J. Szmidt

Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials

BACKGROUND For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. METHODS We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. FINDINGS Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47-72) of patients had primary patency, 73% (57-81) had primary assisted patency, and 97% (85-98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17-40) had primary patency, 38% (26-51) had primary assisted patency, and 89% (74-93) had secondary patency. INTERPRETATION Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. FUNDING Humacyte and US National Institutes of Health.

Effects of the Correction of Renal Artery Stenosis on Blood Pressure, Renal Function and Left Ventricular Morphology

The aim of this study was to evaluate the effect of renal artery stenosis (RAS) correction in hypertensive patients on 24 h SBP, 24 h DBP, creatinine clearance (GFR), urinary albumin excretion (UAE) and LV morphology and mass (LVMI). A total of 61 hypertensive patients with RAS undergoing PTRA and/or surgical treatment entered the prospective study. The final analysis was done in 44 patients (age range 45.8 +/- 16.2 years) with RAS (atherosclerosis (ASC) 31 patients, fibromuscular dysplasia (FMD) 12 patients, arteritis 1 patient) who underwent PTRA (34 patients) or surgical treatment (10 patients) and presented no Doppler signs of restenosis (or a new stenosis) during 1-year observation. The pre-interventional assessment repeated after 6 and 12 months included ABPM, GFR, UAE and echocardiography. The results were analysed in the combined group (CG) and in according aetiology. 24 h SBP and 24 h DBP decreased in all groups 6 months post-intervention and did not change further. Cure of HT was observed in 35% and 29% of ASC patients at 6 and 12 months respectively; and in 58% of FMD patients. Failure rate at 12 months was 48% in ASC against 25% in FMD. The mean GFR in CG was higher 12 months after intervention. The increase in GFR was noted in 45% of patients, the decrease in 25% of patients at 12 months. Normal values of UAE were found in 71% of patients, pre- and post-intervention alike. Mean LVMI and number of patients with LVH in CG decreased already during the initial 6 months post-intervention and did not change further. In conclusion, correction of RAS leads to cure of or improved control of hypertension in the majority of the patients with FMD, but in the ASC group in about half of cases no BP cure or improvement was seen. The renal function was improved or stable in two-thirds of patients after revascularization. Successful renal revascularization was followed by regression of LVH, which was evident within 6 months post-intervention.

Compensated activation of coagulation in patients with abdominal aortic aneurysm: effects of heparin treatment prior to elective surgery

Elective surgery of abdominal aortic aneurysm (AAA) sometimes leads to excessive bleeding and disseminated intravascular coagulation (DIC), even in patients with normal preoperative coagulation parameters. Coagulation screen, performed routinely before surgery is of limited value in the assessment of compensated activation of the haemostatic system. In this study, we used a number of additional tests (D-dimer, prothrombin fragment 1+2, antithrombin, and activation of fibrinolysis in the platelet poor plasma) for the diagnosis of compensated activation of the haemostatic system in AAA-patients. D-dimer and marker of thrombin generation (prothrombin fragment 1+2) positively correlated with each other (r = 0.768, P < 0.001). Out of 71 AAA patients, 15 patients had normal global coagulation times, but those with a D- dimer concentration above 3000 ng/ml were selected for preoperative low molecular weight heparin (LMWH) treatment. Administration of LMWH diminished coagulation abnormalities (D-dimer and prothrombin fragment 1+2 decreased significantly) and resulted in the increase of platelet number and fibrinogen concentration, indicating their previous consumption. Despite differences in aneurysm diameters between the groups of 15 LMWH treated patients (mean 70.9 +/- 16 mm) and the reference group of 20 untreated AAA patients (mean 52.3 +/- 8.0 mm), intraoperative parameters (operation time, blood loss and transfusion demands) were similar.

Vascular Access for Haemodialysis in Patients with Central Vein Thrombosis

OBJECTIVES Dialysis-dependent patients often have central venous drainage complications. In patients with functioning arm arteriovenous fistula, this may result in venous hypertension, arm oedema and vascular access failure. Percutaneous angioplasty and stent implantation might be inadequate to resolve these issues. In these cases, new access can potentially be created with anastomosis to the subclavian vein, iliac vein or vena cava or by making a veno-venous graft to bypass the thrombosis. The aim of this study was to assess the utility of unusual bypasses in vascular access in patients with the central vein thrombosis. MATERIALS A total of 49 patients were treated. The mean number of previous vascular access surgery procedures was 7.6 (3-17). We performed 19 axillo-iliac, 14 axillo-axillary bypasses and 16 conduits from the arm fistula to the jugular (nine conduits) or subclavian (seven conduits) vein for haemodialysis purposes. RESULTS All fistulas except one were used for haemodialysis. One patient died before the first use of the fistula. At 12 months, the primary, primary assisted and secondary patency rates were 85.4%, 89.6% and 95.8%, respectively. The follow-up period ranged from 1 to 84 months. CONCLUSION Unusual grafts are an efficient option as a permanent vascular access for haemodialysis purposes in patients with central vein occlusion.

