Impact of isometric handgrip exercises on cephalic vein diameter in non-AVF candidates, a pilot study.

PURPOSE: Incident arteriovenous fistula (AVF) rates remain low. AVF placement is often not attempted because of small cephalic vein (CV) diameter. We postulated that isometric handgrip exercises would increase forearm CV diameter and allow successful AVF creation in non-AVF candidates. METHODS: Adult subjects without prior vascular access (eGFR<25 mL/min/1.73 m²; CV<2.5 mm) were prospectively enrolled. They performed daily handgrip exercises in the preferred access arm (EA), with the nonexercised arm (NEA) as control. Adherence was assessed by exercise logs and grip strength. CV diameter was measured at baseline, four and eight weeks by ultrasound. The primary endpoint was the mean increase in CV diameter. Secondary endpoints were mean CV diameter increase from baseline, increased proportion of potential AVF sites and successful AVF placement. RESULTS: A total of 17 subjects were enrolled and 15 completed the study. EA grip strength increased significantly. Mean CV diameter increased in both the EA and NEA by 0.48-0.59 and 0.71-0.81 mm (P=NS), respectively. Compared to baseline, all CV diameters increased significantly (P<.05) after four weeks. In the EA, mean distal and proximal CV increased from 1.66 to 2.13 mm and from 2.22 to 2.81 mm, respectively. Similar changes were noted in the NEA. There were also significant increases in the number of sites and subjects eligible for AVF creation. Five subjects had successful AVF placement. CONCLUSIONS: Isometric handgrip exercises resulted in significant CV diameter increases after four weeks, in both the EA and the NEA and potentially allows for AVF creation in those not previously deemed candidates.

Effect of pentoxifylline on GFR decline in CKD: a pilot, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties. It reduces proteinuria in patients with glomerular disease, although its impact on glomerular filtration rate (GFR) is unknown. We hypothesized that pentoxifylline would slow the estimated GFR decrease in patients with chronic kidney disease at high risk of progression. STUDY DESIGN: Pilot randomized double-blind placebo-controlled trial. SETTING & PARTICIPANTS: 40 outpatients with decreased GFR, hypertension, and proteinuria greater than 1 g/24 h currently treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or the combination and followed up in a nephrology clinic at a tertiary medical care facility. INTERVENTION: Pentoxifylline, 400 mg twice daily, or matching placebo. OUTCOMES: Difference in rates of estimated GFR change during the 1-year study period between the 2 groups. MEASUREMENTS: Estimated GFR (4-variable Modification of Diet in Renal Disease Study equation) and proteinuria by 24-hour urine collection were assessed at baseline and 6 and 12 months after enrollment. RESULTS: Baseline characteristics were similar between the 2 groups. At 1 year, the mean estimated GFR decrease was significantly less in the pentoxifylline group than the placebo group (-1.2 +/- 7.0 versus -7.2 +/- 8.2 mL/min/1.73 m2/y; mean difference, -6.0 mL/min/1.73 m2/y; 95% confidence interval, -11.4 to -0.6; P = 0.03). For pentoxifylline-treated participants, the mean estimated GFR decrease during treatment was slower compared with the year before study enrollment (-9.6 +/- 11.9 mL/min/1.73 m2/y; mean difference, -8.4 mL/min/1.73 m2/y; 95% confidence interval, -14.8 to -2.1; P = 0.01). Proteinuria was not different between the pentoxifylline and placebo groups at baseline, 6 months, or 1 year. LIMITATIONS: Small sample size and incomplete follow-up. CONCLUSIONS: Pentoxifylline may slow the estimated GFR decrease in high-risk patients. This may be independent of its antiproteinuric properties and warrants further investigation.

Progressive bevacizumab-associated renal thrombotic microangiopathy.

Vascular endothelial growth factor (VEGF) is integral to the integrity of the glomerular filtration barrier. Bevacizumab is a humanized monoclonal antibody directed against VEGF with expanding clinical applications for metastatic solid tumours. We describe a case of a 61-year-old female with ovarian cancer and baseline chronic kidney disease who received three doses of bevacizumab and subsequently developed progressive renal clearance dysfunction and nephrotic range proteinuria. A renal biopsy was performed 4 months after drug discontinuation and was consistent with TMA. At baseline, prior to bevacizumab exposure, her estimated glomerular filtration rate (eGFR) was 44 mL/min/1.73 m(2) and she had no proteinuria. At the completion of therapy, eGFR was 27 mL/min/1.73 m(2) with 1+ proteinuria on urinalysis. Her renal failure and proteinuria continued to progress 5 months after discontinuation of bevacizumab therapy, at which time eGFR was 11 mL/min/1.73 m(2) and proteinuria was 5.5 g/24 h. Non-remitting TMA after bevacizumab therapy in patients with pre-existing chronic kidney disease has not been previously reported. Further studies are needed to assess the safety of this drug in patients with chronic kidney disease.