥反应中巨噬细胞M1亚型表达的相关基因并构建风险模型预测移植肾存活。
方法 在基因表达综合（GEO ）数据库下载肾移植术后的GSE36059及GSE21374数据集。
GSE36059包括发生排斥反应和稳定移植物的样本，使用该数据集进行加权基因共表达网络分析（WGCNA ）和差异分析筛选差异表达的巨噬细胞M1亚型相关差异表达基因（M1-DEG ）。
随后将GSE21374数据集（包含了移植物丢失的随访数据）按照7∶3拆分为训练集以及验证集，在训练集中使用最小绝对收缩和选择算法（LASSO ）筛选变量构建多因素Cox 模型，并评估模型预测移植物存活的能力。
使用CIBERSORT 分析高、低风险组浸润的免疫细胞的差异，并分析两组间人类白细胞抗原（HLA ）相关基因的分布，基因集富集分析（GSEA ）用于进一步明确高风险组中富集的生物学过程以及通路。
最后使用数据库预测与预后基因互作的微小核糖核酸（miRNA ）。
结果 在GSE36059数据集中，筛选得到14个M1-DEG 。
在GSE21374数据集中，使用LASSO-Cox 回归筛选出Toll 样受体8（TLR8）、Fc γ受体1B （FCGR1B ）、BCL2相关蛋白A1（BCL2A1）、组织蛋白酶S （CTSS ）、鸟苷酸结合蛋白2（GBP2）及半胱氨酸天冬氨酸蛋白酶招募域家族成员16（CARD16），基于这6个M1-DEG 构建多因素Cox 模型。
风险模型在训练集中预测1年及3年移植物存活的受试者工作特征曲线下面积（AUC ）分别为0.918和0.877，在验证集中预测1年及3年移植物存活的AUC 分别为0.765及0.736。
Kidney Transplantation
As with any organ transplant, the kidney recipient will require life-long treatment with medications that suppress the immune response in order to prevent the body’s immune system from rejecting the transplanted kidney.
Renal allograft rupture
Reason: Acute rejection Feature:
1. transplant renal edema, volume increased and renal capsule tension increased 2. The patient's body sodium and water retention, increased blood pressure fluctuation range, in patients with cough, sputum abdominal pressure suddenly increased, and sudden change in body position, the transplanted kidney circumferential pressure increases, causing the capsule rupture then transplanted kidney rupture
Liver injury
Reason:
Some patients with preoperative presence of other chronic liver disease or a history of potential liver function failure after more susceptible to liver disease, liver dysfunction after transplantation gradually increased The other part is due to the postoperative medication due to drug-induced hepatitis
尿毒症门特办理流程
尿毒症门特办理流程英文回答：The process of handling end-stage renal disease, also known as kidney failure, can be quite complex. However, I will try to explain it in a simple and understandable way.Firstly, it is important to understand that end-stage renal disease requires long-term treatment, usually in the form of dialysis or kidney transplantation. Dialysis is a procedure that helps remove waste and excess fluid from the blood when the kidneys are no longer able to do so. Kidney transplantation, on the other hand, involves replacing the failed kidney with a healthy one from a donor.To initiate the process, I would recommend consulting with a nephrologist, a doctor who specializes in kidney diseases. They will evaluate your condition and determine the best treatment option for you. If dialysis is recommended, you will be referred to a dialysis centerwhere you will receive regular treatments.If kidney transplantation is considered as the best option, the next step is finding a suitable donor. This can be done through living donation, where a family member or a friend donates a kidney, or through deceased donation, where a kidney is obtained from a deceased person. The evaluation process for transplantation involves various tests and assessments to ensure compatibility and minimize the risk of rejection.Once a donor is found, the transplantation surgery will be scheduled. After the surgery, you will need to take immunosuppressant medications to prevent rejection of the new kidney. Regular follow-up visits with your transplant team will be necessary to monitor your progress and adjust medications if needed.It is important to note that the process of handling end-stage renal disease can be emotionally and physically challenging. It requires a strong support system and a positive mindset to cope with the changes and uncertaintiesthat come with it. However, with the right treatment and support, many people are able to lead fulfilling lives even with kidney failure.中文回答：处理尿毒症（也称为肾衰竭）的过程可能相当复杂。
