Chronic kidney disease (CKD) is a growing worldwide crisis. According to the 2010 Global Burden of Disease study published in The Lancet, CKD was 27 in the list of causes of total number of deaths worldwide in 1990 but had climbed to 18 by 2010.1 Individuals with diabetes, peripheral artery disease (PAD), hypertension, heart failure, liver diseases and advanced age are among those at risk of CKD and end-stage renal disease (ESRD). Other iatrogenic risk factors include renal toxicity due to medications or other chemical exposure. Treatment of CKD depends on the severity of the disease and in stage 5 ESRD peritoneal dialysis, haemodialysis or kidney transplant is needed. It is estimated that over two million individuals worldwide are stricken with ESRD and depend on dialysis therapy or a kidney transplant for survival. However, this estimation may only represent 10% of the individuals who require these life-sustaining therapies.2 In the US alone, it is estimated that over 600,000 individuals with ESRD are haemodialysis-dependent.2
Every haemodialysis patient requires vascular access which is so vital that it can be considered the patient's lifeline. A central venous catheter may provide for short-term vascular access but for many reasons is not ideal for long-term management.3 There are two types of permanent vascular access options existing for haemodialysis — the arteriovenous fistula (AVF) and the arteriovenous graft (AVG). The AVF is preferred for long-term haemodialysis vascular access due to long-term primary patency rates requiring the fewest interventions of any type of access. More importantly, the AVF, when compared with other types of access, is associated with the lowest incidence of morbidity and mortality.3,4,5,6,7,8 A mean duration of 70 days between access creation to first cannulation was corroborated in a past study.9 AVF complications include aneurysms, infections, steal syndrome, thrombosis as well as venous hypertension. Aneurysms, if left untreated, are at risk of rupture and serious haemorrhage, as well as restricting the accessible locations for cannulation. Given the limited options for haemodialysis access placement, preservation of existing AVF sites is always a priority.
Dehydrated human amnion/chorion membrane (dHACM) allograft (EpiFix, MiMedx Group Inc., US) is a commercially available human tissue matrix allograft. Published, peer-reviewed scientific studies indicate that dHACM retains an assorted array of regulatory proteins comprising of essential growth factors, chemokines and cytokines, which are regulators in inflammation, cell migration and proliferation as well as angiogenesis.10,11,12,13 Clinical evidence including several randomised controlled trials (RCT). support the use of dHACM for healing chronic wounds.14,15,16,17
The purpose of this report is to present our experience with using dHACM as a novel treatment for promotion of wound healing of a failed AVF surgical site with issues of scarring and tissue breakdown.
Case
The individual in this manuscript provided the primary author with written informed consent for images obtained and for publication of these case details. As this was a single case report on the use of a non-experimental allograft, specific written permission for images and publication was obtained from the patient and institutional review board (IRB) approval was not required.
The patient was a 52-year-old male, living in UAE, with an extensive medical history that included hypertension, past cerebrovascular accident (CVA) and serious cardiac problems, as well as ESRD for which he received a renal allograft transplant donated by his brother in Abu Dhabi in 1997. Unfortunately, the renal graft transplant began to show signs of gradual failure in 2007. As a result, over the period of seven years, the patient received alternating right and left internal jugular central venous catheters to maintain haemodialysis access which eventually had associated complications due to long-term use and reinsertions. In 2014, the patient received a right brachiocephalic AVF through which he was receiving haemodialysis. At this point in the patient's clinical course, the options for vascular graft access were limited to the right upper extremity since the patient had a left superior vena cava obstruction complicated further by a pre-existing left subclavian and left internal jugular vein thrombosis, the prior creation and failure of a thrombosed left brachiocephalic fistula as well as a stented right superior vena cava.
In February 2019, the patient presented to the emergency department, at Al-Qassimi Hospital, post-dialysis with a ruptured aneurysmal AVF that was further complicated with an infectious process represented clearly by severely friable tethered skin and discharge from the underlying tissues, extending and involving the anterior wall of the cephalic vein site of anastomosis to the brachial artery. An aneurysmoraphy was performed, preserving function of the fistula, while appropriate antimicrobial therapy was initiated concomitantly.
