Clinical Renal Transplantation Research Articles

Engineered Small Extracellular Vesicles as a FGL1/PD‐L1 Dual‐Targeting Delivery System for Alleviating Immune Rejection (Adv. Sci. 3/2022)

Small Extracellular Vesicles The simultaneous high expression of LAG-3 and PD-1 on T cells in cardiac transplantation mouse models and clinical renal transplantation patients provides the possibility to establish immune tolerance by giving their ligand molecules. In article number 2102634 by Bo Jia, Fang Cheng, Hongbo Chen, and co-workers, small extracellular vesicles derived from bioengineered PD-L1/FGL1-expressed mesenchymal stem cells encapsulated with low-dose FK506 exerted a powerful synergistic inhibitory effect on T cell activation and, therefore, prolonged grafts survival.

Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation

BackgroundAcute Kidney Injury (AKI) is a common clinical complication. Plasma/serum neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as a rapid marker of AKI. However, NGAL is not kidney-specific. It exists in three isoforms (monomeric, homo-dimeric and hetero-dimeric). Only the monomeric isoform is produced by renal tubular cells and plasma NGAL levels are confounded by the release of all NGAL isoforms from neutrophils. Our aim was to investigate whether NGAL is released into blood from injured renal tubules.MethodsKidney transplantation (n = 28) served as a clinical model of renal ischaemic injury. We used ELISA to measure NGAL concentrations at 2 minutes after kidney graft reperfusion in simultaneously taken samples of renal arterial and renal venous blood. Trans-renal gradients (venous–arterial) of NGAL were calculated. We performed Western blotting to distinguish between renal and non-renal NGAL isoforms. Liver-type fatty acid binding protein (LFABP) and heart-type fatty acid binding protein (HFABP) served as positive controls of proximal and distal tubular damage.ResultsSignificant renal release of LFABP [trans-renal gradient 8.4 (1.7–30.0) ng/ml, p = 0.005] and HFABP [trans-renal gradient 3.7 (1.1–5.0) ng/ml, p = 0.003] at 2 minutes after renal graft reperfusion indicated proximal and distal tubular damage. NGAL concentrations were comparable in renal venous and renal arterial blood. Thus, there was no trans-renal gradient of NGAL. Western blotting revealed that the renal NGAL isoform represented only 6% of the total NGAL in renal venous blood.ConclusionsIschaemic proximal and distal tubular damage occurs in kidney transplantation without concomitant NGAL washout from the kidney graft into blood. Plasma/serum NGAL levels are confounded by the release of NGAL from neutrophils. Present results do not support the interpretation that increase in plasma NGAL is caused by release from the renal tubules.

Therapeutic monitoring of mycophenolic acid in renal transplanted patients by a validated HPLC method.

Mycophenolate mofetil and its active metabolite mycophenolic acid are routinely used as immunosuppressant drugs in solid organ transplantation in a fixed daily dose regimen in association with cyclosporine, tacrolimus and steroids. Therapeutic drug monitoring for mycophenolic acid concentration has been suggested to optimize outcomes by reducing rejection and drug related toxicities in clinical renal transplantation. To determine the predose concentration of mycophenolic acid in renal transplanted patients by a validated proposed high-performance liquid chromatography (HPLC) method and to estimate the interindividual variability based on the therapeutic target. An HPLC method combined with protein precipitation has been validated for mycophenolic acid determination in the human plasma obtained from 21 renal transplant recipients. HPLC analysis was carried out using the chromatographic system Agilent Technologies 1200 DAD. Samples were injected manually, and the compounds were separated on a LiChrosphere® select B C18 analytical column. The mobile phase was 45:55 (v/v) acetonitrile-buffer phosphate, pH 2.5, flow rate of 1.0 mL/min and column temperature of 30°C. Detection was performed at 215 nm. Whole blood samples were collected into vacutainers containing EDTA and separated at 6000 g for 10 minutes. A 200-μL aliquot of patient plasma was transferred to a tube, followed by addition of 10 μL of naproxen as internal standard and 400 μL of acetonitrile (v/v) as a protein precipitating agent. Each tube was vortex-mixed for 30 sec and then centrifuged for 10 min at 10000 rpm. 20 μL of the supernatant was injected into the HPLC system for analysis. The method showed appropriate linearity for MPA with correlation coefficient greater than 0.999. High inter-patient variability is observed with 18% of patients within the target trough concentration range, 27% of patients below the target trough concentration range and 54% over the range with risk of toxicity. Therapeutic monitoring of MPA might contribute to a better management of renal transplant recipient with the goal of optimizing therapeutic regimens in order to reduce the risk of rejection and MPA-related toxicity.

