Increased plasma concentrations of midregional proatrial natriuretic Peptide is associated with risk of cardiorenal dysfunction in type 1 diabetes

Abstract

Background: To examine possible associations between midregional proatrial natriuretic peptide (MR-proANP) and diabetic complications at baseline and risk of mortality and end-stage renal disease (ESRD) during follow-up in type 1 diabetes.

Methods: Observational study including 667 patients, with plasma MR-proANP measured at baseline. Complications were defined as micro- (n = 168) or macroalbuminuria (n = 190) (urinary albumin excretion rate (UAER) 30-299 or ≥ 300 mg/24h), previous cardiovascular disease (CVD) (n = 143), cardiac autonomic dysfunction (heart rate variability < 11 beats/min) (n = 369), and retinopathy (n = 523). Adjustments included gender, age, systolic blood pressure, estimated glomerular filtration rate (eGFR), UAER, HbA1c, total cholesterol, 24-hour urinary sodium excretion (24h-U(Na)), body mass index, daily insulin dose, antihypertensive treatment, and smoking in linear regression analyses and analysis of covariance models. Development of ESRD (dialysis, renal transplantation, or GFR/eGFR < 15 ml/min/1.73 m(2)) and mortality was recorded through national registers.

Results: The cohort included 293 (44%) females, aged 55 ± 13 years. Plasma MR-proANP (median (interquartile)) was 74.7 (49.2-116.8) pmol/L. Adjusted, MR-proANP correlated positively with age and UAER and negatively with eGFR, 24h-U(Na), total cholesterol, and HbA1c (P < 0.05). Moreover, MR-proANP levels increased with albuminuria degree and were higher in patients with previous CVD (P ≤ 0.001), but similar in patients with or without autonomic dysfunction or retinopathy (P ≥ 0.076). During follow-up (3.5 (3.1-4.0) years), higher MR-proANP concentrations predicted ESRD and mortality combined (n = 35) adjusted for gender, age, systolic blood pressure, eGFR, and previous CVD (hazard ratio per 1SD increase in logANP: 2.8 (1.6-4.7; P < 0.001)).

Conclusions: Increased plasma MR-proANP was associated with impaired renal function, increased albuminuria, and previous CVD. Moreover, MR-proANP concentrations were associated with increased risk of development of ESRD and mortality combined during follow-up.

Keywords: atrial natriuretic peptide; blood pressure; diabetic complications; hypertension; natriuretic peptide; type 1 diabetes..