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Diabetologia. 2018 Nov;61(11):2277-2289. doi: 10.1007/s00125-018-4691-2. Epub 2018 Jul 21.

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.

Author information

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, Via di Grottarossa, 1035-1039, 00189, Rome, Italy. giuseppe.pugliese@uniroma1.it.

Abstract

AIMS/HYPOTHESIS:

Non-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.

METHODS:

This 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%).

RESULTS:

Mortality 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/INTERPRETATION:

Non-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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00715481.

KEYWORDS:

Albuminuria; All-cause mortality; Diabetic kidney disease; Glomerular filtration rate; Type 2 diabetes

PMID:
30032426
DOI:
10.1007/s00125-018-4691-2
[Indexed for MEDLINE]

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