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Management of Bone and Mineral Abnormalities in Chronic Kidney Disease
Immunosuppression and Malignancy: Directions for Positive Change

Focus on Improving Dialysis Treatment and Updated K/DOQI Guidelines

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

National Kidney Foundation 2006 Spring Clinical Meetings

Chicago, Illinois / April 19-23, 2006

In the original National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines issued in 1997, the Vascular Access Work Group indicated they had two main goals: to increase the use of native arteriovenous fistulas (AVFs) in patients requiring hemodialysis and to more promptly detect access dysfunction prior to the development of thrombosis. Although the prevalence of AVFs use has increased, it has been slow and currently fewer than 40% of hemodialysis patients in the US have an AVF, even though evidence suggests that they reduce the rate of thrombosis and need for interventions, as group chair Dr. Anatole Besarab, Director, Clinical Research, Henry Ford Hospital and Medical Centers, Detroit, Michigan, and Work Group colleague Deborah Brouwer, RN, CNN, noted in a previous publication (Dialysis & Transplantation 2004; 33(11):694-702).

“Vascular access patency and adequate hemodialysis are essential to the optimal management of end-stage renal disease [ESRD],” they stated. The new updated guidelines continue to support the notion of “fistulas first” as the optimal route for permanent hemodialysis access. Indeed, group members indicated that new targets for AVF placement should reach 60%, up from the 40% placement rate recommended in the 2001 guidelines. “We also focused on the role of vein imaging because if you do not have a good vein, you cannot construct a good AVF,” Dr. Besarab said, adding that physicians must also start early. As a result the following guidelines are recommended.

• Patients with a glomerular filtration rate of <30 mL/min/1.73m2 (chronic kidney disease [CKD] stage IV) should be educated on all modalities of renal replacement therapy, including transplantation options, so that timely referral can be made for the appropriate modality and placement of a permanent dialysis access if necessary.

• In patients with stage IV or V CKD, forearm and upper arm veins suitable for placement of vascular access should not be used for venipuncture or for the placement of intravenous catheters, subclavian catheters or peripherally inserted central catheter lines.

• Patients should have a functioning permanent access on initiation of dialysis.

These guidelines emphasize the importance of patients having a functional permanent access in place before they require hemodialysis. Key to the process is early and “timely” referral, members emphasized. Vascular Access Group members also indicated that the wrist is the preferred site for a primary AVF but as wrist fistulas are often not possible, options at the elbow may be pursued. “Data have increasingly convinced us the order of preference of access remains a native arterial fistula, which is associated with longer longevity and less loss overall,” Dr. Besarab indicated.

Maturation of an AVF can be accomplished by selective obliteration of major venous side branches in the absence of a downstream stenosis, the group advised. The group also noted that if a fistula is not maturing as anticipated, patients should be seen at six weeks after construction and corrective measures should be taken early. In recognition that central venous catheters (CVCs) are still likely to be relied upon instead of AVFs—largely, as Dr. Besarab and Ms. Brouwer noted, from a failure to anticipate the need for hemodialysis and from patient reluctance to receive a permanent access—the right internal jugular vein is recommended as the preferred insertion site for tunnelled cuffed catheters or port catheter systems. “We also advocate increasing use of the buttonhole technique,” the chair indicated, “and obviously, infection control measures should be used in all patients, especially when it comes to catheters.” Of note as well, there was no convincing evidence to support tapered over uniform tubes, externally supported over unsupported grafts, thick vs. thin-walled configurations or elastic vs. non-elastic material. The only significant change in design that the work group did note was the development of graft material that can be punctured shortly after insertion and thus avoid the need for catheters in many patients.

Monthly Physical Examination

The group also recommended that a qualified individual perform a monthly physical examination on all fistulas and AV grafts. “Technology is wonderful but it does not substitute for physical exam and knowing how to really examine an access is a lost art that needs to be taught again,” Dr. Besarab remarked. Previous and current K/DOQI guidelines also stipulate that functional accesses, regardless of the type, be able to deliver blood pump flow rates in excess of 300 mL/min. Thus, a flow rate of less than 300 mL/min is a sign of access dysfunction—and in AVFs and grafts, usually indicative of the presence of a high-grade stenosis or impending thrombotic occlusion of the access. Thrombosis of a permanent access that occurs soon after its creation is most often the result of technical error or premature use, as Dr. Besarab and Ms. Brouwer pointed out in their earlier publication. They also noted that the method used for surveillance of access flow for permanent AVFs and AV grafts is less important than the actual detection of functional stenosis prior to thrombosis.

