Mahmoud El-Khatib

Severe venous neointimal hyperplasia prior to dialysis access surgery

BACKGROUND Venous neointimal hyperplasia is the most common cause of arteriovenous (AV) fistula and graft dysfunction following dialysis access surgery. However, the pathogenetic impact of pre-existing venous neointimal hyperplasia at the time of AV access creation on final clinical success is currently unknown in the setting of advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. The aim of this study was to perform a detailed histological, morphometric, and immunohistochemical analysis of vein specimens in advanced CKD and ESRD patients collected at the time of new vascular access placement. METHODS Vein samples from 12 patients were collected at the time of AV access creation near the site of AV anastomosis. Histological, immunohistochemistry and morphometric studies were performed on these vein samples. RESULTS Examination of the tissue specimens obtained at the time of surgery showed neointimal hyperplasia in 10 of 12 specimens, ranging from minimal to very severe. The majority of cells within the neointima were myofibroblasts with a minority of contractile smooth muscle cells present. CONCLUSION Our work represents a detailed description of the morphometric and cellular phenotypic lesions present in the veins of CKD and ESRD patients, prior to dialysis access placement. These studies (i) suggest the future possibility of a new predictive marker (pre-existing venous neointimal hyperplasia) for AV dialysis access dysfunction and (ii) open the door for the future development of novel local therapies for optimization of the venous substrate on which the dialysis access is created.

Decreased Cumulative Access Survival in Arteriovenous Fistulas Requiring Interventions to Promote Maturation

BACKGROUND AND OBJECTIVES New arteriovenous fistulas (AVF) are frequently unsuitable for hemodialysis because of AVF nonmaturation. Aggressive endovascular or surgical interventions are often undertaken to salvage nonmaturing AVFs. The effect of early interventions to promote AVF maturation on subsequent long-term AVF outcomes is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We evaluated 173 hemodialysis patients from two academic centers who received a new AVF. Of these, 96 (56%) required no further intervention, 54 (31%) required one intervention, and 23 (13%) required two or more interventions to achieve suitability for dialysis. We calculated AVF survival and frequency of postmaturation interventions in each group. RESULTS Cumulative AVF survival (access cannulation to permanent failure) in patients with two or more versus one versus zero interventions before maturation was 68% versus 78% versus 92% at 1 year, 57% versus 71% versus 85% at 2 years, and 42% versus 57% versus 75% at 3 years. Using Cox regression analysis with interventions before maturation, age, sex, race, diabetes, peripheral vascular disease, access site, and obesity in the model, intervention before maturation (two or more) was the only factor associated with cumulative AVF survival. The number of interventions required to maintain patency after maturation was 3.51 ± 2.20 versus 1.37 ± 0.31 versus 0.76 ± 0.10 per year in patients with two or more versus one versus zero interventions before maturation. CONCLUSIONS Compared with AVF that mature without interventions, AVF that require interventions have decreased cumulative survival and require more interventions to maintain their patency for hemodialysis.

Successful Use of Indwelling Cuffed Femoral Vein Catheters in Ambulatory Hemodialysis Patients

Three hemodialysis patients with multiple upper extremity vascular access complications and central vein stenosis were treated for as long as 3 months using an indwelling femoral vein catheter having a buried felt cuff in its subcutaneous tunnel. Four catheters were placed in these three patients. In one case, initial failure due to poor flow and clotting occurred using a straight catheter with its tunnel crossing the inguinal ligament and exiting caudally on the anterior thigh. Otherwise, each patient had successful placement of a 180-degree, curved catheter that exited the femoral vein in the usual fashion but had a subcutaneous tunnel and skin exit pointing cephalad in the inferior portion of the right lower quadrant. The three successful devices functioned immediately after placement, having acceptable outflow pressures and recirculation values. One of three catheters was removed 3 weeks after placement when persisting infection was thought to reside on the device. No other bleeding, thromboembolic, or infectious complications occurred in these patients. In conclusion, short-term indwelling femoral vein access may be feasible in ambulatory hemodialysis patients with previous access difficulties that complicate temporary dialysis treatment.

