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Mass disasters are characterized by a disparity between healthcare demand and supply, which hampers complex therapies like kidney transplantation. Considering the scarcity of publications on previous disasters, we reviewed transplantation practice during the recent coronavirus disease 2019 (COVID-19) pandemic, and dwelled upon this experience to guide transplantation strategies in the future pandemic and non-pandemic catastrophes. We strongly suggest continuing transplantation programs during mass disasters, if medical and logistic operational circumstances are appropriate. Postponing transplantations from living donors and referral of urgent cases to safe regions or hospitals are justified. Specific preventative measures in anticipated disasters (such as vaccination programs during pandemics or evacuation in case of hurricanes or wars) may be useful to minimize risks. Immunosuppressive therapies should consider stratifying risk status and avoiding heavy immune suppression in patients with a low probability of therapeutic success. Discharging patients at the earliest convenience is justified during pandemics, whereas delaying discharge is reasonable in other disasters, if infrastructural damage results in unhygienic living environments for the patients. In the outpatient setting, telemedicine is a useful approach to reduce the patient load to hospitals, to minimize the risk of nosocomial transmission in pandemics and the need for transport in destructive disasters. If it comes down to saving as many lives as possible, some ethical principles may vary in function of disaster circumstances, but elementary ethical rules are non-negotiable. Patient education is essential to minimize disaster-related complications and to allow for an efficient use of healthcare resources.

Living donation challenges the ethical principle of non-maleficence in that it exposes healthy persons to risks for the benefit of someone else. This makes safety, informed consent (IC) and education a priority. Living kidney donation has multiple benefits for the potential donor, but there are also several known short- and long-term risks. Although complete standardization of IC is likely to be unattainable, studies have emphasized the need for a standardized IC process to enable equitable educational and decision-making prospects for the prevention of inequities across transplant centers. Based on the Three-Talk Model of shared decision-making by Elwyn et al., we propose a model, named 3-Step (S) Model, where each step coincides with the three ideal timings of the process leading the living donor to the decision to pursue living donation: prior to the need for kidney replacement therapy (team talk); at the local nephrology unit or transplant center, with transplant clinicians and surgeons prior to evaluations start (option talk); and throughout evaluation, after having learned about the different aspects of donation, especially if there are second thoughts or doubts (decision talk). Based on the 3-S Model, to deliver conceptual and practical guidance to nephrologists and transplant clinicians, we provide recommendations for standardization of the timing, content, modalities for communicating risks and assessment of understanding prior to donation. The 3-S Model successfully allows an integration between standardization and individualization of IC, enabling a person-centered approach to potential donors. Studies will assess the effectiveness of the 3-S Model in kidney transplant clinical practice.

Mass disasters are characterized by a disparity between health care demand and supply, which hampers complex therapies like kidney transplantation. Considering scarcity of publications on previous disasters, we reviewed transplantation practice during the recent COVID-19 pandemic, and dwelled upon this experience for guiding transplantation strategies in the future pandemic and non-pandemic catastrophes. We strongly suggest continuing transplantation programs during mass disasters, if medical and logistic operational circumstances are appropriate. Postponing transplantations from living donors and referral of urgent cases to safe regions or hospitals are justified. Specific preventative measures in anticipated disasters (such as vaccination programs during pandemics or evacuation in case of hurricanes or wars) may be useful to minimize risks. Immunosuppressive therapies should consider stratifying risk status and avoiding heavy immune suppression in patients with a low probability of therapeutic success. Discharging patients at the earliest convenience is justified during pandemics, whereas delaying discharge is reasonable in other disasters, if infrastructural damage results in unhygienic living environments for the patients. In the outpatient setting, telemedicine is a useful approach to reduce the patient load to hospitals, to minimize the risk of nosocomial transmission in pandemics and the need for transport in destructive disasters. If it comes down to save as many lives as possible, some ethical principles may vary in function of disaster circumstances, but elementary ethical rules are non-negotiable. Patient education is essential to minimize disaster-related complications and to allow for an efficient use of health care resources.

The 2017 version of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines is the most recent international framework for the evaluation and care of living kidneys donors. Along with the call for an integrative approach evaluating the long-term end-stage kidney disease risk for the future potential donor, several recommendations are formulated regarding the pre-donation glomerular filtration rate (GFR) adequacy with no or little consideration for the donor candidate’s age or for the importance of using reference methods of GFR measurements. Herein, we question the position of the KDIGO guidelines and discuss the rationale and modalities for a more basic, but no less demanding GFR evaluation enabling a more efficient selection of potential kidney donors.

Contains fulltext : 283474.pdf (Publisher’s version ) (Open Access) The Omicron variant, which has become the dominant strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, brings new challenges to preventing and controlling the infection. Moreover, the widespread implementation of vaccination policies before and after transplantation, and the development of new prophylactic and treatment strategies for coronavirus disease 2019 (COVID-19) over the past 12-18 months, has raised several new issues concerning kidney transplant recipients. In this special report, the ERA DESCARTES (Developing Education Science and Care for Renal Transplantation in European States) Working Group addresses several questions related to everyday clinical practice concerning kidney transplant recipients and to the assessment of deceased and live kidney donors: what is the current risk of severe disease and of breakthrough infection, the optimal management of immunosuppression in kidney transplant recipients with COVID-19, the role of passive immunization and the efficacy of antiviral drugs in ambulatory patients, the management of drug-to-drug interactions, safety criteria for the use of SARS-CoV-2-positive donors, issues related to the use of T cell depleting agents as induction treatment, and current recommendations for shielding practices.

Item does not contain fulltext Due to the shortage of deceased and genetically- or emotionally-related living donors, living unrelated paid donor (LURpD) kidney transplantation has been considered; however, this practice may result in medical, ethical and social dilemmas, induce organ trading (commodification), and even criminal activities. Commodification also risks undermining public trust in the transplant system and impeding the development of proper altruistic or deceased donor programs by ignoring altruism, volunteerism, and dignity. However, despite many objections by authoritative organizations, black market practices are involved in up to 10% of all transplants worldwide. The authors strongly discourage any payment or rewards for organ donation, and instead urge the governments of all countries to provide adequate and accessible kidney health care. However, it is an undeniable fact that paid-living donor transplantation is increasing despite all objections, disapprovals and regulations. We feel it as our responsibility not to ignore this uncertain and undesirable practice, but rather to underline the necessity for strict rules and prohibitions to minimize unacceptable medical, social and ethical risks as long as it exists. Furthermore, economic profit, be it direct or indirect, must not be the goal of those involved, and the employment of intermediaries must be avoided entirely. Additionally, the donor should be in a position where not donating has no detrimental effect on his/her future in any way (free agency). In our view, every country has the obligation and responsibility to provide adequate kidney health care and to make kidney transplantation accessible to those in need. This provision is key to stop transplant tourism and commercialization of kidney transplantation. The nephrology community has a duty to establish structures that optimize organ availability within strict ethical limits. The legal position of LURpD varies considerably worldwide. Strictly respecting each country's legislation and local values is mandatory to minimize medical and ethical risks and controversies.