Current guidelines also emphasize the importance of not only detecting the stenosis per se but also of having clinical or diagnostic indications that it is impairing access function.

Indications for referral for diagnosis and treatment include the following:

• One should not respond to a single isolated abnormal value. With all techniques, prospective trend analysis of the test parameter has greater power to detect dysfunction than isolated values alone.

• Persistent abnormalities in any of the monitoring or surveillance parameters should prompt referral for access angiography.

• An access flow rate <600 to 800 mL/min in graft and <400-500 mL/min in fistulae.

• A venous segment static pressure (mean pressures) ratio >0.5 in grafts or fistulae.

• An arterial segment static pressure ratio >0.75 in grafts.

• Ratio of dialyzer (blood pump) flow to pre-pump pressure <1.2 in fistulae and <1.6 in grafts when using 15 gauge needles.

Once detected, prompt treatment with angioplasty or surgery may prevent formation of a thrombotic occlusion, the group noted. However, an anatomic lesion without a physiologic effect that is not progressing should be left alone. Percutaneous transluminal angiography (PTA) is not innocuous and one must always balance the potential for unforeseen outcomes.

Use of Thrombolytics

During the development of the original K/DOQI guidelines in 1997, there were not enough data on the use of thrombolytics in catheter clearance upon which to base any tangible recommendations. The Food and Drug Administration’s (FDA) withdrawal of approval for the use of urokinase in the treatment of thrombotic catheter occlusions also made it difficult for the group to fashion any specific recommendations regarding the use of thrombolytics for occluded catheters in the 2001 K/DOQI guidelines.

Now, however, with FDA approval of the 2-mg dose of tissue plasminogen activator (t-PA or alteplase) for restoring patency to occluded catheters for all age groups, the new guidelines present an algorithm to help physicians identify and manage thrombotic occlusions in new catheters. Upon encountering a dysfunctional catheter—defined by a number of established criteria, including a blood flow rate of <300 mL/min—guidelines recommend both lines and machines be evaluated and recalibrated. If X-ray does not reveal malpositioning of the catheter or kinks of any kind, then t-PA should be administered. “Fibrinolytics can restore function in catheter-related thrombosis in the great majority of cases,” the authors reported, “and the availability of fibrinolytics allows treatment of occlusions…in the hemodialysis clinic, thereby limiting treatment disruption and inconvenience for the patient.”

Four key studies have evaluated the efficacy of t-PA in catheter clearance in the setting of hemodialysis. Results from the four studies indicate that between 83% and 98% of catheters are recanalized following administration of t-PA. Dr. Besarab confirmed, “t-PA is highly effective in opening partly and fully occluded lumens.” In contrast, low-dose warfarin does not work in this setting and is not recommended, nor is the use of endoluminal brushing, except in a sterile hospital setting. The new guidelines also discuss different strategies for administering t-PA, including infusion into the catheter during a dialysis treatment, dwelling it for up to two hours and locking it in between two dialysis treatments.

As Dr. Besarab noted, several studies have now demonstrated that AVF thrombosis can be salvaged if treatment is administered within 72 hours of detection, “which is a radical paradigm shift in terms of how we take care of this,” he indicated. CVC dysfunction may result from catheter kinking or malpositioning and repositioning of the catheter may eliminate the obstruction. Administration of a thrombolytic—an intraluminal lytic dwell for one to two hours, as an intradialytic lock protocol between dialysis treatments or as an intracatheter thrombolytic infusion—all may help restore function to a dysfunctional catheter, Work Group members observed.

The new guidelines and clinical practice recommendations also provide new practice options for clinicians. Thus, if blood flow is still less than 300 mL/min after two consecutive treatments of t-PA, an intraluminal intradialytic lytic should be instilled and left to dwell between two dialysis treatments (up to 68 or 69 hours). If patency is still not achieved, the patient should be sent for radiological examination in order to exclude a fibrin sheath. The Work Group also suggested further research to clarify many of the unknowns in the realm of vascular access. Suggestions include a study comparing how best to administer a lytic (dwell vs. push vs. infusion); a comparison of different lytic agents in terms of efficacy, cost and long-term performance; and the use of a lytic instead of heparin.

