Ultrahigh-pressure angioplasty versus the Peripheral Cutting Balloon™ for treatment of stenoses in autogenous fistulas: comparison of immediate results.

PURPOSE: To compare the immediate results of ultrahigh-pressure (UHP) balloons vs. peripheral cutting balloons (PCB) for the treatment of stenoses associated with autogenous fistulas using intra-access blood flow measurements. MATERIALS AND METHODS: This prospective randomized study consisted of 22 hemodialysis (HD) patients with autogenous fistulas who had decreased intra-access blood flow (<500 mL/min). All patients underwent a fistulogram and intraprocedural blood flow measurements. Patients were randomized once into two groups; one group undergoing UHP angioplasty and the second group undergoing PCB angioplasty. Randomization occurred once after the diagnostic fistulogram and each patient in each arm only underwent percutaneous transluminal angioplasty with either UHP or PCB. The study cohort consisted of 12 patients in the UHP group and 10 patients in the PCB group. Data collected included fistula anatomy, degree of stenosis, length of stenosis, balloon specifications and residual stenosis. RESULTS: The 22 study patients underwent 35 angioplasty procedures; 23 in the UHP group (12 patients) and 12 in the PCB group (10 patients). The technical success rate was 91%. The pre-intervention mean blood flow was 288 mL/min in the UHP group and 391 mL/min in the PCB group. The post-intervention mean blood flow was 613 mL/min in the UHP group and 606 mL/min in the PCB group. The mean increase in blood flow was 325.8 mL/min in the UHP group and 213 mL/min in the PCB group. This represents a relative mean increase in blood flow of 253% in the UHP group and 85% in the PCB group. An unpaired t-test showed there was no significant difference between the groups with respect to pre-flow, post-flow, and mean and relative mean increase in flow. There were two failures; one in the UHP group and one in the PCB group. There was one minor complication (2.8%) but no major complications. CONCLUSIONS: In this small group of HD patients with autogenous fistulas our comparison of UHP to the PCB demonstrated that the immediate results, as determined by measurement of intra-access blood flow, were equivalent. Further long-term follow-up will be required to determine the longevity of these results.

Characterization of a baculovirus nuclear localization signal domain in the late expression factor 3 protein.

The baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) single-stranded DNA binding protein LEF-3 is a multi-functional protein that is required to transport the helicase protein P143 into the nucleus of infected cells where they function to replicate viral DNA. The N-terminal 56 amino acid region of LEF-3 is required for nuclear transport. In this report, we analyzed the effect of site-specific mutagenesis of LEF-3 on its intracellular distribution. Fluorescence microscopy of expression plasmid-transfected cells demonstrated that the residues 28 to 32 formed the core nuclear localization signal, but other adjacent positively-charged residues augmented these sequences. Comparison with other group I Alphabaculoviruses suggested that this core region functionally duplicated residues including 18 and 19. This was demonstrated by the loss of nuclear localization when the equivalent residues (18 to 20) in Choristoneura fumiferana nucleopolyhedrovirus (CfMNPV) LEF-3 were mutated. The AcMNPV LEF-3 nuclear localization domain was also shown to drive nuclear transport in mammalian cells indicating that the protein nuclear import systems in insect and mammalian cells are conserved. We also demonstrated by mutagenesis that two conserved cysteine residues located at 82 and 106 were not essential for nuclear localization or for interaction with P143. However, by using a modified construct of P143 that localized on its own to the nucleus, we demonstrated that a functional nuclear localization domain on LEF-3 was required for interaction between LEF-3 and P143.

Improvement in eGFR in patients with chronic kidney disease attending a nephrology clinic.

BACKGROUND: The adverse effects arising from late referral to a nephrologist of patients with chronic kidney disease (CKD) are well known. Retrospectively we examined the initial characteristics of patients referred in various stages of CKD to our nephrology division and tried to identify potential baseline factors associated with subsequent changes in estimated glomerular filtration rate (eGFR). PATIENTS AND METHODS: Between September 1997 and June 2006 1,443 patients (909 male, 534 female) with CKD, with eGFRs ranging from 15 to 89 ml/min, were referred to our nephrology division and categorized using the National Kidney Foundation classification for CKD based on eGFR. The slope of eGFR change (ml/min-1/1.73/m2-1/year-1) was determined by linear regression analysis and the patients were divided into five groups: (1) significantly progressive slope (deterioration) (more negative than -5 ml/min/year); (2) mildly progressive slope (>-5 to -1 to +1 to or=+5). RESULTS: At the first nephrology referral, 5.8% of the patients were on CKD stage 2 (eGFR: 90-60 ml/m), 46.7% on CKD stage 3 (eGFR: 59-30 ml/m), and 47.5% on CKD stage 4 (eGFR: 29-15 ml/m) CKD. Significantly improved slope was detected in 48.2% of CKD stage 2 patients, 29.3% of CKD stage 3 patients, and only 14.7% of CKD stage 4 patients (P<0.05). Being in stage 4 or stage 3 versus being in stage 2 significantly reduced the likelihood of an improved slope in logistic regression analysis whereas age, gender, presence of hypertension, and diabetes mellitus did not reach the level of significance. CONCLUSION: Referral to a nephrology clinic can lead not only to arrest of progression of CKD but also to regression/improvement. Early referral is a positive predictive factor for improvement in eGFR, which emphasizes the importance of such referral. The previously held idea that, once established, CKD progresses invariably is not valid anymore.