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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:
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
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0012-186X
Link: https://www.ncbi.nlm.nih.gov/pubmed/30032426
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recordid: cdi_gale_infotracacademiconefile_A555858885
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
identifier
0ISSN: 0012-186X
1EISSN: 1432-0428
2DOI: 10.1007/s00125-018-4691-2
3PMID: 30032426
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
rights
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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0Penno, Giuseppe
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
13for the Renal Insufficiency And Cardiovascular Events (RIACE) Study Group
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0Non-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
1Diabetologia
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1Diabetologia
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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2Albuminuria - physiopathology
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6Cardiovascular diseases
7Cholesterol
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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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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
4Article
5Cardiovascular disease
6Cardiovascular diseases
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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1Solini, Anna
2Orsi, Emanuela
3Bonora, Enzo
4Fondelli, Cecilia
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8Lamacchia, Olga
9Scardapane, Marco
10Nicolucci, Antonio
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jtitleDiabetologia
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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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pmid30032426
doi10.1007/s00125-018-4691-2
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