Three recently published sham-controlled studies proved the efficacy of renal denervation (RDN) in hypertensive patients. The study presented here analyzed a nationwide multicentre registry database to clarify which patient subgroups benefit most from radiofrequency RDN.This is a post hoc analysis from the multicentre Austrian Transcatheter Renal Denervation Registry hosted by the Austrian Society of Hypertension. We correlated change of SBP after RDN to sex and presence/absence of comorbidities. Univariable correlation and multiple linear regression analyses were performed.Two hundred and ninety-one patients (43% women, median age 64 years) undergoing RDN between April 2011 and September 2014 were included in this analysis. Mean baseline ambulatory 24 h BP (systolic/diastolic) was 150 ± 18/89 ± 14 mmHg and mean baseline office BP was 170 ± 16/94 ± 14 mmHg.After RDN, mean ambulatory 24 h BP reduction was 9 ± 19/6 ± 16 mmHg. The following features were associated with a good response to RDN: high baseline systolic ambulatory BP, high baseline diastolic office BP, female sex, absence of diabetes mellitus, and absence of peripheral artery disease. Multivariable analysis identified female sex and absence of diabetes mellitus as strongest predictors for ambulatory BP reduction, although those groups had the lowest baseline ambulatory BP.Ambulatory BP reductions after RDN were substantially more pronounced in female and in nondiabetic patients despite lower baseline BP. It is concluded that in terms of efficacy female patients and nondiabetic patients might benefit more from RDN.

Hypertonie ist eine sehr haufige Komorbiditat bei Patienten mit Diabetes mellitus, die – wenn unzureichend behandelt – signifikant zur erhohten Mortalitat und zum Auftreten von mikrovaskularen und makrovaskularen Komplikationen beitragt. Eine Individualisierung der Blutdruckzielwerte in Abhangigkeit vom Patientenalter und vom Vorliegen bestimmter vaskularer Komplikationen wird heute weltweit diskutiert. Blutdruckzielwerte um 130/80 mm Hg waren in den Studien mit der geringsten Ereignisrate an Komplikationen assoziiert. ACE-Hemmer und Angiotensin-Rezeptorblocker sollen in der Hypertonie-Therapie bei Patienten mit Diabetes mellitus bevorzugt werden. Calciumantagonisten und Diuretika sind in der Second-Line-Therapie oft notwendig. Nach Erreichung der Zielwerte muss die antihypertensive Therapie fortgefuhrt werden, wobei regelmasige Blutdruckmessungen durch die Patienten fur die Optimierung der Blutdruckeinstellung sehr hilfreich sind. Neuere Antidiabetika wie SGLT2-Inhibitoren oder GLP1-Rezeptoragonisten haben tragen ebenfalls zur Blutdrucksenkung bei.

Current proposals for waiting times for a renal transplant after malignant disease may not be appropriate. New data on malignancies in end-stage renal disease and recent diagnostic and therapeutic options should lead us to reconsider our current practice.

Background and Aims Studies examining kidney failure patients with COVID-19 reported higher mortality in hemodialysis patients than in kidney transplant recipients. However, hemodialysis patients are often older and have more comorbidities. This study investigated the association of type of kidney replacement therapy with COVID-19 severity adjusting for differences in characteristics. Method Data were retrieved from the European Renal Association COVID-19 Database (ERACODA), which includes kidney replacement therapy patients diagnosed with COVID-19 from all over Europe. We included all kidney transplant recipients and hemodialysis patients who presented between February 1st and December 1st 2020 and had complete information reason for COVID-19 screening and vital status at day 28. The diagnosis of COVID-19 was made based on a PCR of a nasal or pharyngeal swab specimens and/or COVID-19 compatible findings on a lung CT scan. The association of kidney transplantation or hemodialysis with 28-day mortality was examined using Cox proportional-hazards regression models adjusted for age, sex, frailty and comorbidities. Additionally, this association was investigated in the subsets of patients that were screened because of symptoms or have had routine screening. Results A total of 1,670 patients (496 functional kidney transplant recipients and 1,174 hemodialysis patients) were examined. 16.9% of kidney transplant recipients and 23.9% of hemodialysis patients died within 28 days of presentation. In an unadjusted model, the risk of 28-day mortality was 33% lower in kidney transplant recipients compared with hemodialysis patients (hazard ratio (HR): 0.67, 95% CI: 0.52, 0.85). However, in an age, sex and frailty adjusted model, the risk of 28-day mortality was 29% higher in kidney transplant recipients (HR=1.29, 95% CI: 1.00, 1.68), whereas in a fully adjusted model the risk was even 43% higher (HR=1.43, 95% CI: 1.06, 1.93). This association in patients who were screened because of symptoms (n=1,145) was similar (fully adjusted model HR=1.46, 95% CI: 1.05, 2.04). Results were similar when other endpoints were studied (e.g. risk for hospitalization, ICU admission or mortality beyond 28 days) as well as across subgroups. Only age was found to interact significantly, suggesting that the increased mortality risk associated with kidney transplantation was especially present in elderly subjects. Conclusion In this study, kidney transplant recipients had a greater risk of a more severe course of COVID-19 compared with hemodialysis patients when adjusted for age, sex and comorbidities.

SARS-CoV-2 led to considerable morbidity/mortality worldwide and tremendously impacted on daily life. Strict lockdown measures were implemented early to contain the viral outbreak in Austria. Massive changes in organizational structures of healthcare facilities followed with unclear implications on the care of non-COVID-19-affected patients. We studied the nationwide impact of COVID-19 on kidney transplantation in Austria during the first six months of 2020. Concurrent with general lockdown measures, all kidney transplant activity was suspended from 13 March to 9 April. Nevertheless, between January and June, total transplant (p = 0.48) and procured donor organ numbers (p = 0.6) did not differ significantly from earlier years. Ten (0.18%) of 5512 prevalent Austrian kidney transplant recipients were diagnosed with SARS-CoV-2. The case fatality rate (one death, 10%) in renal transplant patients was less than in other countries but higher than in Austria&rsquo, s general population (2.4%). We conclude that early and strict general lockdown measures imposed by the government allowed an early, however cautious, re-opening of Austrian transplant programs and played a crucial role for the favorable outcomes of SARS-CoV-2 in Austrian kidney transplant patients. Even though it may be uncertain whether similar results may be obtainable in other countries, the findings may support early intervention strategies during similar episodes in the future.

Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3–30.2%] in kidney transplant and 25.0% (95% CI 20.2–30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59–1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

Purpose of review With the aging population of kidney transplant candidates, a history of malignancy is an increasingly prevalent finding. Tumors can constitute a contraindication for transplantation or can lead to a delay of acceptance to the waiting-list. Current waiting time guidelines mainly refer to early data collected nearly 30 years ago, when the knowledge on tumors was, by current standards, still limited. Recent findings Today, cancers can usually be divided into many different biological subtypes, according to histological and molecular subclassification and the availability of genetic testing. A more precise stratification and targeted antitumor therapies have led to better therapy outcomes or even cures from certain malignancies and to a better appreciation of tumor risks for the patient. Summary Even though transplant patients do have an increased risk for malignancies, it is often overlooked that patients, while on dialysis, are equally prone to develop a tumor. Competing risks (e.g. cardiovascular, mortality risks) through prolonged time on dialysis have to be equally considered, when the decision for acceptance of a patient to the waiting-list is made. Current waiting time suggestions should be critically reconsidered for every patient after a thorough discussion with an oncologist, including new diagnostic and therapeutic strategies, as well as novel risk stratifications.

Elevated blood pressure remains a major cause of cardiovascular disease, disability, and premature death in Austria, with suboptimal rates of detection, treatment and control also in recent years. Management of hypertension is a common challenge for physicians with different spezializations. In an attempt to standardize diagnostic and therapeutic strategies and, ultimately, to increase the rate of patients with controlled blood pressure and to decrease the burden of cardiovascular disease, 13 Austrian medical societies reviewed the evidence regarding prevention, detection, workup, treatment and consequences of high blood pressure in general and in various clinical scenarios. The result is presented as the first national consensus on blood pressure. The authors and societies involved are convinced that a joint national effort is needed to decrease hypertension-related morbidity and mortality in our country.

BACKGROUND Anticoagulation is a cornerstone in haemodialysis (HD) therapy to avoid clotting of blood when it comes into contact with the dialysis membrane. Although heparins are usually administered as anticoagulants, they are not always sufficient to maintain adequate HD. We investigated the additional effect of acetylsalicylic acid compared with standard anticoagulation on maintaining adequate flow properties during HD in vitro. METHODS We collected blood from 42 healthy volunteers, between 18 and 60 years of age, into bags filled with 1, 1.5 or 2 mg enoxaparin, with (treatment group) or without (control group) 100 mg of aspirin. Blood was evaluated before, during and at the end of each experiment to determine coagulation parameters, whole blood aggregation and thromboelastogram measurements. Transmembrane pressure was recorded as indirect estimate of dialysis patency. The primary endpoint was time to filter clotting. RESULTS Addition of acetylsalicylic acid significantly prolonged the time to circuit clotting from 120 (105-150) min to >180 min (120-180) min (P = 0.047) and allowed lowering the enoxaparin concentration from 2 mg per circuit to 1 mg without an increase in clotting. Furthermore, it reduced the transmembrane pressure from 46 to 4 mmHg (P

Hypertension is one of the most important comorbidities of diabetes, contributing significantly to death and leads to macrovascular and microvascular complications. When assessing the medical priorities for patients with diabetes, treating hypertension should be a primary consideration. In the present review practical approaches to hypertension in diabetes, including individualized targets for preventing specific complications are discussed according to current studies and guidelines. According to recent studies, blood pressure values of about 130/80 mm Hg are associated with the best outcome. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are the most effective drugs for treating hypertension in diabetes. Calcium antagonists or diuretics are acceptable as second-line agents. Once the target is achieved, antihypertensive drugs should be continued. Newer antidiabetic medications such as SGLT-2-inhibitors or GLP1-receptor agonists have also antihypertensive effects.

Summary In 2010, eight Austrian medical societies proposed a joint position statement on the management of metabolic lipid disorders for the prevention of vascular complications. An updated and extended version of these recommendations according to the current literature is presented, referring to the primary and secondary prevention of vascular complications in adults, taking into consideration the guidelines of other societies. The “Austrian Lipid Consensus – 2016 update” provides guidance for individualized risk stratification and respective therapeutic targets, and discusses the evidence for reducing vascular endpoints with available lipid-lowering therapies. Furthermore, specific management in key patient groups is outlined, including subjects presenting with coronary, cerebrovascular, and/or peripheral atherosclerosis; diabetes mellitus and/or metabolic syndrome; nephropathy; and familial hypercholesterolemia.

Blood pressure lowering is one of the most important interventions for reducing the vascular complications and mortality in patients with diabetes mellitus. Recent studies indicate that the optimal blood pressure level might be in the range between 130-140 mmHg systolic and 80‒90 mmHg diastolic. Lower blood pressure levels (e.g. 120/80 mmHg) can further reduce the risk for stroke and diabetic nephropathy, but are associated with increased cardiovascular mortality. In particular, very low blood pressure levels (

BackgroundWe conducted a systematic review and meta-analysis to compare benefits and harms of different antihypertensive drug classes in kidney transplant recipients, as post-transplant hypertension (HTN) associates with increased cardiovascular (CV) morbidity and mortality.MethodsThe Ovid-MEDLINE, PubMed and CENTRAL databases were searched for randomized controlled trials (RCTs) comparing all main antihypertensive agents versus placebo/no treatment, routine treatment.ResultsThe search identified 71 RCTs. Calcium channel blockers (CCBs) (26 trials) reduced the risk for graft loss {risk ratio [RR] 0.58 [95% confidence interval (CI) 0.38–0.89]}, increased glomerular filtration rate (GFR) [mean difference (MD) 3.08 mL/min (95% CI 0.38–5.78)] and reduced blood pressure (BP). Angiotensin-converting enzyme inhibitors (ACEIs) (13 trials) reduced the risk for graft loss [RR 0.62 (95% CI 0.40–0.96)] but decreased renal function and increased the risk for hyperkalaemia. Angiotensin receptor blockers (ARBs) (10 trials) did not modify the risk of death, graft loss and non-fatal CV events and increased the risk for hyperkalaemia. When pooling ACEI and ARB data, the risk for graft failure was lower in renin–angiotensin system (RAS) blockade as compared with control treatments. In direct comparison with ACEIs or ARBs (11 trials), CCBs increased GFR [MD 11.07 mL/min (95% CI 6.04–16.09)] and reduced potassium levels but were not more effective in reducing BP. There are few available data on mortality, graft loss and rejection. Very few studies performed comparisons with other active drugs.ConclusionsCCBs could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss. No definite patient or graft survival benefits were associated with RAS inhibitor use over conventional treatment.

