Metal pollutant pathways in cohesive coastal catchments: Influence of flocculation and biopolymers on partitioning and flux.

The impacts of the partitioning of potentially toxic metals (PTM) within the estuarine environment is highly complex, but is of key significance owing to increases in populations living within such sensitive environments. Although empirical data exist for the partitioning of metals between the dissolved and particulate phases, little is known regarding the impacts of extracellular polymeric substances (EPS) upon the flocculation of particles within such a dynamic system nor the resultant influence on the distribution of metals between the particulate and dissolved phases. This prevents regulators from fully understanding the fate and risks associated with metals in estuaries. This study provides data associated with the simulation of 3 settlings typical of the turbulent mixing found in estuaries and partitioning of copper, cadmium, nickel, arsenic, lead and zinc for 3 salinities (0, 15, 30 PSU) reflecting the full salinity range from freshwater to seawater. Experiments were completed with and without the presence of EPS, using kaolin as the mineral particulate. The results showed significant differences between salinity, PTMs and turbulence for the experiments with and without EPS present. Overall, salinity was the main factor controlling the PTM partitioning to sediment, however the flocculation process did impact on the PTM distribution and with the addition of EPS the impact was more pronounced. The data highlighted the importance of taking account of EPS within any estuarine sediment process modelling, for relying on simple partitioning with corrections for salinity would likely lead to significant bias.

Plasma Biomarkers of AD Emerging as Essential Tools for Drug Development: An EU/US CTAD Task Force Report.

There is an urgent need to develop reliable and sensitive blood-based biomarkers of Alzheimer's disease (AD) that can be used for screening and to increase the efficiency of clinical trials. The European Union-North American Clinical Trials in Alzheimer's Disease Task Force (EU/US CTAD Task Force) discussed the current status of blood-based AD biomarker development at its 2018 annual meeting in Barcelona, Spain. Recent improvements in technologies to assess plasma levels of amyloid beta indicate that a single sample of blood could provide an accurate estimate of brain amyloid positivity. Plasma neurofilament light protein appears to provide a good marker of neurodegeneration, although not specific for AD. Plasma tau shows some promising results but weak or no correlation with CSF tau levels, which may reflect rapid clearance of tau in the bloodstream. Blood samples analyzed using -omics and other approaches are also in development and may provide important insight into disease mechanisms as well as biomarker profiles for disease prediction. To advance these technologies, international multidisciplinary, multi-stakeholder collaboration is essential.

Impact of acute kidney injury on neurological outcome and long-term survival after cardiac arrest - A 10 year observational follow up.

BACKGROUND: Acute kidney injury (AKI) may be associated with short- and long-term patient morbidity and mortality. Therefore, the impact of AKI after cardiac arrest on survival and neurological outcome was evaluated. METHODS: An observational single center study was conducted and consecutively included all out and in hospital cardiac arrest (OHCA/IHCA) patients treated with therapeutic temperature management between 2006 and 2013. Patient morbidity, mortality and neurological outcome according to the widely used Pittsburgh Cerebral Performance Category (CPC) were assessed. A good neurological outcome was defined as a CPC of 1-2 versus a poor neurological outcome with a CPC of 3-5. AKI was defined by using the KDIGO Guidelines 2012. RESULTS: 503 patients were observed in total. 29.4% (n = 148) developed AKI during their intensive care unit (ICU) stay. 70.6% (n = 355) did not experience AKI. The mean age at admission was 62 years, of those 72.8% were male and 77% experienced an out-of-hospital cardiac arrest (OHCA). AKI occurred with 41.2% more often in the group with poor neurological outcome compared to 17.1% in the group with good neurological outcome. The median survival for patients after cardiac arrest with AKI was 0.07 years compared to 6.5 years for patients without AKI. CONCLUSION: Our data suggest that AKI is a major risk factor for a poor neurological outcome and a higher mortality after cardiac arrest. Further important risk factors were age, time to ROSC and high NSE.

EU/US/CTAD Task Force: Lessons Learned from Recent and Current Alzheimer's Prevention Trials.

