ZUSAMMENFASSUNG Die Zahl der Transplantationen ist rückläufig. Umso wichtiger ist eine konsequente Nachsorge zur Erhaltung der Transplantatfunktion. Eine häufige Komplikation (10–40 %) ist der Post-Transplantations-Diabetes mellitus (PTDM). Besonders im ersten Jahr ist das Erkrankungsrisiko hoch. Alter, Übergewicht, männliches Geschlecht, eine präexistente Insulinresistenz sowie die immunsuppressive Therapie begünstigen das Auftreten. Der PTDM führt zu hoher kardiovaskulärer Mortalität. Der orale Glukosetoleranztest (oGTT) stellt den Goldstandard der Diagnostik dar. Zusätzlich werden Nüchtern- und Spontanglukose sowie HbA1c herangezogen. Ein postoperativ diagnostizierter PTDM sollte mit Insulin behandelt werden. Eine frühe Intervention verzögert die Entwicklung einer relevanten Glukosestoffwechselstörung häufig über viele Monate. Die therapeutischen Möglichkeiten sind vielfältig und beinhalten neben der Blutzuckereinstellung die Behandlung kardiovaskulärer Risikofaktoren (Hyperlipidämie, Hypertonie). Patientenschulungen sind sinnvoll.

Transplantation (NTX) associated ischemia-reperfusion-mechanisms and the predisposition for insulin resistance are discussed as causes of a posttransplantation diabetes mellitus (PTDM). Furthermore, immunosuppressants can have a damaging effect on insulin secretion.55 metabolically healthy patients with an endstage renal disease (age 52 ± 14 years, body mass index 27 ± 5 kg / m(2), blood pressure 137 ± 15/82 ± 11 mmHg) were included in a prospectively cohort study. These patients were transplanted between 2009 and 2011 (82 % of the NTX patients). Baseline examination was performed before NTX. Within the 2nd week as well as 6 and 12 months after transplantation an oral glucose tolerance test (oGGT), 3 and 9 months after NTX a glucagon test took place. In these connections the determination of plasma glucose, C-peptide and insulin was performed. Study endpoints were: graft failure, impaired glucose tolerance (iGT), PTDM, patient's death.Over a follow-up-period of 1 year post NTX iGT / PTDM occurred in 31 % and graft failure in 13 %. In comparison with the healthy control group patients with iGT / PTDM were older (59 ± 8 vs. 48 ± 14ys, p = 0.001), overweight (BMI 29 ± 4 vs. 26 ± 5 kg / m(2), p = 0.038), showed an indication of an insulin resistance before NTX (HOMA 4.0 ± 2.9 vs. 2.4 ± 1.4, p = 0.013; C-peptide 10.1 ± 5.2 vs. 7.1 ± 3.6 ng / ml, p = 0.014; insulin 14.6 ± 9.4 vs. 10.6 ± 5.5mU / l, p = 0.045) and higher HbA1c levels (5.6 ± 0.5 vs. 5.4 ± 0.4 %, p = 0.032). Age (p = 0.001), fasting plasma glucose (p = 0.042), the glucose levels of oGTT immediately after transplantation were shown as prognostically relevant (fasting glucose: p = 0.027; 1 h: p = 0.014; 2 h: p = 0.002). An isolated defective secretion as a result of a toxic damage to the β-cells by immunosuppressants couldn't be shown in any of the patients with iGT / PTDM. 4 % of the patients died in the first year after NTX.In 31 % a disorder of glucose metabolism was found as a frequent complication after NTX. The HOMA index was found to be a meaningful marker for an existing insulin resistance. The fasting glucose before and an oGTT in the first weeks after NTX showed itself as clinically valid laboratory parameters for a risk assessment.