BackgroundExisting guidelines on the evaluation and preparation of recipients for kidney transplantation target the entire spectrum of patients with end-stage renal disease. Within the ERA-EDTA Developing Education Science and Care for Renal Transplantation in European States (DESCARTES) Working Group, it was proposed that in a subset of relatively young patients (MethodsAiming for agreement between transplant centres across Europe, we surveyed the opinion of 80 transplant professionals from 11 European states on the composition of a minimal work-up.ResultsWe show that there is a wide agreement among European experts that the work-up for kidney transplantation of the low-risk candidate, as opposed to the standard risk candidate, could include a limited number of investigations. However, there is some disagreement regarding the small number of diagnostic procedures, which is related to geographical location within Europe and the professional background of respondents.ConclusionsBased on the results of the survey, published guidelines and expert meetings by the DESCARTES Working Group, we have formulated a proposal for the work-up of low-risk kidney transplant candidates.

Dialysis patients, receiving erythropoiesis stimulating agents, typically show signs of hemoglobin variability as a consequence of their dosing patterns, bleeding, infection, etc., which is commonly managed adjusting the dose regimen of the erythropoiesis stimulating agent. However, information on dosing strategies used in daily clinical practice and their outcomes in relation to hemoglobin variability is limited. To investigate clinical practice in Austria in relation with the management of hemoglobin variability, defined as a decrease of ³ 1 g/dL within 4 weeks from ³ 11 g/dL to £ 11 g/dL during maintenance therapy with darbepoetin alfa. The nature and incidence of clinical events related to the hemoglobin drop were also assessed. The MAINTAIN non-interventional study was conducted in hemodialysis patients, receiving darbepoetin alfa in accordance to the label approved in the European Union at that time. Patient data were documented retrospectively for the 3 months prior to the hemoglobin drop. Data for the 6 months post hemoglobin drop were collected retrospectively or prospectively, depending on the time of patient inclusion respective to the Hb drop. A hundred thirty six of 154 patients fulfilled all inclusion/exclusion criteria and had prospective documentation of 6 months. The main causes for the hemoglobin drop included surgical and medical procedures (36.1 %), and infections or infestations (24.4 %). The median treatment period was 273 days. The mean hemoglobin drop was − 1.74 g/dL (95 % confidence interval (CI): − 1.60 to − 1.87). Consequently, 81 % of the patients had their dose of darbepoetin alfa increased within a median Kaplan–Meier time to dose increase of 12.5 days (95 % CI: 6–22). The geometric mean weekly darbepoetin alfa dose increased by a factor of 1.1 from 29.1 mg (95 % CI: 24.6–34.4) in the 3 months before hemoglobin drop to 32.4 (95 % CI: 27.2–38.6) in months 4–6 post hemoglobin drop. Three patients had red blood cell transfusions before hemoglobin drop and nine patients after hemoglobin drop. The mean hemoglobin increase was 0.43 g/dL (95 % CI: 0.24–0.62) from immediately prior to 2 weeks after dose increase. The median Kaplan–Meier time to achieve a hemoglobin ³ 11 g/dL after hemoglobin drop was 36 days (95 % CI: 32–45). Frequent darbepoetin alfa dose adjustments were necessary to sustain maintenance levels. No drug-related adverse events were reported. This observational study describes physicians’ reactions to a drop in hemoglobin in clinical practice. Using darbepoetin alfa, the drop was generally compensated without leading to overcorrection.

Die Blutdrucksenkung ist einer der wichtigsten Masnahmen um die vaskularen Komplikationen und die Mortalitat bei Patienten mit Diabetes mellitus zu senken. Rezente Studien zeigen, dass die optimalen Blutdruckzielwerte zwischen 130–135 mmHg systolisch und 80 mmHg diastolisch liegen durften. Niedrigere Blutdruckzielwerte (z. B. 120/80 mmHg) konnen zwar das Risiko fur Schlaganfall und diabetische Nephroopathie weiter senken, sind aber mit einer erhohten Kardiovaskularen Mortalitat assoziiert. Sehr niedrige Blutdruckwerte (< 120 mmHg) sollten insbesondere bei Patienten mit koronarer Herzerkrankung oder mit peripherer arterieller Verschlusskrankheit unbedingt vermieden werden. Der Grosteil der Patienten mit Diabetes und Hypertonie benotigt eine antihypertensive Kombinationstherapie, wobei ACE-Inhibitoren oder Angiotensin-II Receptor Blocker in der first-line Therapie eingesetzt werden sollen.

Renal denervation (RDN) is a new procedure for treatment-resistant hypertensive patients. In order to monitor all procedures undergone in Austria, the Austrian Society of Hypertension established the investigator-initiated Austrian Transcatheter Renal Denervation (TREND) Registry. From April 2011 to September 2014, 407 procedures in 14 Austrian centres were recorded. At baseline, office and mean 24-h ambulatory blood pressure (ABP) were 171/94 and 151/89 mmHg, respectively, and patients were taking a median of 4 antihypertensive medications. Mean 24-h ABP changes after 2-6 weeks, 3, 6 and 12 months were -11/-6, -8/-4, -8/-5 and -10/-6 mmHg (p

Blood pressure lowering is one of the most important interventions for reducing the vascular complications and mortality in patients with diabetes mellitus. Recent studies indicate that the optimal blood pressure level might be in the range between 130-140 mmHg systolic and 80‒90 mmHg diastolic. Lower blood pressure levels (e.g. 120/80 mmHg) can further reduce the risk for stroke and diabetic nephropathy, but are associated with increased cardiovascular mortality. In particular, very low blood pressure levels ( 120 mmHg) should be avoided in patients with coronary heart disease or peripheral arterial disease. Most patients with diabetes mellitus need antihypertensive combination therapies, whereby ACE-inhibitors or Angiotensin-II receptor antagonists should be first line drugs.

