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Rheumatoid arthritis (RA) patients are at increased risk of infection. Aim of the present study was to investigate whether RA patients admitted to an intensive care unit (ICU) due to infection have higher Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk scores compared to control RA patients. Seventy-four RA patients (32.4% male) admitted to an ICU due to infection (from January 2002 to December 2013) and 74 frequency-matched control RA patients (16.2% male) were included in this cross-sectional study. There was strong evidence for a higher RABBIT risk score in ICU patients (median 2.0; IQR 1.3–3.2) as compared to controls (1.3; IQR 0.8–2.0; p

Resumo Objetivos Os pacientes com artrite reumatoide (AR) devem receber uma avaliacao do risco cardiovascular (CV). Para esse fim, existem as calculadoras de risco CV. Alem disso, parâmetros da funcao vascular podem ser medidos e usados para predicao do risco. O objetivo deste estudo foi avaliar a associacao entre esses dois conceitos. Metodos Foram incluidos neste estudo transversal 287 pacientes com AR (58,4 ± 12,6 anos) e 232 controles (49,9 ± 13,4 anos). Calculou‐se o risco CV em 10 anos com o Score e o QRISK2. No Score, usou‐se o multiplicador recomendado de 1,5 em pacientes com AR elegiveis e estimou‐se tambem o risco em pacientes com menos de 40 anos [mScore (0‐65)]. O indice de aumento (AIx) e a pressao de pulso (PP) central, marcadores da integridade vascular e risco CV, foram avaliados pela analise de onda de pulso (PWA). O desfecho primario foi a correlacao entre o AIx e o risco CV estimado com o mScore (0‐65). Resultados Em pacientes com AR, o AIx mostrou correlacao estatisticamente significativa com o mScore (0‐65) (rho = 0,3374; p Conclusoes Os parâmetros de hemodinâmica central se correlacionam com o risco CV calculado. No entanto, ambos nao fornecem exatamente as mesmas informacoes. Pergunta‐se se uma combinacao de ambos os conceitos resultaria em uma melhor predicao do risco CV.

Objectives: Rheumatoid arthritis (RA) patients should receive cardiovascular (CV) risk assessment. For this purpose CV risk calculators are available. In addition, parameters of vascular function can be measured and used for risk prediction. Aim of the present study was to assess the association of these two concepts. Methods: 287 RA patients (58.4 ± 12.6 years) and 232 controls (49.9 ± 13.4 years) were included in this cross-sectional study. We calculated 10 year CV risk with SCORE and QRISK2. For SCORE we used the recommended multiplier of 1.5 in eligible RA patients and estimated the risk also in patients younger than 40 years (mSCORE (0-65)). Augmentation index (AIx) and central pulse pressure (PP), markers of vascular integrity and CV risk, were assessed by pulse wave analysis (PWA). Primary endpoint was the correlation of AIx and the estimated CV risk using mSCORE (0-65). Results: In RA patients AIx showed a statistically significant correlation with mSCORE (0-65) (rho = 0.3374; p < 0.0001) and QRISK2 (rho = 0.3307; p < 0.0001). The correlations of central PP with mSCORE (0-65) (rho = 0.4692; p < 0.0001) and QRISK2 (rho = 0.5828; p < 0.0001) were also statistically significant. Increasing quartiles of central PP were associated with an increased odds of being in the "high risk"category according to SCORE (OR 2.18; 95% CI 1.58-3.01) or QRISK2 (OR 2.18; 95% CI 1.75-2.72). In control patients we also found a correlation of AIx and central PP with SCORE (0-65) and QRISK2. Conclusions: Parameters of central haemodynamics correlate with calculated CV risk. However, both do not give exactly the same information. The question arises whether a combination of both concepts would result in an improved CV risk prediction. Resumo Objetivos: Os pacientes com artrite reumatoide (AR) devem receber uma avaliação do risco cardiovascular (CV). Para esse fim, existem as calculadoras de risco CV. Além disso, parâmetros da função vascular podem ser medidos e usados para predição do risco. O objetivo deste estudo foi avaliar a associação entre esses dois conceitos. Métodos: Foram incluídos neste estudo transversal 287 pacientes com AR (58,4 ± 12,6 anos) e 232 controles (49,9 ± 13,4 anos). Calculou-se o risco CV em 10 anos com o Score e o QRISK2. No Score, usou-se o multiplicador recomendado de 1,5 em pacientes com AR elegíveis e estimou-se também o risco em pacientes com menos de 40 anos [mScore (0-65)]. O índice de aumento (AIx) e a pressão de pulso (PP) central, marcadores da integridade vascular e risco CV, foram avaliados pela análise de onda de pulso (PWA). O desfecho primário foi a correlação entre o AIx e o risco CV estimado com o mScore (0-65). Resultados: Em pacientes com AR, o AIx mostrou correlação estatisticamente significativa com o mScore (0-65) (rho = 0,3374; p < 0,0001). A correlação entre o AIx e o QRISK2 também foi significativa (rho = 0,3307, p < 0,0001). As correlações entre a PP central e o mScore (0-65) (rho = 0,4692; p < 0,0001) e QRISK2 (rho = 0,5828; p < 0,0001) também foram estatisticamente significativas. Os quartis incrementais da PP central estiveram associados a uma maior probabilidade de estar na categoria de "alto risco"de acordo com o Score (OR 2,18; IC 95% 1,58 a 3,01) ou QRISK2 (OR 2,18; IC 95% 1,75-2,72). Nos pacientes do grupo controle também se encontrou uma correlação entre o AIx e a PP central no Score (0-65) e no QRISK2. Conclusões: Os parâmetros de hemodinâmica central se correlacionam com o risco CV calculado. No entanto, ambos não fornecem exatamente as mesmas informações. Pergunta-se se uma combinação de ambos os conceitos resultaria em uma melhor predição do risco CV.