肾移植相关血栓性微血管病的诊断及治疗进展
第14卷 第1期2023年1月Vol. 14 No.1Jan. 2023器官移植Organ Transplantation 【摘要】 血栓性微血管病（TMA ）是肾移植术后较为严重的并发症，以血小板减少、微血管溶血性贫血和急性肾损伤为主要特征，可导致移植肾失功甚至受者死亡。
随着我国实体器官移植数量的不断增加，以及对TMA 认识的提高，其相关研究也在逐步深入。
肾移植相关TMA 病因多样，临床表现各异，缺乏特异性的无创检测手段。
多数TMA 的确诊依赖于肾穿刺活组织检查，但由于TMA 多伴随有血小板明显降低，肾穿刺风险较大，明确诊断存在一定困难。
针对肾移植相关TMA ，目前通常使用血浆置换、静脉注射免疫球蛋白以及停用潜在风险药物等综合治疗方式，但总体预后不佳。
本文现就肾移植术后TMA 的分类、肾移植相关TMA 的诊断及治疗做一综述，以期为临床肾移植相关TMA 的诊断和治疗提供参考。
【关键词】 肾移植；血栓性微血管病；非典型溶血尿毒综合征；血栓性血小板减少性紫癜；免疫抑制药；感染；抗体介导的排斥反应；依库珠单抗【中图分类号】 R617，R543 【文献标志码】A 【文章编号】1674-7445（2023）01-0009-07【Abstract 】 Thrombotic microangiopathy (TMA) is a severe complication after kidney transplantation, mainly characterized by thrombocytopenia, microvascular hemolytic anemia and acute kidney injury, which may lead to kidney allograft failure or even death of the recipients. With the increasing quantity of solid organ transplantation in China and deeper understanding of TMA, relevant in-depth studies have been gradually carried out. Kidney transplantation-associated TMA is characterized with different causes and clinical manifestations. Non-invasive specific detection approach is still lacking. The diagnosis of TMA mainly depends on renal biopsy. However, most TMA patients are complicated with significant thrombocytopenia. Hence, renal puncture is a risky procedure. It is difficult to make a definite diagnosis. For kidney transplantation-associated TMA, plasma exchange, intravenous immunoglobulin and withdrawal of potential risk drugs are commonly employed. Nevertheless, the overall prognosis is poor. In this article, the classification of TMA after kidney transplantation, diagnosis and treatment of kidney transplantation-associated TMA were reviewed, aiming to provide reference for clinical diagnosis and treatment of kidney transplantation-associated TMA.【Key words 】 Kidney transplantation; Thrombotic microangiopathy; Atypical hemolytic uremic syndrome; Thrombotic thrombocytopenic purpura; Immunosuppressant; Infection; Antibody-mediated rejection; Ecurizumab肾移植相关血栓性微血管病的诊断及治疗进展李大伟 张明Progress on diagnosis and treatment of kidney transplantation-associated thrombotic microangiopathy Li Dawei, Zhang Ming. Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200120, China Correspondingauthor:ZhangMing,Email:*******************DOI: 10.3969/j.issn.1674-7445.2023.01.009基金项目：国家自然科学基金（81800657）；中国器官移植发展基金会器官移植专项扶持“菁英计划”（2019JYJH14）作者单位：200120 上海，上海交通大学医学院附属仁济医院泌尿外科作者简介：李大伟，博士，主治医师，研究方向为移植免疫，Email ：*******************通信作者：张明，Email ：*******************·专家论坛·李大伟等．肾移植相关血栓性微血管病的诊断及治疗进展第1期·69·血栓性微血管病（thrombotic microangiopathy，TMA）是一组以微血管血栓形成、溶血性贫血、血小板减少及靶器官功能损伤为主要特征的临床病理综合征，可累及多个器官[1]。
心脏死亡器官捐献肾移植术后肾功能延迟恢复的免疫抑制剂选择
