Nicholas Inston

Revisiting the risks of MRI with Gadolinium based contrast agents—review of literature and guidelines

Gadolinium based contrast agents (GBCA) have been linked to the occurrence of nephrogenic systemic fibrosis (NSF) in renal impaired patients. The exact interaction between the various different available formulations and occurrence of NSF is not completely understood, but has been postulated. This association has triggered public health advisory bodies to issue guidelines and best practice recommendations on its use. As a result, the reported incidence of NSF, as well as the published use of GBCA-enhanced magnetic resonance imaging in renal impairment, has seen a decline. Understanding of the events that led to these recommendations can increase clinical awareness and the implications of their usage. We present a review of published literature and a brief overview of practice recommendations, guidelines and manuals on contrast safety to aide everyday imaging practice.Teaching Points• Low risk gadolinium based contrast agents should be the choice in renal insufficiency.• Higher doses have been linked to NSF development. Doses should be as low as possible.• Clear documentation of date,dose and type of formulation used should be noted.• Post-scan dialysis should be arranged as soon as possible and feasible.• Pre-existing inflammatory state is a risk factor;liver insufficiency is not a contraindication.

A Review on the Hemodialysis Reliable Outflow (HeRO) Graft for Haemodialysis Vascular Access

OBJECTIVES With improved dialysis survival there are increasing numbers of patients who have exhausted definitive access options due to central venous stenosis and are maintaining dialysis on a central venous catheter. The Hemodialysis Reliable Outflow (HeRO) allows an alternative by providing a definitive access solution. The aim of this study is to systematically review the published outcomes of the HeRO graft and discuss the role in complex haemodialysis patients. METHODS Electronic databases were searched for studies assessing the use of the HeRO graft for dialysis in accordance with PRISMA published up to December 31 2014. The primary outcomes for this study were 1-year primary and secondary patency rates. Secondary outcomes were rates of dialysis access associated steal syndrome, HeRO-related bacteraemia rates and rates of interventions. RESULTS Following strict inclusion/exclusion criteria, eight studies including 409 patients were included in our review. Primary and secondary pooled patency rates in this complex cohort of dialysis patients were found to be 21.9% (9.6-37.2%) and 59.4% (39.4-78%). The rate of dialysis access associated steal syndrome was low at 6.3% (1-14.7%) as was the range of HeRO-related bacteraemia (0.13-0.7 events per 1000 days). CONCLUSIONS This literature review shows that the HeRO graft is an acceptable option for complex dialysis patients who are catheter dependent. Owing to device availability, published data are predominantly North American and further longer-term studies in other populations may be necessary. In this challenging patient group, randomized controlled trials are required to allow comparisons with alternative access options.

Current tools for prediction of arteriovenous fistula outcomes

It remains challenging to accurately predict whether an individual arteriovenous fistula (AVF) will mature and be useable for haemodialysis vascular access. Current best practice involves the use of routine clinical assessment and ultrasonography complemented by selective venography and magnetic resonance imaging. The purpose of this literature review is to describe current practices in relation to pre-operative assessment prior to AVF formation and highlight potential areas for future research to improve the clinical prediction of AVF outcomes.

Early cannulation grafts for haemodialysis: a systematic review

Purpose Arteriovenous grafts have advantages compared with central venous catheters for dialysis access and guidelines suggest their use as second choice after arteriovenous fistulas. Standard practice with expanded polytetrafluoroethylene (ePTFE) grafts has been to avoid cannulation for 2 weeks following placement, but new generation grafts have been marketed for their early cannulation properties allowing use as an alternative to central venous catheters for prompt access. The aim of this review is to search the current literature for evidence of early cannulation of new generation grafts and to assess their patency and complication rates. Methods Electronic databases were searched for studies assessing the use of early cannulation grafts for dialysis in accordance with PRISMA. The primary outcomes for this study were primary patency rate, primary-assisted patency rate and secondary patency rate. Secondary outcomes were timing of first cannulation, rates of access thrombosis, steal syndrome, pseudo-aneurysm and infection. Results Following strict inclusion/exclusion criteria by two reviewers, 15 studies were included in our review and divided into the different types of graft. Flixene, Avflo, Rapidax and Acuseal grafts showed that early cannulation within 72 h was possible; there was no evidence of the use of Vectra within 2 weeks of placement. All grafts showed similar patency and complication rates as previously published data on standard ePTFE grafts. Conclusion Our review showed that early cannulation is possible without detriment, but data did not allow specific graft recommendations. Therefore, we feel that a multicentre, randomised controlled trial is necessary to compare early cannulation grafts.

Predictors and consequences of fatigue in prevalent kidney transplant recipients.