DAA-based regimens for chronic hepatitis C infection encourage treatment of "difficult-to-treat" cohorts. This study investigated efficacy and safety of DAA-based regimens in HCV patients on dialysis or postkidney or liver/kidney transplantation. Twenty-five patients treated with DAA combinations were evaluated: 10 were on dialysis (eight: hemodialysis, two: peritoneal dialysis), eight were kidney transplant recipients, and seven were liver/kidney transplant recipients. Except for one patient treated with daclatasvir ([DCV]/60 mg/QD)/simeprevir ([SMV]/150 mg/QD), the others received sofosbuvir-based regimens ([SOF];400 mg/QD) combined with SMV:eight, DCV:13 or either ledipasvir ([LDV]90 mg/QD), ribavirin ([RBV];weight based) or pegylated interferon/RBV. HCV-RNA was determined by Abbott RealTime (LLOQ]:12 IU/ml) or Roche AmpliPrep/COBAS TaqMan assay (LLOQ:15 IU/ml); treatment response evaluated every 4 weeks, at the end of treatment, and 4 and 12 weeks thereafter. Twenty-four (96%) patients achieved SVR 12/24 (ITT-analysis). Mean treatment duration was 15.1 ± 5.1 weeks (±SD), and two patients terminated prematurely - both reached SVR12. Six patients were hospitalized due to complications of underlying disease. One patient achieved SVR24 but was re-infected (week 27). Kidney function remained stable; serum creatinine increased in only one patient - SOF was reduced to 400 mg/48 h. Treatment with DAA combinations in renally impaired HCV patients is highly effective and well tolerated. These findings call for further controlled trials and data from real-life cohorts.

High blood pressure is a major modifiable risk factor for all clinical manifestations of coronary artery disease (CAD). In people without known cardiovascular disease, the lowest systolic (down to 90-114 mmHg) and the lowest diastolic (down to 60-74 mmHg) pressures are associated with the lowest risk for developing CAD. Although diastolic blood pressure is the strongest predictor of CAD in younger and middle-aged people, this relationship becomes inverted and pulse pressure shows the strongest direct relationship with CAD in people above 60 years of age.Pathophysiological mechanisms of blood pressure as a risk factor for CAD are complex and include the influence of blood pressure as a physical force on the development of the atherosclerotic plaque, and the relationship between pulsatile hemodynamics/arterial stiffness and coronary perfusion. Treatment of arterial hypertension has been proven to prevent coronary events in patients without clinical CAD. In patients with established CAD, the effect of blood pressure lowering per se is beneficial, probably more than specific drugs or drug classes. The important exceptions are beta blockers (BBs), which are superior to all other drug classes for use after a recent myocardial infarction. Blood pressure targets in patients with established CAD have created controversy in the light of the so-called J-curve phenomenon, which describes an increase in coronary events at lower diastolic blood pressures. One explanation for this observation is that perfusion of the left ventricle occurs predominantly during diastole, and that coronary autoregulation may be exhausted with low diastolic blood pressure in the setting of left ventricular hypertrophy and atherosclerotic narrowing of the epicardial coronaries. The worst situation is a high systolic blood pressure in the presence of a low diastolic blood pressure, both a hallmark of increased aortic stiffness. However, the lowering of systolic blood pressure is clearly beneficial in this setting, even at the price of further lowering diastolic pressure. Primary blood pressure goal in patients with established CAD is below 140/90 mmHg. Recent studies suggest that a lower systolic blood pressure may be appropriate, whereas caution is advised with diastolic blood pressure below 60 mmHg.

Increased activity of the sympathetic nervous system plays a major role in the pathophysiology of primary arterial hypertension. Interventional renal sympathetic denervation (RSD) is a novel percutaneous treatment, decreasing sympathetic activity and consecutively blood pressure by ablating sympathetic nervous fibers located in the adventitia of the renal arteries. The procedure has been tested in several clinical trials in patients with resistant hypertension (defined as systolic office blood pressure > 160 mmHg—in diabetic patients > 150 mmHg—treated with ³ 3 antihypertensive drugs) and caused a meaningful blood pressure reduction, lasting for at least 3 years. So far, no major adverse events have been identified; however, data on the long-term consequences are lacking. The present position paper of the Austrian Society of Hypertension is aiming to assist in choosing possible indications for RSD in clinical routine, based on the available evidence in 2012.

Anemia is a highly prevalent disorder in recipients of renal allografts. Despite its frequent occurrence, there is still uncertainty with regard to treatment targets and treatment options. This includes questions on appropriate iron management, the choice and dosage of erythropoietin stimulating agents, criteria for the timing of treatment initiation and the targeted hemoglobin values. The review summarizes available data on recent therapeutic strategies for post transplant anemia, as well as for post transplant erythrocytosis, another hematological disorder, that has decreased in recent years.

To evaluate the prevalence of nephrogenic systemic fibrosis (NSF) in a patient population being at highest risk for developing this disease and to evaluate possible risk factors.The radiological records of 552 patients with ESRD being on hemodialysis (HD) or peritoneal dialysis (PD) were retrospectively reviewed to identify whether the patients underwent MR-examinations with or without intravenous administration of GBCA. In case of exposure to GBCA, the number of contrast injections, the benchmark and the cumulative doses of GBCA, and possible cofactors regarding pathogenesis of NSF were recorded. Diagnosis of NSF was confirmed either by deep skin biopsy or by review of medical and histopathological records. Data of NSF patients were compared with data of dialysis patients who did not develop NSF after MR-examinations.146 dialysis patients underwent MRI without i.v.-administration of GBCA. No case of NSF was observed in this patient population. 195/552 patients proved to have a total number of 325 well-documented exposures to GBCA. Seven different types of GBCA were used during these MR-examinations. NSF prevalence rate was 1.6%. One patient died of NSF. Three different types of GBCA were involved in 6 NSF cases. 4/6 proved to be confounded cases. The cumulative dose of GBCA, history of thrombosis, recent surgery, and the combination of HD and PD proved to be significant cofactors for the development of NSF (p.05). No significant difference regarding residual renal clearance (p=.898) and residual urine volume (p=.083) was found between NSF and non-NSF patients.The prevalence of NSF proved to be much lower in this high risk patient group being exposed to GBCA compared to the literature. NSF was not observed in ESRD patients undergoing MRI without administration of GBCA. Our data support a positive association between cumulative dose of GBCA and development of NSF. No positive association was found between residual renal clearance and residual urine volume and NSF.

