The identification of clinical predictors for the development of chronic kidney disease is a critical issue in the management of patients with type 2 diabetes mellitus.
We evaluated 27,029 patients with type 2 diabetes mellitus and estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and normoalbuminuria from the database of the Italian Association of Clinical Diabetologists network. Primary outcomes were eGFR <60 mL/min/1.73 m2 and normoalbuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m2; and eGFR <60 mL/min/1.73 m2 and albuminuria. Secondary outcomes were eGFR <60 mL/min/1.73 m2 and albuminuria. Measurements: eGFR from serum creatinine by chronic kidney disease epidemiology collaboration equation (CKD-EPI), urinary albumin excretion, HbA1c, triglycerides, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c), blood pressure, and body mass index.
Over a 4-year period, 33.2% of patients (n = 8973) developed chronic kidney disease, 10.3% (n = 2788) showed a decline in eGFR <60 mL/min/1.73 m2, 18.4% (n = 4978) developed albuminuria, and 4.5% (n = 1207) developed both features. Relative risk ratios (RRRs) for age (1.37, P < 0.001 by 5 years), sex (0.77, P < 0.001 for being male), body mass index (1.03, P < 0.001 by 1 kg/m2), triglycerides (1.02, P < 0.001 by 10 mg/dL), and LDL-c (0.97, P = 0.004 by 10 mg/dL) were independently related to the onset of eGFR reduction. Age (1.08, P < 0.001 by 5 years), sex (1.36, P < 0.001 for being male), body mass index (1.02, P < 0.001 by 1 kg/m2), triglycerides (1.01, P = 0.02 by 10 mg/dL), HDL-c, and LDL-c (0.97, P = 0.008 and 0.99, P = 0.003 by 5 and 10 mg/dL, respectively) were related to the onset of albuminuria. HbA1c and the intensity of antihypertensive treatment showed a weaker association with renal outcome.
Reduction in eGFR and albuminuria showed distinct sets of risk factors, suggesting that different mechanisms are involved in the development of these 2 components of diabetic kidney disease.
aDepartment of Medical Sciences, Scientific Institute “Casa Sollievo della Sofferenza”, San Giovanni Rotondo (FG)
bUniversità degli Studi and IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genova
cDiabetes and Metabolism Unit ASL Turin 5, Chieri (TO), Italy
dInstitut d’Investigacions Biomèdiques August Pii Sunyer (IDIBAPS) and Centro de Investigación Biomédicaen Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain
eDepartment of Clinical and Experimental Medicine, 2nd University of Naples, Caserta
fDepartment of Clinical and Experimental Medicine, University of Messina, Messina
gCenter for Outcomes Research and Clinical Epidemiology, Pescara
hAssociazione Medici Diabetologi, Rome, Italy.
Correspondence: Salvatore De Cosmo, Department of Medical Sciences, Scientific Institute “Casa Sollievo della Sofferenza”, Viale Cappuccini 1, 71013 San Giovanni Rotondo (FG), Italy (e-mail: firstname.lastname@example.org).
Abbreviations: AMD = Associazione Medici Diabetologi, BP = blood pressure, CKD = chronic kidney disease, DKD = diabetic kidney disease, eGFR = estimated glomerular filtration rate, HDL-c = total and high density lipoprotein cholesterol, LDL-c = low-density lipoprotein cholesterol.
Authorship: SDC and RP designed the study, analyzed and interpreted data, and wrote the manuscript; FV and AP analyzed data, wrote the manuscript, and contributed to discussion; AC, SG, and CG analyzed data and reviewed the manuscript; PG analyzed data and contributed to discussion; GR, MCR, and AN contributed to discussion and reviewed the manuscript. All the authors approved the final version for publication. SDC 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.
The authors report no conflicts of interest.
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Received December 7, 2015
Received in revised form April 28, 2016
Accepted May 31, 2016