Ex vivo confocal microscopy performs real-time assessment of renal biopsy in non-neoplastic diseases.

Ex vivo confocal microscopy is a technique for tissue examination, which generates images of fresh samples with an optical resolution comparable to those obtained by conventional pathology. The objective of this study was to evaluate the feasibility of using ex vivo confocal microscopy in fusion mode (reflectance and fluorescence) and the H&E-like digital staining that is obtained for the analysis of non-neoplastic kidney biopsies. Twenty-four renal samples acquired from autopsies were scanned in a 4th generation ex vivo confocal microscopy device. The imaging process was completed in an average of three minutes. Confocal images correlated very well to the corresponding conventional histological sections, both in normal tissue and in chronic lesions (glomerulosclerosis, fibrosis and tubular atrophy). The ex vivo confocal microscopy protocol did not add artifacts to the sample for the ulterior study with light microscopy, nor to the histochemical or immunohistochemical studies. The ease and speed of grayscale and fluorescence image acquisition, together with the quality of the H&E-like digitally stained images obtained with this approach, suggest that this technique shows promise for use in clinical nephrology and renal transplantation.

Activity-based protein profiling guided identification of urine proteinase 3 activity in subclinical rejection after renal transplantation

BackgroundThe pathophysiology of subclinical versus clinical rejection remains incompletely understood given their equivalent histological severity but discordant graft function. The goal was to evaluate serine hydrolase enzyme activities to explore if there were any underlying differences in activities during subclinical versus clinical rejection.MethodsSerine hydrolase activity-based protein profiling (ABPP) was performed on the urines of a case control cohort of patients with biopsy confirmed subclinical or clinical transplant rejection. In-gel analysis and affinity purification with mass spectrometry were used to demonstrate and identify active serine hydrolase activity. An assay for proteinase 3 (PR3/PRTN3) was adapted for the quantitation of activity in urine.ResultsIn-gel ABPP profiles suggested increased intensity and diversity of serine hydrolase activities in urine from patients undergoing subclinical versus clinical rejection. Serine hydrolases (n = 30) were identified by mass spectrometry in subclinical and clinical rejection patients with 4 non-overlapping candidates between the two groups (i.e. ABHD14B, LTF, PR3/PRTN3 and PRSS12). Western blot and the use of a specific inhibitor confirmed the presence of active PR3/PRTN3 in samples from patients undergoing subclinical rejection. Analysis of samples from normal donors or from several serial post-transplant urines indicated that although PR3/PRTN3 activity may be highly associated with low-grade subclinical inflammation, the enzyme activity was not restricted to this patient group.ConclusionsThere appear to be limited qualitative and quantitative differences in serine hydrolase activity in patients with subclinical versus clinical renal transplant rejection. The majority of enzymes identified were present in samples from both groups implying that in-gel quantitative differences may largely relate to the activity status of shared enzymes. However qualitative compositional differences were also observed indicating differential activities. The PR3/PRTN3 analyses indicate that the activity status of urine in transplant patients is dynamic possibly reflecting changes in the underlying processes in the transplant. These data suggest that differential serine hydrolase pathways may be active in subclinical versus clinical rejection which requires further exploration in larger patient cohorts. Although this study focused on PR3/PRTN3, this does not preclude the possibility that other enzymes may play critical roles in the rejection process.