At a meeting of the EU/US/Clinical Trials in Alzheimer's Disease (CTAD) Task Force in December 2016, an international group of investigators from industry, academia, and regulatory agencies reviewed lessons learned from ongoing and planned prevention trials, which will help guide future clinical trials of AD treatments, particularly in the pre-clinical space. The Task Force discussed challenges that need to be addressed across all aspects of clinical trials, calling for innovation in recruitment and retention, infrastructure development, and the selection of outcome measures. While cognitive change provides a marker of disease progression across the disease continuum, there remains a need to identify the optimal assessment tools that provide clinically meaningful endpoints. Patient- and informant-reported assessments of cognition and function may be useful but present additional challenges. Imaging and other biomarkers are also essential to maximize the efficiency of and the information learned from clinical trials.

[Renal replacement therapy in the elderly]. / Nierenersatztherapie bei Älteren.

Renal function in humans declines with old age. Currently, the normal range for renal function is not differentiated by age but uniformly given, which has evoked criticism. The symptoms of high-grade impairment of renal function are nonspecific. The current data situation does not support early initiation of dialysis: on the contrary, initiation of dialysis should be decided from clinical aspects and not according to the values for the glomerular filtration rate (GFR). Elderly patients should be offered peritoneal dialysis (PD) as well as hemodialysis (HD), which can be performed either at home (PD) or at a dialysis center (HD or PD). Patients and their relatives should be presented with all available information on both therapy options but there are also conservative, palliative therapy options for the very old or for those with a high number of comorbidities. The decision for therapy should be individualized and tailored for each patient. The planning of kidney replacement therapy should be carried out well in advance. A multidisciplinary team should discuss possible barriers to one or the other treatment option and provide assistance for implementation of the individual optimal therapy. In some cases a home-based assisted PD can be a sensible option.

Review article: long-term safety of nucleoside and nucleotide analogues in HBV-monoinfected patients.

BACKGROUND: Nucleos(t)ide analogues (NUCs) for chronic hepatitis B treatment achieve high rates of viral suppression and are generally well tolerated. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the currently preferred first-line agents. The safety of these agents in clinical practice is particularly relevant since long-term treatment is usually required. AIM: To summarise and critically discuss recent real-world evidence on the safety of treatment with ETV or TDF in hepatitis B virus (HBV)-monoinfected patients. METHODS: PubMed and conference proceedings up to 15th June 2015 were searched using the terms ((((Hepatitis_B) OR HBV) AND ((tenofovir) OR entecavir)) AND (((lactic_acidosis) OR bone) OR renal)). RESULTS: In selected populations included in registration studies, both ETV and TDF were well tolerated with no clinically significant renal toxicity or lactic acidosis. Growing 'real-world' clinical experience with these agents includes some reports of ETV-associated lactic acidosis and TDF-associated renal impairment; however, evidence from cohort studies appears to be conflicting. In the case of ETV-related lactic acidosis, a small number of cases have been reported, all in patients with decompensated cirrhosis. The degree of association between TDF treatment and changes in markers of renal function varies between studies: discrepancies may result from the use of different definitions and cut-offs for reporting renal toxicities, and differences in patient populations. CONCLUSIONS: Pre-treatment and on-treatment monitoring of eGFR and phosphorus, with prompt appropriate dose adjustment or treatment switch can minimise the impact of NUC renal toxicity. Standardisation of measures of renal impairment and identification of early molecular markers remain an unmet need.

[Treatment of acute renal failure in Germany: Analysis of current practice]. / Versorgung des akuten Nierenversagens auf deutschen Intensivstationen: Analyse der aktuellen Behandlungspraxis.

BACKGROUND AND OBJECTIVES: There are currently no reliable data on the differential use of renal replacement therapy (RRT) options for critically ill patients with acute renal failure in Germany. PATIENTS AND METHODS: A questionnaire-based survey was delivered to 2265 German intensive care units. The questionnaire contained 19 questions regarding RRT. RESULTS: A total of 423 German intensive care units participated in the survey. The offered modalities of RRT varied significantly: the smaller the facility, the fewer different RRT options were available. Intermittent dialysis procedures were available in only 35% of hospitals with up to 400 beds. In university hospitals, hemodynamically unstable patients were exclusively treated by continuous RRT, whereas in hospitals with up to 400 beds, intermittent RRT was also used. In addition, treatment practice was also dependent on the specialization of the treating physicians: Isolated acute renal failure was treated more often intermittently by nephrologists compared to anesthesiologists (79.7 vs. 43.3%). Nephrologists also used extracorporeal RRT more often in cardiorenal syndrome (54.3 vs. 35.8%), whereas anesthesiologists preferred them in sepsis (37.3 vs. 23.1%). The choice of anticoagulant varied as well: Hospitals with up to 400 beds offered regional citrate anticoagulation in only 50% compared to 90% of university hospitals. CONCLUSIONS: Currently, RRT treatment in acute renal failure on German intensive care units seems to be dependent on the size, local structures, and education of the intensivists rather than patient needs. Our results demonstrate the necessity to establish cross-disciplinary standards for the treatment of acute renal failure in German intensive care units.