Gerhard Giebisch vorzustellen und die wesentlichen Errungenschaften seines Lebens anlasslich der Verlei­ hung der Ehrenmitgliedschaft der Osterreichischen Gesellschaft fur Innere Medizin zusammenzufassen, ist eine besonders ehrenvolle Aufgabe, der ich aus mehreren Grunden mit groser Freude nachkomme. Als Internist und klinisch tatiger Nephrologe bin ich bei­ nahe taglich mit „seinem wissenschaftlichen Leben rund um Elektrolyte“ und den daraus resultierenden Ergebnissen konfrontiert. Gleichzeitig verbinden mei­ ne Familie und mich viele Jahre der Freundschaft mit Gerhard und wie so viele andere durfte ich als junger, wissenschaftlich interessierter Arzt Gerhard als gros­ artigen Mentor kennen lernen, wofur ich auserordent­ lich dankbar bin. Gerhard Giebisch wurde 1927 in Wien geboren. Nach der Matura entschied er sich fur das Medizinstu­ dium und promovierte an der Universitat Wien. Seine medizinische Laufbahn begann er 1951 an der Univer­ sitat Wien am Institut fur Pharmakologie (Prof. Brucke). Seinen ersten Kontakt mit den Vereinigten Staaten von Amerika hatte Gerhard, als er 1952 ein Internship im Milwaukee Hospital in Milwaukee, Wisconsin begann. Im Anschluss daran wechselte er als Fellow an das De­ partment of Physiology an der Cornell University in New York. Von 1953–1954 hatte er die Moglichkeit, mit Dr. Robert Pitts, einem der damals fuhrenden Nieren­ physiologen zusammenzuarbeiten. Die Zusammen­ arbeit mit Dr. Pitts sollten die pragenden Jahre fur Ger­ hard werden. Als Instructor in Physiology entschloss er sich, seinen Aufenthalt in New York um ein Jahr zu ver­ langern. Ab 1956 wahlte Gerhard noch einmal Wien als Ort seiner wissenschaftlichen Tatigkeit und kehrte als Uni­ versitatsassistent in seine Heimatstadt zuruck. Doch bereits 1957 nahm er das Angebot, als Assistant Profes­ sor of Physiology am Cornell University Medical College weiterzuarbeiten, an. 1960 wurde er an der Cornell Uni­ versity zum Associate Professor, 1965 zum Full Profes­ sor ernannt. Die Personlichkeit Gerhard Giebisch’s war uber alle Grenzen hinweg bekannt und war ausschlaggebend da­ fur, dass er 1968 von der Yale University den Lehrstuhl fur Physiologie ubertragen bekam. Es gelang Gerhard, aus dem Department eine weltweit fuhrende Institution fur Nierenphysiologie zu machen, die in den kommen­ den Jahrzehnten fur uber 75 Forscher, die aus der gan­ zen Welt als Fellows nach New Haven kamen, intellek­ tueller Mittelpunkt und wissenschaftliche Heimstatte werden sollte. Eine der grosten Ehren der Yale Universi­ ty wurde Gerhard mit dem Titel Sterling Professor of Laudatio auf Prof. Dr. Gerhard Giebisch anlasslich der Verleihung der Ehrenmitgliedschaft der OGIM

There exists no systematic evaluation of liver function in renal allograft recipients undergoing C2-monitoring with Neoral [cyclosporine A (CsA)-microemulsion]. In the present cohort analysis, we compared the hepatic profiles of C2-monitored (n = 80), C0-monitored (n = 81), and non-CsA-treated renal allograft recipients (n = 29), transplanted between 1/1999 and 2/2004 in our institution. While the C2-targets were set in accordance with (n = 72) or below (n = 8) the consensus on Neoral (1500 +/- 200 ng/ml), non-CsA-patients received FK506 (n = 29), partially in combination with rapamycin (n = 13) as primary immunosuppression. Analysis of maximum hepatic laboratory parameters and also repeated measures by anova within 30 days post-transplant revealed highly significant elevations of direct, indirect and total bilirubin, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase (P0.001) in the C2-group, in comparison with the C0- and the non-CsA-group. Bilirubin-levels were by far the most affected of all hepatic parameters, and correlated with C2-levels (r2 = 0.62). Seventeen CsA-patients had excessive bilirubin-elevations (4 mg/dl) and were therefore considered to be 'CsA-sensitive' [14 C2-patients (17% of all C2-patients), 3 C0-patients (4% of all C0-patients)]. Bilirubin- and the other parameter elevations in these patients were reversible upon withdrawal or lowering of CsA. Most 'CsA-sensitive' patients (n = 12, 70%) displayed pre-transplant hepatic impairment, indicating a pre-existing liver instability. Collectively, our data emphasize the need for increased awareness toward individual predispositions for CsA-sensitivity.

Background. We evaluated cerebrovascular events (CVE) after kidney transplantation (KTx) and sought to identify pre-transplant predictors of transient ischaemic attacks (TIA) and strokes post-transplantation. Methods. A total of 1617 consecutive kidney and 16 kidney–pancreas recipients transplanted between 1995 and 2005wereanalysedinthisretrospectivesingle-centrestudy. Risk factors for CVE, e.g. recipient and donor age and gender, diagnosis of chronic kidney disease, end-stage renal disease (ESRD) duration, histories of hypertension, hyperlipidaemia, smoking, atrial fibrillation (AF), diabetes mellitus (DM), ischaemic heart, peripheral- and cerebrovascular disease, as well as pre-transplant myocardial infarction or CVE (i.e. TIA/strokes) were analysed. Furthermore, the predictive value of pre-transplant screening tests, i.e. echocardiography (n = 1184) and carotid ultrasound (n = 922), was investigated. Results. During a median follow-up of 4 years, 64 CVE (54 strokes and 10 TIA) were observed. Nineteen (5.1%) of 373 deceased patients died from fatal stroke. Recipient age, history of AF and hyperlipidaemia (P = 0.00, respectively), reduced left ventricular function (LVF) (P = 0.01) andthedegreeofstenosisbycarotidultrasound(P =0.002), duration of ESRD (P = 0.03) and interstitial nephritis as renal disease cause (P = 0.04) evolved as predictors of TIA/stroke post-transplant in univariate analysis. In multivariable analysis, AF (P = 0.001) and DM (P = 0.037) were significant predictors for post-transplant CVE. Conclusions. AF and DM are independent predictors of CVE after KTx. Beyond their general ability to detect severely comorbid patients, pre-transplant screening tests (e.g. carotid ultrasound or echocardiography) were not able to identify renal transplant candidates at risk for CVE after transplantation.