心脏死亡器官捐献肾移植术后肾功能延迟恢复的免疫抑制剂选择周异群【摘要】公民死亡器官捐献正在成为我国器官移植供体的主要来源.虽然有研究表明心脏死亡器官捐献(donation after cardiac death,DCD)来源肾移植的长期预后和脑死亡器官捐献(donation after brain death,DBD)肾移植的长期预后相近,但相比DBD移植,DCD来源肾移植的移植物功能延迟恢复(delayed graft function,DGF)发生率增加.目前临床广泛应用诱导治疗应对DGF.维持治疗通常是给予钙调神经磷酸酶抑制剂延迟给药或减量方案,同时加强其他免疫抑制剂,如麦考酚酸(mycophenolic acid,MPA)类药物.同时需要注意的是,DGF的状态下,MPA类药物浓度-时间曲线下面积(area under concenration-time curve,AUC)受到抑制,因此,在合并DGF的DCD肾移植受者中,MPA类药物的剂量更难以把握,需要加强MPA类药物浓度监测.%Donation after cardiac death (DCD) is becoming the main source of organ transplantation in China.DCD has increased the incidence of delayed graft function (DGF) when compared with donation after brain death (DBD) in renal transplantation,though previous studies revealed they both have identical long term outcome ofgrafts.Currently,induction therapy is widely used for preventing DGF.In order to prevent grafts' function,the subsequent maintenance regimens usually include delayed and reduced calcineurin inhibitor (CNI) with strengthened other immunosuppressant,such as mycophenolic acid (MPA).And it should be noticed that,the area under concenration-time curve (AUC) of MPAs is lower when DGF developed.Therefore,the dosageof MPAs in DCD recipients with DGF is more difficult to grasp and therapeutic drug monitoring of MPAs is nessesary in those patients.【期刊名称】《复旦学报（医学版）》【年(卷),期】2018(045)002【总页数】5页(P240-244)【关键词】心脏死亡器官捐献;肾移植;移植物功能延迟恢复;免疫抑制剂【作者】周异群【作者单位】上海罗氏制药有限公司上海 201102【正文语种】中文【中图分类】R699.2肾移植术后,移植物功能延迟恢复(delayed graft function,DGF)可伴随急性排斥反应和慢性移植肾肾病发生,是移植物存活的主要障碍[1]。
他克莫司缓释胶囊在肾移植术后的早期应用
第14卷 第2期2023年3月Vol. 14 No.2Mar. 2023器官移植Organ Transplantation ·论著·他克莫司缓释胶囊在肾移植术后的早期应用邹志宇 陈松 昌盛 代林睿 潘梓文 张倩倩 杨圆源 侯轶博 陈任杰 余陈真 张伟杰【摘要】 目的 探讨肾移植术后早期应用他克莫司缓释胶囊（Tac-ER ）的有效性及安全性。
方法 回顾性分析接受34对供肾所行肾移植的68例受者临床资料，接受同一供者两侧肾脏的2例受者术后分别采用Tac-ER （Tac-ER 组）和他克莫司胶囊（Tac-IR ）（Tac-IR 组）作为基础免疫抑制药之一。
比较两组他克莫司剂量及血药浓度变化、药物浓度个体内变异度（IPV ）、肾功能、急性排斥反应发生率、受者和移植物存活率、不良事件发生情况。
结果 Tac-ER 组的平均他克莫司日剂量高于Tac-IR 组（F =8.386，P =0.005）。
Tac-ER 组术后4 d 平均谷浓度未达目标浓度，为（6.14±4.04）ng/mL ，低于Tac-IR 组的（9.41±5.47）ng/mL （F =7.854，P =0.007）。
Tac-ER 组术后1个月内他克莫司谷浓度IPV 高于Tac-IR 组（0.44±0.15比0.36±0.12，P =0.032）。
术后第6个月时，Tac-ER 组和Tac-IR 组肾功能比较差异无统计学意义[血清肌酐为（126±26）μmol/L 比（120±28）μmol/L ，估算肾小球滤过率为（56±13）mL/（min·1.73 m 2）比（60±15）mL/（min·1.73 m 2），均为P >0.05]。
两组移植物和受者存活率均为100%。
Tac-ER 组和Tac-IR 组急性排斥反应均于术后1个月内发生，发生率分别为18%和3%，差异无统计学意义（P >0.05）。
Kidney_Transplantation 肾移植
Great events in history of transplantation
1945年，Medawar提出移植排斥是免疫反应
Nobel Prize in Physiology or Medicine 1960
Peter Brian Medawar Discovery of acquired immunological tolerance
Great events in history of transplantation
1954年，成功地进行第一例肾移植
Nobel Prize in Physiology or Medicine 1990
Joseph E. Murray
Discoveries concerning organ transplantation in the treatment of human disease
The donated kidney can be from a live donor or from a recently deceased donor.
20世纪初，器官移植实验探索
Nobel Prize in Physiology or Medicine 1912
Alexis Carrel (France) Work on vascular suture and the transplantation of blood vessels and organs
But if complications arise , additional medicines……..
Complications
Imbalances in electrolytes
Transplant rejection
肾移植麻醉指南2020