Clindamycin-primaquine for pneumocystis jiroveci pneumonia in renal transplant patients.

BACKGROUND: Trimethoprim/sulfamethoxazole (TMP/SMX) is considered first-line therapy for pneumocystis jiroveci pneumonia (PCP) in renal transplant patients. Alternatives have not been formally studied. Clindamycin-primaquine (C-P) is effective in HIV-associated PCP, but data in renal transplant patients are lacking. PATIENTS AND METHODS: Retrospective cohort study of 57 consecutive renal transplant patients who developed PCP and were treated with C-P (n = 23) or TMP/SMX (n = 34). RESULTS: A non-significantly higher failure rate was observed in patients on C-P due to lack of efficacy (30.4 versus 20.6%, p = 0.545). The difference was more pronounced in severe PCP (60 versus 37.5%, p = 0.611) and a significantly lower efficacy of C-P was seen when used as salvage therapy. The two patients who had received C-P after not responding to TMP/SMX failed this regimen, but all seven patients who had failed initial treatment with C-P and had been switched to TMP/SMX were cured (p = 0.028). No treatment-limiting adverse reactions were reported for patients on C-P while six patients (17.6%) on TMP/SMX developed possibly related treatment-limiting toxicity (p = 0.071). However, in only two patients adverse events were definitely related to TMP/SMX (5.9%). CONCLUSIONS: Clindamycin-primaquine appears to be safe and well tolerated for treating PCP in renal transplant patients but is probably less effective than TMP/SMX, the standard regimen. However, our data indicates that C-P represents an acceptable alternative for patients with contraindications or treatment emergent toxicities during TMP/SMX use. Notably, TMP/SMX was also acceptably tolerated in most patients. TMP/SMX remains an effective salvage regimen in case of C-P failure.

[Treatment of acute renal failure in Germany: a structural analysis]. / Versorgung des akuten Nierenversagens in Deutschland--Eine strukturelle Analyse.

INTRODUCTION: There are no reliable data on the structure and practice of the care of critically ill patients with acute renal failure in Germany. METHODS: We carried out a detailed survey by sending a questionnaire to 2265 German Intensive Care Units. The questionnaire contained 19 questions regarding renal replacement therapy. RESULTS: 423 German intensive care units participated in the survey. Most of the ICUs are headed interdisciplinary (47%) or by anesthesiologists (30%), with significant differences depending on the size of the clinic, with primarily interdisciplinary management in smaller clinics. The offered type of renal replacement therapy varies significantly, the smaller the house the fewer methods are available. Thus, intermittent dialysis procedures are offered only in 35% of hospitals with up to 400 beds. The indication for the initiation of acute renal replacement therapy in intensive care is provided predominantly (53%) by an anesthesiologist. A nephrologist is only involved in 22% of all intensive care units. The indication is based primarily on a "clinical criteria", but these are poorly defined. CONCLUSION: Our results demonstrate the need for cross-disciplinary standards for the treatment of acute renal failure in German intensive care units.

Elimination of middle-sized uremic solutes with high-flux and high-cut-off membranes: a randomized in vivo study.

The elimination of substances between 10 and 50 kDa by conventional high-flux membranes is not satisfactory. We investigated in vivo the elimination of middle-sized uremic solutes by conventional polyflux (PF) and modified high-cut-off (HCO) membranes. All 12 patients underwent four treatments, two with the HCO dialyzer and two with the PF dialyzer, each in either a haemodialysis (HD) or haemodiafiltration (HDF) mode. The reduction ratio of urea, creatinine, ß2-microglobulin (ß2M), leptin, soluble TNF-RI, complement factor D, IL-6, sIL-6 receptor, advanced glycation end-products (AGEs) and albumin was determined. In addition, the amount removed was determined in the dialysate for ß2M, complement factor D, AGEs and albumin. Treatment with HCO removed ß2M, sTNF-RI, factor D, and high molecular AGE significantly better than conventional high-flux membranes. The albumin loss was higher when using HCO membranes. HCO membranes are a promising approach to improve removal of uremic toxins not affected by conventional high-flux membranes.