Is Severe Atherosclerosis in the Aortoiliac Region a Contraindication for Kidney Transplantation

BACKGROUND Atherosclerosis is common in end-stage renal disease patients on dialysis. However, it has previously been considered to be a relative contraindication to kidney transplantation. Currently, patients with extended indications are accepted onto the waiting list, including those with severe atherosclerosis. These patients require vascular procedures before or during kidney transplantation. The aim of this study was to present our experience with vascular reconstruction before kidney transplantation. MATERIAL AND METHODS Twelve atherosclerotic, uremic patients referred to be candidates for kidney transplantation were refused because of occlusive lesions of the iliac arteries or the distal aorta. The 10 males and 2 females had an age range of 45 to 68 years. Preoperative assessments consisted of a Doppler ultrasound and an angio computed tomography scan. The reconstructions were performed with aorto-biliac, aorto-bifemoral, or ilio-femoral dacron grafts in 7, 4, and 1 patient, respectively, under general anesthesia. RESULTS There were no major postoperative complications; the patients were discharged and placed on a special waiting list. Eight patients received kidney allografts, including one living-related transplantation. All procedures were performed with arterial anastomosis of the transplanted kidney to the side of the prosthesis. No patient developed signs of arterial graft infection. In the postoperative period, there were no arterial or transplanted kidney-related complications, except for delayed graft function in four cases. The remaining four patients are still on the waiting list. CONCLUSION In end-stage renal disease patients with severe atherosclerosis in the aortoiliac region, vascular reconstruction allows kidney transplantation.

Reoperations for persistent or recurrent primary hyperparathyroidism: results of a retrospective cohort study at a tertiary referral center.

Background Parathyroid reoperations are challenging and achieving a cure requires multidisciplinary treatment team cooperation. The aims of this study were to summarize our experience in revision surgery for persistent (pHPT) or recurrent primary hyperparathyroidism (rHPT) and to explore factors underlying failure to cure at initial surgery. Material/Methods This was a retrospective cohort study of patients who underwent reoperations for pHPT or rHPT at a tertiary referral center. The database of parathyroid surgery was searched for eligible patients (treated in the years 2000–2012). The primary outcome was the cure rate. All the patients were followed-up for at least 12 months postoperatively. Factors underlying failure to cure at initial surgery were reviewed based on hospital records. Results The study group comprised 88 patients (69 women, 19 men) operated on for persistent (n=57) or recurrent disease (n=31), who underwent 98 reoperations, including 26 (2.4%) patients first operated on at our institution, and 72 (81.8%) patients operated on elsewhere, but referred for revision surgery. A long-term cure was achieved in 83/88 patients (94.3%). The mean post-reoperation follow-up was 91.7 (12–176) months. Missed hyperfunctioning parathyroid gland was found on reoperation in eutopic position in 49 (55.5%) patients, and in ectopic position in 39 (44.3%) patients, including 20 (22.7%) cases of cervical ectopy and 19 (21.6%) cases of mediastinal ectopy. Conclusions Multidisciplinary treatment team cooperation at a tertiary referral center, consisting of an accurate preoperative localization, expertise in parathyroid re-explorations, and correct use of intraoperative adjuncts, contribute to the high success rate of parathyroid reoperations.

Dietary supplements and herbal preparations in renal and liver transplant recipients.

BACKGROUND Dietary supplements (DS) and herbal preparations (HP) are advertised to be safe and have therapeutic potential. They are sold over the counter. Therefore, a considerable increase in the frequency of their use has been observed; for example in the United States one in four persons taking medicines uses DS. The use of DS and HP in renal and liver transplant recipients remains unknown. OBJECTIVES The aim of our study was to determine the proportion of patients who used DS or HP, as well as to assess their awareness of the benefits and risks related to ingestion of these products. METHODS We enrolled 100 renal, liver, or combined renal and heart transplant patients into the study. They underwent a survey consisting of 14 multiple-choice questions, concerning demographic features, transplant-related data, and information about the use of DS and HP, including the frequency of use, the reasons for the purchase, the knowledge of risks and benefits, as well as the sources of information about these products. RESULTS Among the 58 (58%) patients who admitted their use of DS and/or HP, 20 (34.5%) ingested more than one preparation. Among liver patients, 51%, and among renal, 44%, of patients took these products for a variety of indications. Vitamins, minerals, diuretics, gastrointestinal tract-regulating, and sedative herbs were chosen most frequently. While 27% of respondents alleged to have obtained the information on DS and HP from a physician, 14% were from a pharmacist, 9% from a friend, acquaintance or neighbor, 8% from an attached leaflet, 4% from an advertisement, and 4% from the internet. CONCLUSIONS A high proportion of patients use DS and HP. Most preparations were taken without medical consultation. Awareness of their toxicity or drug interactions was low. Therefore, a tailored education program should be proposed for this group of patients.