Comparison of the immunogenicity of Dukoral® oral cholera vaccine between renal transplant recipients on either a calcineurin inhibitor or mycophenolate – A controlled trial

BackgroundThe evidence for recommendations regarding vaccination in solid organ transplant recipients is sparse. There is little data comparing vaccine responses between groups on different immunosuppressive drugs. This study was conducted to evaluate the antibody response to Dukoral® oral cholera vaccine in renal transplant recipients (RTR). MethodsIn a single-center non-randomized controlled clinical trial, healthy volunteers (n = 21) and renal transplant recipients (n = 30) were vaccinated with the oral whole cell/recombinant B subunit cholera vaccine Dukoral® (Valneva Inc., Vienna, Austria). The RTR were stratified according to their maintenance immunosuppressive therapy: either prednisone and a calcineurin inhibitor (cyclosporine A or tacrolimus; P/CNI group; n = 15) or prednisone and mycophenolate (P/MMF group; n = 15). All volunteers ingested Dukoral® at baseline and at day 14. Serum samples were drawn at day 0 and day 21. The primary outcome was seroconversion, defined as either a 3-fold IgA serum titer increase in anti-cholera toxin B antibodies and/or a 4-fold rise in the serum vibriocidal titer. ResultsFollow-up was complete. Seroconversion after vaccination was 57% (standard error, SE 9%) in RTR and 81% (SE 9%) in healthy controls (Relative Risk, RR 0.70; 95% CI 0.48–1.02). When stratified according to maintenance immunosuppression, the seroconversion rate was 67% (SE 12%) in the P/CNI group (RR compared with controls 0.82; 95% CI 0.55–1.25) and 47% (SE 13%) in the P/MMF group (RR compared with controls 0.58; 95% CI 0.32–1.03). ConclusionAdverse events were mild to moderate and transient. The response to Dukoral was weaker and the seroconversion rate was lower in renal transplant recipients than in healthy controls. In particular, those using mycophenolate had a poor response. Nevertheless, more than half of the transplant recipients seroconverted. Therefore oral vaccines should not be discarded as a potential tool for protection of solid organ transplant recipients.This trial is registered in clinicaltrials.gov under NCT01109914.

Current Trend of Pediatric Renal Replacement Therapy in Japan.

End-stage renal disease (ESRD) in children is considered a rare but serious condition. Information on the epidemiology, demographics, treatment modality at the start of renal replacement therapy (RRT), and mortality of pediatric patients with ESRD is essential for a better understanding of this disease. Additionally, international comparisons of this information on pediatric patients with ESRD may improve outcomes in these children. Here, I will provide information on epidemiological and demographic characteristics of pediatric Japanese patients with ESRD and the current trend of pediatric RRT in Japan. The Japanese Society for Pediatric Nephrology (JSPN), in collaboration with the Japanese Society for Dialysis Therapy (JSDT) and the Japanese Society for Clinical Renal Transplantation (JSCRT), conducted a cross-sectional nationwide survey in 2012 to update information on the incidence, primary renal disease, initial treatment modalities, and survival in pediatric Japanese patients with ESRD aged less than 20 years during the period 2006-2011. The average incidence of ESRD was 4.0 per million age-related populations, much lower than in other high-income countries. Congenital anomalies of the kidney and urinary tract were the most common cause of ESRD, present in 39.8% of these patients, which was similar to the data reported from USA, Europe, and Australia and New Zealand. While the previous Japanese survey in 1998 reported that only 1 patient (0.9%) underwent preemptive transplantation, the JSPN ESRD Survey 2012 found that 22.3% of patients were initially treated by preemptive transplantation. Thus, the use of preemptive transplantation as the initial treatment modality for Japanese children with ESRD is comparable to that for ESRD children in the USA, Europe, and Australia and New Zealand. The 5-year survival rate of Japanese children with ESRD who received RRT was 91.5%, which was similar to the rates observed in other high-income countries. Key Messages: The incidence of ESRD is lower in Japanese children than in children in other high-income countries. There has been a marked increase in the use of preemptive transplantation as the initial treatment modality for pediatric Japanese patients with ESRD.

