Management of Arteriovenous Fistula After Successful Kidney Transplantation in Long-Term Follow-Up.

Arteriovenous fistula (AVF) is the best method of vascular access for hemodialysis. This approach can lead to several complications, such as hyperkinetic heart failure due to a hyperfunctional AVF or dilatation of the feeding artery. These are late complications, especially in patients after a successful kidney transplantation. An observational study was performed focusing on patients more than 12 months after kidney transplantation. The AVF was evaluated by ultrasound and, if the outflow exceeded 1.5 L/min, an echocardiogram was performed. Surgical management was indicated if the cardiac index was higher than 3.9 L/min/m2 or upon finding a brachial artery aneurysm. A total of 208 post- kidney transplantation patients were examined over a 3-year period, of which 46 subjects (22.11%) had hyperfunctional AVF and 34 cases (16.34%) of feeding artery dilatation were determined. In total, 40 AVF flow reduction and 6 AVF ligation procedures were performed. The median AVF flow before and after the reduction was 2955 mL/min and 1060 mL/min, respectively. Primary patency after flow reduction was 88.3% at 12 months. Late AVF complications in patients following kidney transplantation are quite common. It is necessary to create a screening program to monitor AVFs in these patients.

Arteriovenous Grafts' Types of Indications and Their Infection Rate.

BACKGROUND: Arteriovenous graft infection is a well-known and frequent complication. The objective of this study was to compare infection rates of primary and secondary indicated arteriovenous grafts (AVGs). SUBJECTS AND METHODS: Retrospectively, we evaluated the indications for AVGs created at our institution which became infected. One hundred forty AVGs were evaluated. Of these AVGs, 33 (23.6%) were primary and 107 (76.4%) secondary indicated. RESULTS: Infection of a primary AVG was detected in 5 patients (15.2 %). Infection of a secondary AVG was detected in 30 patients (28.0%). Primary and secondary patency were significantly lower in patients with infected AVG (P = 0.006; P = 0.0001). The effect of diabetes mellitus and age on development of infection was not confirmed. CONCLUSIONS: Indications for AVG creation clearly influence the future risk of infection. If the indication to use the AVG is to correct a complicated arteriovenous fistula, the risk of infection is 2 times higher.

Interaction of rocuronium with human liver cytochromes P450.

Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver microsomal CYP3A4 down to 42% (at rocuronium concentration 189 µM) was found. This effect has been confirmed with two CYP3A4 substrates, testosterone (formation of 6ß-hydroxytestosterone) and diazepam (temazepam formation). CYP2C9 and CYP2C19 activities were inhibited down to 75-80% (at the same rocuronium concentration). Activities of other microsomal CYPs have not been inhibited by rocuronium. To prove the possibility of rocuronium interaction with other drugs (diazepam), the effect of rocuronium on formation of main diazepam metabolites, temazepam (by CYP3A4) and desmethyldiazepam, (also known as nordiazepam; formed by CYP2C19) in primary culture of human hepatocytes has been examined. Rocuronium has caused inhibition of both reactions by 20 and 15%, respectively. The results open a possibility that interactions of rocuronium with drugs metabolized by CYP3A4 (and possibly also CYP2C19) may be observed.

Effects of oral anorexiant sibutramine on the expression of cytochromes P450s in human hepatocytes and cancer cell lines.

Sibutramine is a serotonin-norepinephrine reuptake inhibitor that was used for weight-loss management in obese patients. Even though it was officially withdrawn from the market in 2010, it is still present in some tainted weight-loss pills (as reported by US Food and Drug Administration). Thus, it is still reasonable to study the effects of this compound. The aim of this work was to investigate the potential of sibutramine to induce CYP1A1/CY3A4 in human cancer cell lines and CYP1A1/2, CYP2A6, CYP2B6, and CYP3A4 in human hepatocytes, a competent model of metabolically active cells. The levels of mRNA and protein of CYP1A1/1A2/3A4/2A6/2B6 were compared with the typical inducers, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and rifampicin (RIF) for CYP1A1/2 and for other CYPs, respectively. The mRNA and protein levels of all genes in either cancer cell lines or human hepatocytes were induced when treated with typical inducers but not with sibutramine.

Brachial artery aneurysm as a late complication of arteriovenous fistula.

