Association of vascular function and estimated cardiovascular risk in patients with rheumatoid arthritis / Associação entre a função vascular e o risco cardiovascular estimado em pacientes com artrite reumatoide

Abstract 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.

RABBIT risk score and ICU admission due to infection in patients with rheumatoid arthritis.

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 < 0.0001). Traditional disease-modifying anti-rheumatic drugs (DMARDs) (82.4 vs 64.9%; p = 0.015) and biological DMARDs (28.4 vs 14.9%; p = 0.012) were more frequently given to RA patients without ICU admission. Glucocorticoid users were more frequently found in the ICU group (51.4 vs 31.1%; p = 0.012). In a multivariable analysis tDMARD use was associated with lower (OR 0.38; 95% CI 0.15-0.93; p = 0.034) and glucocorticoid use with borderline higher odds of ICU admission (OR 2.05; 95% CI 0.92-4.58; p = 0.078). Chronic obstructive pulmonary disease (OR 2.89; 95% CI 1.10-7.54; p = 0.03), chronic kidney disease (OR 16.08; 95% CI 2.00-129.48; p = 0.009), and age category (OR 2.67; 95% CI 1.46-4.87; p = 0.001) were strongly associated with ICU admission. There was a strong trend towards higher odds of ICU admission with increasing RABBIT risk score. Use of tDMARDs was associated with lower odds of ICU admission. In an adjusted analysis, bDMARDs were not associated with ICU admission. COPD, CKD, and age were strong risk factors for ICU admission.

Association of vascular function and estimated cardiovascular risk in patients with rheumatoid arthritis.

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.

Urinary albumin excretion in patients with rheumatoid arthritis in a large cross-sectional study.

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.

Austrian Lipid Consensus on the management of metabolic lipid disorders to prevent vascular complications: A joint position statement issued by eight medical societies. 2016 update.

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.

Urinary Albumin Excretion and Vascular Function in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients.

Power of national economy, disease control and employment status in patients with RA-an analytical multi-site ecological study.

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.

Heart rate, ejection duration and subendocardial viability ratio in patients with rheumatoid arthritis as compared to controls.

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.

Will antirheumatic treatment improve cardiovascular outcomes in patients with rheumatoid arthritis?

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.

Using cyclophosphamide in inflammatory rheumatic diseases.

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.

Patients with arthritis undergoing surgery: how should we manage tumour necrosis factor blocking agents perioperatively?-A systematic literature review.

We systematically reviewed the literature on the infectious risk in patients treated with tumour necrosis factor blocking agents (TNF-BA) undergoing surgery: we searched the Medline (PubMed) and the online archive from the Annual European Congress of Rheumatology and the Annual Scientific Meeting of the American College of Rheumatology. Of total 1259 reports, 14 were finally analysed. With one exception all were retrospective. Four of 6 studies compared patients on TNF-BA with those not receiving TNF-BA, and found an increased risk of infection with the use of TNF-BA. None of the other studies which compared continued with discontinued treatment at surgery found an increased risk of infection, when the medication was continued perioperatively. In conclusion, while in theory there is an increased risk of infections when TNF-BA are administered perioperatively, the available literature does not necessarily support this. It rather appears that patients receiving TNF-BA are a priori at a higher risk of postoperative infections. Scheduling surgery at the end of the drug interval and adding one "safety" week prior to surgery should be an acceptable plan in daily clinical practice.

Rheumatoid arthritis is an independent risk factor for an increased augmentation index regardless of the coexistence of traditional cardiovascular risk factors.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: The mean unadjusted AIx was 30.5 ± 9.0% for RA patients and 24.0 ± 11.0% for the n-RA group (P < 0.001). In the regression model, the following variables are statistically significant at approximately the same level (P < 0.001); the order of impact of these variables is age > diastolic blood pressure > sex > RA > height > smoking status. RA, height, and smoking had a nearly equal impact on the AIx. CONCLUSIONS: 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.

Augmentation index in patients with rheumatoid arthritis and ankylosing spondylitis treated with infliximab.

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 (p < 0.001). 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.

Arterial stiffness in a muscular artery in women with longstanding rheumatoid arthritis compared with healthy controls and patients with traditional cardiovascular risk factors.

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 duration >5 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.

Impact of daclizumab, low-dose cyclosporine, mycophenolate mofetil and steroids on renal function after kidney transplantation.

BACKGROUND: Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA. METHODS: We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months. RESULTS: Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 +/- 17) than standard patients (29 +/- 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017). CONCLUSION: We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reactions.

Serum levels of N-terminal pro-B-type natriuretic peptide are associated with allograft function in recipients of renal transplants.

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.

Chronic allograft nephropathy--a clinical syndrome: early detection and the potential role of proliferation signal inhibitors.

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.