肾移植麻醉指南2020English Answer:Introduction.Kidney transplantation is a life-saving procedure for patients with end-stage renal disease (ESRD). The success of kidney transplantation depends on several factors, including the patient's overall health, the quality of the donor organ, and the expertise of the surgical team. Anesthesia plays a vital role in kidney transplantation, as it ensures the patient's safety and comfort during the surgery.Preoperative Assessment.Prior to surgery, the patient should undergo a thorough preoperative assessment. This includes a complete medical history and physical examination, as well as laboratory tests and imaging studies. The anesthesia team should beaware of any allergies, current medications, and previous surgeries.Intraoperative Management.The goals of intraoperative anesthesia management for kidney transplantation include:Maintaining hemodynamic stability.Providing adequate analgesia.Preventing and treating nausea and vomiting.Monitoring for and treating complications.The choice of anesthetic technique for kidney transplantation depends on the patient's overall health and the surgical approach. General anesthesia is typically used for open nephrectomy, while regional anesthesia (e.g., epidural anesthesia) may be used for laparoscopic nephrectomy.Postoperative Management.After surgery, the patient will be transferred to the intensive care unit (ICU) for close monitoring. The anesthesia team will continue to provide pain management and monitor for complications. The patient will typically remain in the ICU for 24-48 hours before being transferred to the ward.Discharge Planning.Prior to discharge, the anesthesia team will provide the patient with instructions on pain management, wound care, and activity restrictions. The patient should follow these instructions carefully to ensure a successful recovery.Specific Considerations.There are several specific considerations for anesthesia management in kidney transplantation patients.These include:Immunosuppression: Kidney transplant recipients are typically immunosuppressed to prevent rejection of thedonor organ. This immunosuppression can increase the riskof infection and other complications.Renal function: The patient's renal function may be impaired after surgery. This can affect the choice of anesthetic agents and the need for dialysis.Coagulation disorders: Kidney transplant recipients may have coagulopathies, which can increase the risk of bleeding during surgery.Conclusion.Anesthesia plays a vital role in kidney transplantation. By understanding the unique needs of these patients, the anesthesia team can help to ensure a safe and successful outcome.Chinese Answer:导言。
两种方法检测群体反应性抗体的比较分析
O A B是指尿急[1,5],伴有或不伴有急迫型尿失禁,常伴有尿频和夜尿增多,尿动力学上可表现为逼尿肌过度活动,也可为其他形式的尿道-膀胱功能障碍,存在病理或代谢因素可以解释这些症状㊂因为这些症状会给患者造成极大的困扰,有证据显示,O A B 症状对患者的Q O L造成严重的负面影响㊂目前O A B尽管能用尿急感觉评分或尿急严重程度评分(O A B S S),这些都是基于患者的主观报告㊂尿急-尿频症状源于心理因素,排尿次数增加㊁不能节制的排尿冲动源于中枢神经系统的损害,以及逼尿肌的过度活动㊂因而,临床诊断O A B存在很多的差异,需要找到一种更为客观的诊断与评价治疗O A B的结果的方法,尤其对于没有经历泌尿外科培训的保健医疗提供者㊂有研究表明,尿液中某些蛋白分子,如神经生长因子(N G F)㊁P G E2等在O A B㊁膀胱出口梗阻(B O O)㊁逼尿肌过度活动以及间质性膀胱炎等疾病中表达明显增高;而病理状态下,O A B患者在其小的膀胱容量和感觉尿急时,尿N G F也会增加㊂B D N F是另一种在下尿路功能中无处不在的神经生长因子,无论是在正常状态还是病理状态下㊂本研究表明尿液中B D N F表达的检测,可以作为治疗O A B诊断和评价的判断指标[2-5]㊂参考文献[1]D MO C H OW S K I R R,N E WMA N D K.I m p a c t o f o v e r a c t i v e b l a d-d e r o n w o m e n i n t h e U n i t e d S t a t e s:r e s u l t s o f a n a t i o n a l s u r v e y[J].C u r r M e d R e s O p i n,2007,23(1):65-76.[2]T Y A G I P,K I L L I N G E R K,T Y A G I V,e t a l.U r i n a r y c h e m o k i n e sa s n o n i n v a s i v e p r e d i c t o r s o f u l c e r a t i v e i n t e r s t i t i a l c y s t i t i s[J].JU r o l.2012,187(6):2243-2248.