Defining the immunogenicity and antigenicity of HLA epitopes is crucial for optimal epitope matching in clinical renal transplantation.

Transplantation of an human leukocyte antigen (HLA) mismatched graft can lead to the development of donor-specific antibodies (DSA), which can result in antibody mediated rejection and graft loss as well as complicate repeat transplantation. These DSA are induced by foreign epitopes present on the mismatched HLA antigens of the donor. However, not all epitopes appear to be equally effective in their ability to induce DSA. Understanding the characteristics of HLA epitopes is crucial for optimal epitope matching in clinical transplantation. In this review, the latest insights on HLA epitopes are described with a special focus on the definition of immunogenicity and antigenicity of HLA epitopes. Furthermore, the use of this knowledge to prevent HLA antibody formation and to select the optimal donor for sensitised transplant candidates will be discussed.

Current status of kidney transplantation in Japan in 2015: the data of the Kidney Transplant Registry Committee, Japanese Society for Clinical Renal Transplantation and the Japan Society for Transplantation

The first deceased and living donor kidney transplants were performed in 1956 and 1964 in Japan, respectively. Larger numbers of transplants were performed after the introduction of cyclosporine in 1983. After that, the number has gradually and steadily increased and 1661 transplants were performed in 2015. In addition, the outcomes have improved year by year. The indications for transplantation have also expanded in various aspects, such as recipient and donor age, primary diseases, ABO incompatible and highly sensitized cases, and preemptive transplant. We here report the current status of kidney transplantation in Japan. The number of transplants, detail transplant characteristics in the past decade, and outcomes are described.

Immunomodulatory effects of OX40Ig gene-modified adipose tissue-derived mesenchymal stem cells on rat kidney transplantation.

Recent studies have suggested that adipose tissue-derived mesenchymal stem cell (ADSC) therapy and OX40 costimulation blockade are two immunomodulatory strategies used to suppress the immune response to alloantigens. However, relatively little has been reported regarding the immunomodulatory potential of the abilityof these two strategies to synergize. Thus, in the present study, we aimed to investigate OX40-Ig fusion protein (OX40Ig) expression in ADSCs and to validate their more potent immunosuppressive activity in preventing renal allograft rejection. For this purpose, ADSCs from Lewis rats were transfected with the recombinant plasmid, pcDNA3.1(−)OX40Ig, by nucleofection. The ADSCs transduced with the plasmid (termed ADSCsOX40Ig) or untransduced ADSCs (termed ADSCsnative) were added to allostimulated mixed lymphocyte reaction (MLR) in vitro. In vivo, ADSCsOX40Ig, ADSCsnative, or PBS were administered to an allogeneic renal transplantation model, and the therapeutic effects, as well as the underlying mechanisms were examined. The results revealed that both the ADSCsnative and ADSCsOX40Ig significantly suppressed T cell proliferation and increased the percentage of CD4+CD25+ regulatory T cells in allogeneic MLR assays, with the ADSCsOX40Ig being more effective. Furthermore, the results from our in vivo experiments revealed that compared with the ADSCsnative or PBS group, the administration of autologous ADSCsOX40Ig markedly prolonged the mean survival time of renal grafts, reduced allograft rejection, and significantly downregulated the mRNA expression of intragraft interferon-γ (IFN-γ), and upregulated the mRNA expression of interleukin (IL)-10, transforming growth factor-β (TGF-β) and forkhead box protein 3 (Foxp3). The findings of our study indicate that the use of ADSCsOX40Ig is a promising strategy for preventing renal allograft rejection. This strategy provides the synergistic benefits of ADSC immune modulation and OX40-OX40L pathway blockade, and may therefore have therapeutic potential in clinical renal transplantation.

