Impact of Isometric Exercise in Adolescents With End Stage Kidney Disease and Unsuitable Vessels For An Autologous Arteriovenous Fistula.

INTRODUCTION: Despite the lack of calcification, to perform a native Arteriovenous Fistula (AVF) in young patients may pose a challenge due to small vessel diameter. We report a case series with no options of AVF in which vessel caliber improvement after isometric exercise allowed for radiocephalic fistula creation in all of them. METHODS: Since 2017 to 2019, four patients were referred to our unit to create an AVF. Following a first assessment with physical examination and doppler ultrasound, none of them were eligible for AVF performance due to small vessel caliber. Once they were considered unsuitable for it, they started an isometric exercise program. RESULTS: Age ranged from 13 to 19 years. There were three males and one female. Two were in predialysis and two in hemodialysis program. Initial diameters of the forearm cephalic vein and the radial artery respectively were: case A < 1.5/2.3 mm, case B 1.5/1.6 mm, case C < 1.5/1.6 mm and case D 2.1/1.3 mm. Median duration of exercise program was 13 weeks (range 5-23). Post-exercise vessel diameters were: case A 2.7/2.3 mm, case B 2.5/2 mm, case C 2.8/1.8 mm and case D 2.7/2 mm. Radiocephalic AVF were performed in the four cases. After a median follow up of 19 months (range 9-30 months), 75% of patients required further interventions but all of them had a functional AVF. CONCLUSIONS: In these four cases isometric preoperative exercise allowed the creation of AVF. Without the improvement in vessel diameter observed afterwards, all of them would have been rejected for AVF performance. Despite the high rate of adjunctive interventions needed, given the safety of the program and the potential risks of Central Venous Catheters, we consider it a valuable option.

Efficacy and safety of intramuscular administration of allogeneic adipose tissue derived and expanded mesenchymal stromal cells in diabetic patients with critical limb ischemia with no possibility of revascularization: study protocol for a randomized controlled double-blind phase II clinical trial (The NOMA Trial).

BACKGROUND: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. METHODS: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. DISCUSSION: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.

Rationale and design of the PHYSICALFAV trial: a randomized controlled trial to evaluate the effect of preoperative isometric exercise on vascular calibre and maturation of autologous arteriovenous fistulas.

BACKGROUND: A good vascular access (VA) is vital for haemodialysis (HD) patients. HD with an autologous arteriovenous fistula (AVF) is associated with higher survival, lower health care costs and fewer complications. Although a distal forearm AVF is the best option, not all patients are good candidates for this approach and the primary failure rate ranges from 20% to 50%. The optimal AVF depends mainly on the anatomical and haemodynamic characteristics of the artery and the vein chosen for the anastomosis. These characteristics can be modified by performing physical exercise. VA guidelines suggest that isometric exercises should be performed both before and after the AVF is created. While the literature contains few data on the potential efficacy of preoperative exercise, small observational studies point to an improvement in venous and arterial calibre. Postoperative exercise also seems to improve maturation, although there is no consensus on the appropriate exercise protocol. METHODS: The PHYSICALFAV trial (NCT03213756) is an open-label, multicentre, prospective, controlled, randomized trial designed to evaluate the usefulness of preoperative isometric exercise (PIE) in pre-dialysis patients or in prevalent HD patients who are candidates for a new AVF. Patients are randomized 1:1 to the PIE group (isometric exercises for 8 weeks) or the control group (no exercise). The main endpoint is whether the rate of primary failure is lower in the PIE group than in the control group. RESULTS: The trial has already started, with 40 patients having been enrolled as of 21 March 2018; 26.5% of the estimated sample.

A new approach for bone marrow-derived stem cells intrapancreatic autotransplantation in diabetic rats.

PURPOSE: A new technique for stem cells intrapancreatic autotransplantation in rats. BASIC PROCEDURES: Section of a femoral diaphysis and aspirations of the bone marrow in both femoral segments were performed. A Kirschner needle was placed into the femur. Cells were isolated in Ficoll gradients and preserved at 4-6 degrees C. The second day, cells were injected, via aortic celiac trunk, into the pancreas of the same rat. RESULTS: Femoral surgery were well tolerated. Intrapancreatic homing of the injected cells was suggested with methylene blue injection that stained the pancreas, and proved by labeled cells in pancreas sections. Cell counts after Ficoll isolation were 1 x 10(6) +/- 2 x 10(5) ES. CONCLUSIONS: A technique is described for stem cell autotransplantation in rats. First we obtain autologous bone marrow-derived stem cells. Second, we inject the cells in the pancreas of the donor rat. This approach can be applied to experimental diabetes and other pancreatic processes.