At 17 days post-aneurysmoraphy, a subsequent episode of active bleeding after dialysis occurred requiring further surgical intervention (Fig 1a). In the operating room, the skin covering the AVF was found to be severely tethered along with a significant amount of unhealthy underlying tissue. During the surgical procedure all the unhealthy tissues involving the covering skin, the subcutaneous tissues and almost the entire anterior wall of the anastomosed cephalic vein to the brachial artery, was excised completely, as a basic surgical concept to allow a clean healing process. A synthetic cardiovascular patch was placed, using 4/0 proline, double round needle to baffle the anterior wall of the right cephalic vein extending near the communication with the brachial artery maintaining the fistula patency on either side, thus securing haemostasis. A 2.5x3.5cm skin defect resulted secondary to the required excision of unhealthy tissue, which mandated further extensive undermining to approximate the skin edges. A 4x4cm2 dHACM allograft was applied partly to the deep part of the wound with evaginated edges of the allograft to the exterior sides of the edges of the wound (Fig 1b). The surgical wound edges were approximated as much as possible with 2/0 proline sutures (Fig 1c). A non-absorbable paraffin dressing was applied, before any other type of dressing.
Following the surgical repair, the patient was monitored over three weeks, at weekly intervals, and he received haemodialysis through a temporary right femoral catheter. Complete healing of the surgical wound was noted at 23 days, (Fig 1d) postoperatively. A total of 36 days postoperatively from revision using the synthetic cardiovascular patch and dHACM application (10 days after complete healing), the temporary femoral catheter began to malfunction. At that time, the repaired AVF was cannulated without any event. During a nephrology clinic visit in June 2019, the patient was further evaluated and was found to have subacute bacterial endocarditis with blood cultures positive for Staphylococcus aureus. Intravenous vancomycin was initiated and continued for six weeks. As of the last week of July 2019, the repaired AVF remained free of complications such as bleeding, signs of infection, tethering of skin over the AVF site or underlying tissue breakdown.
Conclusion
Existing clinical data and practice guidelines support reduction in the use of venous catheters in order to decrease the occurrence of central venous line access complications and to improve patient survival, especially among male haemodialyses patients.18 An AVF causes extra pressure and extra blood to flow into the vein, making it grow large and strong. The larger vein provides easy, reliable access for haemodialysis.
The elements necessary for a healthy tissue repair response include angiogenesis, a regulated inflammatory response, matrix deposition and cell recruitment. Regulatory proteins with the ability to promote fibroblast migration as well as dampen matrix metalloproteinase (MMP) activity have been identified in dHACM, in addition to over 500 other unique microRNAs.11,12 More specifically, dHACM has been shown to contain stimulatory growth factors such as PDGF-AA, PDGF-BB, bFGF, TGF-b1, EGF, VEGF, and PlGF, as well as anti-inflammatory interleukins (IL-1ra, IL-4, IL-10), and TIMP-1, TIMP-2, TIMP-4 which, as previously mentioned, help regulate the MMP activity.11,12
The use of dHACM for wound healing is not unprecedented. Application of dHACM to chronic lower extremity ulcers has been shown to significantly improve the trajectory towards wound closure.14 There are also numerous clinical examples where the use of dHACM has favourably impacted the reconstructive ladder in scenarios where the surgical options for wound closure were limited.16,17
This case report is unique in that it shows how the combination of appropriate surgical intervention, using a synthetic cardiovascular patch and the application of dHACM during the closure of a complex surgical wound, can lead to a successful outcome, including an expedited return to haemodialysis via this patient's AVF. Indeed, in this case, healing was sufficient to allow use of the AVF for haemodialysis 36 days post-revision, approximately half the mean of the 70 days reported between access creation to first cannulation by Yoo et al.9 These results support the use of dHACM in a variety of surgical wounds and in patients with comorbidities that can influence successful healing.