Roles of mTOR complexes in the kidney: implications for renal disease and transplantation.

The mTOR pathway has a central role in the regulation of cell metabolism, growth and proliferation. Studies involving selective gene targeting of mTOR complexes (mTORC1 and mTORC2) in renal cell populations and/or pharmacologic mTOR inhibition have revealed important roles of mTOR in podocyte homeostasis and tubular transport. Important advances have also been made in understanding the role of mTOR in renal injury, polycystic kidney disease and glomerular diseases, including diabetic nephropathy. Novel insights into the roles of mTORC1 and mTORC2 in the regulation of immune cell homeostasis and function are helping to improve understanding of the complex effects of mTOR targeting on immune responses, including those that impact both de novo renal disease and renal allograft outcomes. Extensive experience in clinical renal transplantation has resulted in successful conversion of patients from calcineurin inhibitors to mTOR inhibitors at various times post-transplantation, with excellent long-term graft function. Widespread use of this practice has, however, been limited owing to mTOR-inhibitor- related toxicities. Unique attributes of mTOR inhibitors include reduced rates of squamous cell carcinoma and cytomegalovirus infection compared to other regimens. As understanding of the mechanisms by which mTORC1 and mTORC2 drive the pathogenesis of renal disease progresses, clinical studies of mTOR pathway targeting will enable testing of evolving hypotheses.

The Use of Genomics and Pathway Analysis in Our Understanding and Prediction of Clinical Renal Transplant Injury.

The development and application of high-throughput molecular profiling have transformed the study of human diseases. The problem of handling large, complex data sets has been facilitated by advances in complex computational analysis. In this review, the recent literature regarding the application of transcriptional genomic information to renal transplantation, with specific reference to acute rejection, acute kidney injury in allografts, chronic allograft injury, and tolerance is discussed, as is the current published data regarding other "omics" strategies-proteomics, metabolomics, and the microRNA transcriptome. These data have shed new light on our understanding of the pathogenesis of specific disease conditions after renal transplantation, but their utility as a biomarker of disease has been hampered by study design and sample size. This review aims to highlight the opportunities and obstacles that exist with genomics and other related technologies to better understand and predict renal allograft outcome.

Matrix Metalloproteinase-9 and Graft Preservation Injury in Clinical Renal Transplantation

BackgroundDeleterious effects of matrix metalloproteinase-9 (MMP-9) have been established in experimental renal ischemia-reperfusion models but not in clinical renal transplantation thus far. MethodsWe studied MMP-9 and its physiological inhibitor tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in 45 consecutive patients of a larger trial in renal transplantation: perioperative anti-thymocyte globulin (group A, n = 15), perioperative basiliximab (group B, n = 16), and conventional triple therapy (group C, n = 14). In addition to systemic blood samples, local blood samples were obtained simultaneously at 1 and 5 minutes after reperfusion from iliac artery and graft vein for calculation of transrenal changes. Because anti-thymocyte globulin activates inflammation, group A was analyzed separately. Groups B and C were pooled (group BC). ResultsAnti-thymocyte globulin infusion caused a robust rise of MMP-9 in the systemic circulation in group A. No significant transrenal difference of MMP-9 or TIMP-1 occurred in either group during graft reperfusion. In group BC, strong transrenal release of MMP-9 at 1 minute after reperfusion correlated with cold ischemia time (R = 0.66, P = .0001) and was associated with delayed graft function (P = .052). ConclusionsRenal production of MMP-9 on graft reperfusion is associated with cold ischemia time and emergence of delayed graft function. MMP inhibition may offer a means to reduce reperfusion injury in renal transplantation.