A multi-center, dose-escalation study of human type I pancreatic elastase (PRT-201) administered after arteriovenous fistula creation

Purpose To explore the safety and efficacy of PRT-201. Methods Randomized, double-blind, placebo-controlled, single-dose escalation study of PRT-201 (0.0033 to 9 mg) applied after arteriovenous fistula (AVF) creation. Participants were followed for one year. The primary outcome measure was safety. Efficacy measures were the proportion with intra-operative increases in AVF outflow vein diameter or blood flow ≥25% (primary), changes in outflow vein diameter and blood flow, AVF maturation and lumen stenosis by ultrasound criteria and AVF patency. Results The adverse events in the PRT-201 group (n=45) were similar to those in the placebo group (n=21). There were no differences in the proportion with ≥25% increase in vein diameter or blood flow, successful maturation or lumen stenosis. There was no statistically significant difference in primary patency between the dose groups (placebo n=21, Low Dose n=16, Medium Dose n=17 and High Dose n=12). In a subgroup analysis that excluded three participants with early surgical failures, the hazard ratio (HR) for primary patency loss of Low Dose compared with placebo was 0.38 (95% CI 0.10-1.41, P=0.15). In a Cox model, Low Dose (HR 0.27, 95% CI 0.04-0.79, P=0.09), white race (HR 0.17, 95% CI 0.03-0.79, P=0.02), and age <65 years (HR 0.25, CI 0.05-1.15, P=0.08) were associated (P<0.10) with a decreased risk of primary patency loss. Conclusions PRT-201 was not different from placebo for safety or efficacy measures. There was a suggestion for improved AVF primary patency with Low Dose PRT-201 that is now being studied in a larger clinical trial.

Back to the Future: How Biology and Technology Could Change the Role of PTFE Grafts in Vascular Access Management

Although the arteriovenous fistula (AVF) is the preferred mode of dialysis vascular access, AVF maturation failure remains a huge clinical problem, often resulting in a prolonged duration of use of tunneled dialysis catheters. In contrast, polytetrafluoroethylene (PTFE) grafts do not suffer from early failure, but have significant problems with later stenosis and thrombosis. This review will initially summarize the pathology and pathogenesis of PTFE graft dysfunction and will then use this as a basis for describing some novel therapies, which may have the potential to reduce PTFE graft dysfunction. Finally, we will emphasize that the introduction of such therapies could be an important first step toward individualizing overall vascular access care.

Role of C-reactive protein, reticulocyte haemoglobin content and inflammatory markers in iron and erythropoietin administration in dialysis patients

Aim:  C‐reactive protein (CRP) is an acute phase reactant protein, which becomes elevated in response to inflammation, infections or malignancies. These conditions are well known causes of bone marrow hyporesponsiveness and erythropoietin resistance in dialysis patients. The role of iron‐deficiency as a cause of hyporesponsiveness under these conditions is not clear. Reticulocyte haemoglobin content (CHr) is one of several iron indices used to determine iron deficiency in dialysis patients. The aim of this study is to evaluate the role of CRP and CHr in iron administration and anaemia management in dialysis patients

Repeated Pregnancy does not Accelerate Glomerulosclerosis in Rats with Subtotal Renal Ablation

We studied the effect of repeated pregnancy on renal function and histology in female rats subjected to approximately 5/6 renal ablation, using both the surgical nephrectomy (P-Neph) and renal infarction (P-Inf) models, comparing these to paired rats not subjected to pregnancy (C-Neph and C-Inf), and Sham operated controls (CON). Though both P-Neph and P-Inf rats had multiple litters (mean 2.66, 2.33 respectively), when compared at 20 weeks post operatively with C-Neph and C-Inf respectively, there was no deterioration in renal function in respect of serum creatinine, proteinuria or histology including the frequency of focal glomerulosclerosis (FGS).Successive pregnancy in the subtotal renal ablated rat appears to have no adverse effect on the lesions of FGS nor to alter the course of progressive renal failure in this animal.

Combining novel technologies with improved logistics to reduce hemodialysis vascular access dysfunction.

Hemodialysis (HD) vascular access dysfunction is currently a huge clinical problem for which there are no effective therapies. There are, however, a number of promising technologies that are currently at the experimental or clinical trial stage. We believe that the application of these novel technologies in combination with better clinical protocols for vascular access care could significantly reduce the current problems associated with HD vascular access.