The study participants (n = 91) had an average age of 59 years, with 47% of the cohort male, 100% Blacks and an average length of time on dialysis of 5.7 years (Table ). Among the participants, the average patient BMI was 29.1 ± 6.9 kg/m2, 49% had diabetes, 98% had hypertension, 44% had a history of cardiovascular disease, 22% peripheral vascular disease, 4% had a hypercoagulable state, 39% had a history of smoking, and 49% of participants used an AVG and 51% used an AVF for hemodialysis at study enrollment.
Baseline characteristics of study participants by number of retained thrombosed AVGs
Among the overall cohort, 67% (61) patients had a previous permanent AV access (either an AVF or AVG) and 47% of patients had one or more retained AVG; of these, 77% had 1–2 thrombosed, retained AVG and 23% had 3 or more thrombosed, retained AVG. Of the patients currently using an AVG, 58% had a history of one or more retained AVG, while among patients using an AVF, 37% had one or more retained AVG. Patient characteristics associated with one or more thrombosed, retained AVG included length of time on dialysis, which was significantly longer among patients with one or more AVG (P< 0.001) compared with patients with none. Of marginal significance was patient age (P= 0.054), as younger patients tended to have had one or more retained thrombosed AVG. There were no significant differences in gender, BMI, primary renal disease, comorbidities, tobacco use, current type of AV access, EPO use or serum hemoglobin among patients with 0, 1–2 or 3+ previous, thrombosed, retained AVGs (Table ).
Upon stratification of inflammatory biomarkers by the number of thrombosed, retained AVGs, in general, their concentrations were greater as the number of retained AVGs increased from 0 to 3+ (Figure ), although these differences did not reach statistical significance. In contrast, patients with a history of one or more nonfunctional, retained AVG had significantly greater log-CRP concentrations compared with patients who had never had an AVG (1.68 mg/L versus 1.17 mg/L, P= 0.045), while no significant difference was observed between groups in log-IL-6, TNF-alpha, or serum albumin concentrations (data not shown).
Mean inflammatory biomarker concentration stratified by the number of retained thrombosed AVGs (none, 1–2, 3+), where CRP and IL-6 are log-transformed.
Figure shows the unadjusted, partially adjusted and fully adjusted effects of thrombosed, retained AVGs on plasma inflammatory biomarker concentrations, where biomarkers with a skewed distribution were log-transformed. In the unadjusted model, each additional retained AVG was significantly associated with an increase in the plasma concentrations of log-CRP and TNF-alpha of 0.25 mg/L (P= 0.014) and 0.57 pg/mL (P= 0.048), respectively, while there was no significant increase in log-IL-6 concentration (P= 0.13). After adjusting for age, length of time on dialysis and current type of AV access in the partially adjusted model, for every additional retained AVG, the log-CRP concentration significantly increased by 0.35 mg/L (P= 0.003), while no significant change occurred in log-IL-6 concentration (P= 0.058) or in TNF-alpha concentration (P= 0.11). Finally, in the fully adjusted model, controlling for sex, BMI, smoking status and diabetes, each additional retained thrombosed AVG accounted for a significant increase in plasma log-CRP (0.30 mg/L, P= 0.011), log-IL-6 (0.18 pg/mL, P= 0.046) and TNF-alpha (0.72 pg/mL, P= 0.046). There was no significant change in serum albumin concentration as the number of retained AVGs increased in the adjusted models.
FIGURE 2: Change in inflammatory biomarker level for each additional retained thrombosed AVG, treated as a continuous variable, where CRP and IL-6 are log-transformed. Partially Adjusted: adjusted for age, length of time on dialysis and type of AV access (AVF versus (more ...)
To further examine the relationship between the number and type of previous vascular access to inflammation, patients were stratified by current AVF versus AVG use, prior AVG use and prior AVF use (Table ), and regression coefficient estimates representing group differences were calculated. The plasma concentrations of log-CRP, log-IL-6, and TNF-alpha were not statistically different between patients currently using an AVG versus AVF, or those whose vascular access history was limited to AVF use. In contrast, current AVG use had a significant negative effect on serum albumin concentration compared with current AVF use, and was 0.20 g/dL lower among current AVG users (P= 0.032). When comparing the effect of one or more retained thrombosed AVG versus none on log-CRP, log-IL-6, TNF-alpha and serum albumin, log-CRP concentration was significantly greater (0.58 mg/L) among patients with a retained nonfunctional AVG (P= 0.036). There was no significant difference in inflammatory biomarkers between patients with prior AVF use versus none.
Estimated difference in inflammatory biomarker between groups defined by current AVG/AVF use, prior AVG use (0 versus 1+) and prior AVF use (0 versus 1+)
Finally, we examined the relationship between inflammation and EPO resistance, defined as the weekly EPO dose/ hematocrit ratio [10
]. Following adjustment for age, sex, BMI, smoking status, diabetes, length of time on dialysis and type of AV access (AVF versus others), there was a statistically significant association between EPO resistance and greater plasma log-CRP (P= 0.003) and log IL-6 concentrations (P= 0.003).