Mid-regional pro-atrial natriuretic peptide predicts cardiovascular mortality in patients undergoing hemodialysis

Abstract

Abstract Background Cardiovascular diseases are major contributors to morbidity and mortality among patients with renal disease. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a fragment of the precursor molecule of atrial natriuretic peptide, a hormone released from cardiomyocytes in response to volume overload. Small studies have shown that MR-proANP decreases during hemodialysis (HD). No studies have been large enough to investigate the predictive ability of MR-proANP for cardiovascular or all-cause mortality in HD patients. Purpose To investigate the effect of HD on the concentration of MR-proANP and the prognostic value for cardiovascular- and all-cause mortality among HD patients. Methods This was a cohort study of stable patients receiving maintenance HD from two centers. Blood samples were drawn before and after a dialysis session. We calculated the Kaplan-Meier survival estimate (KM) and performed Cox regressions for cardiovascular and all-cause mortality. We estimated hazard ratios (HR) both unadjusted and adjusted for age, sex, diabetes mellitus, years in HD and history of ischemic heart disease and stroke. Results All 306 patients in the cohort had data on at least one MR-proANP measurement and were included. Of these, 284 (93%) had a measurement both before and after HD. Baseline characteristics are shown in table 1. The mean MR-proANP was 762 pmol/L (IQR 419–858 pmol/L) before and 447 pmol/L (IQR 198–537 pmol/L) after HD, a mean decrease of 330 pmol/l (43%) (IQR 152–434 pmol/l, (P<0.01). The median follow-up was 32 months (IQR 31–33) during which 110 (36%) patients died. The most common cause of death was cardiac (n=29, 26%). Figure 1 shows the KM for cardiovascular- (panel A) and all-cause mortality (panel B) in quartiles 1–3 (before HD: green, after HD: black) compared to the 4. Quartile (before HD: red, after HD: yellow) for MR-ProANP concentration measurements before and after HD. The 4. quartile was >863.2 pmol/L before and >537.9 pmol/L after HD. A Cox regression including both the MR-ProANP concentration before and after HD showed that only the concentration after HD was an independent predictor of both cardiovascular and all-cause mortality (both P<0.01). In the unadjusted analysis a MR-ProANP in the 4. quartile after dialysis was associated with a HR of 5.5 (95% CI 2.6–11.7, P<0.01) for cardiovascular mortality. This was even stronger in the adjusted model with a HR of 6.5 (95% CI 2.9–14.4). For all-cause mortality there was a significant rise in mortality among patients in the 3. and 4. quartiles after dialysis, HR 2.5 (95% CI 1.3–4.8) and 5.7 (95% CI 3.1–10.5), respectively (P<0.01). This remained significant in the adjusted model, HR 2.0 (95% CI 1.0–4.0, P=0.04) and 4.7 (95% CI 2.5–8.7, P<0.01), for patients in the 3. and 4. quartile respectively. Conclusion The biomarker MR-ProANP level was almost halved after hemodialysis and the level measured after dialysis was a strong marker for mortality. Figure 1 Funding Acknowledgement Type of funding source: None