While there is a lot of evidence published on the association of cardiovascular (CV) disease and rheumatoid arthritis (RA), little is known about urinary albumin excretion (UAE)-a marker of CV risk-in this particular high-risk population. Therefore, we investigated UAE in a large cross-sectional study. We used data from the US National Health and Nutrition Examination Survey (NHANES), including the years 2007-2012. Primary outcome was the proportion of patients with a urinary albumin-creatinine ratio (ACR) >30 mg/g. A total of 14,648 study participants (representing a population size of 174,663,008) with available ACR were included in the study (14,179 without RA and 469 with RA). In the RA group, the proportion of patients with an ACR >30 mg/g was 10.46 % (95 % CI 7.47-14.45 %) and in the non-RA group this proportion was 13.39 % (95 % CI 12.65-14.16 %; p = 0.09). There was a strong association between RA and DM (OR 5.84; 95 % CI 4.48-7.62). In the RA group, significantly more patients had a former CV event (OR 3.01; 95 % CI 2.28-3.97). Adjustments for DM, smoking status, former CV event, age, systolic blood pressure, and gender did not substantially alter the association between RA and ACR >30 mg/g (OR 0.82; 95 % CI 0.51-1.33). We did not find evidence for a difference in UAE in patients with or without RA, despite the fact that RA was associated with DM and, in addition, RA patients more often had a previous CV event. These findings may support the assumption that despite an increased CV risk, UAE does not play a major role in RA patients.

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.

In rheumatology, sufficient disease control is a central part of the treatment concept. However, modern treatment strategies are associated with a substantial economic burden for health care systems. Ecological studies offer the unique opportunity to analyse differences between groups as well as group level effects. In the present analytical multi-site ecological study, we investigated whether more powerful national economies as measured by the gross domestic product per capita (GDPpc) are associated with better disease control in RA patients as measured by the disease activity score 28 (DAS28). We used aggregated data on RA patients from the recently published COMORA study as well as the World Health Organization database. There was a strong negative correlation between DAS28 and GDPpc (r = −0.815; p = 0.0002). Adjustment for sex, smoking status, disease duration or current employment status did not significantly change this association. There was a strong, negative correlation between DAS28 and age (r = −0.870; p < 0.001) and a strong, positive correlation between GDPpc and age (r = 0.737; p = 0.002). Adjustment for age reduced the regression coefficient (DAS28/GDPpc) to −0.000018 (p = 0.054). There was a negative correlation between DAS28 and current employment status (r = −0.642; p = 0.008) and a positive correlation between GDPpc and employment status (r = 0.722; p = 0.002). In conclusion, there is evidence of an association between disease control and GDPpc. This association is alleviated after adjustment for age. Of note, in countries with higher GDPpc, a higher proportion of RA patients are currently employed. This is true despite the fact that RA patients in countries with higher GDPpc are also older.

Cyclophosphamide (CYC), primarily introduced into clinical practice as an anti-cancer substance, is a potent immunosuppressive drug. Today, it is used in a number of organ- or life -threatening autoimmune diseases such as systemic vasculitides or connective tissue diseases. While being effective, CYC has a small therapeutic index and is associated with significant toxicity. CYC has been used in oncology in a variety of diseases and a lot of data has been derived from this area. This knowledge is often extrapolated to the rheumatologic settings. However, besides some similarities substantial differences between these two specialties considering the underlying diseases as well as the kind of application of the drug exist. The aim of the present review is to describe the general characteristics of the use of CYC from the rheumatologist's point of view, including pharmacologic and pharmacokinetic properties, drug interactions, toxicity and possible preventive and/or therapeutic measures; all of which are important to consider when using this particular drug in the treatment of inflammatory rheumatic diseases.

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity. It was previously shown that the augmentation index (AIx), a marker of vascular dysfunction, is higher in RA patients without traditional cardiovascular risk factors than in healthy controls. In this study we determined whether the impact of RA on the AIx is diminished in the context of coexisting, strong cardiovascular risk factors.A total of 411 participants were included [203 with RA; 208 in the non-RA (n-RA) group]. Pulse-wave analysis was performed on the radial artery using applanation tonometry. The impact of RA on the AIx was determined in a single and in a multiple linear regression model.The mean unadjusted AIx was 30.5 ± 9.0% for RA patients and 24.0 ± 11.0% for the n-RA group (P0.001). In the regression model, the following variables are statistically significant at approximately the same level (P0.001); the order of impact of these variables is agediastolic blood pressuresexRAheightsmoking status. RA, height, and smoking had a nearly equal impact on the AIx.The AIx is increased in RA patients regardless of the coexistence of traditional cardiovascular risk factors, thereby reflecting vascular dysfunction in this population. The impact of RA on the vascular system is comparable to that of smoking.

BACKGROUND: B-type natriuretic peptide (BNP) plays a key role in the regulation of volume homeostasis, and elevated blood levels of BNP are associated with end-stage renal disease. Renal transplantation leads to a decrease of elevated BNP levels with established graft function. Assessment of N-terminal pro-BNP (NT-proBNP) is established as reflecting volume homeostasis, and we therefore studied the relationship between NT-proBNP and allograft function in a prospective study. METHODS: NT-proBNP was assessed in 76 patients with end-stage renal disease undergoing renal transplantation. Patients were grouped according to immediate or delayed graft function. The degree of allograft function was assessed from the estimated glomerular filtration rate according to the MDRD formula. RESULTS: In patients with immediate graft function (n = 48), median NT-proBNP decreased immediately after transplantation; in patients with delayed function (n = 28), median NT-proBNP first increased and then decreased as function improved. Patients with early acute rejection showed significantly higher NT-proBNP levels prior to transplantation than patients without rejection. NT-proBNP levels measured 2 or 3 weeks post-transplant were significantly correlated with the estimated glomerular filtration rate 1 year after transplantation. CONCLUSIONS: An association was observed between renal allograft function and post-transplant levels of NT-proBNP. The association was not found to be a useful general predictor for graft function in individual patients in a clinical setting, as the range of NT-proBNP levels measured was too wide.

