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Cardiac autonomic neuropathy predicts renal function decline in patients with type 2 diabetes: a cohort study

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Abstract

Aims/hypothesis

The aim of this work was to assess the impact of cardiac autonomic neuropathy (CAN) on the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes.

Methods

We conducted a cohort study in adults with type 2 diabetes. Patients with end-stage renal disease were excluded. CKD was defined as the presence of albuminuria (albumin/creatinine ratio GFR > 3.4 mg/mmol) or an estimated (eGFR) < 60 ml min−1 1.73 m−2. CKD progression was based on repeated eGFR measurements and/or the development of albuminuria. CAN was assessed using heart rate variability.

Results

Two hundred and four patients were included in the analysis. At baseline, the prevalence of CKD and CAN was 40% and 42%, respectively. Patients with CAN had lower eGFR and higher prevalence of albuminuria and CKD. Spectral analysis variables were independently associated with eGFR, albuminuria and CKD at baseline. After a follow-up of 2.5 years, eGFR declined to a greater extent in patients with CAN than in those without CAN (−9.0 ± 17.8% vs −3.3 ± 10.3%, p = 0.009). After adjustment for baseline eGFR and baseline differences, CAN remained an independent predictor of eGFR decline over the follow-up period (β = −3.5, p = 0.03). Spectral analysis variables were also independent predictors of eGFR decline.

Conclusions/interpretation

CAN was independently associated with CKD, albuminuria and eGFR in patients with type 2 diabetes. In addition, CAN was an independent predictor of the decline in eGFR over the follow-up period. CAN could be used to identify patients with type 2 diabetes who are at increased risk of rapid decline in eGFR, so that preventative therapies might be intensified.

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Abbreviations

ACR:

Albumin/creatinine ratio

CAN:

Cardiac autonomic neuropathy

CKD:

Chronic kidney disease

DN:

Diabetic nephropathy

E/I:

Expiratory/inspiratory

ESRD:

End-stage renal disease

HRV:

Heart rate variability

LFa:

Low-frequency area

pNN50:

Percentage of adjacent R–R intervals that varied by more than 50  ms

RAAS:

Renin–angiotensin–aldosterone system

RFa:

Respiratory-frequency area

RMSSD:

Square root of the mean squared differences of successive RR intervals

RRT:

Renal replacement therapy

SDNN:

Standard deviation of normal RR intervals

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Acknowledgements

A. Tahrani is a Clinician Scientist fellow supported by the National Institute for Health Research (UK). The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the National Institute for Health Research or the Department of Health.

We acknowledge F. Hanna, H. Hodgson and R. Barakam (University Hospital of North Staffordshire, Stoke-on-Trent, UK) for their help in recruitment.

Funding

This project was funded by the National Institute for Health Research (UK), the UK Novo Nordisk Research Foundation and Sanofi Aventis.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

AAT was responsible for the conception and design of the study and obtaining funding, acquired, analysed and interpreted data and wrote the first draft of the manuscript. NTR was responsible for statistical analysis and interpretation and reviewed the manuscript. SB acquired data, designed the study and reviewed the manuscript. KD and QAA designed the study and reviewed the manuscript. HS acquired data and reviewed the manuscript. MKP acquired data and reviewed the manuscript. MJS was responsible for the study conception and design, analysed and interpreted data and reviewed the manuscript. All authors gave final approval for the publication of this manuscript.

AAT is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. Centre of Endocrinology, Diabetes and Metabolism, Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, B15 2TT, UK

    Abd A. Tahrani, Kiran Dubb & Martin J. Stevens

  2. Department of Diabetes and Endocrinology, Heart of England NHS Foundation trust, Birmingham, UK

    Abd A. Tahrani, Safia Begum, Quratul A. Altaf, Hamed Sadiqi & Martin J. Stevens

  3. Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK

    Neil T. Raymond

  4. Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, UK

    Milan K. Piya

  5. Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK

    Milan K. Piya

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  1. Abd A. Tahrani
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Correspondence to Abd A. Tahrani.

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Tahrani, A.A., Dubb, K., Raymond, N.T. et al. Cardiac autonomic neuropathy predicts renal function decline in patients with type 2 diabetes: a cohort study. Diabetologia 57, 1249–1256 (2014). https://doi.org/10.1007/s00125-014-3211-2

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