Safety and Tolerance of Sodium Mycophenolate in Patients After Renal Transplantation—An Observational Study

BACKGROUND Enteric-coated mycophenolate sodium (EC-MPS) was developed as an alternative agent to mycophenolate mofetil (MMF), aimed at reduction of gastrointestinal (GI) complications. METHODS Seventy-four patients (mean age 42.3 years) switched from MMF to MPS were included in the study and followed-up for 3 months (Visit 0, Visit 2 after 1 month and Visit 3 after 3 months). The mean time from transplantation to switch was 3.7 years. During Visit 2 and 3 the following were recorded: impact of treatment change on the severity of GI symptoms (4 point scale: 1-worsening, 2-no change, 3-improvement, 4-resolution), EC-MPS tolerance, adverse events (AEs), patient compliance and physician satisfaction with treatment (4 point scale: 1-bad, 2-fair, 3-good, 4-very good). RESULTS Sixty-three patients completed the study (85.1%). EC-MPS dose ranged from 720 to 1440 mg. GI symptom severity score averaged at 3.41. Symptoms most commonly compelling a conversion were: abdominal pain, diarrhea, abdominal colic, nausea, anorexia and vomiting. Out of 175 complaints, 144 (82%) either improved or resolved, 5 (2.86%) aggravated, and 25 (14.86%) persisted. Patient compliance and mean physician satisfaction score averaged at 3.70 and 3.02 at Visit 3, respectively. 9 AEs (2 severe) were reported. Causal relationship with the medication was suspected in 5 cases (1 case of SAE). The most common AEs were: anemia, infection (including sepsis), GI symptoms (abdominal pain, diarrhea). CONCLUSIONS The following was concluded in our study: (1) sodium mycophenolate is well tolerated; (2) after switching from MMF to EC-MPS, gastrointestinal symptoms alleviated; (3) EC-MPS is a safe medication, with a low adverse events rate.

36-Month follow-up of 75 renal allograft recipients treated with steroids, tacrolimus, and azathioprine or mycophenolate mofetil

OBJECTIVES The aim of this retrospective study was to assess the incidence of acute rejection episodes (AR), diabetes mellitus (DM), and serum creatinine (SCr) among renal transplant recipients treated with tacrolimus (Tac), steroids (S), and mycophenolate mofetil (MMF) or azathioprine (Aza). METHODS Seventy-five renal allograft recipients enrolled in the COSTAMP study were followed for a period of 3 years. Patients were randomized to receive either Tac and MMF (n = 41) or Tac and Aza (n = 34) concomitantly with steroids. Follow-up assessments were performed at 3, 6, 12, 24, and 36 months. RESULTS Patient survival at month 36 was 91.18% in the Tac/Aza/S group and 97.56% in the Tac/MMF/S group. Graft survival at month 36 was 82.35% and 85.37%, respectively. During the study period, 22 cases of biopsy-proven AR were diagnosed in 17 patients (22.6%). After 36 months the total number of AR was 11 in the Aza-treated group (32.4%) and 11 in the MMF-treated group (26.8%). DM was diagnosed de novo in 17 individuals (22.6%). During 36 months, 10 patients from Aza-treated group (29.4%) and seven from MMF-treated group developed DM (17.1%). Serum creatinine values were not significantly different in both arms of the study. Comparison of arterial blood pressure and total cholesterol revealed no significant changes in any of the studied groups. CONCLUSIONS We conclude that combinations of steroids, tacrolimus, and azathioprine or MMF provide good results with regard to renal function.

Surgical Complications Related to Transplanted Pancreas After Simultaneous Pancreas and Kidney Transplantation

OBJECTIVE Simultaneous pancreas and kidney transplantation (SPTKx) is characterized by the high rate and variability of postoperative complications, which could be a limitation of this treatment. The aim of this study was to evaluate prevalence, types, and severity of postoperative complications due to pancreas graft among the simultaneous pancreas and kidney recipients. METHODS Postoperative complications related to transplanted pancreas among 112 SPTKx recipients were analyzed. The cumulative survival rates for pancreas graft function and cumulative freedom from complication on day 60 after transplantation were assessed. Severity of complications was classified according to a modified Clavien-Dindo scale. RESULTS The 12-month cumulative survival rate for pancreatic graft was 0.74. Cumulative freedom from complication on the 60th day after transplantation was 0.57. The rates for II, IIIA, IIIB, IVA, and IVB severity grades were 10,6%, 4,5%, 19,7%, 44%, and 21,2%, respectively. The most severe (IVB) transplanted pancreas complications were due to graft inflammation, infection, pancreatic abscess, and local or diffuse necrosis. The most frequent reason for graft pancreatectomy was vascular thrombosis 35.9% (14/39). The mortality rate after graft pancreatectomy was significantly lower for vascular thrombosis than for infection (0/14 vs 11/25; P < .05). CONCLUSION Reducing vascular thrombosis could preserve graft function rate. Preventing graft inflammation and infection would reduce mortality.