Dendritic cells (DC) are the most potent antigen-presenting cells (APC) and are pivotal for initiating allograft immunity. Recently, particular DC subsets have been implicated also in allogeneic T cell hyporesponsiveness. Alemtuzumab (anti-CD52, Campath-1H) is a novel T cell depleting antibody that is currently under investigation for the use in allogeneic organ transplantation. While recent studies demonstrated a conspicuous effect of alemtuzumab on peripheral DC in clinical graft-versus-host disease, its efficiency in patients receiving allogeneic organ transplants is still undefined. In the present study we assessed the peripheral DC repertoire in kidney transplant recipients after either alemtuzumab induction therapy followed by FK506 monotherapy or after conventional immunosuppression (FK506, mycophenolate mofetil and steroids) without any induction agent. Induction with alemtuzumab caused a strong and sustained reduction of the total number of peripheral DC and a significant shift from myeloid to plasmacytoid DC subsets (mDC/pDC ratio) as early as 1 month post-transplantation. These data show that alemtuzumab induction targets the peripheral DC repertoire, which might add another mechanism allowing immunosuppressive drug minimization. Further studies are warranted to further elucidate the functional significance of these finding in the setting of allogeneic organ transplantation.

A stable supramolecular cluster in T cells at the contact site of APCs, the immunological synapse (IS), is essential for full T cell activation. Failure of IS maturation, as determined by defective relocalization of the TCR/CD3 complex at the T cell/APC contact site, is linked with T cell hyporesponsiveness. The effects of clinically used immunosuppressants on these critical events, however, are undefined. Here, we show that treatment of T cells with cyclosporin A, FK506, and dexamethasone, which are known to inhibit calcineurin and NF-κB, respectively, but not rapamycin, the inhibitor of mammalian target of rapamycin, selectively prevented TCR/CD3 relocalization into the IS, while relocalization of adhesion and cytoskeletal proteins as well as T cell/APC conjugate formation remained unaltered. The involvement of calcineurin and NF-κB in IS maturation was confirmed by using specific inhibitors of these molecules (FR901725, gossypol, SN50). FK778, as an inhibitor of DNA replication and also TCR/CD3-activated tyrosine kinases, globally abrogated cytoskeletal, adhesion, and signaling molecule relocalization, thereby preventing formation of an IS at an earlier, immature stage along with impaired, antigen-specific T cell/APC conjugate formation. Collectively, blocking IS formation at distinct stages may mediate effects on T cell activation of currently used immunosuppressants, apart from their capacity to block gene transcription, cytokine signaling, and DNA replication. Furthermore, these data imply novel functions of calcineurin and NF-κB for successful IS maturation.

Background. Lower concentrations of endothelial progenitor cells (EPCs) maybe associated with increased cardiovascular risk. EPC counts and their correlates have not yet been studied in kidney transplant recipients (KTR). Methods. We cross-sectionally studied EPC counts in 105 middle-aged KTR (mean estimated glomerular filtration rate 45.2 ml/min/1.73m 2 ; range: 5.4 to 117.5). Using univariate and multivariate linear regression assuming a gamma distribution of the outcome, we examined the associations between counts of cultured EPCs and traditional cardiovascular disease risk factors (hypertension, diabetes, hyperlipidemia, smoking), kidney function, and immunosuppressive agents, amongst others. Results. The median count of cultured EPCs was 34 cells per high-power field (interquartile range: 19 to 64), comparable to healthy individuals. From multivariate analyses, we found independent inverse associations between counts of cultured EPCs and body mass index, mean arterial pressure, and history of cardiovascular disease. Statin use was associated with greater EPC counts, whereas patients receiving azathioprine or angiotensin II receptor treatment had lower EPC counts (all P

Background. The heme oxygenase (HO) isoenzyme HO-1 has recently been suggested to protect transplants from ischemia/reperfusion and immunologic injury. Inducibility of this enzyme is modulated by a (GT)n dinucleotide length polymorphism in the HO-1 gene promoter. Short (class S) repeats are associated with greater up-regulation of HO-1 than are long repeats. In the present study we investigated the impact of the promoter polymorphism of kidney allograft donors on clinical outcomes after transplantation. Methods. We enrolled 101 recipients of cadaveric donor kidney allografts (who underwent transplantation between June 1998 and September 1999) in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from cryopreserved donor splenocytes. Results. Fifty patients (49.5%) had received a kidney from a donor with at least one class S allele. Recipients of allografts from a class S allele carrier had significantly lower 1-year serum creatinine levels (median 1.46 mg/dL, interquartile range 1.17-1.68 mg/dL) compared with recipients of a non-class S allele donor kidney (median 1.61 mg/dL, interquartile range 1.38-2.22 mg/dL, P=0.01). After adjustment for cold ischemia time, retransplantation, donor age, delayed graft function, and HLA mismatch, recipients of a class S allele transplant had serum creatinine levels 0.81 times (95% confidence interval: 0.70-0.96, P=0.01) those of recipients of a non-class S allele transplant. The two patient groups did not differ significantly with respect to the incidence of delayed graft function, allograft rejection, or immunologic graft loss. Conclusion. Our data suggest an influence of the HO-1 gene promoter polymorphism on kidney allograft function and thus support previous studies indicating a protective effect of HO-1 induction in organ transplantation.

Endothelial deposition of the complement split product C4d is an established marker of antibody-mediated acute renal allograft rejection. A contribution of alloantibody-dependent immune reactions to chronic rejection is under discussion. In this study, the association of immunohistochemically detected endothelial C4d deposition in peritubular capillaries (PTC) with morphologic features of chronic renal allograft injury was investigated in a large study cohort. C4d deposits in PTC were detected in 73 (34%) of 213 late allograft biopsies performed in 213 patients more than 12 mo after transplantation (median, 4.9 yr) because of chronic allograft dysfunction. Endothelial C4d deposition was found to be associated with chronic transplant glomerulopathy (CG) (P < 0.0001), with basement membrane multilayering in PTC (P = 0.01), and with an accumulation of mononuclear inflammatory cells in PTC (P < 0,001). Furthermore, C4d deposits in PTC (in biopsies with normal glomerular morphology) were associated with development of CG in follow-up biopsies. Other morphologic features of chronic allograft nephropathy (with exception of tubular atrophy) were not associated with C4d deposits in PTC. Analyses of previous and follow-up biopsies revealed that C4d deposits may occur de novo and may also disappear at any time after transplantation. In conclusion, the data suggest that complement activation in renal microvasculature, indicating humoral alloreactivity, contributes to chronic rejection characterized by chronic transplant glomerulopathy and basement membrane multilayering in PTC.