Background Fatigue has been underinvestigated in stable kidney transplant recipients (KTRs). The objectives of this study were to investigate the nature, severity, prevalence, and clinical awareness of fatigue in medically stable KTRs, examine the impact of fatigue on quality of life (QoL), and explore the underlying causes of posttransplantation fatigue. Methods This single-center cross-sectional study enrolled 106 stable KTRs. Multi-dimensional Fatigue Inventory-20 was used to measure five fatigue dimensions: General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation, and Mental Fatigue. Clinical awareness of fatigue was determined by reviewing medical records. QoL was assessed by Medical Outcomes Study Short Form-36 Questionnaire. Demographic, clinical, psychosocial, and behavioral parameters were evaluated as fatigue predictors. Results Fatigue was found in 59% of KTRs. Only 13% had this symptom documented in medical records. Fatigue in KTRs was in the same range as chronically unwell patients, with Physical Fatigue, Reduced Activity, and Reduced Motivation approached levels observed in chronic fatigue syndrome. All fatigue dimensions significantly and inversely correlated with QoL (P<0.001 for all associations). Demographic predictors were male, older age, and non-Caucasian ethnicity (P⩽0.05 for all associations). Clinical predictors included elevated highly sensitive C-reactive protein (inflammation), decreased estimated glomerular filtration rate (graft dysfunction), and reduced lean tissue index (P⩽0.05 for all associations). Psychosocial and behavioral predictors were inferior sleep quality, anxiety, and depression (P<0.01 for all associations). Conclusions Fatigue is common and pervasive in clinically stable KTRs. It is strongly associated with reduced QoL. This study identified modifiable fatigue predictors and sets the scene for future interventional studies.

Development and Evaluation of a Composite Risk Score to Predict Kidney Transplant Failure

BACKGROUND Although risk factors for kidney transplant failure are well described, prognostic risk scores to estimate risk in prevalent transplant recipients are limited. STUDY DESIGN Development and validation of risk-prediction instruments. SETTING & PARTICIPANTS The development data set included 2,763 prevalent patients more than 12 months posttransplant enrolled into the LOTESS (Long Term Efficacy and Safety Surveillance) Study. The validation data set included 731 patients who underwent transplant at a single UK center. PREDICTOR Estimated glomerular filtration rate (eGFR) and other risk factors were evaluated using Cox regression. OUTCOME Scores for death-censored and overall transplant failure were based on the summed hazard ratios for baseline predictor variables. Predictive performance was assessed using calibration (Hosmer-Lemeshow statistic), discrimination (C statistic), and clinical reclassification (net reclassification improvement) compared with eGFR alone. RESULTS In the development data set, 196 patients died and another 225 experienced transplant failure. eGFR, recipient age, race, serum urea and albumin levels, declining eGFR, and prior acute rejection predicted death-censored transplant failure. eGFR, recipient age, sex, serum urea and albumin levels, and declining eGFR predicted overall transplant failure. In the validation data set, 44 patients died and another 101 experienced transplant failure. The weighted scores comprising these variables showed adequate discrimination and calibration for death-censored (C statistic, 0.83; 95% CI, 0.75-0.91; Hosmer-Lemeshow χ(2)P = 0.8) and overall (C statistic, 0.70; 95% CI, 0.64-0.77; Hosmer-Lemeshow χ(2)P = 0.5) transplant failure. However, the scores failed to reclassify risk compared with eGFR alone (net reclassification improvements of 7.6% [95% CI, -0.2 to 13.4; P = 0.09] and 4.3% [95% CI, -2.7 to 11.8; P = 0.3] for death-censored and overall transplant failure, respectively). LIMITATIONS Retrospective analysis of predominantly cyclosporine-treated patients; limited study size and categorization of variables may limit power to detect effect. CONCLUSIONS Although the scores performed well regarding discrimination and calibration, clinically relevant risk reclassification over eGFR alone was not evident, emphasizing the stringent requirements for such scores. Further studies are required to develop and refine this process.

Metabolomic analysis of perfusate during hypothermic machine perfusion of human cadaveric kidneys.

Background The metabolic processes occurring within the preserved kidney during hypothermic machine perfusion (HMP) are not well characterized. The aim of this study was to use nuclear magnetic resonance (NMR) spectroscopy to examine the metabolomic profile of HMP perfusate from human cadaveric kidneys awaiting transplantation and to identify possible discriminators between the profiles of kidneys with delayed graft function (DGF) and immediate graft function (IGF). Methods Perfusates from HMP kidneys were sampled at 45 min and 4 hr of preservation with the LifePort Kidney Transporter 1.0 (Organ Recovery Systems, Chicago, IL) using KPS-1. Prepared samples underwent 1-D Proton-NMR spectroscopy, and resultant spectra were analyzed. Clinical parameters were collected prospectively. Results Perfusate of 26 transplanted cadaveric kidneys was analyzed; 19(73%) with IGF and 7(27%) with DGF. Glucose concentrations were significantly lower in DGF kidneys compared to those with IGF at both 45 min (7.772 vs. 9.459 mM, P = 0.006) and 4 hr (8.202 vs. 10.235 mM, P = 0.003). Concentrations of inosine and leucine were significantly different between DGF and IGF kidneys at 45 min (0.002 vs. 0.013 mM, P = 0.009 and 0.011 vs. 0.006 mM, P = 0.036), and gluconate levels were also significantly different between DGF and IGF kidneys at 4 hr (49.099 vs. 59.513 mM, P = 0.009). Conclusion Significant metabolic activity may be occurring in kidneys during HMP. The NMR spectroscopy of the perfusate can identify differences in the metabolomic profiles of DGF and IGF kidneys that might have a predictive role in viability assessment. Modification of harmful metabolic processes may improve outcomes for HMP kidneys.