Increasing success in renal transplantation and longer patient survival has meant that post-transplant malignancies are having an increasing impact on long-term graft and patient survival. Choice of the immunosuppressive agents provides one of the controllable risk factors for the development of malignancies in this population. Calcineurin inhibitors (CNIs) are associated with an increased incidence of cancers, whereas the proliferation signal inhibitors (PSIs), everolimus and sirolimus have demonstrated anti-oncogenic effects in pre-clinical models and are currently being investigated as anti-cancer agents in clinical trials. There is increasing evidence demonstrating a lower incidence of post-transplant malignancies in renal transplant recipients receiving PSI-based immunosuppression compared with those receiving CNIs. Conversion from CNIs to PSIs has been shown to lead to the regression of Kaposi's sarcoma in renal transplant recipients and is now part of accepted standard care for this tumour in this setting. The anti-cancer properties of PSI-based regimens have the potential to combine the dual benefits of immunosuppression without the use of CNIs and the direct anti-oncogenic effects through their inhibition of the mammalian target of rapamycin (mTOR) signalling pathway. In the absence of formal clinical trial evidence on the best way to use PSIs in this setting, a workshop was held to provide practical guidance on immunosuppressive strategies in the context of malignancy, given the current state of knowledge.

Registry data show that there is an overall 3-5-fold increase in cancer risk in transplant recipients compared with the general population, with skin cancers and lymphoma particularly prevalent. Cancers in transplant recipients are often more aggressive than those in the general population, with poor prognosis, particularly for gastrointestinal tumours and lymphomas. Risk factors for post-transplant malignancy include factors common to the general population, such as increasing age, cigarette smoking and sun exposure. In addition, immunosuppression is an important factor in the development of post-transplantation cancer, although data for individual agents are not definitive. A number of studies have demonstrated that ciclosporin is associated with an increased risk of malignancy, whereas a few studies report no increase in risk of cancer after the introduction of ciclosporin into treatment regimens. Similarly, studies have shown that the mycophenolic acid-based agent mycophenolate mofetil is associated with an increased risk of malignancy, whereas other studies have demonstrated that mycophenolate mofetil is in fact associated with a lower risk. Polyclonal anti-thymocyte antibodies used for induction therapy appear to be related to an increased incidence of post-transplant lymphoproliferative disorder, but this effect is not observed with monoclonal anti-interleukin 2 antibodies. Azathioprine has been implicated in the development of skin tumours, possibly as a result of increased photosensitivity to ultraviolet light. The proliferation signal inhibitors appear to be associated with a reduced risk of some malignancies. Further research will elucidate the role of these newer immunosuppressive agents in post-transplantation malignancies.

In earlier registry analyses, cyclosporine at doses of3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST.Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (65 mL/min) included donor or recipient age60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point.Compared to higher doses, CsA-ME3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.

Background Long-term success of renal transplantation depends upon the quality of the donor organ, avoidance of peritransplant and early posttransplant damage (rejection), and optimal maintenance of graft function after the first 6-12 months. Glomerular filtration rate (GFR) at 1 year is a standard way to evaluate short-term success, whereas calculated GFR at 5 years gives a better appreciation of long-term outcomes. The objective of this study was to assess the effect of various demographic and transplant-related parameters on renal function via GFR at 1 year and 5 years post transplantation, using univariate and multivariate data analysis. Methods Data on 1-year GFR were available from 10,397 patients, whereas 2,889 patients provided data on both 1-year and 5-year GFR. All patients were enrolled in the Neoral Multinational Observational Study in Transplantation (Neoral-MOST), an ongoing, prospective, observational study of adult renal transplant recipients. Results One-year GFR was the most relevant predictor for 5-year GFR. In a multifactorial analysis (ANCOVA) using 1-year GFR as a continuous variable, the effects of several highly relevant parameters from univariate analysis (such as acute rejection and delayed graft function) on 5-year GFR appeared to be fully mediated by their influence on 1-year GFR, whereas immunological risk factors like HLA match or previous transplantation had an ongoing effect on graft function beyond year 1. Conclusions The findings of this study corroborate and augment data from previous registry surveys, and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome.

The hyperlipidemic and hypertensive effects of ciclosporin constitute a cardiovascular risk. Cosmetic side-effects are known to reduce patients' quality of life. This was a 6-month, open, prospective, multicentre study in 296 adult kidney transplant patients to evaluate the conversion from ciclosporin to a tacrolimus-based regimen. Primary indications for conversion were hyperlipidemia (n =77), hypertension (n = 72), hypertrichosis (n = 32) and gingival hyperplasia (n = 115). At month 6, hyperlipidemia and hypertension were at least moderately improved in 59.1% and 63.5% of patients, and strongly or completely resolved in 29% and 25%. Gingival hyperplasia and hypertrichosis were strongly or completely resolved in 73% and 72% of patients. Mean total cholesterol was reduced from 255 to 218 mg/dl. Mean systolic blood pressure (SBP) was reduced from 152.9 to 137.5 mmHg and mean diastolic blood pressure (DBP) from 90.7 to 85.8 mmHg. Ciclosporin-related side-effects resolved or improved after conversion to tacrolimus.

Background. This study determined whether cyclosporine A (CsA)-treated renal allograft recipients with deteriorating renal function (“creeping creatinine”) secondary to chronic allograft nephropathy (CAN) benefit from the addition of mycophenolate mofetil (MMF) to their immunosuppressive regimen, followed by withdrawal of CsA. Methods. In a controlled, open, multicenter study, CsA-treated renal allograft recipients with progressively deteriorating renal function were randomized to have their CsA discontinued with the concomitant addition of MMF to their regimen (group A) or to continue treatment with CsA (group B). The primary endpoint was the response rate over the 6-month period after withdrawal of CsA in group A or the equivalent time in group B. Response was defined as a stabilization or reduction of serum creatinine (SCr), as evidenced by a flattening or positive slope of the 1/SCr plot and no graft loss. Secondary endpoints included the incidence of acute rejection, graft and patient survival, and changes in selected metabolic parameters. Results. The response rate in the primary intent-to-treat population (n=122) was 58% (36/62) in group A versus 32% (19/60) in group B (P=0.0060). The corresponding percentages of responders in the per-protocol population (n=107) were 60% (36/60) and 26% (12/47), respectively (P=0.0008). There were no acute rejections in group A during the study period. Patients in this group also experienced a significant decrease in total cholesterol. Conclusions. In patients with progressively deteriorating renal function secondary to CAN, addition of MMF followed by withdrawal of CsA results in a significant improvement in transplant function without the risk of acute rejection.