Background: Transplantation (NTX) associated ischemia-reperfusion-mechanisms and the predisposition for insulin resistance are discussed as causes of a posttransplantation diabetes mellitus (PTDM). Furthermore, immunosuppressants can have a damaging effect on insulin secretion. Methods: 55 metabolically healthy patients with an endstage renal disease (age 52 ± 14 years, body mass index 27 ± 5 kg / m(2), blood pressure 137 ± 15/82 ± 11 mmHg) were included in a prospectively cohort study. These patients were transplanted between 2009 and 2011 (82 % of the NTX patients). Baseline examination was performed before NTX. Within the 2nd week as well as 6 and 12 months after transplantation an oral glucose tolerance test (oGGT), 3 and 9 months after NTX a glucagon test took place. In these connections the determination of plasma glucose, C-peptide and insulin was performed. Study endpoints were: graft failure, impaired glucose tolerance (iGT), PTDM, patient's death. Results: Over a follow-up-period of 1 year post NTX iGT / PTDM occurred in 31 % and graft failure in 13 %. In comparison with the healthy control group patients with iGT / PTDM were older (59 ± 8 vs. 48 ± 14ys, p = 0.001), overweight (BMI 29 ± 4 vs. 26 ± 5 kg / m(2), p = 0.038), showed an indication of an insulin resistance before NTX (HOMA 4.0 ± 2.9 vs. 2.4 ± 1.4, p = 0.013; C-peptide 10.1 ± 5.2 vs. 7.1 ± 3.6 ng / ml, p = 0.014; insulin 14.6 ± 9.4 vs. 10.6 ± 5.5mU / l, p = 0.045) and higher HbA1c levels (5.6 ± 0.5 vs. 5.4 ± 0.4 %, p = 0.032). Age (p = 0.001), fasting plasma glucose (p = 0.042), the glucose levels of oGTT immediately after transplantation were shown as prognostically relevant (fasting glucose: p = 0.027; 1 h: p = 0.014; 2 h: p = 0.002). An isolated defective secretion as a result of a toxic damage to the β-cells by immunosuppressants couldn't be shown in any of the patients with iGT / PTDM. 4 % of the patients died in the first year after NTX. Conclusion: In 31 % a disorder of glucose metabolism was found as a frequent complication after NTX. The HOMA index was found to be a meaningful marker for an existing insulin resistance. The fasting glucose before and an oGTT in the first weeks after NTX showed itself as clinically valid laboratory parameters for a risk assessment.

You have accessJournal of UrologyTransplantation & Vascular Surgery I1 Apr 2014PD30-08 URINE PROTEIN PROFILING IDENTIFIED ALPHA-1-MICROGLOBULIN AND HAPTOGLOBIN AS BIOMARKERS FOR EARLY DIAGNOSIS OF ACUTE ALLOGRAFT REJECTION FOLLOWING KIDNEY TRANSPLANTATION Beatrice Stubendorff, Stephanie Finke, Martina Walter, Olaf Kniemeyer, Ferdinand von Eggeling, Torsten Gruschwitz, Thomas Steiner, Undine Ott, Gunter Wolf, Heiko Wunderlich, and Kerstin Junker Beatrice StubendorffBeatrice Stubendorff More articles by this author , Stephanie FinkeStephanie Finke More articles by this author , Martina WalterMartina Walter More articles by this author , Olaf KniemeyerOlaf Kniemeyer More articles by this author , Ferdinand von EggelingFerdinand von Eggeling More articles by this author , Torsten GruschwitzTorsten Gruschwitz More articles by this author , Thomas SteinerThomas Steiner More articles by this author , Undine OttUndine Ott More articles by this author , Gunter WolfGunter Wolf More articles by this author , Heiko WunderlichHeiko Wunderlich More articles by this author , and Kerstin JunkerKerstin Junker More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2131AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Early diagnosis of acute allograft rejection and effective immunosuppressive therapy lead to improvements in graft survival following kidney transplantation. However, there are no non-invasive diagnostic parameters available that enable early and reliable detection of acute rejection. The objective of our study was to establish a urinary protein profile suitable to determine rejection-specific changes following kidney transplantation and to predict early acute rejection at a postoperative stage. Furthermore, we focused on identification of candidate proteins for the use as biomarkers in clinical practice for diagnosis of acute rejection. METHODS Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n=58) and stable transplant function was monitored for at least 2 years (n=58). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were analyzed by SELDI-TOF-MS. Multiplex-Fluorescence-2DE and Peptide Mass Fingerprinting were used for identification of candidate proteins. Urinary concentration of candidate proteins was validated by ELISA. RESULTS A protein signature including 4 masses differentiated acute rejection from stable transplant patients at the postoperative stage with 73% sensitivity and 88% specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative biomarkers for acute rejection. Protein levels were significantly higher in postoperative urine samples from patients with upcoming rejection than in stable transplant patients (A1MG: 29.13 μg/ml vs. 22.06 μg/ml, p=0.001; Hp: 628.34 ng/ml vs. 248.57 ng/ml, p=0.003). The combination of both proteins enabled the diagnosis of early rejection with 85% sensitivity and 80% specificity. CONCLUSIONS Protein profiling using mass spectrometry is suitable for non-invasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers. Further analyses have to show if early diagnosis is possible for patients with allograft rejection that occurs several month after transplantation by analyzing changes in urine protein pattern in regular intervals. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e776-e777 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Beatrice Stubendorff More articles by this author Stephanie Finke More articles by this author Martina Walter More articles by this author Olaf Kniemeyer More articles by this author Ferdinand von Eggeling More articles by this author Torsten Gruschwitz More articles by this author Thomas Steiner More articles by this author Undine Ott More articles by this author Gunter Wolf More articles by this author Heiko Wunderlich More articles by this author Kerstin Junker More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PURPOSE:Early diagnosis of acute rejection and effective immunosuppressive therapy lead to improvement in graft survival following kidney transplantation. In this study, we aimed to establish a urinary protein profile suitable to distinguish between patients with rejection and stable graft function and to predict acute rejection based on postoperatively collected urine samples. A further objective was to identify candidate proteins for the use as biomarkers in clinical practice.METHODS:Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n = 58), and stable transplant function was monitored for at least 2 years (n = 58). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Protein identification and validation were performed using multiplex fluorescence 2DE, peptide mass fingerprinting and enzyme-linked immunosorbent assay.RESULTS:A protein profile including four mass peaks differentiated acute rejection from stable transplants at the time point of rejection and at the postoperative state with 73 % sensitivity and 88 % specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative rejection biomarkers. Protein levels were significantly higher in postoperative urine from patients with rejection (A1MG 29.13 vs. 22.06 μg/ml, p = 0.001; Hp 628.34 vs. 248.57 ng/ml, p = 0.003). The combination of both proteins enabled the diagnosis of early rejection with 85 % sensitivity and 80 % specificity.CONCLUSION:Protein profiling using mass spectrometry is suitable for noninvasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables the prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers.

In the present study, antibody response to seasonal influenza vaccination and to the adjuvanted one-shot influenza A H1N1 vaccine (Pandemrix®) was investigated in 57 hemodialysis (HD) patients and 48 renal transplant (RT) recipients. Specific antibodies were measured by hemagglutination inhibition (HI) test using a pandemic H1N1 strain and a seasonal H3N2 virus. HI titers of ≥1:40 were considered as protective. Hemodialysis patients showed seroprotection against pandemic H1N1 in 35.1%, against seasonal influenza in 36.8% and against both in 14.0%. In comparison, renal transplant recipients developed protective antibody titers against the pandemic H1N1 virus in 47.9%, against the seasonal H3N2 strain in 31.3% and against both in 18.8%. HD patients and renal transplant recipients younger than 60 years developed protective antibody response to the pandemic influenza H1N1 vaccine in 50.0% of the HD patients and 55.2% of the RT recipients and against seasonal influenza in 45.0/20.7% (HD/RT) of the cases. Patients aged ≥60 years showed seroprotection against pandemic influenza in 27.0/36.8% (HD/RT) and against seasonal influenza in 32.4/47.4% (HD/RT). Side effects were reported in only four patients. In hemodialysis patients and renal transplant recipients, vaccination against pandemic H1N1 and seasonal influenza is well tolerated. However, more than a half of these patients did not develop seroprotective antibody levels. Thus, new vaccines and altered vaccination regimes are likely necessary to achieve relevant antibody levels in these patient groups.

Tumorerkrankungen treten bei Dialysepatienten im Vergleich zur Normalbevölkerung häufiger auf. Die Haupttodesursache dieser Patienten sind aber kardiovaskuläre Erkrankungen, sodass die Mortalität durch Tumoren in den Hintergrund tritt. Bereits in der Normalbevölkerung ist der Vorteil des Tumorscreenings eher gering, für Dialysepatienten ist der Vorteil von Vorsorgeuntersuchungen nicht belegt. Es gibt für dieses spezielle Patientenklientel keine Empfehlungen für ein Tumorscreening bis auf die allgemeinen Empfehlungen, die für die Bevölkerung angewendet werden. Vorsorgeuntersuchungen sollten bei einer langen Lebenserwartung oder im Rahmen der Betreuung auf der Nieren-Transplantations-Warteliste zur Anwendung kommen. Unter der immunsuppressiven Behandlung nach Nierentransplantation ist das Risiko für die Entwicklung einer malignen Erkrankung deutlich erhöht. Tumoren des Harntraktes kommen bei Patienten mit terminaler Niereninsuffizienz besonders häufig vor. Zusätzlich zu den allgemeinen Vorsorgeuntersuchungen sind sonografische Untersuchungen der Eigennieren und ggf. eine Zystoskopie bei eumorpher Mikrohämaturie nach zytostatischer Therapie mit Cyclophosphamid oder bei Analgetikanephropathie sinnvoll.