These strategies also need to be compared to simple exchange of the catheter over a guide wire with respect to access site preservation. “Replacement of the vascular access is time-consuming, inconvenient, costly and exposes the patient to undue physical risk and psychological stress,” Dr. Besarab and Ms. Brouwer noted. Moreover, loss of an access site limits future options and when access sites are exhausted, patients face an increased mortality risk unless they are candidates for peritoneal dialysis or transplantation. “Salvage of an established access is more cost-effective than its replacement and in general, fibrinolytic therapy is deemed to be much less expensive than the cost associated with the insertion of a new CVC,” they stated, adding that physicians still need randomized clinical trials to clarify these issues.

Infection in ESRD Patients

As Dr. Besarab and Ms. Brouwer pointed out in their earlier publication, the second leading cause of mortality in ESRD adults is infection, “much of it associated with vascular access complications.” Septicemia is responsible for more than 75% of all deaths due to infection in hemodialysis patients and the risk of infection is highest for uncuffed CVCs, followed by cuffed catheters, then by AV grafts. Infection risk is lowest for AVFs and is a key reason why they continue to be recommended as the best form of vascular access.

The updated guidelines underscore the importance of educating patients and staff on infection control measures to minimize infection risk in these vulnerable patients. Infection control strategies include proper aseptic skin preparation techniques, examining the vascular access exit site in catheterized patients and changing the dressing at each session. “Only trained staff should manipulate CVCs,” the authors advised, “and gloves and masks should be worn during procedures.” If the patient develops catheter-related bacteremia, parenteral antibiotics should be administered, they added. “The current standard is to exchange the catheter, although there may be additional research to see if this is necessary under all conditions,” Dr. Besarab noted. “What is important is that you can exchange this catheter without waiting for a negative blood culture.”

Infection in AV grafts should also be treated with antibiotics and the infected portion of the graft should be either incised or resected. Infected primary AVFs are rare but if they do occur, they require a six-week course of antibiotic therapy. Only septic emboli warrant removal of the AVF, as the authors noted in their previous article. They also pointed out that an occluding thrombus often forms a substrate for bacterial infection. Thus, the use of concomitant fibrinolytic therapy with an antibiotic may improve antimicrobial penetration and allow for salvage of a CVC rather than its replacement (although evidence for this remains inconclusive).

The new guidelines also recommend that every centre offering permanent access placement recruit a multifaceted group of individuals to develop a database so as to better monitor their results.

Specific guidelines for pediatric ESRD patients have been incorporated into the new updated guidelines as well. At the same time, the Working Group recognized that good vascular access surgeons who specialize in pediatric patients are limited in number and that surgeons may have to rely on the expertise of surgeons familiar with vascular access techniques in adults for their expertise.

Questions and Answers

The following question-and-answer section was conducted with Dr. Adeera Levin, Director, Renal Insufficiency Clinic, St. Paul’s Hospital, and Clinical Associate Professor of Medicine, University of British Columbia, Vancouver.

Q: The group made recommendations regarding the use of thrombolytics in the treatment of vascular access complications for the first time. Why are these recommendations especially important?

A: This is not the first time comments were made regarding thrombolytic agents, but the comments now include the updated agents [i.e. t-PA], as other ones [i.e. urokinase] are no longer used.

Q: Why did you feel it was important to make a clear distinction between the new guidelines and clinical practice recommendations, as these newly updated K/DOQI guidelines do?

A: Practice guidelines should be evidence-based and be able to be used as clinical performance measures or standards if they are evidence-based. Clinical practice recommendations are those statements which do not have a substantial evidentiary base, but are intended to give guidance to complex clinical issues. The reason to distinguish the two is to encourage research into those areas of uncertainty.

Q: Is there any single prevailing message in these new updated vascular access guidelines that you feel is the most important theme to emerge?

A: The overriding message is to have a systematic approach to referral, evaluation and follow-up of vascular access in order to maximize outcomes.

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