Paul Gibbs

Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (3C) study: background, rationale, and study protocol

BackgroundKidney transplantation is the best treatment for patients with end-stage renal failure, but uncertainty remains about the best immunosuppression strategy. Long-term graft survival has not improved substantially, and one possible explanation is calcineurin inhibitor (CNI) nephrotoxicity. CNI exposure could be minimized by using more potent induction therapy or alternative maintenance therapy to remove CNIs completely. However, the safety and efficacy of such strategies are unknown.Methods/DesignThe Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy (3C) Study is a multicentre, open-label, randomized controlled trial with 852 participants which is addressing two important questions in kidney transplantation. The first question is whether a Campath (alemtuzumab)-based induction therapy strategy is superior to basiliximab-based therapy, and the second is whether, from 6 months after transplantation, a sirolimus-based maintenance therapy strategy is superior to tacrolimus-based therapy. Recruitment is complete, and follow-up will continue for around 5 years post-transplant. The primary endpoint for the induction therapy comparison is biopsy-proven acute rejection by 6 months, and the primary endpoint for the maintenance therapy comparison is change in estimated glomerular filtration rate from baseline to 2 years after transplantation. The study is sponsored by the University of Oxford and endorsed by the British Transplantation Society, and 18 centers for adult kidney transplant are participating.DiscussionLate graft failure is a major issue for kidney-transplant recipients. If our hypothesis that minimizing CNI exposure with Campath-based induction therapy and/or an elective conversion to sirolimus-based maintenance therapy can improve long-term graft function and survival is correct, then patients should experience better graft function for longer. A positive outcome could change clinical practice in kidney transplantation.Trial registrationClinicalTrials.gov, NCT01120028 and ISRCTN88894088

Good Long Term Patency Rates Associated with an Alternative Technique in Vascular Access Surgery – The Adductor Loop Arteriovenous Graft

INTRODUCTION We have modified the arteriovenous groin loop procedure and present a technique associated with good patency rates and low infection rates. METHODS We describe an alternative femoro-femoral arteriovenous loop technique which utilises the mid-thigh sub-sartorial Superficial Femoral Artery and Femoral Vein. We then performed a retrospective analysis of all such cases performed in our unit to date and analysed the patency and infection rates associated with the technique. RESULTS 16 cases have been performed to date with a median follow-up of 18 months. The primary and secondary patency rates at one year were 70% and 90% respectively. The overall infection rate was only 12.5%. CONCLUSIONS Our technique is associated with good patency rates and low infection rates. In addition it preserves modesty whilst on dialysis and the groin vessels for further vascular access surgery if needed.

Arteriovenous access ischemic steal (AVAIS) in haemodialysis: a consensus from the Charing Cross Vascular Access Masterclass 2016

Arteriovenous access ischaemic steal (AVAIS) is a serious and not infrequent complication of vascular access. Pathophysiology is key to diagnosis, investigation and management. Ischaemia distal to an AV access is due to multiple factors. Clinical steal is not simply blood diversion but pressure changes within the adapted vasculature with distal hypoperfusion and resultant poor perfusion pressures in the distal extremity. Reversal of flow within the artery distal to the AV access may be seen but this is not associated with ischaemia in most cases. Terminology is varied and it is suggested that arteriovenous access ischemic steal (AVAIS) is the preferred term. In all cases AVAIS should be carefully classified on clinical symptoms as these determine management options and allow standardisation for studies. Diabetes and peripheral arterial occlusive disease are risk factors but a ‘high risk patient’ profile is not clear and definitive vascular access should not be automatically avoided in these patient groups. Multiple treatment modalities have been described and their use should be directed by appropriate assessment, investigation and treatment of the underlying pathophysiology. Comparison of treatment options is difficult as published studies are heavily biased. Whilst no single technique is suitable for all cases of AVAIS there are some that suit particular scenarios and mild AVAIS may benefit from observation whilst more severe steal mandates surgical intervention.

Does bicarbonate prevent contrast-induced nephropathy in cardiovascular patients undergoing contrast imaging?