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery1 Apr 20112251 PROTEIN SIGNATURE IN URINE INDICATES REJECTION AFTER KIDNEY TRANSPLANTATION AT AN EARLY POSTOPERATIVE STATE Stefanie Finke, Beatrice Stubendorff, Torsten Gruschwitz, Undine Ott, Thomas Steiner, Heiko Wunderlich, Ferdinand von Eggeling, Marc-Oliver Grimm, and Kerstin Junker Stefanie FinkeStefanie Finke Jena, Germany More articles by this author , Beatrice StubendorffBeatrice Stubendorff Jena, Germany More articles by this author , Torsten GruschwitzTorsten Gruschwitz Jena, Germany More articles by this author , Undine OttUndine Ott Jena, Germany More articles by this author , Thomas SteinerThomas Steiner Jena, Germany More articles by this author , Heiko WunderlichHeiko Wunderlich Jena, Germany More articles by this author , Ferdinand von EggelingFerdinand von Eggeling Jena, Germany More articles by this author , Marc-Oliver GrimmMarc-Oliver Grimm Jena, Germany More articles by this author , and Kerstin JunkerKerstin Junker Jena, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2493AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES An effective immunosuppressive therapy leads to improvements in kidney graft survival after transplantation. However, successful treatment requires an early detection of allograft rejection. Currently no non-invasive diagnostic tools exist which allow for early and reliable detection of acute rejections after kidney transplantation. In a previous study we identified a specific urine protein pattern that correlates with rejection at the time of biopsy. This pattern enables a differentiation between patients with and without allograft rejection. In the current investigations we examined if allograft rejection is already detectable within few days after transplantation based on our identified protein signature. METHODS 52 urine samples (collected between postoperative day 5 and 10) from patients with and without allograft rejection (26 each) were analysed by SELDI-TOF-MS technology using two different ProteinChip® surfaces (Q10 and CM10). Bioinformatic analysis was conducted using software XLMiner. Based on the previously defined protein signature, samples were assigned to “rejection” and “no rejection” respectively. The timeframe between postoperative sample collection and rejection was 9 days to 14 months. RESULTS Using our predefined urine protein pattern as predictor for rejection resulted in an accuracy of 63%. In case of 42% of patients with proven rejection the protein signature was able to predict the allograft rejection at an early postoperative state. Considering the time point of rejection, in case of 8 of 11 patients that were assigned correctly to undergo a rejection, the period until rejection was less than 30 days. Vice versa, in 11 of 15 patients those were false negative (rejection was not predicted), the period until rejection was 1 to 14 months. CONCLUSIONS The identified specific urine protein pattern enables the prediction of early acute allograft rejection already a few days after kidney transplantation if rejection occurs during the first 30 days. Further analyses have to show if early and reliable diagnosis is possible for patients with allograft rejection that occurs several month after transplantation by analyzing changes in urine protein pattern in regular intervals. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e903 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stefanie Finke Jena, Germany More articles by this author Beatrice Stubendorff Jena, Germany More articles by this author Torsten Gruschwitz Jena, Germany More articles by this author Undine Ott Jena, Germany More articles by this author Thomas Steiner Jena, Germany More articles by this author Heiko Wunderlich Jena, Germany More articles by this author Ferdinand von Eggeling Jena, Germany More articles by this author Marc-Oliver Grimm Jena, Germany More articles by this author Kerstin Junker Jena, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Die Nierenbiopsie hat in der Diagnostik nephrologischer Erkrankungen einen unverändert hohen Stellenwert. Zur Differenzialdiagnostik der Nierenfunktionseinschränkung sowie der Proteinurie mit oder ohne glomeruläre Hämaturie ist die Durchführung einer Nierenbiopsie nach wie vor der Goldstandard. Die Transplantatnierenbiopsie ist ein etabliertes Verfahren zur Diagnostik der Transplantatfunktionsverschlechterung. In den letzten Jahren wurde mit alternativen, nichtinvasiven Methoden wie der Proteomanalyse im Urin oder im Blut versucht, die gleiche diagnostische Sicherheit wie mit der Nierenbiopsie zu erreichen. Bisher ist die diagnostische Sicherheit der histologischen Untersuchung des Nierengewebes am größten. Da sich aus der Diagnose die anschließende Therapie ableitet, kommt der zuverlässigen Differenzierung eine unmittelbare Bedeutung für die weitere Entwicklung der Erkrankung zu. Die Nierenbiopsie sollte in den Grundzügen standardisiert durchgeführt werden. Eine gewissenhafte Planung und Vorbereitung hilft, die Risiken, die in erster Linie Gerinnungsabweichungen betreffen, zu erkennen. Schwerwiegende Komplikationen kommen selten vor, sind aber aufgrund der Anatomie der Nieren nicht komplett vermeidbar.

