Plasma N-terminal pro-brain natriuretic peptide as an independent predictor of mortality in diabetic nephropathy

Aims/hypothesis: Raised N-terminal pro-brain natriuretic peptide (NT-proBNP) is independently associated with an increased risk of death in chronic heart failure and acute coronary syndromes in nondiabetic populations. Diabetic nephropathy is characterised by an increased risk of cardiovascular morbidity and mortality. This study investigated the prognostic value of NT-proBNP in a large cohort of type 1 diabetic patients with and without diabetic nephropathy. Methods: In a prospective observational follow-up study, 198 type 1 diabetic patients with overt diabetic nephropathy ( 122 men, age [ mean +/- SD] 41 +/- 10 years, duration of diabetes 28 +/- 8 years, GFR 74 +/- 33 ml min(-1)) and a matched control group of 188 patients with longstanding type 1 diabetes and persistent normoalbuminuria ( 114 men, age 43 +/- 10 years, duration of diabetes 27 +/- 9 years) were followed for 9.3 ( 0.0 - 9.5) years. Plasma NT-proBNP concentration was determined by immunoassay at baseline. Results: In patients with diabetic nephropathy, plasma NT-proBNP concentration was elevated to ( median [ range]) 110 ( 5 - 79640) ng l(-1) vs. 27 ( 5 - 455) ng l(-1) in normoalbuminuric patients (p< 0.0001). Among patients with nephropathy, 39 (39%) patients with plasma NT-proBNP concentrations above the median and 12 (12%) with values below the median died from any cause ( unadjusted hazard ratio 3.86 [95% CI 2.02 - 7.37], p< 0.0001; covariate- adjusted hazard ratio 2.28 [1.04 - 4.99], p= 0.04). This lower mortality rate was attributable to fewer cardiovascular deaths: 31 ( 31%) and 7 ( 7%) above and below the median NT-proBNP level respectively ( unadjusted hazard ratio 5.25 [2.31 - 11.92], p< 0.0001; covariate- adjusted hazard ratio 3.81 [1.46 - 9.94], p= 0.006). Conclusions/interpretation: Elevated circulating NT-proBNP is a new independent predictor of the excess overall and cardiovascular mortality in diabetic nephropathy patients without symptoms of heart failure.