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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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.
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.
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.
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).
KeywordsType 2 diabetes Chronic kidney disease Albuminuria Glomerular filtration rate All-cause mortality Cardiovascular risk factors
Chronic kidney disease
Estimated glomerular filtration rate
RECursive Partitioning and Amalgamation
Renal Insufficiency and Cardiovascular Events
Body mass index
Albumin excretion rate
Italian National Institute of Statistics
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.
Compliance with ethical standards
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.
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 was obtained from all patients for being included in the study.
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