Although the detrimental effect of preformed donor-specific antibodies (DSA) became apparent in the 1960s, the possible pathogenic role of de novo DSA production against allografts after renal transplantation remained controversial for many years ([1][1]). An interesting initial observation, however

Nephrogenic adenomas are benign, tumor-like lesions within the urothelial mucosa of the urinary tract that are not uncommon in renal-transplant recipients. We investigated the origin of nephrogenic adenomas in renal-transplant recipients.Tissue sections were analyzed by fluorescence in situ hybridization with the use of probes for the X and Y chromosomes, by immunohistochemical methods with the use of antibodies to renal tubular antigens, and by lectin histochemical methods. Forty-six nephrogenic adenomas from 29 patients were analyzed.All nephrogenic adenomas in 14 female recipients of transplants from male donors and 10 male recipients of transplants from female donors showed the same sex-chromosome status as the donor kidney, but not the same sex-chromosome status as the recipient's surrounding bladder tissue. The nephrogenic adenomas from all 6 female recipients of transplants from female donors showed female chromosomes, and those from the 16 male recipients of transplants from male donors showed male chromosomes. The presence of aquaporin 1, PAX2, and lectin-binding capacity for peanut agglutinin, Lotus tetragonolobus agglutinin, and Sophora japonica agglutinin in nephrogenic adenomas indicated an origin from renal tubular cells.Nephrogenic adenomas in renal-transplant recipients are derived from tubular cells of the renal transplants and are not metaplastic proliferations of the recipient's bladder urothelium.

Although in Western Europe and North America the prevalence of chronic hepatitis B virus (HBV) infection has declined in patients awaiting renal transplantation, it remains a relevant clinical problem, mainly in patients with a long history of renal replacement therapy (RRT) who may have been infected many years ago. At the same time, a significant proportion of renal transplant recipients (RTR) is at risk for HBV infection in areas with endemic HBV. HBV infection may increase morbidity and mortality in RTR. The majority of long-term studies reported reduced patient survival compared with hepatitis B surface antigen (HBsAg)-negative RTR. The risk for morbidity and mortality of HBsAg-positive RTR transplantation is probably related to the extent of pretransplant liver disease. A thorough evaluation, including liver biopsy in many patients, is required to assess the individual HBsAg-positive patient's risk-benefit ratio. The influence of immunosuppressive therapy on HBV replication and HBV-associated complications is not well established and for clinical practice individually tailored immunosuppression is recommended in HBsAg-positive RTR. Careful screening for HBV reactivation in HBsAg-positive RTR and a regular clinical follow-up after renal transplantation (RTX) including liver sonography is required for early detection of HBV-associated complications. With the availability of new antiviral drugs, new options for pre- and posttransplant therapy might improve the prognosis of RTR with chronic HBV infection.

Capillary deposition of the complement split product C4d has been discussed as a marker for antibody-mediated kidney allograft rejection. The relationship between C4d staining and posttransplant alloantibody detection remains to be thoroughly investigated, however. In this study, C4d staining in peritubular capillaries (PTC) and the incidence of alloantibody formation, as detected with sensitive techniques, were evaluated among a cohort of transplant recipients who had undergone biopsies and had not been selected for a specific histologic diagnosis. One hundred thirteen biopsies, obtained from 58 cadaveric kidney transplant recipients, were tested. Serum samples obtained at the time of biopsy were evaluated by flow cytometric crossmatch (FCXM) testing and FlowPRA (One Lambda, Inc., Canoga Park, CA) analysis of anti-HLA panel reactivity. Most biopsies with C4d deposits in PTC (C4d(PTC)(+), n = 21 of 24) were associated with positive posttransplant FCXM results (T and/or B cell FCXM) and/or > or =5% FlowPRA (anti-HLA class I and/or II) reactivity. Approximately 50% of the C4d(PTC)(-) biopsies were observed to be associated with donor-specific alloantibodies. Accordingly, high specificity (93%) but low sensitivity (31%) were calculated for capillary C4d staining (with FCXM testing as the standard method). For clinical evaluation, three patient groups were defined, i.e., a group of recipients with positive C4d staining in at least one allograft biopsy (C4d(PTC)(+), n = 16) and two C4d(PTC)(-) groups, which were discriminated on the basis of posttransplant FCXM results as C4d(PTC)(-)/FCXM(+) (n = 22) and C4d(PTC)(-)/FCXM(-) (n = 20) groups. Univariate analyses revealed significant differences between these groups with respect to serum creatinine levels at 12 mo [median, 2.83 mg/dl (interquartile range, 1.93 to 4.2 mg/dl) versus 1.78 mg/dl (1.47 to 2.24 mg/dl) versus 1.59 mg/dl (1.2 to 1.71 mg/dl), P < 0.001]. Of the five immunologic graft losses, four occurred in the C4d(PTC)(+) group and one occurred in the C4d(PTC)(-)/FCXM(+) group. In a multivariate analysis, C4d positivity was observed to have an independent predictive value for inferior 12-mo graft function (P = 0.02), whereas the observed moderate difference between C4d(PTC)(-)/FCXM(+) and C4d(PTC)(-)/FCXM(-) recipients did not achieve significance. In conclusion, these data demonstrate that positive C4d staining, which is an independent predictor of kidney graft dysfunction, represents a reliable specific marker for antibody-dependent graft injury.

While belatacept has shown favorable short- and midterm results in kidney transplant recipients, only projections exist regarding its potential impact on long-term outcome. Therefore, we performed a retrospective case-match analysis of the 14 belatacept patients originally enrolled in the phase II multicenter trial at our center. Fifty six cyclosporine (CyA)-treated patients were matched according to age at transplantation, first/retransplant, and donor type. Ten years after kidney transplantation, kidney function remained superior in belatacept-treated patients compared with the CyA control group. Moreover, none of the belatacept-treated patients had donor-specific antibodies ≥10 years post-transplantation compared with 38.5% of tested CyA-treated subject (0/10 vs. 5/13; P = 0.045). Notably, however, patient and graft survival was virtually identical in both groups (71.4% vs. 71.3%; P = 0.976). In the present single-center study population, patients treated with belatacept demonstrated a patient and graft survival at 10 years post-transplant which was comparable to that of similarly selected CNI-treated patients. Larger studies with sufficient statistical power are necessary to definitively determine long-term graft survival with belatacept.