Risk of hemodialysis graft thrombosis: analysis of monthly flow surveillance.

BACKGROUND: During clinical application of flow surveillance of hemodialysis grafts, the risk of thrombosis is assessed month after month, rather than after one or several measurements, as has been done in published studies. Adequate assessment of risk should consider the many measurements obtained over time. STUDY DESIGN: Prospective cohort diagnostic test study. SETTING & PARTICIPANTS: 176 patients with hemodialysis grafts from 2 university-affiliated dialysis units during a 6-year period. INDEX TESTS: Monthly measurement of graft blood flow or change in flow. OUTCOME: Graft thrombosis. RESULTS: We used logistic regression analysis to compute the risk of thrombosis and used receiver operating characteristic (ROC) curves to assess the accuracy in predicting thrombosis within 1 month. Newer grafts were most likely to thrombose, whereas older grafts were unlikely to thrombose even at low flows or large decreases in flow. Areas under the ROC curves were 0.698 for flow and 0.713 for change in flow measured over 2 months. Flow predicted thrombosis with a sensitivity of 53% at a specificity of 79%, and change in flow had a sensitivity of 58% at a specificity of 75%. More than half the thromboses lacked a change in flow measurement, usually because thrombosis occurred before a change could be measured. Thus, the effective predictive accuracy of change in flow was much less than the ROC curves indicated because the curves do not consider missing measurements. LIMITATIONS: Performance characteristics of index tests may vary across patient populations. CONCLUSION: Flow and change in flow are inaccurate predictors of thrombosis. Many thromboses are not predicted, and intervention based on surveillance likely yields many unnecessary procedures. Thus, this study does not support routine application of surveillance to prevent thrombosis.

Thresholds for significant decrease in hemodialysis access blood flow.

During hemodialysis access surveillance, referral for evaluation and correction of stenosis is based upon determination that a significant decrease in blood flow (Q) has occurred. However, criteria for determining when a decrease is statistically significant have not yet been established. In this study we established such criteria by analyzing Q variation with the glucose pump test (GPT). We took nine Q measurements in each of 25 patients (18 grafts, 7 fistulas) during three dialysis sessions within a 2-week period (predialysis and during hours 1 and 3). We determined thresholds that define a significant percentage decrease in Q (deltaQ) for various p values. In order to confirm the general applicability of these thresholds, we computed the average within-patient Q variation during the three sessions (computed as a coefficient of variation and referred to as short-term variation). We then determined the relative influences of biological (true) variation and analytical error on short-term variation. We found that deltaQ must be > 33% to be significant at p < 0.05, whereas the threshold is > 17% for p < 0.20. Measuring Q at uniform versus different times during the sessions did not significantly reduce these thresholds. We also found that biological variation was nearly as large as short-term Q variation, whereas analytical error contributed minimally to short-term variation. In conclusion, this study defines thresholds for a significant deltaQ that have wide application in determining access referral for evaluation and correction of stenosis. Selection of a particular threshold should consider the relative importance of avoiding thrombosis versus avoiding unnecessary procedures. If avoiding unnecessary procedures is a priority, then we recommend a threshold of > 33%. These thresholds apply to other methods of measuring Q, provided analytical error is significantly less than biological variation.

Stenosis surveillance of hemodialysis grafts by duplex ultrasound reduces hospitalizations and cost of care.