Rapamycin is a new immunosuppressive agent approved for maintenance therapy after kidney transplantation. It may allow calcineurin-inhibitor-free, non-nephrotoxic immunosuppression. We report, however, on four kidney-transplant recipients who developed post-transplantation glomerulonephritis after conversion from a calcineurin-inhibitor-based immunosuppression to rapamycin. In all four patients nephrotic-range proteinuria occurred 2-9 months after conversion to rapamycin. Renal biopsy confirmed membrano-proliferative glomerulonephritis type 1 in one case, membranous glomerulonephritis in another and IgA-nephropathy in two cases, respectively. Calcineurin-inhibitor-based immunosuppression was reintroduced and resulted in complete remission of proteinuria and in stabilised renal function in all patients. We conclude that in the case of rapamycin-associated post-transplantation glomerulonephritis an attempt should be made to replace rapamycin by a calcineurin inhibitor.

Levels of glycated albumin seem to predict mortality and hospitalization more accurately than does levels of glycated hemoglobin in patients with diabetes mellitus who are on dialysis. Should we be measuring glycated albumin instead of glycated hemoglobin in this group of patients?

Aim Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. In the general population, an increased heart rate is associated with increased mortality. Only a few studies have investigated heart rate in RA patients and compared the results with patients that do not have RA (n-RA). Therefore, little is known as to whether an increased heart rate, at least in part, could explain the increased mortality found in RA patients. The aim of the present study was to investigate whether heart rate is increased in RA patients. Methods In this cross-sectional study, heart rate was determined in a total of 282 patients (131 RA, 151 n-RA). In addition, non-invasive pulse wave analysis of the radial artery was performed to determine cardiac ejection duration using the Sphygmocor apparatus. Furthermore, the subendocardial viability ratio (SEVR), a marker of cardiac workload, was investigated, whereby higher values indicate a more favorable supply/demand relationship for the myocardium. Patients using chronotropic drugs were not included in the study. Results Heart rate was virtually the same in RA patients (71.9 ± 11.2 beats/min [bpm]) as compared with controls (72.3 ± 11.7 bpm; P > 0.05). Also SEVR (RA 144 ± 25% vs. n-RA 147 ± 27%; P > 0.05) and ejection duration (RA 321 ± 24 ms vs. n-RA 318 ± 24 ms; P > 0.05) were comparable between the groups. Conclusion It could not be shown that heart rate in RA patients differs significantly from heart rate in controls. Therefore, heart rate does not appear to explain or contribute to the increased cardiovascular risk found in RA patients.

An increasing number of immunosuppressive drugs became available for clinical use over the past few decades. These include substances with recently recognized immunosuppressive properties, which needed careful evaluation in various trials before they could be approved for use in different diseases. The effectiveness of other agents was already established, but knowledge about their modes of action or the mechanisms that lead to side effects was acquired much later. This understanding also contributed to the development of new drugs that display synergistic effects or lack certain adverse effects. The greater choice afforded by such research endeavours allows us to select the best therapeutic strategy for an individual patient; however, this requires a comprehensive knowledge of the available options. The present review provides an update of current knowledge of the most important substances (including calcineurin and target of rapamycin inhibitors, regulators of gene expression, and inhibitors of purine and pyrimidine synthesis) and surveys some of the novel agents that are expected to play an important role in the future.

Purpose: To evaluate broadband ultrasound attenuation (BUA) for the assessment of bone status and to correlate this to dual-energy X-ray absorptiometry (DXA) in haemodialysis patients. Material and Methods: In 60 patients, BUA (dB/MHz) was determined for the calcaneus. the results were expressed as Z-scores and T-scores, i.e. units of standard deviations respectively from age- and sex- matched normal values and from sex-matched normal mean values in healthy young adults. Ultrasound data were correlated to relevant clinical, biochemical and DXA data (g/cm2), which were examined at the femoral neck and at the lumbar spine in 50 patients. Results: the BUA Z-score was Conclusion: Calcaneal BUA is an additional tool for the surveillance of bone density in haemodialysed patients.

Background. Posttransplant hemolytic uremic syndrome (pHUS) is a rare but severe disorder that confers a poor prognosis on an allograft due to thrombotic microangiopathy. Immunosuppression with cyclosporine (CsA) is implicated as a significant risk factor for the development of pHUS. In early reports, it was hypothesized that immunosuppression with FK506 (tacrolimus) would avoid the development of pHUS. However, this initially supposed beneficial effect remains controversial, because pHUS associated with tacrolimus therapy has been published in some later case reports. This article aims to further evaluate FK506 with respect to the development and resolution of pHUS. Methods. We describe the course of seven adult kidney graft recipients with pHUS, treated with FK506 either as initial immunosuppression for retransplantation or after discontinuation of CsA for resolution of pHUS. Work-up for pHUS was initiated when certain clinical features, such as hemolytic anemia, thrombocytopenia, and deterioration of graft function, were found. The diagnosis was confirmed by histologic examination of a renal allograft biopsy specimen (thrombotic microangiopathy). With the onset of pHUS, additional plasma exchange was performed in all patients. Results. Two patients suffered from end-stage renal disease due to primary HUS and had a history of recurrent pHUS in previous renal transplants. In both patients, the attempt to regraft was only made because of the early optimistic reports using FK506. Despite initial FK506 therapy, both recipients developed pHUS again, leading to loss of graft function. Two additional kidney graft recipients with primary renal failure other than HUS also received FK506 as initial immunosuppression. One of them (loss of the first kidney graft due to CsAinduced pHUS) was successfully treated with FK506 for his second renal transplant. The other recipient, a patient in whom de novo pHUS had occurred in the first graft despite initial therapy with FK506, was treated with CsA for his second graft and again developed pHUS. The latter process, however, could be reversed by a switch to steroids and azathioprine. In all three patients regrafted for reasons other than pHUS, development of de novo pHUS was treated by CsA withdrawal and a switch to FK506; this approach was effective in two patients. Conclusion. Our results demonstrate that three of seven renal allograft recipients benefited from FK506 therapy for prevention or resolution of pHUS. Treatment or prophylaxis with FK506 can be considered advantageous in some patients with de novo pHUS, but FK506 fails to prevent recurrent pHUS in patients with primary HUS.