Aneurysms and pseudoaneurysms in dialysis access

Aneurysms are a common and often difficult complication seen with arteriovenous vascular access for haemodialysis. The purpose of this narrative review is to define and describe the scale of the problem and suggested therapeutic strategies. A narrative review of the published literature illustrated by individual cases is presented with the aim of summarising the relevant literature. The definitions of aneurysm are inconsistent throughout the literature and therefore systematic review is impossible. They vary from qualitative descriptions to quantitative definitions using absolute size, relative size and also size plus characteristics. The incidence and aetiology are also ill defined but separation into true aneurysms and false, or pseudoaneurysms may be helpful in planning treatment, which may be conservative, surgical or radiological. The lack of useful definitions and classification along with the multitude of management strategies proposed make firm evidence based conclusions difficult to draw. Further robust well designed studies are required to define best practice for this common problem.

Systematic review of drug eluting balloon angioplasty for arteriovenous haemodialysis access stenosis

Background Native or prosthetic arteriovenous (AV) fistulas are preferred for permanent haemodialysis (HD) access. These are marked with circuit steno-occlusive disease leading to dysfunction or even failure. Late failure rates have been reported as high as 50%. Standard angioplasty balloons are an established percutaneous intervention for HD access stenosis. Reported restenosis rates remain high and practice guidelines recommend a wide 6-month primary patency (PP) of at least 50% for any intervention. Neointimal hyperplasia is one of the main causes for access circuit stenosis. Drug eluting balloon (DeB) angioplasty has been proposed as an alternative intervention to reduce restenosis by local drug delivery and possible inhibition of this process. Purpose To systematically assess the reported efficacy and safety of DeB angioplasty in percutaneous management of prosthetic and autologous HD access stenosis. Methods Protocol for the review was developed following the PRISMA-P 2015 statement. An electronic database (Medline, EMBASE, Clinical Trials.gov and Cochrane CENTRAL) search was conducted to identify articles reporting on the use of DeB intervention in HD AV access. Backward and forward citation search as well as grey literature search was performed. The MOOSE statement and PRISMA 2009 statement were followed for the reporting of results. Data from the included studies comparing DeBs with non-DeBs were pooled using a random effects metaanalysis model and reported separately on randomised and non-randomised studies. Results Six studies reported on 254 interventions in 162 participants (mean 27 ± 10 SD). The pooled mean and median duration of follow-up was 12 and 13 months (range 6-24 months). These comprised two randomised control trials (RCTs) and four cohort studies. Participants mean age was 64 ± 5 years and 61% were male. Target lesions (TLs) ranged from under 2 mm to 5.9 mm and 51 were reported as de novo stenosis. Device failure described as wasting of the DeB was reported in two studies (55% and 92.8%). At 6 months TL PP was reported between 70% to 97% for DeBs in the RCTs and cohort studies, and 0% to 26% for non-DeBs. TLs treated with DeBs were associated with a higher primary patency at 6 months as compared to non-DeB balloons (RCTs: odds ratio [OR] 0.25, 95% CI 0.08 to 0.77 and I2 = 19%, cohort studies: OR 0.10, 95% CI 0.03 to 0.31 and an I2 = 20%). No procedure-related major or minor complications were reported. Conclusions Current literature reports DeBs as being safe and may convey some benefit in terms of improved rate of restenosis when used to treat AV access disease. However, this body of evidence is small and clinically heterogeneous. A large multicentre RCT may help to clarify the role of DeBs in the percutaneous treatment of AV HD access stenosis.

The use of NGAL and IP‐10 in the prediction of early acute rejection in highly sensitized patients following HLA‐incompatible renal transplantation

Acute rejection is a significant problem for patients undergoing HLA‐incompatible renal transplantation, affecting between 12 and 53% of patients. Any mechanism of detecting rejection in advance of current methods would offer significant benefit. This study aimed to evaluate whether serum biomarkers could predict rejection in HLAi transplants recipients. Sera from 94 HLAi transplant recipients from a single centre were analysed for a panel of biomarkers including: NGAL, KIM‐1, IP‐10, cystatin C, cathepsin L and VEGF. Biomarker levels pre‐operatively, day 1 and at day 30 post‐transplant were correlated with the development of early rejection. Significantly higher levels of IP‐10 and NGAL were seen on day 1 following transplant in those patients who developed acute rejection (P < 0.001 and 0.005) and generated AUC of 0.73 and 0.67, respectively. No differences were seen for the other biomarkers or at the other time points. In this study cohort, IP‐10 and NGAL have demonstrated good predictive ability for the development of acute rejection at a very early time point. They may have a role in identifying patients at higher risk for rejection and stratifying immunosuppression or surveillance.