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Defining the contribution of chronic kidney disease to all-cause mortality in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study

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Abstract

Aims

To define the contribution of chronic kidney disease (CKD) to excess mortality in patients with type 2 diabetes and identify the baseline variables associated with all-cause death in those with and without CKD using the RECursive Partitioning and Amalgamation (RECPAM) method.

Methods

This observational, longitudinal, cohort study enrolled 15,773 consecutive non-dialytic patients with type 2 diabetes in 19 Diabetes Clinics throughout Italy in 2006–2008. Based on the presence of albuminuria ≥ 30 mg day−1 and/or estimated glomerular filtration rate (eGFR) < 60 mL min−1·1.73 m−2 at baseline, patients were classified as having or not CKD. Vital status was verified on October 31, 2015 for 99.26% of patients.

Results

Mortality increased with increasing albuminuria and eGFR category. Excess risk versus the general population was maximal in patients aged < 55 years in the worse albuminuria or eGFR category. Conversely, in subjects aged ≥ 75 years with albuminuria < 10 mg day−1 or eGFR ≥ 75 mL min−1·1.73 m−2, excess mortality was no longer detectable. At RECPAM analysis, the main correlates of death in the whole cohort were albuminuria > 44 mg day−1, prevalent CVD, and eGFR < ~ 75 mL min−1·1.73 m−2; gender, prevalent CVD, and higher albuminuria in the normoalbuminuric range, in patients without CKD; and CVD, eGFR ~ < 50 mL min−1·1.73 m−2, and albuminuria > 53 mg day−1, in those with CKD.

Conclusions

CKD is a major contributor to excess mortality in type 2 diabetes, conferring a very high risk in younger patients and fully accounting for excess risk in the older ones. Higher albuminuria and lower eGFR, even in the normal range, identify individuals with increased mortality risk.

Trial registration ClinicalTrials.gov (NCT00715481; https://clinicaltrials.gov/ct2/show/NCT00715481).

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Abbreviations

CVD:

Cardiovascular disease

HR:

Hazard ratio

CI:

Confidence interval

CKD:

Chronic kidney disease

eGFR:

Estimated glomerular filtration rate

RECPAM:

RECursive Partitioning and Amalgamation

RIACE:

Renal Insufficiency and Cardiovascular Events

BP:

Blood pressure

BMI:

Body mass index

HbA1c :

Hemoglobin A1c

AER:

Albumin excretion rate

DR:

Diabetic retinopathy

ISTAT:

Italian National Institute of Statistics

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Acknowledgements

This research was supported by the Research Foundation of the Italian Diabetes Society (Diabete Ricerca) and the Diabetes, Endocrinology and Metabolism (DEM) Foundation, and by unconditional grants from Eli Lilly, Sigma-Tau, Takeda, Chiesi Farmaceutici, and Boehringer Ingelheim.

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Giuseppe Penno

  2. Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy

    Anna Solini

  3. Division of Endocrinology, Diabetes and Metabolism, University and Hospital Trust of Verona, Verona, Italy

    Enzo Bonora

  4. Diabetes Unit, IRCCS “Cà Granda - Ospedale Maggiore Policlinico” Foundation, Milan, Italy

    Emanuela Orsi

  5. Diabetes Unit, University of Siena, Siena, Italy

    Cecilia Fondelli

  6. Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milan, Italy

    Gianpaolo Zerbini

  7. Endocrinology and Diabetes Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy

    Roberto Trevisan

  8. Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy

    Monica Vedovato

  9. Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy

    Franco Cavalot

  10. Department of Emergency and Transplants - Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy

    Luigi Laviola

  11. Center for Outcomes Research and Clinical Epidemiology (CORESEARCH), Pescara, Italy

    Antonio Nicolucci

  12. Department of Clinical and Molecular Medicine, “La Sapienza” University, Via di Grottarossa, 1035-1039, 00189, Rome, Italy

    Giuseppe Pugliese

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  1. Giuseppe Penno
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Consortia

for the Renal Insufficiency and Cardiovascular Events (RIACE) Study Group

Corresponding author

Correspondence to Giuseppe Pugliese.

Ethics declarations

Conflict of interest

Dr. Penno reported receiving personal fees from Astra-Zeneca, Boehringer Ingelheim, Eli Lilly, and Merck Sharp & Dohme. Dr. Solini reported receiving grant from Astra-Zeneca and personal fees from Boehringer Ingelheim and Eli Lilly. Dr. Bonora reported receiving grants from Astra-Zeneca, Novo Nordisk, Roche, and Takeda and personal fees from Abbot, Astra-Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck Sharp & Dohme, Novo Nordisk, Roche, Sanofi-Aventis, and Takeda. Dr. Orsi reported personal fees from Abbot, Astra-Zeneca, Boehringer Ingelheim, Eli Lilly, Lifescan, Novo Nordisk, Sanofi-Aventis, and Takeda. Dr. Trevisan reported receiving personal fees from Astra-Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Medtronic, Novartis, Novo Nordisk, and Sanofi-Aventis and grants from Astra-Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, and Sanofi-Aventis. Dr. Cavalot reported receiving personal fees from Astra-Zeneca, Sanofi-Aventis, and Takeda. Dr. Nicolucci reported receiving grants from Artsana, Astra-Zeneca, Eli Lilly, Novo Nordisk, and Sanofi-Aventis and personal fees from Eli Lilly and Novo Nordisk. Dr. Pugliese reported receiving personal fees from Astra-Zeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Mylan, Shire, Sigma-Tau, and Takeda. No other disclosures were reported.

Ethical standard

The study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments. The study protocol was approved by the locally appointed ethics committees.

Informed consent

Informed consent was obtained from all patients for being included in the study.

Additional information

Managed by Massimo Porta.

A complete list of the RIACE Investigators can be found in the Online-only Supplementary Materials.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 3853 kb)

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Penno, G., Solini, A., Bonora, E. et al. Defining the contribution of chronic kidney disease to all-cause mortality in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. Acta Diabetol 55, 603–612 (2018). https://doi.org/10.1007/s00592-018-1133-z

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  • DOI: https://doi.org/10.1007/s00592-018-1133-z

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