Background. To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. Methods. A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. Results. At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P

Background Delayed graft function (DGF) is a common complication after renal transplantation, and may affect graft function. The aim of this analysis was to evaluate risk factors for DGF, as well as parameters and events influencing graft function after DGF. We analyzed data collected in an ongoing international, prospective; observational study, the Neoral-MOST (Multinational Observational Study in renal Transplantation), and included in the analysis all patients with cadaveric kidney transplants for whom renal function at 1 year posttransplantation was documented ( N = 8950). Logistic regression was used to evaluate the risk factors for DGF occurrence, and multifactorial analysis of variance (ANCOVA) to assess the relevance of different factors for GFR at 1 year. Results Higher donor age, longer CIT, male recipients, Caucasian recipients, high recipients body mass index, and PRA were all associated with a higher risk for DGF. Renal function of former DGF kidneys at 1 year was lower in kidneys of elder donors, or which had experienced rejection or CMV infection. Variations of the maintenance regimen at 1 year posttransplantation were not associated with better graft function. Multifactorial analysis showed donor age and acute rejection as significant independent factors. Conclusions Most factors increasing the risk for DGF or having a negative impact on renal function at 1 year in grafts with DGF are predetermined. Additional posttransplant damage by acute rejection was associated with further reductions in GFR. Preventing acute rejection is an important step in achieving optimal function of DGF grafts.

In recent years, the scientific community has gained significant insight into the complex interaction between inflammation and the cardiovascular system in patients with rheumatoid arthritis (RA), which leads to increased cardiovascular (CV) morbidity and mortality in these patients. Our common understanding of this association is that persistent inflammation contributes to the development of premature atherosclerosis. Consequently, the question arises whether control of inflammation with antirheumatic treatment will be able to improve CV outcome. While there are a lot of data that demonstrate improvement of numerous CV surrogate markers in patients treated with virtually all antirheumatic drug classes, there is much less information about the possible translation of these beneficial effects into improved CV outcome. In summary, the published evidence suggests that tumor necrosis factor (TNF) alpha inhibitors may improve CV outcome. The same is true for methotrexate (MTX). However, it is not clear whether MTX works via suppression of inflammation or through drug specific mechanisms. For other traditional disease-modifying antirheumatic drugs and biologic therapies, there are no convincing data for improved CV outcome. Only a few drugs (glucocorticoids and NSAIDs) have been associated with increased CV risk. Treating RA aggressively, as recommended by current guidelines, is likely to have a beneficial effect on CV outcomes.

IntroductionTransplant recipient are knows n to b susceptible teoprimary viral infection or tso reactivatio on f a persist-ent virus. Mos otf the clinically relevant infection are scaused by the herpes-viridae group (CMV, EBV VZV, ,HSV I and II) Huma. n parvoviru B19 wa firstssdiscovered 1975 huma in n packed bloo [1]d and sub-sequently show tno cause fifth diseas or erytheme ainfectiosum in childre [2]n . Th virue s also causesaplastic crise isn patients with underlying haemolyticanaemia [3-5].Chronic parvoviru B1s infectio9 can inducn e purered cell anaemi ina patients with congenital immuno-deficiency, acquired immunodeficiency an syndromed ,children with lymphoblastic leukaemia red cell. Pureanaemia due to chroni c parvoviru B1s9 infectio n hasrarely been describe in orgad n transplant recipients:Nour et al. [6 reporte] odn five paediatric live andrheart recipients, Ramag et al. [7e] described the cas eof a liver transplant recipien and itn a report o n renaleffects o immunoglobulif n therap et al.y Cant [8] umentioned a patient with parvoviru B1 infectio9 s nafter combined heart-kidney transplantation of . Somethese patients with persistent parvovirus infection weretreated successfully with high-dose intravenousimmunoglobulin (HD-IVIG).In this pape we reporr otn a kidney transplantrecipient developing parvovirus B19-induce red d purecell anaemi 6a months after transplantatio and its nsuccessful treatment with intravenous immuno-globulin.

Diabetic nephropathy is the most common cause for end-stage renal disease (ESRD). Chronic renal failure is associated with miscellahous alterations in carbohydrate and insulin metabolism.. Moreover, several specific therapies employed in renal insufficiency also influence pharmacological therapy of diabetes in uraemic patients.. In patients with altered renal function, therapeutic possibilities are limited due to the accumulatin of some oral agents and/or their metabolites at the reduced glomerular filtration rate (GFR). The connection between kidney and insulin metabolism is well known for many years (Horton et al, 1968). For insulin metabolism the kidneys are one of its target organs. Chronic renal failure is associated to multiple alterations in the carbohydrate and insulin metabolism that should be taken into account when treating diabetic patients with altered renal function (DeFronzo et al, 1973). Specific therapeutic needs (oral agents or insulin) will be determined based on the degree of insulin resistance or insulin deficiency of patients with renal insufficiency (Rabkin e al,1984). A good metabolic control is not only important in the early phase of diabetic nephropathy but also in diabetic patients with ESRD. It was shown in several studies, that metabolic control under antidiabetic therapy is a predictor for prognosis of patents with renal replacement therapy (Morokia et al, 2001). A good glycemic control can reduce the progression of atherosclerosis (Oomichi et al, 2006) and improve the survival in patients treated with hemodialysis (Kovesdy et al, 2008). Though, in a recent study it was suggested that aggressive glycemic control cannot be routinely recommended for all diabetic hemodialysis patients on the basis of reducing mortality risk (Williams et al, 2010). The majority of uremic type 2-diabetic patients need insulin, however, a smaller part of these diabetic patients can also be treated with oral antidiabetic agents. The problem of the topic of this study is the fact, that there are only few data in the literature concerning antidiabetic therapy in type 2 diabetic patients with ESRD (Biesenbach et al, 2010). This paper offers a review of the relevant findings related to insulin therapy in diabetic patients with ESRD. Additionally, we review the relevant aspects related to oral antidiabetic therapy in diabetic patients with impaired renal function.