INTRODUCTION: Brachial artery aneurysm (BAA) is a rare late complication of arteriovenous fistula (AVF). It brings the risk of peripheral embolism and hand ischemia and is defined by brachial artery diameter above 10 mm or by regional dilatation by >50%. BAA is described in the literature in closed radiocephalic arteriovenous fistulas after kidney transplantation. The aim of the study was to analyze the prevalence of BAA and of their more dangerous forms. METHOD: A observational one center study performed on patients after kidney transplantation with AVF or arteriovenous graft (AVG). We invited all patients followed up for kidney transplantation in our center. Arterial diameter greater than 10 mm was considered as a brachial artery aneurysm to simplify the detection and evaluation of aneurysms. RESULTS: About 162 patients with AVF after kidney transplantation were examined between 4/2018 and 4/2020. Brachial artery aneurysm was detected in 34 patients (21%) with AVF or AVG, of them 7 had confirmed wall thrombi. AVF flow volume of more than 1500 ml/min increased the risk of BAA development by 4.54x. Eight aneurysms were treated surgically. After this surgery, the primary patency was 87.5% in 12 months. CONCLUSION: Brachial artery aneurysm was relatively frequent in our study compare to the literature. Aneurysm or dilatation of the brachial artery is more frequent in functional AVFs. Surgical correction is necessary in cases of complicated aneurysms to prevent distal embolization.

Robotic assisted living donor nephrectomy - the first in the Czech Republic.

INTRODUCTION: A kidney transplant is the best method for treating terminal kidney failure. Long-term results of kidney transplants from living donors are significantly better than transplants from dead donors. Living kidney donors are healthy people who undergo a major operation in order to improve the health of another person. Therefore, major emphasis is on safety, low level of invasiveness and a desirable cosmetic effect of the donor nephrectomy. Since 2012, the Department of Urology at the University Hospital in Olomouc has performed 12 kidney harvestings from living donors. The kidney harvesting was conducted using various techniques. CASE REPORT: The first robotic assisted kidney harvesting in the Czech Republic was performed in June 2022. The donor was a 57-year-old man who donated his kidney to his 32-year-old daughter. The left kidney was evaluated as suitable for kidney harvesting. The operation took 174 min. The kidney's warm ischemia was 145 s. Based on the Clavien Dindo classification, no 2nd degree or high post-operative complications were recorded. The donor's pre-operative glomerular filtration was 1.63 mL/s. Six months post-operation, it went down to 1.19 mL/s. This represents a 27% decrease. The kidney recipient did not require early dialysis. Six months post-operation, the recipient's glomerular filtration was 2.03 mL/s. CONCLUSION: In the hands of experienced professionals and transplantation centres, robotic assisted donor nephrectomy is a feasible and safe option for this operation. It not only provides all the advantages of a laparoscopic operation but it also adds other technical improvements and minimizes intraoperative stress on the surgeon. Currently, the global trend is moving towards increasing the ratio of robotic assisted donor nephrectomies.

Creation of arteriovenous fistula for hemodialysis in the older population.

OBJECTIVE: To evaluate the results of arteriovenous fistula (AVF) created for haemodialysis in patients older than 65 years of age. SUBJECTS AND METHODS: A retrospective analysis of patients with AVF or arteriovenous graft (AVG) creation, who were older than 65 years of age and were operated on at the II. Surgical Clinic at the University Hospital in Olomouc from 2014 - 2018 was performed. RESULTS: 212 patients were evaluated and a total of 239 AVF/AVG were created. 194 AVFs (81.18%) and 45 AVGs (18.82%) were created. Primary failure was seen in 19 arteriovenous fistulas (9.8%) and 2 arteriovenous grafts (4.44%). The primary patency of AVF was 69.9%, 62.8% after 12 and 24 months, respectively, and in the case of AVG it was 54.7% and 32.3% after 12 and 24 months, respectively. Primarily assisted patency of AVF was 77.6% and 66.3% after 12 and 24 months, respectively, and in case of AVG it was 69.1% and 39.7% after 12 and 24 months, respectively. Secondary patency of AVF was 77.6% and 66.3% after 12 and 24 months, respectively, and for AVG it was 69.1% and 39.7% after 12 and 24 months, respectively. CONCLUSION: The type of vascular access should be selected based on a thorough, protocol-based examination. In most seniors, AVF is the method of choice. The AVG is a suitable choice for patients with an exhausted venous bed, in acute need of haemodialysis, in the elderly and in females. A "customized" approach should be matter of fact for older generations.