Prophylaxis of recurrent urinary tract infection after renal transplantation by cranberry juice and L-methionine.

BACKGROUND: Recurrent urinary tract infections (UTIs) increase mortality and reduce graft survival after renal transplantation. Strategies to prevent recurrent UTIs include L-methionine, cranberry juice, and antibiotics. Data on the efficacy of cranberry and L-methionine, however, are controversial in the general population; there are few data in renal transplant recipients. METHODS: We performed a retrospective analysis of 82 transplant recipients with recurrent UTIs, who underwent prophylaxis with cranberry juice (2 × 50 mL/d, n = 39, 47.6%), or L-methionine (3 × 500 mg/d, n = 25, 30.5%), or both modalities (n = 18, 21.9%). Thirty patients without prophylaxis served as controls. We analyzed symptoms, pyuria/nitrituria, and incidence of UTI events during 1 year before versus after initiation of prophylaxis. RESULTS: Prophylaxis highly significantly decreased the annual UTI incidence by 58.3% (P < .001) in the study population with no change in the control group (P = .85); in addition, 53.7% of symptomatic patients reported relief of symptoms and pyuria/nitrituria disappeared in 42.4% of the dipstick-positive patients (P < .001 each). Cranberry reduced the annual number of UTI episodes by 63.9% from 3.6 ± 1.4 to 1.3 ± 1.3/year (P < .001) and L-methionine by 48.7% from 3.9 ± 1.8 to 2.0 ± 1.3/year (P < .001). CONCLUSION: Cranberry juice and L-methionine successfully reduced the incidence of UTI after renal transplantation.

5-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-phenyl-2,3,6,7-tetrahydro-1,4-thiazepines as compounds with high affinity at the benzodiazepine binding site on GABA(A) receptors.

A series of thiazepines has been studied as new ligands for the benzodiazepine binding site of the GABAA receptor. Compounds with high affinity and weak selectivity regarding alpha beta3gamma2, alpha2beta3gamma2, alpha3beta3gamma2, and alpha5beta3gamma2 subtypes were found. The pharmacophore is discussed based on experimental and theoretical results. The thiazepine sulfur atom was found to be able to act as hydrogen bond acceptor.

Report of the task force on designing clinical trials in early (predementia) AD.

BACKGROUND: A large number of promising candidate disease-modifying treatments for Alzheimer disease (AD) continue to advance into phase II and phase III testing. However, most completed trials have failed to demonstrate efficacy, and there is growing concern that methodologic difficulties may contribute to these clinical trial failures. The optimal time to intervene with such treatments is probably in the years prior to the onset of dementia, before the neuropathology has progressed to the advanced stage corresponding to clinical dementia. METHOD: An international task force of individuals from academia, industry, nonprofit foundations, and regulatory agencies was convened to discuss optimal trial design in early (predementia) AD. RESULTS: General consensus was reached on key principles involving the scope of the AD diagnosis, the selection of subjects for trials, outcome measures, and analytical methods. CONCLUSION: A consensus has been achieved in support of the testing of candidate treatments in the early (predementia) AD population.

Role of RAS inhibition in the regulation of Cu/Zn-SOD in the cardiac and peripheral arterial beds in humans.

Inhibition of the renin-angiotensin system (RAS) improves hemodynamics and may ameliorate oxidative stress in heart failure (HF). Through activation of nicotinamide adenine dinucleotide phosphate oxidase, angiotensin II induces superoxide, which is primarily cleared by cytosolic copper-zinc superoxide dismutase (Cu/Zn-SOD). We examined the interdependency of hemodynamics and levels of Cu/Zn-SOD and oxidized low-density lipoprotein (oxLDL) in HF patients, using a randomized, double-blinded, crossover design to compare (i) the outcomes of single-agent therapy with either benazepril or valsartan alone vs. the combination thereof and (ii) the outcome of single-agent treatment with benazepril vs. single-agent treatment with valsartan. After each treatment, arterial (ART) and coronary sinus (CS) blood samples were collected. Cu/Zn-SOD and oxLDL levels were higher in CS samples than in ART samples. Furthermore, patients under combined treatment exhibited the highest CS levels of Cu/Zn-SOD, whereas there was no significant difference between the groups on either benazepril or valsartan alone. This finding suggests an augmentation of the cardiac antioxidative potential under more complete RAS inhibition. Cu/Zn-SOD and oxLDL levels correlated with measures of afterload rather than preload, which in turn suggests a beneficial effect of afterload reduction on oxidative stress in HF.