[3]H A N N-C HO R N G K U O.P o t e n t i a l u r i n e a n d s e r u m b i o m a r k e r sf o r p a t i e n t s w i t h b l a d d e r p a i n s y n d r o m e/i n t e r s t i t i a l c y s t i t i s[J].I n t J U r o l,2014,21(1):34-41.[4]L I U H T,L I N H,K U O H C.I n c r e a s e d s e r u m n e r v e g r o w t h f a c-t o r l e v e l s i n p a t i e n t s w i t h o v e r a c t i v e b l a d d e r s y n d r o m e r e f r a c t o r y t o a n t i m u s c a r i n i c t h e r a p y[J].N e u r o u r o l U r o d y n,2011,30(8): 1525-1529.[5]T Y A G I P,K I L L I N G E R K,T Y A G I V,e t a l.U r i n a r y c h e m o k i n e sa s n o n i n v a s i v e p r e d i c t o r s o f u l c e r a t i v e i n t e r s t i t i a l c y s t i t i s[J].JU r o l,2012,187(6):2243-2248.㊃短篇论著㊃两种方法检测群体反应性抗体的比较分析*王琳1,赵云平2,胡伟3,贾蔚4,黄范怡1,白敏凤1,尹利民2ә(1.昆明医科大学,云南昆明650500;2.昆明市第一人民医院检验科,云南昆明650011;3.昆明市第一人民医院泌尿外科,云南昆明650011;4.昆明市第一人民医院健康体检中心,云南昆明650011)摘要:目的对流式荧光法和酶联免疫吸附实验(E L I S A)法在群体反应性抗体(P R A)的检测中进行比较和评价㊂方法选取昆明市第一人民医院2016年9月至2019年4月门诊及住院患者2907例,采用流式荧光法或E L I S A法检测患者血清P R A,比较两种方法的阳性率,同时抽取40例患者采用两种方法同时进行检测㊂结果 E L I S A法P R AⅠ类㊁Ⅱ类及总阳性率分别为9.0%(103/1142)㊁8.1%(92/1142)㊁13.7%(156/1142),流式荧光法分别为22.9%(404/1765)㊁21.9%(387/1765)㊁34.3%(606/1765)㊂采用两种不同方法同时对40例患者P R A进行检测,两种方法的一致性极低㊂结论流式荧光法检测P R A阳性率明显高于E L I S A法,实验室宜采用灵敏度较高的流式荧光法进行P R A检测㊂关键词:群体反应性抗体;流式荧光法;酶联反应吸附法器官移植已成为许多实质器官终末期疾病唯一有效的治疗方法,但同时也面临着移植排斥等诸多问题[1-2]㊂群体反应性抗体(P R A)是一种由人类白细胞抗原(H L A)错配产生的抗体㊂P R A与移植物存活和排斥反应的发生密切相关[3-6]㊂准确检测P R A对于科学评估移植患者的免疫状态至关重要[7]㊂传统P R A的检测采用酶联免疫吸附实验(E L I S A)的方法,近年来出现了流式荧光法的检测方法,但关于两种不同方法的阳性率及一致性的研究报道相对较少㊂本研究拟将两种不同P R A检测方法的阳性率及一致性进行比较,为P R A检测的方法选择及临床应用提供参考依据㊂1资料与方法1.1一般资料选取本院2016年9月至2019年4月门诊及住院患者2907例㊂其中1142例采用E L I S A法进行检测,1765例采用流式荧光法进行检测㊂同期抽取40例患者同时采用两种不同方法进行检测㊂*基金项目:昆明市卫健委医药卫生科技计划项目(2017-11-01-021)㊂ә通信作者,E-m a i l:y l m b j@163.c o m㊂1.2 仪器与试剂 两种不同方法的P R A 检测试剂均购于美国O N E L AM B D A 公司,分别为L A T 1240和L A B S c r e e n P R A 试剂㊂仪器主要有L u m i n e x 200流式点阵分析仪(L u m i n e x 公司)㊁E L X 800酶标仪(B i o T e k 公司)㊂1.3 方法 两种方法均严格按照试剂说明书进行,结果判定依据试剂盒规定的标准进行判定㊂1.4 统计学处理 采用S P S S V 22.0统计学软件对数据资料进行统计分析㊂计数资料率的组间比较采用χ2检验㊂配对计数资料采用M c N e m a r 检验与K a p pa 检验,以P <0.05为差异有统计学意义㊂2 结 果2.1 两种不同方法的P R A 阳性率比较 E L I S A 法P R AⅠ类㊁Ⅱ类及总阳性率分别为9.0%(103/1142)㊁8.1%(92/1142)㊁13.7%(156/1142),流式荧光法分别为22.9%(404/1765)㊁21.9%(387/1765)㊁34.3%(606/1765);两种不同方法P R AⅠ类㊁Ⅱ类及总阳性率差异具统计学意义(P <0.01),见表1㊂表1 两种不同方法的P R A 阳性率比较[n (%)]项目nP R A Ⅰ类阳性P R A Ⅱ类阳性P R A Ⅰ类+Ⅱ类阳性E L I S A 法1142103(9.0)92(8.1)156(13.7)流式荧光法1765404(22.9)387(21.9)606(34.3)χ292.6496.93153.22P<0.01<0.01<0.012.2 两种不同检测方法P R A 结果一致性比较 采用两种不同方法同时对40例患者P R A 进行检测,见表2,从结果可见,两种方法的一致性极低,差异有统计学意义(P <0.01;K a p pa =0.01~0.06)㊂表2 两种不同方法P R A 结果一致性比较(n )项目P R A Ⅰ类E L I S A 法+-P R AⅡ类E L I S A 法+-P R AⅠ类+Ⅱ类E L I S A 法+-流式荧光法 +223223434 -15152P<0.01<0.01<0.01K a p pa 0.060.060.013 讨 论20世纪60年代,P R A 开始应用于临床,在肾移植患者的筛选以及减少移植后排斥反应的发生方面都起到了很好的指导作用[8-9]㊂近年来,随着体液免疫理论的不断完善及P R A 实验技术的进步,P R A 在体液免疫的作用越来越受到重视㊂最初,P R A 的检测是采用微量淋巴细胞毒(C D C )试验方法㊂但该方法试剂贮藏㊁运输不便,容易出现假阳性和假阴性反应,而且无法区分Ⅰ类和Ⅱ类抗体㊂随着技术的发展,出现了比C D C 方法更方便㊁灵敏的E L I S A 法,并在临床广泛应用㊂近年来,随着技术的进步,出现了流式荧光的检测方法㊂但关于流式荧光法与E L I S A 法的阳性率及一致性的研究报道相对较少㊂本研究通过对两种不同P R A 检测方法的阳性率及一致性进行比较,结果显示,流式荧光法检测P R A 灵敏度明显高于E L I S A 法,两种不同方法的一致性极低㊂E L I S A 法是将H L A 抗原包被在泰萨奇板上,通过碱性磷酸酶标记,在酶标仪上进行检测㊂流式荧光法是将提纯后的抗原包被在微颗粒免疫磁珠上,通过荧光物质标记抗体,在流式荧光仪进行检测㊂流式荧光法标记的抗原种类㊁数量多于E L I S A 法,而且所用的标记技术的灵敏度也高于E L I S A 法㊂因此,本研究结果与理论预期相符㊂灵敏度更高的P R A 检测方法意味着能够提高阳性检出率,更加及时发现抗H L A 抗体阳性患者,指导临床及时制定脱敏方案,降低移植排斥反应的发生,延长移植器官长期有功能存活时间㊂此外,流式荧光法的检测时间及精密度均优于E L I S A 法㊂因此,流式荧光法在临床上的应用将会越来越普遍,逐步替代E L I S A 法㊂流式荧光法检测P R A 具有诸多优点,然而也存在着一些的不足之处,例如,实验仪器对环境温度要求较高;试剂成本相对于E L I S A 法偏高;实验操作对人员的要求高,操作过程不当会使微珠丢失过多,影响实验结果等㊂由于存在这些问题,实验室需要做好全面的质量控制工作,保证检测结果的质量㊂综上所述,流式荧光法检测P R A 阳性率明显高于E L I S A 法,实验室宜采用灵敏度较高的流式荧光法进行P R A 检测,更好地指导临床的实践,不断降低排斥反应的发生率,延长移植物的存活时间㊂参考文献[1]张磊.