An increased incidence of hyperlipidemia places kidney graft recipients at increased risk for cardiovascular disease and may contribute to a decline in graft function. A study was undertaken to evaluate the safety and efficacy of lovastatin in these patients. Twelve kidney graft recipients with stable graft function and a cholesterol (chol) level over 250 mg/dl (6.46 mmol/l) were included. The lipid-lowering treatment consisted of 20 mg lovastatin daily, and all patients received immunosuppression with ciclosporin (CS) and prednisolone. Total chol decreased by 27% (300 +/- 56 to 219 +/- 28 mg/dl; 7.76 +/- 1.45 to 5.66 +/- 0.72 mmol/l; p < 0.01), LDL-chol by 35% (220 +/- 38 to 143 +/- 17 mg/dl; 5.69 +/- 0.98 to 3.70 +/- 0.44 mmol/l; p < 0.01) and triglycerides by 33% (207 +/- 127 to 138 +/- 56 mg/dl; 2.36 +/- 1.44 to 1.57 +/- 0.64 mmol/l; p < 0.05). HDL-chol increased by 10% (57 +/- 11 to 63 +/- 13 mg/dl; 1.47 +/- 0.28 to 1.63 +/- 0.34 mmol/l; NS). The ratio of total chol/HDL-chol, a generally accepted risk predictor of atherosclerosis, fell from 5.4 +/- 1.3 to 3.3 +/- 1.2, p < 0.01. Lipoprotein (a) [lp(a)], an independent risk predictor for atherosclerosis, was also evaluated at baseline and after 6 months of lovastatin treatment and showed a decrease of 39% (32.9 +/- 27.6 to 19.9 +/- 22.9 mg/dl; 0.85 +/- 0.71 to 0.51 +/- 0.59 mmol/l; p < 0.05). No adverse side effects were seen at this dosage, and hepatic and renal parameters remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Premature atherosclerosis is linked to inflammation. Arterial stiffness is a marker of vascular dysfunction. We tested the hypothesis that treatment with infliximab, which is effective in reducing inflammation in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), also lowers the augmentation index (AIx) in patients with active disease. We also analyzed the subendocardial viability ratio (SEVR), which is a measure of myocardial perfusion relative to cardiac workload. Included in the study were 30 patients (17 RA, 13 AS). Conventional treatment failed in all patients. The AIx and SEVR were determined by radial applanation tonometry before and after treatment with infliximab, at baseline and at week 7. After treatment with infliximab, Disease Activity Score for 28 joints (RA patients), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index (AS patients), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) improved significantly (p0.001). The AIx for all patients increased from 22.0 +/- 14.0% to 24.6 +/- 13.0% (p = 0.03). The increase in the RA sub-group (p = 0.01) was also significant. The SEVR decreased from 148.6 +/- 23.7% to 141.2 +/- 23.7% (p = 0.04). Infliximab did not reduce the AIx in patients with RA and AS, although there were clinical improvements and CRP and ESR decreased. Instead, the AIx increased. This could negatively influence cardiac workload.

Pulse wave velocity (PWV), a marker of arterial stiffness, reflects vascular dysfunction and is associated with cardiovascular risk. Rheumatoid arthritis (RA) is associated with profound changes in vascular function and premature death, mainly caused by cardiovascular diseases. The aim of this study was to investigate arterial stiffness in the brachial artery (a muscular type of artery) as measured by PWV in women with longstanding RA and to compare the results with healthy controls and to patients with traditional cardiovascular risk factors without RA. A total of 80 female participants underwent non-invasive measurement of PWV. Participants were allocated to one of three groups: patients with longstanding RA (disease duration5 years) without traditional cardiovascular risk factors (n = 30), patients with traditional cardiovascular risk factors (n = 20) and healthy controls (n = 30). Patients and controls were matched for age. PWV was significantly higher in RA patients (8.6 +/- 0.9 m/s) as compared with healthy controls (8.1 +/- 0.7 m/s; P = 0.02). PWV was virtually the same in RA patients and patients who had traditional cardiovascular risk factors (8.6 +/- 1.5 m/s; NS). PWV was also higher in this group as compared with healthy controls, but this difference did not reach statistical significance (NS). RA is associated with a higher PWV as compared with healthy controls and is comparable to patients with known traditional risk factors. This reflects vascular dysfunction in patients with RA.

Hepatitis B (HBV) and hepatitis C (HCV) virus infections are major risk factors affecting long-term morbidity and mortality after renal transplantation. Hepatitis prevalence is subject to geographical variations.To compare and analyze the geographical prevalence, risk factors and impact of HBV and HCV infection in multinational cohorts of renal transplant recipients.From 1989 - 2002, data on 12,856 kidney transplant recipients in 37 countries were collected within the prospective MOST (Multinational Observational Study in Transplantation). Subgroup analyses of hepatitis-related prevalence, risk factors and impact were conducted on patients whose HBV and HCV status was available at time of transplantation. Countries were substratified according to population prevalence ofor = 5% HBV oror = 10% HCV.The prevalence of HBV was 2.9%, of HCV 8.7% and of HBV together with HCV 0.4%. Risk factors for hepatitis infection in renal transplant recipients were long dialysis time, retransplantation and blood transfusions. At each study endpoint up to 5 years after transplantation, no significant differences in graft function were observed, although the 1-year acute rejection rate tended to be lower in HCV+ patients. At 5 years post-transplant, there were no differences between the subgroups and regions regarding infections, post-transplant diabetes mellitus or malignancies including PTLD.Overall, HCV infections are more prevalent than HBV. Despite large geographical differences in prevalence, HBV and HCV status did not appear to have a significant impact on renal graft function, infections, malignancies and post-transplant diabetes mellitus up to 5 years after renal transplantation throughout the MOST countries.