GM-007 Plan to improve medical records at the outpatient pharmacy service

Background It is commendable to improve routine processes. However, they have to be checked once implemented, to verify if they are being done properly. One way to do this is by performing an audit. When audits are performed and abnormalities are detected, an improvement plan must be established to prevent errors. Purpose To evaluate the impact of an improvement plan (IP) in the database in the outpatient setting. Material and methods A methodology of continuous quality improvement was applied following the Deming cycle (Plan, do, check and act). The audit was carried out in June 2013. Patients were selected who attended the pharmaceutical care outpatient consultation; belonging to several Hospital Units: General Clinical Nephrology (GCN), Renal Transplantation (RT) and Dialysis (D). These services were selected because their records are complex. These patients frequently shift from unit to unit. The general ATHOS-APD data were reviewed and checked against each patient’s medical record (paper/digital). An IP was developed based on the results of this audit. The IP consisted of sending out the results of the review and holding a training session showing the professionals the correct way to keep patient records. Six months later another audit was performed, to compare the results. Variables were collected: hospital unit, health area, type of patient (depending on the dispensed drug). Results In both audits 26 patients were reviewed. In the first audit there were 9 patients (35%) in RT, 6 in GCN (26%) and 11 in D (42%). In the second, 5 in RT (19%), 8 in GCN (31%) and 13 in D (50%). The records had 15% of errors in the first audit: 4 patients, 2 belonging to RT and 2 D who were registered in GCN. In the second, there was one error (4%): a patient belonging to D was recorded as in GCN. The health area had a 19% errors in the first audit (5 patients). In the second no errors were detected. The type of patient was wrongly recorded, in the first audit 4 patients (8%), and 2 (4%) in the second. Conclusion The IP was successful. The first audit showed worse results than the second. Therefore using the Deming cycle enabled us to improve the quality of medical records. References and/or acknowledgements No conflict of interest.

Japanese society for dialysis therapy clinical guideline for "hemodialysis initiation for maintenance hemodialysis".

Yuzo Watanabe, Kunihiro Yamagata, Shinichi Nishi, Hideki Hirakata, Norio Hanafusa, Chie Saito, Motoshi Hattori, Noritomo Itami, Yasuhiro Komatsu, Yoshindo Kawaguchi, Kazuhiko Tsuruya, Yoshiharu Tsubakihara, Kazuyuki Suzuki, Ken Sakai, Hideki Kawanishi, Daijo Inaguma, Hiroyasu Yamamoto, Yoshiaki Takemoto, Noriko Mori, Kazuyoshi Okada, Hiroshi Hataya, Takashi Akiba, Kunitoshi Iseki, Tadashi Tomo, Ikuto Masakane, Tadao Akizawa, and Jun Minakuchi, for “Hemodialysis Initiation for Maintenance Hemodialysis” Guideline Working Group, Japanese Society for Dialysis Therapy

The First Clinical Case of Intermediate Ex Vivo Normothermic Perfusion in Renal Transplantation

A short period of ex vivo normothermic perfusion (EVNP) immediately before transplantation can revive the kidney and reduce the effects of cold ischemic (CI) injury. Herein, we report a clinical case of EVNP carried out at an intermediate period of the preservation interval. The kidney was retrieved from a 63-year-old extended criteria donor. After 10 h 29 min of CI the kidney underwent EVNP with 1 unit of compatible packed red blood cells mixed with a priming solution at 35.0°C while the recipient was being prepared for surgery. The mean renal blood flow was 93.6 mL/min/100 g and the kidney produced 60 mL of urine. Shortly after the start of surgery the first intended recipient became unfit for transplantation. After 60 min EVNP the kidney was flushed with cold preservation solution and re-packed in ice. The second period of CI was 5 h and 21 min. The kidney was transplanted without any complications into a 54-year-old predialysis patient. The recipient had immediate graft function with serum creatinine levels falling from 315 to 105 µmol/L by day 7. This is the first report of an intermediate period of EVNP in clinical renal transplantation. This case demonstrates the feasibility and safety of the technique.