群体反应性抗体对再次肾移植患者的影响研究[J ].现代生物医学进展,2014,33(14):6496-6498.[2]A L T H A F M M,E L K O S S I M,J I N J K,e t a l.H u m a n l e u k o c y t ea n t i g e n t y p i n g a n d c r o s s m a t c h:A c o m p r e h e n s i v e r e v i e w[J].W o r l d J T r a n s p l a n t,2017,7(6):339-348.[3]S A P I R-P I C HH A D Z E R,T I N C K AM K J,L A U P A C I S A,e t a l.I mm u n e S e n s i t i z a t i o n a n d M o r t a l i t y i n W a i t-L i s t e d K i d n e y T r a n s-p l a n t C a n d i d a t e s[J].J A m S o c N e p h r o l,2016,27(2):570-578.[4]S A Y I N B,O Z D E M I R A,A Y V A Z O G L U S O Y E H,e t a l.O v e r5Y e a r s o f E x c e l l e n t G r a f t K i d n e y F u n c t i o n D e t e r m i n a n t s:B a s k e n t U n i v e r s i t y E x p e r i e n c e[J].E x p C l i n T r a n s p l a n t,2019,17(S u p p l 1):75-77.[5]F U Q,Z H A N G H,N I E W,e t a l.R i s k F a c t o r s f o r A c u t e R e j e c t i o nA f t e r D e c e a s e d D o n o r K i d n e y T r a n s p l a n t a t i o n i n C h i n a[J].T r a n s p l a n t P r o c,2018,50(8):2465-2468.[6]N A K AMU R A Y,Y O S H I O K A D,M I Y A G AWA S,e t a l.S u c c e s s-f u l H e a r t T r a n s p l a n t a t i o n A f t e r D e s e n s i t i z a t i o n i n a P a t i e n t W i t hE x t r e m e l y H i g h P a n e l-R e a c t i v e A n t i b o d y L e v e l s a n d P r e t r a n s-p l a n t D o n o r-S p e c i f i c A n t i b o d y:A C a s e R e p o r t[J].T r a n s p l a n t P r o c,2018,50(10):4067-4070.[7]T A I T B D.D e t e c t i o n o f H L A A n t i b o d i e s i n O r g a n T r a n s p l a n tR e c i p i e n t s-T r i u m p h s a n d C h a l l e n g e s o f t h e S o l i d P h a s e B e a d A s-s a y[J].F r o n t I mm u n o l,2016,7(5):710-719.[8]朱兰.预致敏受者行死亡捐献供肾肾移植的处理策略及临床效果[J].中华医学杂志,2019,12(99):1011-1016.㊃短篇论著㊃补肾活血方治疗腰椎间盘突出症的康复护理效果检验*刘逸,陈晓峰,刘奕(广州市番禺区中医院,广东广州511400)摘要:目的观察对腰椎间盘突出症采用补肾活血方治疗时的康复护理结果㊂方法研究选取2018年3月至2018年12月该院收治的76例腰椎间盘突出症患者,入院后两组均接受补肾活血方治疗;随机抽签法分为两组,各38例,在治疗基础上对照组患者采用常规护理,观察组患者采用康复护理干预,对比两组护理后治疗效果㊂结果干预前对照组V A S评分与观察组对比,差异无统计学意义(P>0.05),干预2周后,观察组V A S 评分然低于对照组,差异有统计学意义(P<0.05);两组椎间盘功能对比,干预前观察组O D I评分与对照组对比,差异无统计学意义(P>0.05),经2周干预后,观察组患者O D I评分低于对照组,差异有统计学意义(P< 0.05)㊂随访3月后,观察组患者直腿抬高试验阳性㊁腰腿疼痛发生率低于对照组,差异有统计学意义(P< 0.05)㊂结论临床对腰椎间盘突出症患者实施补肾活血方治疗基础上,联合康复护理干预,有助于提高患者认知水平,减少腰腿疼痛发生率,巩固临床治疗效果,值得推广㊂关键词:康复护理;腰椎间盘突出症;腰腿疼痛;康复认知水平腰椎间盘突出症是临床脊柱外科常见的多发性疾病,其主要因椎间盘退变压迫神经根㊁脊髓等敏感部位所致,病症以行动困难㊁腰腿疼痛为主要表现,其多发于中老年群体[1]㊂有研究指出,再给予患者手术治疗同时,早期康复护理干预,对改善患者生存质量,降低腰腿疼痛具有积极作用㊂鉴于此,本研究对76例腰椎间盘突出症患者实施补肾活血方同时,予以早期康复护理干预,观察其效果,现报道如下㊂1资料与方法1.1一般资料随机抽取本院2018年3-12月收治的腰椎间盘突出症76例患者,入院经M R I㊁螺旋C T检查,直腿抬高试验㊁体格检查确诊为腰椎间盘突出症,均接受补肾活血方治疗,研究经医院伦理会批准㊂采用随机抽签法将76例分为两组,对照组38例,其中男22例,女16例,年龄35~73岁,平均(47.25ʃ2.33)岁;观察组38例,其中男23例,女15例,年龄34~75岁,平均(47.81ʃ3.02)岁㊂纳入标准:患者均自愿参与研究,并签署知情书;且患者确诊为腰椎间盘突出症,符合手术适应证㊂排除标准:不愿配合研究者,合并精神疾病㊁认知障碍患者㊂1.2方法入院后,两组患者均给予补肾活血方治疗,补肾活血方:取白芍㊁丹参各30g,菟丝子㊁巴戟天㊁山萸肉㊁鹿角胶各15g,乳香㊁牛膝㊁枸杞子㊁杜仲㊁川芎㊁当归各10g,甘草5g;以水煎煮,每日一剂,早晚分服㊂中药熏洗,采用M D-99C型电脑熏蒸治疗床,患者腰背部进行熏蒸,注意盖好毛巾,30m i n/次, 1次/d㊂中药封包制成后,控制70ħ左右温度,对患者腰背部治疗,注意避免烫伤患者,根据其耐受控制温度,30m i n/次,2次/d㊂穴位敷贴选穴分别为阿是穴㊁承山穴㊁腰阳关㊁双侧肾俞等,每隔2d对选穴敷贴1次㊂两组都口服抗炎止痛药塞来昔布胶囊0.2m g/次,1次/d,甲钴胺片口服0.5m g/次,3次/d等㊂在此基础上,对照组予以心理㊁饮食干预㊁用药指导等常规护理干预;观察组接受早期康复护理,具体*基金项目:广东省中医药局中医药科研项目(20191262)㊂。