Chronic allograft nephropathy (CAN) leads to the majority of late graft loss following renal transplantation. Detection of CAN is often too late to permit early intervention and successful management. Most current strategies for managing CAN rely on minimizing or eliminating calcineurin inhibitors (CNIs) once CAN has become established. The proliferation signal inhibitors everolimus and sirolimus have potent immunosuppressive and antiproliferative actions, with the potential to alter the natural history of CAN by reducing CNI exposure whilst avoiding acute rejection. Whilst data will be forthcoming from a number of clinical trials investigating this potential, we discuss early detection of CAN and the rationale for a role for this class of agent.

During the past decades, organ transplantation has become a frequently performed routine procedure offered to patients with end-stage organ failure. Transplant recipients live longer, have a good quality of life, and represent therefore a rapidly growing population. Although the follow-up, and especially the immunosuppressive therapy, are maintained by specialized transplant centers, such patients increasingly appear in private offices or hospitals that lack particular expertise in transplant medicine. Thus, there is need for an educational network for physicians and health care workers and for guidelines how to care best for this cohort of patients.

Calcineurin-inhibitor therapy can lead to renal dys- function in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal trans- plantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomi- tant IS consisted of mycophenolate mofetil ± steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0- 9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Pa- tients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in car- diac transplant patients after switch to Srl, which may have an adverse effect on renal function in these pa- tients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.

Die Nierentransplantation ist die optimale Form der Nierenersatztherapie, weil sie einer physiologischen Organfunktion am nachsten kommt, die Lebensqualitat verbessert und die Mortalitat im Vergleich zur Dialyse reduziert (A). Eine Transplantation sollte immer in Betracht gezogen werden; entscheidend ist der Ausschluss von Erkrankungen, die durch Immunsuppression verschlechtert werden und den Empfanger gefahrden (z. B. Tumore, entzundliche Herde, erhohtes kardiovaskulares Risiko oder intestinale Ulzerationen). Solche Probleme sollen nicht als absolute Kontraindikation betrachtet werden, sondern konnen durch adaquate Masnahmen beseitigt werden (B). Fur die praoperative Abklarung moglicher Empfanger wurden klare Richtlinien erstellt.

The aim of our study was to investigate a potential influence of elevated serumcobalt and serumchromiumlevels on renal function at minimum 10 years after implantation of a metal-on-metal hip.Between November 1992 and June 1994 98 patients (44 m, 54 f) with an average age of 56 (22-79) years received a metal-on-metal bearing Metasul. At the time of the 10-year follow-up, 15 patients had died and 8 were lost to follow-up. The remaining 75 patients had laboratory analysis including serumcreatinine and full blood cell count as well as chromium and cobalt serum levels.Ten years postoperatively the median serumcreatinine level was 0.86 (0.55-1.51) mg/dl, the serumcreatinine clearance Ccr was in the normal range. The hemogram did not differ from that measured at the time of surgery. The median serumcobalt concentration was 0.75 (0.3-50.10) microg/l and the serumchromium concentration was 0.95 (0.3-58.6) mug/l, 10 years postoperatively.Our long-term data do not show any influence of serum cobalt or chromium concentrations on renal function following total hip arthroplasty.

The aim of this study was to determine whether plasma concentrations of the acyl (AcMPAG) and phenolic (MPAG) glucuronide metabolites of mycophenolic acid (MPA) were related to diarrhoea in renal transplant patients on mycophenolate mofetil (MMF) with cyclosporine (CsA) or tacrolimus (TCL). Blood samples (0, 30, 120 min) were taken at days 3, 10, week 4, months 3, 6 and 12 for determination of MPA, MPAG and AcMPAG. MPA-AUC was estimated using validated algorithms. Two hour AUCs were calculated for MPAG and AcMPAG. Immunosuppressive therapy consisted of CsA/MMF (n = 110) and of TCL/MMF (n = 180). In 70/290 (24%) patients 86 episodes of diarrhoea were recorded during 12 months. Significantly more patients on TCL (31.1%) suffered from diarrhea compared to CsA (12.7%). MMF dose, MPA-AUC and the 2 h AUCs of MPAG and AcMPAG did not differ between patients with and without diarrhoea. Plasma AcMPAG and MPAG concentrations were substantially higher in patients on CsA compared with TCL, while MPA-AUC was lower in the former group. These data support the concept that CsA inhibits the biliary excretion of MPAG and AcMPAG, thereby potentially reducing the risk of intestinal injury through enterohepatic recycling of MPA and its metabolites.

Summary Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary nonfunction and delayed graft function (DGF) than heart beating cadaveric donor (CAD) kidneys, but little is known about long-term function of DCD grafts that survive to 1 year. To investigate the outcomes of renal transplant recipients whose DCD graft functioned for at least 1 year, this study analyzed data collected from 326 DCD graft recipients and 340 CAD-matched controls enrolled in a prospective, multinational, observational study – Neoral®-MOST (Multinational Observational Study in Transplantation) (Novartis, Basel, Switzerland). No differences were found in the demographics or immunosuppression between the two groups. All patients received a Neoral®-based immunosuppressive regimen. Donors after cardiac death graft recipients had a higher incidence of DGF (40% vs. 27% CAD; P

Calcineurin inhibitors (CNIs) are associated with important side effects, such as nephrotoxicity, and thus there is an interest in developing CNI-sparing protocols using agents such as the proliferation signal inhibitor/mammalian target of rapamycin inhibitor everolimus. In a 3-month pilot study using an abrupt conversion protocol, ciclosporin (CsA) treatment was stopped after the morning dose and everolimus was started at 3.0 mg/day. Mycophenolic acid (MPA)-based therapy was continued, or prednisolone increased to 10 mg/day until target everolimus trough blood levels (3-8 ng/ml) were achieved. To date, seven patients have been enrolled, with three having completed at least 3 months of follow-up. Overall, conversion was effective and well-tolerated. Patients consistently achieved everolimus trough blood levels >3 ng/ml, and no episodes of acute rejection or proteinuria were reported after 3 months. In patients who completed the study, there were no major changes in the leucocyte or platelet counts during everolimus treatment. Serum creatinine levels were maintained or decreased slightly. One patient experienced a transient increase in serum creatinine during an episode of pneumonia, but levels decreased again after resolution of infection and temporary everolimus dose reduction. Serum cholesterol and triglyceride levels increased, but remained within acceptable limits. One patient receiving enteric-coated mycophenolate sodium 1440 mg/day experienced increasing everolimus trough blood levels and anaemia after conversion, and was therefore likely to have been over-immunosuppressed. Abrupt conversion to everolimus from CsA was effective and well-tolerated in renal transplant recipients. A reduction in MPA dosage at the time of conversion may be necessary to prevent over-immunosuppression.

