Non-albuminuric renal impairment is a strong predictor of mortality in individuals with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study |
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| Authors: | Giuseppe?Penno Anna?Solini Emanuela?Orsi Enzo?Bonora Cecilia?Fondelli Roberto?Trevisan Monica?Vedovato Franco?Cavalot Olga?Lamacchia Marco?Scardapane Antonio?Nicolucci Giuseppe?Pugliese for the Renal Insufficiency And Cardiovascular Events Study Group |
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| Affiliation: | 1.Department of Clinical and Experimental Medicine,University of Pisa,Pisa,Italy;2.Department of Surgical, Medical, Molecular and Critical Area Pathology,University of Pisa,Pisa,Italy;3.Diabetes Unit,IRCCS ‘Cà Granda - Ospedale Maggiore Policlinico’ Foundation,Milan,Italy;4.Division of Endocrinology, Diabetes and Metabolism,University and Hospital Trust of Verona,Verona,Italy;5.Diabetes Unit,University of Siena,Siena,Italy;6.Endocrinology and Diabetes Unit,Azienda Ospedaliera Papa Giovanni XXIII,Bergamo,Italy;7.Department of Clinical and Experimental Medicine,University of Padua,Padua,Italy;8.Department of Clinical and Biological Sciences,University of Turin,Orbassano,Italy;9.Department of Medical Sciences,University of Foggia,Foggia,Italy;10.Centre for Outcomes Research and Clinical Epidemiology (CORESEARCH),Pescara,Italy;11.Department of Clinical and Molecular Medicine,‘La Sapienza’ University,Rome,Italy |
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| Abstract: | Aims/hypothesisNon-albuminuric renal impairment has become the prevailing diabetic kidney disease (DKD) phenotype in individuals with type 2 diabetes and an estimated GFR (eGFR) <60 ml min?1 1.73 m?2. In the present study, we compared the rate and determinants of all-cause death in individuals with this phenotype with those in individuals with albuminuric phenotypes.MethodsThis observational prospective cohort study enrolled 15,773 individuals with type 2 diabetes in 2006–2008. Based on baseline albuminuria and eGFR, individuals were classified as having: no DKD (Alb?/eGFR?), albuminuria alone (Alb+/eGFR?), reduced eGFR alone (Alb?/eGFR+), or both albuminuria and reduced eGFR (Alb+/eGFR+). Vital status on 31 October 2015 was retrieved for 15,656 individuals (99.26%).ResultsMortality risk adjusted for confounders was lowest for Alb?/eGFR? (reference category) and highest for Alb+/eGFR+ (HR 2.08 [95% CI 1.88, 2.30]), with similar values for Alb+/eGFR? (1.45 [1.33, 1.58]) and Alb?/eGFR+ (1.58 [1.43, 1.75]). Similar results were obtained when individuals were stratified by sex, age (except in the lowest age category) and prior cardiovascular disease. In normoalbuminuric individuals with eGFR <45 ml min?1 1.73 m?2, especially with low albuminuria (10–29 mg/day), risk was higher than in microalbuminuric and similar to macroalbuminuric individuals with preserved eGFR. Using recursive partitioning and amalgamation analysis, prevalent cardiovascular disease and lower HDL-cholesterol were the most relevant correlates of mortality in all phenotypes. Higher albuminuria within the normoalbuminuric range was associated with death in non-albuminuric DKD, whereas the classic ‘microvascular signatures’, such as glycaemic exposure and retinopathy, were correlates of mortality only in individuals with albuminuric phenotypes.Conclusions/interpretationNon-albuminuric renal impairment is a strong predictor of mortality, thus supporting a major prognostic impact of renal dysfunction irrespective of albuminuria. Correlates of death partly differ from the albuminuric forms, indicating that non-albuminuric DKD is a distinct phenotype. |
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