肝肾移植受者环孢素AUC监测评估
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多巴胺在肾移植术中临床应用价值的再认识
· 综述·多巴胺在肾移植术中临床应用价值的再认识钟羽琦 王於尘 苗芸【摘要】 多巴胺是去甲肾上腺素生物合成的前体，小剂量多巴胺主要兴奋多巴胺受体，可扩张肾及肠系膜血管，增加肾血流量，改善微循环。
近年来，小剂量多巴胺以其血管活性作用广泛应用于肾移植领域。
然而，随着循证医学的发展，多巴胺在肾移植术中保护移植肾灌注功能的作用开始受到人们的质疑。
多项研究发现多巴胺在肾移植术中对肾功能、心功能无明显益处，升压效能较低，甚至会增加围手术期并发症的发生风险，而去甲肾上腺素可成为一种较安全的替代。
因此，本文就多巴胺在肾移植术中对肾功能、心功能以及血流动力学影响的新进展进行综述，以期为多巴胺在肾移植术中的临床应用提供参考。
【关键词】 肾移植；血管活性药物；多巴胺；小剂量；去甲肾上腺素；肾灌注；心律失常；急性肾损伤【中图分类号】 R617, R347 【文献标志码】 A 【文章编号】 1674-7445（2024）04-0018-05Re-understanding of the clinical application value of dopamine in kidney transplantation Zhong Yuqi *, Wang Yuchen,Miao Yun. *Department of Anesthesiology , Sun Yat-sen University Cancer Center , Guangzhou 510060, China Corresponding author: Miao Yun, Email: *******************【Abstract 】 Dopamine is the precursor of biosynthesis of norepinephrine. Low-dose dopamine mainly excites dopamine receptors, which may dilate renal and mesenteric vessels, increase renal blood flow and improve the microcirculation. In recent years, low-dose dopamine has been widely applied in the field of kidney transplantation due to its vasoactive effect. However, with the development of evidence-based medicine, the role of dopamine in protecting the perfusion function of renal allograft in kidney transplantation has been questioned. Multiple studies have shown that dopamine brings no significant benefit to renal and cardiac function in kidney transplantation, exerts low pressor effect,and may even increase the risk of perioperative complications. Norepinephrine may be used as a safe substitute. In this article, recent progress in the effect of dopamine upon renal and cardiac function and hemodynamics during kidney transplantation was reviewed, aiming to provide reference for clinical application of dopamine in kidney transplantation.【Key words 】 Kidney transplantation; Vasoactive drug; Dopamine; Low dose; Norepinephrine; Renal perfusion;Arrhythmias; Acute kidney injury多巴胺是去甲肾上腺素生物合成的前体，主要激动α、β和多巴胺受体，呈剂量依赖性[1]。
2023年国内肾移植文献盘点
· 学术盘点·2023年国内肾移植文献盘点曾心悦 周王天旭 孙启全【摘要】 肾移植手术在解决终末期肾病的问题上取得巨大成功，但在术后依然面临着一系列复杂而棘手的挑战，如感染、排斥反应、缺血-再灌注损伤和慢性移植肾失功等。
随着科技发展，生物材料、基因测序等新兴技术的蓬勃发展，我国的研究者们在肾移植领域为解决这些问题展开了一系列引人瞩目的研究。
2023年，我国肾移植研究不仅关注于解决上述挑战，更着眼于拓展新的技术和理念，推动肾移植事业走向更为辉煌的未来。
本文将系统综述我国研究团队在2023年在肾移植领域取得的学术成果，涵盖基础与临床研究的前沿，以及新兴技术的应用，旨在以本土化视角，为肾移植领域的重大临床问题提供新的思路和策略，推动我国肾移植事业迈向更高峰。
【关键词】 肾移植；排斥反应；缺血-再灌注损伤；感染；炎症反应；慢性移植肾失功；移植物功能延迟恢复；供肾【中图分类号】 R617, R692 【文献标志码】 A 【文章编号】 1674-7445（2024）03-0008-07Research progress on domestic kidney transplantation of 2023 Zeng Xinyue, Zhou Wangtianxu, Sun Qiquan. Department of Kidney Transplantation , Guangdong Provincial People's Hospital Affiliated to Southern Medical University , Guangdong Academy of Medical Sciences , Guangzhou 510080, ChinaCorresponding author: Sun Qiquan, Email: ****************【Abstract 】 Kidney transplantation has achieved significant success in treating end-stage renal disease.Nevertheless, it still faces a series of complex and significant challenges after surgery, such as infection, rejection,ischemia-reperfusion injury and chronic renal allograft dysfunction, etc. With the development of science and technology,including biomaterials, gene