Non-Compliance Assessed By Variability of Blood Calcineurin Inhibitor (CNI) Levels Is Associated With Poor Long-Term Outcomes in Kidney Transplant Recipients (KTRs).

Non-compliance with treatment is a major problem in clinical renal transplantation. There is an emerging interest in the development of objective markers of non-compliance. Variability of CNI drug levels is one such marker. In this large single centre retrospective analysis, we examined the relationship between the overall graft outcomes and CNI variability. A total of 10 plasma CNI levels were examined between the 2nd and 3rd post-transplant year for the analysis in 1235 consecutive KTRs. Patients were divided into three tertiles based on their CNI (2y-3y) variability. Grafts lost prior to third transplant year were excluded to minimize the effect of early therapeutic modifications. Overall graft survival was examined over 10 years by Kaplan Meier analysis. The mean variability was significantly higher for younger KTRs {age lowest tertile (20yrs), 24.7 vs. middle tertile (40yrs), 21.9, vs. highest tertile (59yrs), 22.9; P<0.05, ANOVA}. Overall, patients in the highest tertile group of CNI (2y-3y) variability had the worst overall graft survival when compared to the other tertiles. When the analysis was stratified by the age of the KTRs, patients with high variability in the lowest tertile group of age (i.e. youngest age group) had the worst outcomes. CNI (2y-3y) variability was not strongly associated with increased overall graft loss in older KTRs. The utility of CNI variability was re-examined in 118 KTRs with allograft dysfunction. These patients underwent an indication biopsy for either creeping creatinine or proteinuria. Patients in the highest tertile group of CNI variability had higher microcirculation inflammation score (glomerulitis+peritubular capillaritis) and a higher percentage of these grafts were positive for C4d deposition despite no significant difference in the prevalence of DSA in the serum. There was no significant difference in the mean score for scarring (ct+ci). However, patients in the lowest tertile group for CNI level variability had significantly superior post-biopsy graft survival when compared to the highest two tertiles in this selective group of patients with allograft dysfunction. To conclude, CNI drug level variability is a potential marker for predicting allograft outcomes especially in the younger patient cohort where non-compliance is a major problem. This has to be validated in further prospective studies

The history of organ transplantation in Austria

In 1902, the first successful kidney transplant ever was performed by E. Ullmann in Vienna. Also, the first clinical renal transplant in Austria was performed on June 17, 1965, by F. Piza in the same city. The first combined pancreas–kidney transplant was performed by R. Margreiter in 1979 in Innsbruck. H.J. Bohmig did the first liver transplant in 1972 in Vienna. The world’s first combined liver–kidney transplant was carried out by R. Margreiter in 1983 in Innsbruck. The same year as the first heart transplant, in 1985 the first combined heart–lung transplant and in 1986 the first double lung transplant were performed in Innsbruck by R. Margreiter and F. Gschnitzer, respectively. In 1989, for the first time, a single lung was transplanted in Vienna by W. Klepetko and E. Wolner. In 1989, the first successful multivisceral transplant including the entire small bowel worldwide took place in Innsbruck, with R. Margreiter and A. Konigsrainer being the surgeons. An isolated bowel transplant was performed in Vienna by F. Muhlbacher in 1983. The world’s second double-hand transplant was performed in Innsbruck in 2000 by a team led by H. Piza and R. Margreiter. These pioneering transplants led to three multiorgan- and two kidney-transplant programs in Austria and generated activities that are among the best worldwide in terms of volume, and also quality.