Study design considerations: conducting global clinical trials in early Alzheimer's disease.

An increasing number of Alzheimer's disease (AD) clinical trials are being conducted in countries in which such trials have infrequently, if ever, been conducted. The infrastructure for conducting trials in many of these regions is not well developed, leading to particular challenges in collection of biomarkers, which are becoming increasingly important in trials in early AD. Linguistic and cultural differences make scale translation, adaptation, validation and implementation across countries and regions difficult. In addition, multiple translations and versions of scales and differences in their administration increase variability and thus decrease the chance of detecting a signal. These issues are magnified in trials in early AD, where detecting subtle neuropsychological deficits is even more challenging. Two additional significant factors for global AD research include: 1) Differing regulatory authority requirements resulting in the need for repeat studies to satisfy diverse regulatory requirements in different parts of the world; and 2) reimbursement and access may be limited due to different data requirements for country specific economic evaluations. While standardization of biochemical assays and neuroimaging protocols have recently been undertaken, there remains a pressing need for standardization of clinical measures (including translation, linguistic and cultural validation and administration). In addition, a global consensus on regulatory requirements for approval of drugs for the treatment of early AD and identification of universally accepted variables from a cost-effectiveness or value perspective would have significant impact on advancing drug development in early AD.

Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe.

BACKGROUND: There is some evidence that statins may have a protective and symptomatic benefit in Alzheimer disease (AD). The LEADe study is a randomized controlled trial (RCT) evaluating the efficacy and safety of atorvastatin in patients with mild to moderate AD. METHODS: This was an international, multicenter, double-blind, randomized, parallel-group study. Subjects had mild to moderate probable AD (Mini-Mental State Examination score 13-25), were aged 50-90 years, and were taking donepezil 10 mg daily for > or 3 months prior to screening. Entry low-density lipoprotein cholesterol levels (LDL-C) were > 95 and < 195 mg/dL. Patients were randomized to atorvastatin 80 mg/day or placebo for 72 weeks followed by a double-blind, 8-week atorvastatin withdrawal phase. Coprimary endpoints were changes in cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog]) and global function (Alzheimer's Disease Cooperative Study Clinical Global Impression of Change [ADCS-CGIC]) at 72 weeks. RESULTS: A total of 640 patients were randomized in the study. There were no significant differences in the coprimary endpoints of ADAS-cog or ADCS-CGIC or the secondary endpoints. Atorvastatin was generally well-tolerated. CONCLUSIONS: In this large-scale randomized controlled trial evaluating statin therapy as a treatment for mild to moderate Alzheimer disease, atorvastatin was not associated with significant clinical benefit over 72 weeks. This treatment was generally well-tolerated without unexpected adverse events. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that intensive lipid lowering with atorvastatin 80 mg/day in patients with mild to moderate probable Alzheimer disease (aged 50-90), taking donepezil, with low-density lipoprotein cholesterol levels between 95 and 195 mg/dL over 72 weeks does not benefit cognition (as measured by Alzheimer's Disease Assessment Scale-Cognitive Subscale) (p = 0.26) or global function (as measured by Alzheimer's Disease Cooperative Study Clinical Global Impression of Change) (p = 0.73) compared with placebo.

The primary care physician and Alzheimer's disease: an international position paper.

