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

for the Renal Insufficiency and Cardiovascular Events (RIACE) Study Group

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2277-2289
JournalDiabetologia
Volume61
Issue number11
DOIs
Publication statusPublished - 2018

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Albuminuria
Type 2 Diabetes Mellitus
Multicenter Studies
Renal Insufficiency
Diabetic Nephropathies
Phenotype
Kidney
Mortality
Cardiovascular Diseases
HDL Cholesterol
Cause of Death
Cohort Studies
Prospective Studies

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / for the Renal Insufficiency and Cardiovascular Events (RIACE) Study Group.

In: Diabetologia, Vol. 61, No. 11, 2018, p. 2277-2289.

Research output: Contribution to journalArticle

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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",
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",
author = "{for the Renal Insufficiency and Cardiovascular Events (RIACE) Study Group} and Giuseppe Penno and Anna Solini and Emanuela Orsi and Enzo Bonora and Cecilia Fondelli and Roberto Trevisan and Monica Vedovato and Franco Cavalot and Olga Lamacchia and Marco Scardapane and Antonio Nicolucci and Giuseppe Pugliese",
year = "2018",
doi = "10.1007/s00125-018-4691-2",
language = "English",
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journal = "Diabetologia",
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T1 - Non-albuminuric renal impairment is a strong predictor of mortality in individuals with type 2 diabetes

T2 - the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study

AU - for the Renal Insufficiency and Cardiovascular Events (RIACE) Study Group

AU - Penno, Giuseppe

AU - Solini, Anna

AU - Orsi, Emanuela

AU - Bonora, Enzo

AU - Fondelli, Cecilia

AU - Trevisan, Roberto

AU - Vedovato, Monica

AU - Cavalot, Franco

AU - Lamacchia, Olga

AU - Scardapane, Marco

AU - Nicolucci, Antonio

AU - Pugliese, Giuseppe

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Albuminuria

KW - All-cause mortality

KW - Diabetic kidney disease

KW - Glomerular filtration rate

KW - Type 2 diabetes

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U2 - 10.1007/s00125-018-4691-2

DO - 10.1007/s00125-018-4691-2

M3 - Article

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VL - 61

SP - 2277

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JO - Diabetologia

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SN - 0012-186X

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