Subclinical toxicity of calcineurin inhibitors in repeated protocol biopsies: an independent risk factor for chronic kidney allograft damage.

The purpose of the prospective study was to determine the prevalence of subclinical toxicity of calcineurin inhibitors (CI) in repeated protocol renal allograft biopsies and to assess its impact on the development of chronic graft changes. A total of 424 biopsies were conducted in a cohort of 158 patients; of these biopsies, 158 were in the third week, 142 were in the third month and 124 were in the first year after transplantation. Histological signs of toxicity occurred in the third week in 33 (20.1%) patients, with persistence after CI dose reduction in the third month in 27 (19.0%) and in the first year in 23 (18.5%) patients. Of the toxic changes, 52% were clinically silent. At the end of the one-year follow-up, both subclinical and clinically manifest toxicity resulted in a similar progression of chronic changes quantified by Banff chronicity score and they significantly differed from the control group (P < 0.05). Subclinical toxicity affects a significant percentage of grafts; it occurs independently of dosage, blood level and type of applied CI. It is associated with the progression of chronic changes as early as in the first year after transplantation and represents an independent risk factor for chronic allograft damage. We report here our clinical approach to toxicity.

The effect of graphene oxide on signalling of xenobiotic receptors involved in biotransformation.

Graphene oxide (GO) is an engineered nanomaterial which was demonstrated to have outstanding capacity for adsorption of organic pollutants such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), the ligands and activators of the aryl hydrocarbon receptor (AhR). Due to the partially overlapping ligand capacity of AhR and pregnane X receptor (PXR), we tested the impact of GO particles on their signalling. While reporter gene assay revealed potentiating effect of GO on ligand-activated AhR-dependent luciferase activity, there was no effect for PXR. However, inducible target genes for AhR (CYP1A1) or PXR (ABCB1) were decreased at mRNA as well as protein levels by the presence of GO in HepG2 (for AhR), LS180 (for PXR) or primary human hepatocytes (both receptors). Moreover, the presence of GO diminished PXR and AhR protein levels in primary cultures of human hepatocytes. This was partially reversed by proteasome inhibitor MG132 for AhR but not for PXR. In conclusion, GO decreases ligand-stimulated activities of AhR and PXR in human cells.

Endotension after endovascular treatment of abdominal aortic aneurysm: percutaneous treatment.

Endotension is one of the possible specific late complications of endovascular treatment of abdominal aortic aneurysm (AAA). We describe the treatment of endotension in a small group of 3 patients (all men, aged 58, 70, and 70-years-old) by translumbar puncture of the aneurysm sac and aspiration of its content. It was transudate and its culture was negative. Sac size reduced after aspiration in all patients and no subsequent enlargement was seen. Percutaneous translumbar puncture of the aneurysm sac with aspiration of sac content could be an easy and effective method of treatment in endotension. But a larger group of patients and long-term follow-up are needed.

Activation of MAPKs influences the expression of drug-metabolizing enzymes in primary human hepatocytes.

We examined the effects of model activators of mitogen-activated protein kinases (MAPKs) on basal and rifampicin-, phenobarbital- and dioxin-inducible expression of phase I and phase II biotransformation enzymes in primary human hepatocytes. Cells were treated for 24 h with sorbitol (SOR), anisomycin (ANI) and epidermal growth factor (EGF) in the presence or absence of inducers. The levels of CYP1A1, CYP1A2, CYP2B6, CYP3A4, UGT1A1, UGT2B17, SULT1A1, SULT2A1, SULT1B2, GSTA1, GSTA2 mRNAs were determined. SOR and EGF inhibited the expression of the tested genes, while ANI had no effect. We conclude that MAPKs play important role in the transcriptional regulation of drug-metabolizing enzymes.

18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT effectively contribute to early diagnosis of infection of arteriovenous graft for hemodialysis.