Most recent randomized controlled trials (RCTs) have found that hemodialysis graft surveillance combined with preemptive correction of stenosis does not prolong graft survival. Nevertheless, such programs may be justified if they reduce other adverse outcomes or decrease the cost of care. This study tested this hypothesis by applying a secondary analysis to our original RCT. This study of 101 patients evaluated correction of stenosis based upon blood flow (Q) and stenosis surveillance. Patients were randomly assigned to control, flow, or stenosis groups, and were followed for up to 28 months. Q was measured monthly by ultrasound dilution; stenosis was measured quarterly by duplex ultrasound. Stenosis of 50% was corrected by percutaneous transluminal angioplasty (PTA) after referral for angiography. Referral criteria were: control group, clinical criteria; flow group, Q < 600 ml/min or clinical criteria; stenosis group, stenosis > 50% or clinical criteria. We compared access-related hospitalizations and cost of care, and use of central venous dialysis catheters (CVCs), among the three groups. Hospitalization rates were higher in the control and flow groups than in the stenosis group (0.50, 0.57, 0.18/patient-year, respectively [p < 0.01]), and hospitalization costs were lowest in the stenosis group (p = 0.026). The stenosis group had a trend toward lowest CVC rates (0.44, 0.32, 0.20/patient-year, respectively [p = 0.20]). The costs of care were higher in the control and flow groups than in the stenosis group (dollar 3727, dollar 4839, dollar 3306/patient-year, respectively [p = 0.015]). The costs of stenosis (dollar 142/patient-year) and Q (dollar 279/patient-year) measurements were minimal compared to the total cost of access-related care. In conclusion, stenosis surveillance by duplex ultrasound combined with preemptive correction yielded reduced hospitalization rates and costs, reduced total cost of access-related care, and a trend of reduced CVC rates. In contrast, flow surveillance did not yield a significant benefit. Stenosis surveillance provides important benefits that may justify application of such programs.

Expression of the proto-oncogene eIF4E in inflammation of the oral cavity.

OBJECTIVE: eIF4E (4E) is elevated in 100% of head and neck squamous cell carcinoma (HNSCC) and in premalignant lesions of the larynx. However, it is not elevated in normal mucosa. In this study, we hypothesize that 4E is not significantly elevated in inflammation unlike its expression in premalignant lesions of the oral cavity. STUDY DESIGN: Biopsies from the oral cavity were divided into 5 groups: (1) normal mucosa, (2) chronic inflammation, (3) mild dysplasia from leukoplakic lesions, (4) mild dysplasia in surgical margins of patients with HNSCC, and (5) HNSCC. Immunohistochemical qualitative analysis was then performed. RESULTS: None of the 15 specimens in group 1 and 100% of the 15 specimens in group 5 expressed 4E. Of the 29 specimens in group 2 only 4/29 (13%) overexpressed 4E compared with 10/31 (32%) in group 3 and 9/21 (42%) in group 4. There was a significant difference between groups 2 and 3 and groups 2 and 4 (P < 0.0001 and P < 0.003 respectively) but no significant difference between groups 1 and 2 (P = 0.13) and between groups 3 and 4 (P = 0.30). CONCLUSION: 4E is not significantly elevated in inflammation of the oral cavity thus fulfilling one of the criteria that biomarkers require to be useful in a clinical setting.

Relative contribution of wall shear stress and injury in experimental intimal thickening at PTFE end-to-side arterial anastomoses.

BACKGROUND: Intimal hyperplastic thickening (IHT) is a frequent cause of prosthetic bypass graft failure. Induction and progression of IHT is thought to involve a number of mechanisms related to variation in the flow field, injury and the prosthetic nature of the conduit. This study was designed to examine the relative contribution of wall shear stress and injury to the induction of IHT at defined regions of experimental end-to-side prosthetic anastomoses. METHODS AND RESULTS: The distribution of IHT was determined at the distal end-to-side anastomosis of seven canine Iliofemoral PTFE grafts after 12 weeks of implantation. An upscaled transparent model was constructed using the in vivo anastomotic geometry, and wall shear stress was determined at 24 axial locations from laser Doppler anemometry measurements of the near wall velocity under conditions of pulsatile flow similar to that present in vivo. The distribution of IHT at the end-to-side PTFE graft was determined using computer assisted morphometry. IHT involving the native artery ranged from 0.0+/-0.1 mm to 0.05+/-0.03 mm. A greater amount of IHT was found on the graft hood (PTFE) and ranged from 0.09+/-0.06 to 0.24+/-0.06 mm. Nonlinear multivariable logistic analysis was used to model IHT as a function of the reciprocal of wall shear stress, distance from the suture line, and vascular conduit type (i.e. PTFE versus host artery). Vascular conduit type and distance from the suture line independently contributed to IHT. An inverse correlation between wall shear stress and IHT was found only for those regions located on the juxta-anastomotic PTFE graft. CONCLUSIONS: The data are consistent with a model of intimal thickening in which the intimal hyperplastic pannus migrating from the suture line was enhanced by reduced levels of wall shear stress at the PTFE graft/host artery interface. Such hemodynamic modulation of injury induced IHT was absent at the neighboring artery wall.