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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

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)

Journal Title: Diabetologia 2018-07-21, Vol.61 (11), p.2277-2289
Main Author: Penno, Giuseppe
Other Authors: Solini, Anna , Orsi, Emanuela , Bonora, Enzo , Fondelli, Cecilia , Trevisan, Roberto , Vedovato, Monica , Cavalot, Franco , Lamacchia, Olga , Scardapane, Marco , Nicolucci, Antonio , Pugliese, Giuseppe
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0012-186X
Link: https://www.ncbi.nlm.nih.gov/pubmed/30032426
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title: 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
format: Article
creator:
  • Penno, Giuseppe
  • Solini, Anna
  • Orsi, Emanuela
  • Bonora, Enzo
  • Fondelli, Cecilia
  • Trevisan, Roberto
  • Vedovato, Monica
  • Cavalot, Franco
  • Lamacchia, Olga
  • Scardapane, Marco
  • Nicolucci, Antonio
  • Pugliese, Giuseppe
subjects:
  • Aged
  • Albuminuria - mortality
  • Albuminuria - physiopathology
  • Analysis
  • Article
  • Cardiovascular disease
  • Cardiovascular diseases
  • Cholesterol
  • Death
  • Diabetes
  • Diabetes mellitus
  • Diabetes mellitus (non-insulin dependent)
  • Diabetes Mellitus, Type 2 - mortality
  • Diabetes Mellitus, Type 2 - physiopathology
  • Diabetic Nephropathies - mortality
  • Diabetic Nephropathies - physiopathology
  • Epidermal growth factor receptors
  • Female
  • Genotype & phenotype
  • Glomerular Filtration Rate - physiology
  • Health risk assessment
  • High density lipoprotein
  • Human Physiology
  • Humans
  • Internal Medicine
  • Kaplan-Meier Estimate
  • Kidney diseases
  • Male
  • Medicine
  • Medicine & Public Health
  • Metabolic Diseases
  • Microvasculature
  • Middle Aged
  • Mortality
  • Patient outcomes
  • Phenotypes
  • Proportional Hazards Models
  • Prospective Studies
  • Renal function
  • Renal insufficiency
  • Renal Insufficiency, Chronic - mortality
  • Renal Insufficiency, Chronic - physiopathology
  • Retinopathy
  • Type 2 diabetes
ispartof: Diabetologia, 2018-07-21, Vol.61 (11), p.2277-2289
description: 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)
language: eng
source:
identifier: ISSN: 0012-186X
fulltext: no_fulltext
issn:
  • 0012-186X
  • 1432-0428
url: Link


