INTRADIALYTIC KINETICS OF CARDIAC BIOMARKERS DURING HIGH-FLUX HEMODIALYSIS AND POST-DILUTION HEMODIAFILTRATION: A RANDOMIZED CROSSOVER TRIAL

Cardiovascular disease (CVD) is a major cause of mortality in patients treated with hemodialysis (HD). Furthermore, diagnosing CVD in this population presents several challenges, which include atypical or absent symptoms of myocardial infarction (MI), a high presence of elevated troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and limited data on how dialysis treatment affects cardiac biomarker concentrations. The aim of this study was to investigate the intradialytic kinetics of high-sensitivity cardiac troponin I and T (hs-cTnI and hs-cTnT) and NT-proBNP during HD and hemodiafiltration (HDF). 

Randomized, crossover trial comparing high-flux HD and post-dilution HDF in patients treated with HD without acute CVD. Objectives were to measure levels of hs-cTnI, hs-cTnT, and NT-proBNP before, during, and after HD and HDF, to compare changes between the two dialysis modalities, and to calculate blood dialyzer clearance. Patients were randomized to start with either HD or HDF, had a washout period of 1-3 weeks, and then crossed over to receive the other modality. Dialysis settings were similar on both trial days. Blood samples were collected before dialysis started, after 10, 30, 60, 120, 180, and 240 minutes of dialysis, and 30 minutes post-dialysis. After 120 minutes of dialysis, clearance was calculated, and spent dialysate was collected. Linear mixed-effects models were used to investigate concentration changes and to compare dialysis modalities. One-sample t-tests were used to investigate whether clearance was significant.

The study included 23 patients with a median age of 67 years (Q1-Q3: 57-77), and 61% were male. Median concentration of hs-cTnI, hs-cTnT, and NT-proBNP was 19 ng/L (Q1-Q3: 9-31), 57 ng/L (Q1-Q3: 36-66), and 5088 ng/L (Q1-Q3: 2579-11129), respectively. HD did not influence hs-cTnI and hs-cTnT concentrations; however, HDF resulted in a significant decline in both biomarkers (Figure 1). At the end of dialysis, the change was -7.7 ng/L (95% CI: -11.8 to -3.7) for hs-cTnI and -23.4 ng/L (95% CI: -31.9 to -14.9) for hs-cTnT. NT-proBNP was significantly reduced with both modalities, with a change of -5161 ng/L (95% CI: -6678 to -3645) in HDF and -2954 ng/L (95% CI: -4434 to -1474) in HD. All cardiac biomarkers were significantly lower with HDF compared to HD (Figure 2). The estimated difference in concentrations at the end of dialysis, between HD and HDF, was 3.7 ng/L (95% CI: 1.9 to 5.6) for hs-cTnI, 13 ng/L (95% CI: 9.9 to 16.1) for hs-cTnT, and 2199 ng/L (95% CI: 1397 to 3001) for NT-proBNP. There was no evidence of a rebound increase in hs-cTnI, hs-cTnT, or NTprobNP 30 minutes post dialysis. Additionally, there was no blood dialyzer clearance of hs-cTnI; however, hs-cTnT and NT-proBNP clearance were significant during both HD and HDF (Table 1). Hs-cTnI was not detectable in the spent dialysate, whereas hs-cTnT and NTproBNP were detectable in both dialysis sessions. 

In this randomized crossover trial, hs-cTnI, hs-cTnT, and NT-proBNP concentrations were significantly reduced with HDF in stable patients treated with dialysis. Conventional HD only reduced NT-proBNP concentrations. This emphasizes the necessity of considering dialysis clearance when using cardiac biomarkers for diagnostic purposes in patients treated with dialysis.