F. Seyfarth, S. Goetze, Y. Gräser, M. Kaatz, U. Ott, C. Rüster, B. Edel, P. Elsner and U.-C. Hipler Universitätsklinikum Jena, Klinik für Hautkrankheiten, Jena, Germany, Charité – Universitätsmedizin Berlin, Institut für Mikrobiologie und Hygiene, Campus Charité Mitte, Berlin, Germany, Universitätsklinikum Jena, Klinik für Innere Medizin III, Jena, Germany and Universitätsklinikum Jena, Insitut für Medizinische Mikrobiologie, Jena, Germany

BACKGROUND:Cardiovascular risk in hemodialysis patients is enhanced, resulting in a higher mortality rate compared with the general population, yet the average wait time for renal transplantation in Germany is 5-7 years. The age of wait-listed patients has risen progressively. The aim of this study was to evaluate the prevalence of cardiovascular disease in patients on the waiting list in our center before and after renal transplantation as well as the extent to which invasive treatment was required in these patients.METHODS:The study investigated 2 groups: 350 patients on the renal transplantation waiting list at our center in 2008 and 324 patients who underwent renal transplantation at the same center in the years 2003-2007.RESULTS:In 2008, 141 women and 209 men with a mean age of 48.6 years (range 13-71 years) were on the waiting list. In the years 2003-2007, 98 women and 226 men with a mean age of 54.3 years (range 16-78 years) received renal transplants. One hundred six patients on the waiting list for renal transplantation had to undergo coronary angiography. There is no upper age limit for donors or recipients in our program. Mean age at admission on the waiting list was 48.6 years (range 13-71 years). Mean age at transplantation was 54.3 years (range 16-78 years) in our center. Most of these patients were asymptomatic but presented a risk profile that included diabetes mellitus, severe general atherosclerosis, a pathologic ergometric test, or abnormal myocardial scintigraphy. Only in 1 case could coronary heart disease be excluded. Seventy patients (20%) suffered from mild to moderate coronary heart disease without the need for intervention. In 5 patients (1.4%) coronary bypass surgery was necessary due to severe 3-vessel coronary heart disease. In 2 cases (0.6%) replacement of the aortic valve was performed because of aortic valvular stenosis. Coronary angioplasty without implantation of stents was done in 2 patients (0.6%). Twenty-two patients (6.8%) were treated with implantation of bare metal stents and 6 patients (1.7%) with drug-eluting stents. After renal transplantation, 22 patients (6.8%) suffered from peripheral arterial occlusive disease. In 58 patients, coronary heart disease was documented by angiography. 16 patients (4.9%) had 1-vessel disease, 23 patients (7%) 2-vessel disease, and 19 patients (5.8%) 3-vessel disease. Myocardial infarction was documented in 18 patients (5.5%) before and in 5 patients (1.5%) after renal transplantation. Bare metal stent implantation was performed in 6 patients (1.8%) after transplantation. One patient received a drug-eluting stent after renal transplantation. In the years 2003-2007, 22 patients underwent coronary bypass surgery before kidney transplantation.CONCLUSION:The prevalence of coronary heart disease is high in patients on the waiting list and after renal transplantation. The majority of these patients are clinically asymptomatic. One-third of the patients with coronary heart disease had to be treated invasively. Nevertheless, many diabetic patients are very sick from multiple complications after the waiting time, making theme unsuitable for transplantation.