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titleNon-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
creatorPenno, Giuseppe ; Solini, Anna ; Orsi, Emanuela ; Bonora, Enzo ; Fondelli, Cecilia ; Trevisan, Roberto ; Vedovato, Monica ; Cavalot, Franco ; Lamacchia, Olga ; Scardapane, Marco ; Nicolucci, Antonio ; Pugliese, Giuseppe
creatorcontribPenno, Giuseppe ; Solini, Anna ; Orsi, Emanuela ; Bonora, Enzo ; Fondelli, Cecilia ; Trevisan, Roberto ; Vedovato, Monica ; Cavalot, Franco ; Lamacchia, Olga ; Scardapane, Marco ; Nicolucci, Antonio ; Pugliese, Giuseppe ; Renal Insufficiency And Cardiovascular Events (RIACE) Study Group ; for the Renal Insufficiency And Cardiovascular Events (RIACE) Study Group
descriptionAims/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
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languageeng
publisherBerlin/Heidelberg: Springer Berlin Heidelberg
subjectAged ; Albuminuria - mortality ; Albuminuria - physiopathology ; Analysis ; Article ; Cardiovascular disease ; Cardiovascular diseases ; Cholesterol ; Death ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - mortality ; Diabetes Mellitus, Type 2 - physiopathology ; Diabetic Nephropathies - mortality ; Diabetic Nephropathies - physiopathology ; Epidermal growth factor receptors ; Female ; Genotype & phenotype ; Glomerular Filtration Rate - physiology ; Health risk assessment ; High density lipoprotein ; Human Physiology ; Humans ; Internal Medicine ; Kaplan-Meier Estimate ; Kidney diseases ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Microvasculature ; Middle Aged ; Mortality ; Patient outcomes ; Phenotypes ; Proportional Hazards Models ; Prospective Studies ; Renal function ; Renal insufficiency ; Renal Insufficiency, Chronic - mortality ; Renal Insufficiency, Chronic - physiopathology ; Retinopathy ; Type 2 diabetes
ispartofDiabetologia, 2018-07-21, Vol.61 (11), p.2277-2289
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0Springer-Verlag GmbH Germany, part of Springer Nature 2018
1COPYRIGHT 2018 Springer
2Diabetologia is a copyright of Springer, (2018). All Rights Reserved.
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1Solini, Anna
2Orsi, Emanuela
3Bonora, Enzo
4Fondelli, Cecilia
5Trevisan, Roberto
6Vedovato, Monica
7Cavalot, Franco
8Lamacchia, Olga
9Scardapane, Marco
10Nicolucci, Antonio
11Pugliese, Giuseppe
12Renal Insufficiency And Cardiovascular Events (RIACE) Study Group
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descriptionAims/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
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10Diabetes mellitus
11Diabetes mellitus (non-insulin dependent)
12Diabetes Mellitus, Type 2 - mortality
13Diabetes Mellitus, Type 2 - physiopathology
14Diabetic Nephropathies - mortality
15Diabetic Nephropathies - physiopathology
16Epidermal growth factor receptors
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18Genotype & phenotype
19Glomerular Filtration Rate - physiology
20Health risk assessment
21High density lipoprotein
22Human Physiology
23Humans
24Internal Medicine
25Kaplan-Meier Estimate
26Kidney diseases
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28Medicine
29Medicine & Public Health
30Metabolic Diseases
31Microvasculature
32Middle Aged
33Mortality
34Patient outcomes
35Phenotypes
36Proportional Hazards Models
37Prospective Studies
38Renal function
39Renal insufficiency
40Renal Insufficiency, Chronic - mortality
41Renal Insufficiency, Chronic - physiopathology
42Retinopathy
43Type 2 diabetes
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titleNon-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
authorPenno, Giuseppe ; Solini, Anna ; Orsi, Emanuela ; Bonora, Enzo ; Fondelli, Cecilia ; Trevisan, Roberto ; Vedovato, Monica ; Cavalot, Franco ; Lamacchia, Olga ; Scardapane, Marco ; Nicolucci, Antonio ; Pugliese, Giuseppe
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1Albuminuria - mortality
2Albuminuria - physiopathology
3Analysis
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5Cardiovascular disease
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7Cholesterol
8Death
9Diabetes
10Diabetes mellitus
11Diabetes mellitus (non-insulin dependent)
12Diabetes Mellitus, Type 2 - mortality
13Diabetes Mellitus, Type 2 - physiopathology
14Diabetic Nephropathies - mortality
15Diabetic Nephropathies - physiopathology
16Epidermal growth factor receptors
17Female
18Genotype & phenotype
19Glomerular Filtration Rate - physiology
20Health risk assessment
21High density lipoprotein
22Human Physiology
23Humans
24Internal Medicine
25Kaplan-Meier Estimate
26Kidney diseases
27Male
28Medicine
29Medicine & Public Health
30Metabolic Diseases
31Microvasculature
32Middle Aged
33Mortality
34Patient outcomes
35Phenotypes
36Proportional Hazards Models
37Prospective Studies
38Renal function
39Renal insufficiency
40Renal Insufficiency, Chronic - mortality
41Renal Insufficiency, Chronic - physiopathology
42Retinopathy
43Type 2 diabetes
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1Solini, Anna
2Orsi, Emanuela
3Bonora, Enzo
4Fondelli, Cecilia
5Trevisan, Roberto
6Vedovato, Monica
7Cavalot, Franco
8Lamacchia, Olga
9Scardapane, Marco
10Nicolucci, Antonio
11Pugliese, Giuseppe
12Renal Insufficiency And Cardiovascular Events (RIACE) Study Group
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abstractAims/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
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