Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes: a prospective cohort study

Introduction In addition to favoring renal disease progression, renal ‘hyperfiltration’ has been associated with an increased risk of death, though it is unclear whether and how excess mortality is related to increased renal function. We investigated whether renal hyperfiltration is an independent p...

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Main Authors: Giuseppe Penno, Emanuela Orsi, Anna Solini, Cecilia Fondelli, Roberto Trevisan, Monica Vedovato, Franco Cavalot, Gabriella Gruden, Luigi Laviola
Format: Article
Language:English
Published: BMJ Publishing Group 2020-04-01
Series:BMJ Open Diabetes Research & Care
Online Access:https://drc.bmj.com/content/8/1/e001481.full
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author Giuseppe Penno
Emanuela Orsi
Anna Solini
Cecilia Fondelli
Roberto Trevisan
Monica Vedovato
Franco Cavalot
Gabriella Gruden
Luigi Laviola
author_facet Giuseppe Penno
Emanuela Orsi
Anna Solini
Cecilia Fondelli
Roberto Trevisan
Monica Vedovato
Franco Cavalot
Gabriella Gruden
Luigi Laviola
author_sort Giuseppe Penno
collection DOAJ
description Introduction In addition to favoring renal disease progression, renal ‘hyperfiltration’ has been associated with an increased risk of death, though it is unclear whether and how excess mortality is related to increased renal function. We investigated whether renal hyperfiltration is an independent predictor of death in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian multicenter study.Research design and methods This observational, prospective cohort study enrolled 15 773 patients with type 2 diabetes consecutively attending 19 Italian diabetes clinics in 2006–2008. Serum creatinine, albuminuria, cardiovascular risk factors, and complications/comorbidities were assessed at baseline. Vital status on 31 October 2015 was retrieved for 15 656 patients (99.26%). Patients were stratified (A) by absolute estimated glomerular filtration rate (eGFR) values in eGFR deciles or Kidney Disease: Improving Global Outcomes (KDIGO) categories and (B) based on age-corrected thresholds or age and gender-specific 95th and 5th percentiles in hyperfiltration, hypofiltration, and normofiltration groups.Results The highest eGFR decile/category and the hyperfiltration group included (partly) different individuals with similar clinical features. Age and gender-adjusted death rates were significantly higher in deciles 1, 9, and 10 (≥103.9, 50.9–62.7, and <50.9 mL/min/1.73 m2, respectively) versus the reference decile 3 (92.9–97.5 mL/min/1.73 m2). Mortality risk, adjusted for multiple confounders, was also increased in deciles 1 (HR 1.461 (95% CI 1.175 to 1.818), p=0.001), 9 (1.312 (95% CI 1.107 to 1.555), p=0.002), and 10 (1.976 (95% CI 1.673 to 2.333), p<0.0001) versus decile 3. Similar results were obtained by stratifying patients by KDIGO categories. Death rates and adjusted mortality risks were significantly higher in hyperfiltering and particularly hypofiltering versus normofiltering individuals.Conclusions In type 2 diabetes, both high-normal eGFR and hyperfiltration are associated with an increased risk of death from any cause, independent of confounders that may directly impact on mortality and/or affect GFR estimation. Further studies are required to clarify the nature of this relationship.Trial registration number NCT00715481.
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spelling doaj.art-b97910c3d3a340318ba82337fd106a5e2022-12-21T22:53:21ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972020-04-018110.1136/bmjdrc-2020-001481Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes: a prospective cohort studyGiuseppe Penno0Emanuela Orsi1Anna Solini2Cecilia Fondelli3Roberto Trevisan4Monica Vedovato5Franco Cavalot6Gabriella Gruden7Luigi Laviola8Department of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyDiabetes Service, Endocrinology Unit, IRCCS “Cà Granda - Ospedale Maggiore Policlinico” Foundation, Milan, ItalyDepartment of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, ItalyDiabetes Unit, University of Siena, Siena, ItalyEndocrinology and Diabetes Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, ItalyDepartment of Clinical and Experimental Medicine, University of Padua, Padua, ItalyDepartment of Clinical and Biological Sciences, University of Turin, Orbassano, ItalyDepartment of Internal Medicine, University of Turin, Turin, ItalyDepartment of Emergency and Transplants, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, ItalyIntroduction In addition to favoring renal disease progression, renal ‘hyperfiltration’ has been associated with an increased risk of death, though it is unclear whether and how excess mortality is related to increased renal function. We investigated whether renal hyperfiltration is an independent predictor of death in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian multicenter study.Research design and methods This observational, prospective cohort study enrolled 15 773 patients with type 2 diabetes consecutively attending 19 Italian diabetes clinics in 2006–2008. Serum creatinine, albuminuria, cardiovascular risk factors, and complications/comorbidities were assessed at baseline. Vital status on 31 October 2015 was retrieved for 15 656 patients (99.26%). Patients were stratified (A) by absolute estimated glomerular filtration rate (eGFR) values in eGFR deciles or Kidney Disease: Improving Global Outcomes (KDIGO) categories and (B) based on age-corrected thresholds or age and gender-specific 95th and 5th percentiles in hyperfiltration, hypofiltration, and normofiltration groups.Results The highest eGFR decile/category and the hyperfiltration group included (partly) different individuals with similar clinical features. Age and gender-adjusted death rates were significantly higher in deciles 1, 9, and 10 (≥103.9, 50.9–62.7, and <50.9 mL/min/1.73 m2, respectively) versus the reference decile 3 (92.9–97.5 mL/min/1.73 m2). Mortality risk, adjusted for multiple confounders, was also increased in deciles 1 (HR 1.461 (95% CI 1.175 to 1.818), p=0.001), 9 (1.312 (95% CI 1.107 to 1.555), p=0.002), and 10 (1.976 (95% CI 1.673 to 2.333), p<0.0001) versus decile 3. Similar results were obtained by stratifying patients by KDIGO categories. Death rates and adjusted mortality risks were significantly higher in hyperfiltering and particularly hypofiltering versus normofiltering individuals.Conclusions In type 2 diabetes, both high-normal eGFR and hyperfiltration are associated with an increased risk of death from any cause, independent of confounders that may directly impact on mortality and/or affect GFR estimation. Further studies are required to clarify the nature of this relationship.Trial registration number NCT00715481.https://drc.bmj.com/content/8/1/e001481.full
spellingShingle Giuseppe Penno
Emanuela Orsi
Anna Solini
Cecilia Fondelli
Roberto Trevisan
Monica Vedovato
Franco Cavalot
Gabriella Gruden
Luigi Laviola
Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes: a prospective cohort study
BMJ Open Diabetes Research & Care
title Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes: a prospective cohort study
title_full Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes: a prospective cohort study
title_fullStr Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes: a prospective cohort study
title_full_unstemmed Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes: a prospective cohort study
title_short Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes: a prospective cohort study
title_sort renal hyperfiltration is independently associated with increased all cause mortality in individuals with type 2 diabetes a prospective cohort study
url https://drc.bmj.com/content/8/1/e001481.full
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