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Clinical significance of nonalbuminuric renal impairment in type 2 diabetes

Penno, Giuseppea; Solini, Annab; Bonora, Enzoc; Fondelli, Ceciliad; Orsi, Emanuelae; Zerbini, Gianpaolof; Trevisan, Robertog; Vedovato, Monicah; Gruden, Gabriellai; Cavalot, Francoj; Cignarelli, Maurok; Laviola, Luigil; Morano, Susannam; Nicolucci, Antonion; Pugliese, Giuseppeofor the Renal Insufficiency And Cardiovascular Events (RIACE) Study Group

doi: 10.1097/HJH.0b013e3283495cd6
Original papers: Kidney

Objective In type 2 diabetes, prevalence of nonalbuminuric renal impairment is increasing worldwide, though its clinical significance remains unclear. This large-cohort study aimed at evaluating the association of this phenotype with cardiovascular risk factors and other complications.

Methods Type 2 diabetic patients from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study (n = 15 773), visiting consecutively 19 hospital-based Diabetes Clinics in years 2007–2008, were examined. Serum creatinine was assessed by the Jaffe method; albuminuria was measured by immunonephelometry or immunoturbidimetry.

Results Of patients with renal impairment, as identified by an estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m2, 56.6% were normoalbuminuric, 30.8% were microalbuminuric, and 12.6% were macroalbuminuric. Percentages were similar when GFR was estimated using the more accurate Chronic Kidney Disease Epidemiology Collaboration equation instead of the simplified Modification of Diet in Renal Disease formula, and were independent of age, thus indicating that the increasing prevalence of this phenotype does not reflects misclassification of elderly patients. Nonalbuminuric renal impairment was not associated with HbA1c and correlated less strongly with retinopathy and hypertension than albuminuria, either alone or associated with reduced eGFR. It was associated with a higher prevalence of cardiovascular disease (CVD) than albuminuria alone, but lower than albuminuric renal impairment. Female sex correlated with nonalbuminuric renal impairment and male sex with the albuminuric forms.

Conclusions These data show that type 2 diabetic patients with nonalbuminuric renal impairment exhibit distinct clinical features, suggesting predominance of macroangiopathy as underlying renal pathology, and that this phenotype is associated with significant CVD burden.

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aDepartment of Endocrinology and Metabolism

bDepartment of Internal Medicine, University of Pisa, Pisa

cDivision of Endocrinology and Metabolic Diseases, University of Verona, Verona

dDiabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, University of Siena, Siena

eEndocrinology and Diabetes Unit, Department of Medical Sciences, Fondazione IRCCS ‘Cà Granda – Ospedale Maggiore Policlinico’

fComplications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milan

gDiabetes Unit, Hospital of Bergamo, A.O. Ospedali Riuniti, Bergamo

hDepartment of Clinical and Experimental Medicine, University of Padua, Padua

iDepartment of Internal Medicine, University of Turin, Turin

jUnit of Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Orbassano

kUnit of Endocrinology and Metabolic Diseases, Department of Medical Sciences, University of Foggia, Foggia

lSection of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari, Bari

mDepartment of Internal Medicine and Medical Specialties

oDepartment of Clinical and Molecular Medicine, ‘La Sapienza’ University, Rome

nDepartment of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro, Chieti, Italy

*A complete list of the RIACE Investigators can be found as on-line appendix,

Correspondence to Giuseppe Pugliese, MD, PhD, Diabetes Unit, Sant’Andrea Hospital, Via di Grottarossa, 1035 – 00189 Rome, ItalyTel: +39 0633775440; fax: +39 0633775001; e-mail:

Abbreviations: A/C, albumin/creatinine ratio; ACE-Is, angiotensinconverting enzyme inhibitors; AER, albumin excretion rate; ARBs, angiotensin II-receptor blockers; BP, blood pressure; CKD, chronic kidney disease; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CVD, cardiovascular disease; eGFR, estimated GFR; ESRD, end-stage renal disease; GFR, glomerular filtration rate; HbA1c, glycated hemoglobin; IDMS, isotope dilution mass spectrometry; KDOQI, Kidney Disease Outcomes Quality Initiative; MDRD, Modification of Diet in Renal Disease; NEFRON, National Evaluation of the Frequency of Renal impairment cOexisting with NIDDM; NHANES III, Third National Health and Nutrition Examination Survey; NKF, National Kidney Foundation; OR, odds ratio; RIACE, Renal Insufficiency And Cardiovascular Events; UKPDS, U.K. Prospective Diabetes Study

Received 5 April, 2011

Revised 17 May, 2011

Accepted 31 May, 2011

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© 2011 Lippincott Williams & Wilkins, Inc.