sequencing and other emerging technologies, Chinese researchers have launched a series of remarkable research in the field of kidney transplantation, aiming to solve these thorny issues. In 2023, relevant research of kidney transplantation in China not only focused on resolving the above challenges, but also highlighting on expanding novel technologies and concepts to build a brighter future of kidney transplantation. In this article, academic achievements of Chinese research teams in the field of kidney transplantation in 2023 were systematically reviewed, covering the frontiers of basic and clinical research and the application of emerging technologies, aiming to provide novel ideas and strategies for major clinical problems in the field of kidney transplantation from the local perspective and accelerate the advancement of kidney transplantation in China to a higher peak.【Key words 】 Kidney transplantation; Rejection; Ischemia-reperfusion injury; Infection; Inflammation; Chronic renal allograft dysfunction; Delayed graft function; Donor kidneyDOI: 10.3969/j.issn.1674-7445.2024059基金项目：国家自然科学基金（82270783、82271805、82100797、82200843）；广东省自然科学基金（2021A1515110434）；广州市科技计划项目（2023A04J0498）作者单位： 510080 广州，南方医科大学附属广东省人民医院（广东省医学科学院）肾移植科作者简介：曾心悦（ORCID 0009-0003-6290-5024），硕士研究生，Email ：*********************；周王天旭（ORCID 0009-0009-7517-1481），硕士研究生，Email ：*****************（曾心悦、周王天旭为共同第一作者）通信作者：孙启全（ORCID 0000-0002-7296-316X ），博士，主任医师，研究方向为肾移植相关疾病，Email ：****************第 15 卷 第 3 期器官移植Vol. 15 No.3 2024 年 5 月Organ Transplantation May 2024 肾移植是长期透析的终末期肾病患者的主要治疗手段[1]。
器官移植的好处和风险英语作文
器官移植的好处和风险英语作文Organ transplantation is a common method to treat organ failure. It can be said that organ transplantation has advantages and disadvantages. The advantage of organ transplantation is that it can solve the problem of organ failure in time. Of course, it also has disadvantages, that is, it is difficult to find a suitable organ, and the transplant operation is complicated, and there are also problems such as rejection after operation.Taking kidney transplantation as an example, a successful kidney transplantation can make patients exempt from dialysis, and it is more effective in treating renal failure than peritoneal dialysis or dialysis. Successful kidney transplantation can provide 10 times more functions than dialysis.Compared with dialysis patients, transplant patients have fewer restrictions and higher quality of life. Most patients feel better and have more physical strength than during dialysis.The process of finding a suitable transplanted kidney is complicated, and it needs various tests to determine whether the transplanted kidney is well matched with the recipient inblood type and tissue type.Even well-matched patients are not always suitable recipients. Neither the donor nor the patient needs infection or other medical problems, which will not complicate the patient's rehabilitation.The transplant patients must use immunosuppression drugs to prevent the rejection of the transplanted kidney. These drugs have side effects, which will increase the risk of getting some infections, viruses and some types of tumors.Transplant patients need to take medicine for life, or at least while the graft is still working.Kidney grafts don't last forever. Younger patients may need two or more transplants in their lifetime.。