Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes

Sara J Jenks,David J Webb,Paul Welsh,Wei Leng Teoh,Naveed Sattar,Rachel M Williamson,Stela Mclachlan,Jackie F Price,Bryan R Conway,Mark W J Strachan

doi:10.1007/s00125-017-4297-0

Abstract

Aims/hypothesisWe investigated whether biochemical cardiovascular risk factors and/or markers of subclinical cardiovascular disease were associated with the development of reduced renal function in people with type 2 diabetes.MethodsA cohort of 1066 Scottish men and women aged 60–74 years with type 2 diabetes from the Edinburgh Type 2 Diabetes Study were followed up for a median of 6.7 years. New-onset reduced renal function was defined as two eGFRs <60 ml−1 min−1 (1.73 m)−2 at least 3 months apart with a > 25% decline from baseline eGFR. Ankle brachial pressure index (ABI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) were measured at baseline. Pulse wave velocity (PWV) and carotid intima media thickness were measured 1 year into follow-up. Data were analysed using Cox proportional hazards models.ResultsA total of 119 participants developed reduced renal function during follow-up. ABI, PWV, NT-proBNP and hsTnT were all associated with onset of decline in renal function following adjustment for age and sex. These associations were attenuated after adjustment for additional diabetes renal disease risk factors (systolic BP, baseline eGFR, albumin:creatinine ratio and smoking pack-years), with the exception of hsTnT which remained independently associated (HR 1.51 [95% CI 1.22, 1.87]). Inclusion of hsTnT in a predictive model improved the continuous net reclassification index by 0.165 (0.008, 0.286).Conclusions/interpretationOur findings demonstrate an association between hsTnT, a marker of subclinical cardiac ischaemia, and subsequent renal function decline. Further research is required to establish the predictive value of hsTnT and response to intervention.

Highlights

The development of reduced renal function and chronic kidney disease (CKD) in people with type 2 diabetes predicts an increase in both morbidity and mortality rates [1]
Of the cardiovascular biomarkers analysed, the presence of cardiovascular disease (CVD), lower ankle brachial pressure index (ABI), higher pulse wave velocity (PWV), NT-proBNP and high-sensitivity troponin T (hsTnT) were all associated with the onset of reduced renal function
Our study confirms the tremendous burden of kidney disease for people with type 2 diabetes with 347 (33%) of the 1066 participants in the ET2DS cohort having CKD at baseline and a further 119 (17%) developing a clinically relevant decline in renal function during follow-up

Summary

Introduction

The development of reduced renal function and chronic kidney disease (CKD) in people with type 2 diabetes predicts an increase in both morbidity and mortality rates [1]. It has been proposed that many people with type 2 diabetes develop impaired renal function as a result of vascular disease, rather than classical diabetic nephropathy, consistent with ACR being a poor kidney disease biomarker in many individuals [5]. It would be reasonable to hypothesise that cardiovascular disease (CVD) biomarkers may improve on risk stratification using conventional risk factors for diabetic CKD Support for this hypothesis comes from previous studies demonstrating an association between the development of end-stage renal disease and biochemical markers of CVD, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT), in people with type 2 diabetes, even after adjustment for eGFR and albuminuria [6, 7]. Some of the evidence is conflicting and there have been no large longitudinal studies focusing on people with type 2 diabetes [8,9,10,11,12]

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