This paper aims to define the role of the primary care physician (PCP) in the management of Alzheimer's disease (AD) and to propose a model for a work plan. The proposals in this position paper stem from a collaborative work of experts involved in the care of AD patients. It combines evidence from a literature review and expert's opinions who met in Paris, France, on July 2009 during the International Association of Geriatrics and Gerontology (IAGG) World Congress. The PCP's intervention appears essential at many levels: detection of the onset of dementia, diagnostic management, treatment and follow-up. The key role of the PCP in the management of AD, as care providers and care planners, is consolidated by the family caregiver's confidence in their skills. In primary care practice the first step is to identify dementia. The group proposes a "case finding" strategy, in target situations in which dementia should be detected to allow, secondarily, a diagnosis of AD, in certain cases. We propose that the PCP identifies 'typical' cases. In typical cases, among older subjects, the diagnosis of "probable AD" can be done by the PCP and then confirm by the specialist. While under-diagnosis of AD exists, so does under-disclosure. Disclosure to patient and family should be done by both specialist and PCP. Then, the PCP has a central role in management of the disease with the general objectives to detect, prevent and treat, when possible, the complications of the disease (falls, malnutrition, behavioural and psychological symptoms of dementia). The PCP needs to give basic information to the caregiver on respite care and home support services in order to prevent crisis situations such as unplanned institutionalisation and "emergency" hospital admission. Finally, therapeutic research must be integrated in the daily practice of PCP. It is a matter of patients' right to benefit from access to innovation and clinical research whatever his age or diseases, while of course fully respecting the rules and protective measures that are in force.

Impaired insulin sensitivity as an underlying mechanism linking hepatitis C and posttransplant diabetes mellitus in kidney recipients.

Aim of this study was to investigate the mechanism/s associating hepatitis C virus (HCV) infection and posttransplant diabetes mellitus in kidney recipients. Twenty HCV-positive and 22 HCV-negative kidney recipients, 14 HCV-positive nontransplant patients and 24 HCV-negative nontransplant (healthy) subjects were analyzed. A 3-h intravenous glucose tolerance test was performed; peripheral insulin sensitivity was assessed by minimal modeling. Pancreatic insulin secretion, hepatic insulin uptake, pancreatic antibodies and proinflammatory cytokines in serum (tumor necrosis factor-alpha, intereukin-6, high-sensitive C-reactive protein) were also assessed. HCV-positive recipients showed a significantly lower insulin sensitivity as compared to HCV-negative recipients (3.0 +/- 2.1 vs. 4.9 +/- 3.0 min(-1).microU.mL(- 1).10(4), p = 0.02), however, insulin secretion and hepatic insulin uptake were not significantly different. Pancreatic antibodies were negative in all. HCV status was an independent predictor of impaired insulin sensitivity (multivariate analysis, p = 0.008). The decrease of insulin sensitivity due to HCV was comparable for transplant and non-transplant subjects. No significant correlation was found between any of the cytokines and insulin sensitivity. Our results suggest that impaired peripheral insulin sensitivity is associated with HCV infection irrespective of the transplant status, and is the most likely pathogenic mechanism involved in the development of type 2 diabetes mellitus associated with HCV infection.

New-onset diabetes mellitus after renal transplantation.

BACKGROUND: New-onset diabetes mellitus after organ transplantation (PTDM) significantly impairs patient and organ survival. Published rates of PTDM range from 2% to 54%, depending on the definition. OBJECTIVES: To analyze incidence of PTDM after renal transplantation according to recent guidelines and to evaluate implementation of a prospective standardized screening protocol. PATIENTS AND METHODS: Data for all consecutive patients who underwent transplantation from 2000 to 2006 were analyzed retrospectively for PTDM. In a prospective pilot trial all candidates for living related donor transplantation underwent a 75-g oral glucose tolerance test at evaluation prior to renal transplantation and at 3, 6, and 12 months thereafter. RESULTS: Data for 181 out of 271 consecutive patients were analyzed. Of these patients, 36 (19.9%) developed PTDM. Age, body mass index, pretransplantation fasting glucose concentration, and number of HLA mismatches were significant predictive risk factors. Posttransplantation diabetes mellitus occurred more frequently in patients receiving a cadaver organ compared with a living donor organ and in those receiving tacrolimus therapy vs cyclosporine therapy. Preliminary results demonstrated a 55.5% incidence of PTDM at 3 months in patients who received a living donor organ, much higher than expected. CONCLUSIONS: With an incidence of approximately 20%, PTDM is a frequent complication of transplantation. Prospective screening using oral glucose tolerance testing is a more sensitive method for detection of impaired glucose metabolism and PTDM. Relevance and therapeutic consequences must be determined in large-scale prospective studies.