Introduction. Mycophenolate mofetil (MMF) has greatly reduced the risk of acute rejection episodes (ARE) after renal transplantation, but dose reductions/withdrawals could jeopardize long-term results. Methods. The MOST database of de novo patients treated with MMF at month 1 and functioning grafts at month 12 were divided into 2 groups: groups 1, 2 g MMF at month 1 and month 12; and group 2, 2 g MMF at month 1 but MMF

In an open, prospective, multicenter study, stable renal graft recipients were converted to tacrolimus because of cyclosporine-related side effects. Seventy-five patients were switched primarily because of hyperlipidemia. After the switch to tacrolimus, mean total cholesterol was reduced by 15% at month 6. One hundred seventy-seven additional patients were switched primarily for other indications: hypertrichosis, gingival hyperplasia, and arterial hypertension, and these symptoms also improved after the switch. In this analysis, serum lipid levels were categorized according to a modified standard classification of lipid parameters for renal transplant patients (published by the NKF Work Group). The aim was to estimate the proportion of patients reaching normal lipid levels after the conversion to tacrolimus therapy. In patients with primary indication hyperlipidemia, the proportion with normal cholesterol levels increased significantly from 5.6% at baseline to 37.5% at month 6 (P

Enteric-coated mycophenolate sodium (EC-MPS) is an enteric-coated formulation of mycophenolic acid. A 12-month, multicenter, double-blind, randomized clinical study demonstrated that converting maintenance renal transplant patients from mycophenolate mofetil (MMF) to EC-MPS is safe and does not affect efficacy. In an open-label study extension, 130 patients initially randomized to MMF were converted to EC-MPS (newly exposed); 130 initially randomized to EC-MPS continued on EC-MPS (EC-MPS long-term). A composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, or death occurred in 3 (2.3%) newly exposed and 2 (1.5%) EC-MPS long-term patients during the extension phase. One patient died and one lost his graft. BPAR occurred in 3 (2.3%) newly exposed patients and 1 (0.8%) EC-MPS long-term patient. During the first 12 months of the extension phase, incidence and type of adverse events was similar in both groups and comparable to that seen in the core study. Nine cases of malignancy were reported, mainly nonmelanoma skin cancers. EC-MPS dose adjustments for adverse events were required in12% of patients. At the end of the 12-month extension, 58 (44.6%) and 64 (49.2%) newly exposed and EC-MPS long-term patients, respectively, had reported at least one gastrointestinal adverse event. Mean serum creatinine remained stable at the 12-month visit of the extension study (137 micromol/L in the newly exposed and 142 micromol/L in the EC-MPS long-term groups). The results of this study demonstrate the long-term safety of EC-MPS and reconfirm the safety of converting MMF maintenance renal transplant patients to EC-MPS.

This study determined whether cyclosporine A (CsA)-treated renal allograft recipients with deteriorating renal function ("creeping creatinine") secondary to chronic allograft nephropathy (CAN) benefit from the addition of mycophenolate mofetil (MMF) to their immunosuppressive regimen, followed by withdrawal of CsA.In a controlled, open, multicenter study, CsA-treated renal allograft recipients with progressively deteriorating renal function were randomized to have their CsA discontinued with the concomitant addition of MMF to their regimen (group A) or to continue treatment with CsA (group B). The primary endpoint was the response rate over the 6-month period after withdrawal of CsA in group A or the equivalent time in group B. Response was defined as a stabilization or reduction of serum creatinine (SCr), as evidenced by a flattening or positive slope of the 1/SCr plot and no graft loss. Secondary endpoints included the incidence of acute rejection, graft and patient survival, and changes in selected metabolic parameters.The response rate in the primary intent-to-treat population (n=122) was 58% (36/62) in group A versus 32% (19/60) in group B (P=0.0060). The corresponding percentages of responders in the per-protocol population (n=107) were 60% (36/60) and 26% (12/47), respectively (P=0.0008). There were no acute rejections in group A during the study period. Patients in this group also experienced a significant decrease in total cholesterol.In patients with progressively deteriorating renal function secondary to CAN, addition of MMF followed by withdrawal of CsA results in a significant improvement in transplant function without the risk of acute rejection.

Background Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study—Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1- and 5-year renal function and their relationship to 1-year serum creatinine was assessed. Results Donor age, delayed graft function, acute rejection, and donor type significantly increased the risk for serum creatinine > 130 μmol/L at 1 year posttransplant, and 1-year serum creatinine was the strongest predictor of 5-year renal function. After adjustment for 1-year serum creatinine, an ongoing influence was observed for donor age, donor type, and previous graft. Delayed graft function and acute rejection had a significant effect on serum creatinine at year 1 but no additional impact on long-term graft function. Conclusions Serum creatinine at 1 year is influenced by risk factors known to affect overall graft survival and is predictive of 5-year renal graft function. The effects of delayed graft function and acute rejection appear to be limited to their influence on serum creatinine at 1 year, whereas donor type and previous graft predominantly affect later stages of graft life.

BACKGROUND Leukopenia due to immunosuppressive drugs represents a well-known complication in graft recipients, which might put patients at an increased risk for infections. In this study, recombinant human granulocyte colony-stimulating factor (rhG-CSF), a hematopoietic growth factor that selectively stimulates neutrophil colony formation and neutrophil cell differentiation, was tested for safety and efficacy. METHODS We evaluated 30 episodes of leukopenia (