Diagnosis and treatment of cytomegalovirus (CMV) infection post renal transplantation (The guidelines for CMV infection post renal transplantation in Japanese Society for Clinical Renal Transplantation)

Diagnosis and treatment of cytomegalovirus (CMV) infection post renal transplantation (The guidelines for CMV infection post renal transplantation in Japanese Society for Clinical Renal Transplantation)

Presidential Address Upon Appointment to the Japanese Society for Dialysis Therapy

JSDT was founded in 1968 as the Society for the Study of Dialysis (Jinkou Touseki Igakukai), a private academic society. In 1985, it was renamed the Japanese Society for Dialysis Therapy (Nihon Touseki Ryouhou Gakkai). In 1993, it was approved as an incorporated association, the Japanese Society for Dialysis Therapy (Nihon Touseki Igakukai). On 3 September 2012, in accordance with the reforming of public service corporations, it became a general incorporated association, one of the largest academic societies in Japan with over 16 000 members comprising regular, institutional, and supporting members. I hope to work towards the smooth transition to a new corporation as well as for the development of research and promotion of knowledge on dialysis and related medicine to contribute widely to patients and society. In recent clinical research, it has been identified that degradation of renal function increases the risk of cerebrovascular disorders, coronary artery disease, myocardial infarction, and cardiac failure, as well as the risk of death and hospitalization due to cerebrovascular disorders. However, blood purification for patients with chronic renal failure is inadequate in terms of both quality and quantity to achieve the effect of a normal renal function, and patients are constantly exposed to the above-mentioned risks. Therefore, to improve the prognosis of patients with chronic renal failure, it is necessary to develop and provide a better blood purification service. I believe that the problems to solve and our therapeutic strategies will be identified through looking back over the 40-year history of blood purification and resolving major problems, such as those related to urotoxin removal, biocompatibility of the dialysis membrane, dialysis fluid, vascular access, malnutrition, arteriosclerosis, and aging. Based on such a perspective, I would like to establish a committee to study new technologies that can improve the existing blood purification system as well as create guidelines for dialysis therapy for properly conducting blood purification using practicable technologies and guidelines for the nutritional care of dialysis patients, which is one of the most important issues in dialysis therapy. As one of the problems in the treatment of chronic renal failure in Japan, it has been pointed out that the number of patients who undergo peritoneal dialysis or renal transplantation is extremely low compared to Western countries in spite of having the world's highest proportion of patients receiving dialysis as a percentage of the population. To provide well-balanced medical treatment for chronic renal failure, it is important to provide patients with a choice of three therapeutic methods, which are dialysis, peritoneal dialysis, and renal transplantation. It has been reported that the option of renal transplantation has been given to only 30% of the patients and peritoneal dialysis to only 50%. We would like to establish a well-balanced medical care system for chronic renal failure according to the therapeutic methods required for each patient by promoting knowledge of the three therapeutic methods in cooperation with other organizations, such as the Japanese Society of Nephrology, Japan Society for Transplantation, Japanese Society for Clinical Renal Transplantation, and Japanese Society for Peritoneal Dialysis. Another major problem is the declining number of young clinicians who treat chronic renal failure and young researchers who study dialysis medicine. To treat Japan's 300 000 patients with chronic renal failure and further develop dialysis medicine, it is vital to nurture ambitious young doctors. We plan to provide seminars on blood purification for young doctors involving residents and other young doctors in order to promote their interest in dialysis medicine. We hope to contribute to securing human resources in dialysis medicine by helping young doctors deepen their understanding of maintenance dialysis as well as acute blood purification, which has become essential in emergency medical services. To manage the JSDT effectively, it is important to facilitate both the activities of its standing committees and cooperation with related academic societies. With regard to this, we would like to manage JSDT activities to cooperate and share duties with other organizations, such as the Japanese Society of Nephrology, The Japan Society for Transplantation, Japanese Society for Clinical Renal Transplantation, Japanese Society for Peritoneal Dialysis, The Japan Diabetes Society, Japanese Association of Dialysis Physicians, Japan Academy of Nephrology Nursing, and Japan Association for Clinical Engineers. Further, to facilitate team medical care in the field of dialysis, we plan to provide education and training for nurses, clinical engineers, pharmacists, nutritionists, and other people of related occupations in cooperation with related organizations. I will make my best effort to resolve these issues during my term. I would appreciate the support of JSDT members as well as the members of related academic societies, organizations, and companies.