OBJECTIVE: An arteriovenous graft (AVG) is indicated in hemodialysis patients with failed arteriovenous access. Early treatment of AVG infection is important because an advanced prosthetic infection leads to the removal of the prosthesis. The aim of this study was to evaluate the benefits of 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT in early detection of AVG infections. SUBJECTS AND METHODS: Fifty-one AVGs were evaluated. 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT studies were performed at intervals of 10, 20-30, and 40-50 weeks after AVG insertion. Agreement between the imaging methods and reference parameters (i.e. clinical presentation, C-reactive protein and microbiological findings on the hemodialysis cannula extracted after hemodialysis from AVG) was evaluated. RESULTS: The study results showed that focal accumulation of the radiopharmaceuticals can be considered a sign of AVG infection. At 10 weeks after AVG implantation, the focal 18F-FDG findings showed the best agreement with the reference parameters (agreement coefficients AC1 - clinical status: 0.693, CRP: 0.605, cannula microbiology: 0.518, respectively). At 20 to 30 weeks after AVG implantation, the diagnostic value of focal 99mTc-HMPAO-WBC accumulation increased (AC1 coefficients: 0.658, 0.658, 0.408) and was similar to that of focal 18F-FDG uptake (AC1s: 0.656, 0.570, 0.409). Between 40 and 50 weeks since AVG implantation, the diagnostic significance of focal 99mTc-HMPAO-WBC accumulation (AC1 coefficients: 0.771, 0.811, 0.611) slightly exceeded the diagnostic value of focal 18F-FDG accumulation (AC1 coefficients: 0.524, 0.456, 0.569). CONCLUSION: 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT can both serve as important tools contributing to early diagnosis of AVG infection.

Surgical revision vs. stent-graft to treat venous anastomosis stenosis following surgical thrombectomy of hemodialysis grafts.

BACKGROUND: There is no unanimous strategy for treating stenosis of the venous anastomosis (VA) of an occluded arteriovenous graft (AVG) following surgical thrombectomy. In this study, we compared classical surgical treatment and endovascular treatment procedures with the use of stent- graft in a single center study. The aim was to evaluate whether, the VA stenosis of thrombosed AVG treated endovascularly by stent-graft implantation, have as good results as surgical VA treatment, so that it may be considered the method of choice. METHODS: The study included patients who underwent surgical AVG thrombectomy with subsequent angiographically confirmed VA stenosis between 1/2009 and 12/2014. Surgical angioplasty was then performed in 15 patients and 17 patients underwent primary stent-graft implantation. RESULTS: In the surgically treated patients, the postintervention primary patency, primary assisted patency and secondary patency after 12 months were 50.7%, 56.3%, 62.4%, respectively. In the group of patients with occluded AVG who underwent stent-graft implantation, the postintervention primary patency, primary assisted patency and secondary patency after 12 months were 32.8%, 44.1% a 55.6%, respectively. No statistically significant difference in primary patency (P=0.391), primary assisted patency (P=0.605), and secondary patency (P=0.702) was observed between the groups. CONCLUSIONS: Stent-graft implantation into stenotic VA of an occluded AVG showed to be effective and maintained good long-term patency. It is the preferred method due to its minimal invasiveness. The superiority of this method must be confirmed on a larger set of patients.

Autogenous arteriovenous elbow fistula for haemodialysis and upper extremity ischemia.

BACKGROUND: The autogenous brachiocephalic or brachiobasilic arteriovenous elbow fistula is not considered to be only the secondary haemodialysis access. In patients with an unsuitable forearm vessel bundle, it is indicated as primary access and it is the method preferred to the fistula creation using a vascular prosthesis. Its rather rare complication is the development of upper extremity ischemia. AIM: To summarise current knowledge of this fistula type and its associated complications METHODS: Review of the literature. RESULTS: The creation and maturation of the fistula and occurrence of the steal syndrome is influenced by a number of factors. The analysis and awareness of such factors will provide for creation of a suitable fistula as well as for timely complication diagnostics and treatment. CONCLUSIONS: The autogenous elbow fistula utilising the brachial artery and the cephalic or basilic vein in the upper extremity represents a high-quality haemodialysis access. Its potential complication is the occurrence of the steal syndrome. Its occurrence and manifestations do not constitute indications for ligation of the access. The gathered information shows that a suitable surgical procedure can help meet the basic rule for haemodialysis access--resolving the ischemia and maintaining the access.

