Increasing the likelihood of AVF Survival
Nephrologists loath placing tunneled dialysis catheters in their hemodialysis patients. Not only are the blood flows limited by these devices, but the infectious risk to patients are high and increase both morbidity and mortality. While the arteriovenous fistula (AVF) is considered the “gold standard” of dialysis vascular access, too often fistulas can experience “primary failure”. In these cases, end-stage renal disease patients are left with no alternative but to have a tunneled catheter placed. Work by Lok et al (JASN 2006; 17:3204) has led to the development of an evidence-based model to predict the likelihood of primary AVF maturation failure. The REDUCE FTM model helps nephrologists and patients quantify the risk of primary AVF failure and avoid a tunneled catheter by proceeding with an arteriovenous graft or peritoneal dialysis catheter. Unfortunately, an all too common problem arises when a patient, predicted to have a high risk of primary AVF maturation failure, is still better served with an AVF than an AVG or PD catheter. How can nephrologists tip the scale in favor of successful AVF maturation and avoid a tunneled catheter?
Investigators from Turkey addressed this dilemma by analyzing 96 diabetic ESRD patients undergoing AVF creation. They postulated that drug therapy would alter the two most common causes of fistula failure: thrombosis and stenosis. They randomized these patients into receiving clopidogrel (an anti-platelet agent) at 75 mg daily with an oral prostacyclin agent (iloprost at 200 mg daily) against patients receiving placebo. Drug therapy began 7–10 days before the creation of the AVF and continued for 1 year post-surgery. The investigators believed that drug therapy would benefit patients by decreasing the rate of primary AVF maturation failure. They measured the average blood flow through the fistula (defining maturation as a mean blood flow of ≥300 ml/min) and arterial end-diastolic velocity (minimum of 70 cm/second) to prove their hypothesis.
Indeed those patients receiving clopidogrel plus oral prostacyclin had a 2.27 times greater odds of AVF maturation than the placebo arm (95% CI 1.07–8.5; p 0.001). Fistula maturation occurred in 38±7 days with the combination therapy than placebo (53±13 days; p 0.02). Only 8% of the patients in the intervention arm suffered a primary AVF maturation failure (compared to 30.4% in the placebo arm). All of the patients completed the follow-up period with none dropping out or discontinuing the study medications.
This is an extremely interesting study with significant implications. Provided that these results can be replicated in a larger randomized trial, nephrologists and ESRD patients may have a way to actively change the fate of an AVF. It remains to be seen if clopidogrel plus oral prostacyclin can reduce the rates of primary failure in high-risk patients (as identified by the REDUCE FTM model). To the credit of the investigators, their study population contained diabetic ESRD patients: patients who already had a higher risk of failure than their non-diabetic counterparts. Though the study was small, it was refreshing to see that none of the participants dropped out or were lost to follow-up. Even more impressive was the fact that the study drug was tolerable for one-year post-AVF creation. One wonders if high-risk patients can lower their risk of subsequent fistula failures by taking this drug combination indefinitely.
This small study reports impressive results and needs to be interpreted with enthusiastic caution. While I personally would not recommend using this drug combination at this time, a larger study that subcategorized patients based on their a priori risk of fistula failure would be needed to unequivocally convince me of the value of this therapy.
You can find the REDUCE FTM calculator by downloading the Nephrology On-Demand Plus App (for iOS and Android). Visit goo.gl/mfziXG for details.