A best evidence topic in cardiovascular surgery was written according to a structured protocol. The question addressed was whether administering sodium bicarbonate (NaHCO3) prevents contrast-induced nephropathy (CIN) in cardiovascular patients undergoing contrast imaging. In total, 266 papers were found using the reported search, 16 of which represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. CIN is thought to occur as a result of ischaemic or oxidative injury to the kidney. It is postulated that NaHCO3attenuates this renal damage by alkanizing renal tubular fluid thus reducing the generation of contrast-induced free radicals, which damage the kidney. Of the 16 trials, 15 recruited patients with various degrees of renal dysfunction at baseline. The benefit of using NaHCO3 was demonstrated at all stages of chronic kidney disease. Apart from four studies, 12 studies used low toxicity, low-osmolar contrast. Merten et al. published the first trial of NaHCO3 vs (saline) NaCl in preventing CIN, demonstrated a significantly lower rate in the NaHCO3 group and advocated its widespread use. Subsequent trials using the same regimen have collaborated these results. However, more recently, Gomes et al. concluded that NaHCO3 is not superior to saline-based hydration. Similarly, Brar et al. randomized 323 patients with moderate-to-severe renal insufficiency to receive either an NaHCO3 or an NaCl infusion and observed no difference in CIN rates. Two studies investigated the effects of rapid urine alkanization with bolus injections of NaHCO3 prior to contrast and found significant reductions in CIN rates compared with NaCl-treated groups. One study observed that NaCl is superior to NaHCO3, while all other studies showed a beneficial effect or no difference between NaCl- and NaHCO3-based hydration. The most recent meta-analysis by Jang et al. incorporated 3609 patients across 19 trials and concluded that NaHCO3-based hydration regimens are superior to NaCl-based ones. Based on this review, the authors recommend NaHCO3 alongside an NaCl hydration regimen. The exact regimen will depend on the context within which contrast is being administered and needs further evaluation.

Aneurysms in vascular access: State of the art and future developments

A master class was held at the Vascular Access at Charing Cross (VA@CX2017) conference in April 2017 with invited experts and active audience participation to discuss arteriovenous (AV) vascular access aneurysms, a serious and common complication of vascular access (VA). The natural history of aneurysms in VA is poorly defined, and although classifications exist they are not uniformly applied in studies or clinical practice. True and pseudo aneurysms of AV access occur. Whilst an AV fistula by definition is an abnormal dilatation of a blood vessel, an agreed definition of 18 mm, or 3 times accepted maturation diameter, is proposed. The mechanism of aneurysmal dilatation is unknown but appears to be a combination of excessive external remodeling, wall changes due to injury, and obstruction of outflow. Diagnosis of AV aneurysms is based on physical examination and ultrasound. Venography and cross-sectional imaging may assist and be required for the investigation of outflow stenosis. Treatment of pseudo aneurysms and true aneurysms of VA (AVA) is not evidence-based, but relies on clinical experience and available facilities. In many AVA, a conservative approach with surveillance is suitable, although intervals and modalities are unclear. Avoidance of rupture is imperative and preemptive treatment should aim for access preservation, ideally with avoidance of prosthetic materials. Different techniques of aneurysmorrhaphy are described with good results in published series. Although endovascular approaches and stenting are described with good short-term results, issues with cannulation of stented areas occur and, while possible, this is not recommended, and long-term access revision is recommended.

Good long-term patency: 10-year follow-up using the mid-thigh adductor loop arteriovenous graft

Introduction: Definitive access in patients requiring renal replacement therapy is an ever-increasing challenge. For those where autogenous venous access is no longer a viable option, arteriovenous grafts can be considered. This article describes long-term follow-up, complications and patency rates of the mid-thigh ‘adductor loop’ arteriovenous graft. Methods: 50 mid-thigh loop arteriovenous grafts have been inserted into 48 patients in our unit over the past 11 years. A prospective database was collected on patients receiving an arteriovenous graft at our unit by the senior author. All remained under the care of our unit ensuring accurate follow-up data collection and database was updated at regular intervals. Results: Death-only censored primary patency at 1, 3 and 5 years was 76%, 44% and 23%, respectively. Patients receiving transplants were not censored as follow-up of the arteriovenous grafts was possible. Secondary patency at 1, 3 and 5 years was 95%, 63% and 45%. These rates are higher than previous studies looking at lower limb arteriovenous grafts. Graft thrombosis occurred in 14 patients (28%). Six patients were treated for an infection (12%) but only four grafts were excised; much lower than documented in previous studies. Conclusion: Autogenous venous access remains the perceived gold standard for patients requiring dialysis for end stage renal failure, despite some published data reporting poor outcomes. We have shown that adductor loop arteriovenous grafts can be a reliable, safe and long-term alternative in those whom fistula formation is not possible and may have a role earlier in the patient journey than previously thought, as a result of good patency and lower complications.