Itraconazole cis-diastereoisomers activate aryl hydrocarbon receptor AhR and pregnane X receptor PXR and induce CYP1A1 in human cell lines and human hepatocytes.

Triazole antimycotic itraconazole contains in its structure three chiral centres; therefore, it forms eight stereoisomers. Commercial preparations of itraconazole are a mixture of four cis-diastereoisomers. There is much evidence that efficacy, adverse effects, and toxicity of chiral drugs may be stereospecific. Therefore, we have prepared 4 pure cis-diastereoisomers of itraconazole and investigated their effects on transcriptional activities of xenoreceptors aryl hydrocarbon receptor AhR and pregnane X receptor PXR. Gene reporter assays showed that itraconazole dose-dependently activated both AhR and PXR, and the activation of AhR but not of PXR was enantiospecific. Itraconazole diastereoisomers transformed AhR and PXR into their DNA-binding forms, as demonstrated by electromobility shift assays. Cytochrome P450 CYP1A1 mRNA and protein were induced by itraconazole diastereoisomers in human hepatoma cells HepG2, human skin cells HaCaT, and in primary human hepatocytes. The expression of CYP3A4 in human intestinal LS180 cells was not influenced by itraconazole, but we observed downregulation of CYP3A4 in human hepatocytes. Collectively, we show that itraconazole is a dual activator of AhR and PXR, with differential effects on the target genes for xenoreceptors. The enantiospecific pattern was observed only in gene reporter assays for AhR. The data presented here might be of toxicological and clinical importance.

Hydroxystilbenes and methoxystilbenes activate human aryl hydrocarbon receptor and induce CYP1A genes in human hepatoma cells and human hepatocytes.

Natural polyphenol resveratrol (trihydroxystilbene) is a partial agonist of human aryl hydrocarbon receptor AhR, thereby, displaying a plethora of biological effects. Biological activities of metoxylated and hydroxylated stilbenes were studied in the past. The aim of the current study was to describe the effects of 13 different hydroxy- and methoxystilbenes, including their cis/trans isomers on the transcriptional activity of AhR and the expression of CYP1A genes in hepatic cancer cells HepG2 and in primary human hepatocytes. Techniques of gene reporter assays, qRT-PCR, Simple Western blotting by Sally Sue™ and electrophoretic mobility shift assay EMSA were employed. All compounds activated AhR, but their efficacies, potencies and dose-response profiles differed substantially. The strongest activators of AhR and inducers of CYP1A1 in HepG2 cells were DMU-212 ((E)-3,4,5,4´-tetramethoxystilbene), trans-piceatannol, cis-piceatannol, trans-trismethoxyresveratrol and trans-pinostilbene. While DMU-212 and trans-trismethoxyresveratrol also induced CYP1A1 and CYP1A2 in primary human hepatocytes, the effects of trans-piceatannol, cis-piceatannol and trans-pinostilbene weaned off. On the other hand, trans-4-methoxystilbene was strong CYP1A inducer in hepatocytes but not in HepG2 cells. Differences between effects of stilbenes in HepG2 cells and human hepatocytes are probably due to the extensive phase I and phase II xenobiotic metabolism in human hepatocytes. The data obtained may be of toxicological relevance.

Access sites to vascular system for endovascular abdominal aortic aneurysms repair.

The authors describe their experience with access sites for endovascular abdominal aortic aneurysm repair in a group of 165 patients treated over a 10-year period.

Conversion to open surgery after endovascular abdominal aortic aneurysms repair.

The authors describe experience with conversions to open surgery after endovascular abdominal aneurysm repair and evaluate the frequency, causes and results of a total of 7 cases in their series of 165 patients treated over a 10-year period.

Axillofemoral fistula for hemodialysis access.

The authors describe the technique of axillo-femoral arteriovenous prosthesis interposition and evaluate their experience with this non-conventional access for hemodialysis.

Surgical corrections of endovascular aneurysms: repair complications.

The authors describe their experience with the use of 21 open surgical corrections after endovascular abdominal aneurysm repair, reporting the frequency, type and outcome of these procedures in their group of 165 patients treated during a 10-year period.