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Diabetic nephropathy in a sibling and albuminuria predict early GFR decline: a prospective cohort study

BACKGROUND: Diabetic nephropathy is a growing clinical problem, and the cause for >40% of incident ESRD cases. Unfortunately, few modifiable risk factors are known. The objective is to examine if albuminuria and history of diabetic nephropathy (DN) in a sibling are associated with early DN progre...

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Autores principales: Gunzler, Douglas, Bleyer, Anthony J, Thomas, Robert L, O’Brien, Alicia, Russell, Gregory B, Sattar, Abdus, Iyengar, Sudha K, Thomas, Charles, Sedor, John R, Schelling, Jeffrey R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703258/
https://www.ncbi.nlm.nih.gov/pubmed/23773264
http://dx.doi.org/10.1186/1471-2369-14-124
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author Gunzler, Douglas
Bleyer, Anthony J
Thomas, Robert L
O’Brien, Alicia
Russell, Gregory B
Sattar, Abdus
Iyengar, Sudha K
Thomas, Charles
Sedor, John R
Schelling, Jeffrey R
author_facet Gunzler, Douglas
Bleyer, Anthony J
Thomas, Robert L
O’Brien, Alicia
Russell, Gregory B
Sattar, Abdus
Iyengar, Sudha K
Thomas, Charles
Sedor, John R
Schelling, Jeffrey R
author_sort Gunzler, Douglas
collection PubMed
description BACKGROUND: Diabetic nephropathy is a growing clinical problem, and the cause for >40% of incident ESRD cases. Unfortunately, few modifiable risk factors are known. The objective is to examine if albuminuria and history of diabetic nephropathy (DN) in a sibling are associated with early DN progression or mortality. METHODS: In this longitudinal study of adults >18 yrs with diabetes monitored for up to 9 yrs (mean 4.6 ± 1.7 yrs), 435 subjects at high risk (DN family history) and 400 at low risk (diabetes >10 yrs, normoalbuminuria, no DN family history) for DN progression were evaluated for rate of eGFR change using the linear mixed effects model and progression to ESRD. All-cause mortality was evaluated by Kaplan-Meier analyses while controlling for baseline covariates in a Cox proportional hazards model. Covariates included baseline eGFR, age, gender, race, diabetes duration, blood pressure, hemoglobin A1c and urine albumin:creatinine ratio. Propensity score matching was used to identify high and low risk group pairs with balanced covariates. Sensitivity analyses were employed to test for residual confounding. RESULTS: Mean baseline eGFR was 74 ml/min/1.73 m(2) (86% of cohort >60 ml/min/1.73 m(2)). Thirty high risk and no low risk subjects developed ESRD. eGFR decline was significantly greater in high compared to low risk subjects. After controlling for confounders, change in eGFR remained significantly different between groups, suggesting that DN family history independently regulates GFR progression. Mortality was also significantly greater in high versus low risk subjects, but after controlling for baseline covariates, no significant difference was observed between groups, indicating that factors other than DN family history more strongly affect mortality. Analyses of the matched pairs confirmed change in eGFR and mortality findings. Sensitivity analyses demonstrated that the eGFR results were not due to residual confounding by unmeasured covariates of a moderate effect size in the propensity matching. CONCLUSIONS: Diabetic subjects with albuminuria and family history of DN are vulnerable for early GFR decline, whereas subjects with diabetes for longer than 10 years, normoalbuminuria and negative family history, experience slower eGFR decline, and are extremely unlikely to require dialysis. Although we would not recommend that patients with low risk characteristics be neglected, scarce resources would be more sensibly devoted to vulnerable patients, such as the high risk cases in our study, and preferably prior to the onset of albuminuria or GFR decline.
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spelling pubmed-37032582013-07-07 Diabetic nephropathy in a sibling and albuminuria predict early GFR decline: a prospective cohort study Gunzler, Douglas Bleyer, Anthony J Thomas, Robert L O’Brien, Alicia Russell, Gregory B Sattar, Abdus Iyengar, Sudha K Thomas, Charles Sedor, John R Schelling, Jeffrey R BMC Nephrol Research Article BACKGROUND: Diabetic nephropathy is a growing clinical problem, and the cause for >40% of incident ESRD cases. Unfortunately, few modifiable risk factors are known. The objective is to examine if albuminuria and history of diabetic nephropathy (DN) in a sibling are associated with early DN progression or mortality. METHODS: In this longitudinal study of adults >18 yrs with diabetes monitored for up to 9 yrs (mean 4.6 ± 1.7 yrs), 435 subjects at high risk (DN family history) and 400 at low risk (diabetes >10 yrs, normoalbuminuria, no DN family history) for DN progression were evaluated for rate of eGFR change using the linear mixed effects model and progression to ESRD. All-cause mortality was evaluated by Kaplan-Meier analyses while controlling for baseline covariates in a Cox proportional hazards model. Covariates included baseline eGFR, age, gender, race, diabetes duration, blood pressure, hemoglobin A1c and urine albumin:creatinine ratio. Propensity score matching was used to identify high and low risk group pairs with balanced covariates. Sensitivity analyses were employed to test for residual confounding. RESULTS: Mean baseline eGFR was 74 ml/min/1.73 m(2) (86% of cohort >60 ml/min/1.73 m(2)). Thirty high risk and no low risk subjects developed ESRD. eGFR decline was significantly greater in high compared to low risk subjects. After controlling for confounders, change in eGFR remained significantly different between groups, suggesting that DN family history independently regulates GFR progression. Mortality was also significantly greater in high versus low risk subjects, but after controlling for baseline covariates, no significant difference was observed between groups, indicating that factors other than DN family history more strongly affect mortality. Analyses of the matched pairs confirmed change in eGFR and mortality findings. Sensitivity analyses demonstrated that the eGFR results were not due to residual confounding by unmeasured covariates of a moderate effect size in the propensity matching. CONCLUSIONS: Diabetic subjects with albuminuria and family history of DN are vulnerable for early GFR decline, whereas subjects with diabetes for longer than 10 years, normoalbuminuria and negative family history, experience slower eGFR decline, and are extremely unlikely to require dialysis. Although we would not recommend that patients with low risk characteristics be neglected, scarce resources would be more sensibly devoted to vulnerable patients, such as the high risk cases in our study, and preferably prior to the onset of albuminuria or GFR decline. BioMed Central 2013-06-17 /pmc/articles/PMC3703258/ /pubmed/23773264 http://dx.doi.org/10.1186/1471-2369-14-124 Text en Copyright © 2013 Gunzler et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Gunzler, Douglas
Bleyer, Anthony J
Thomas, Robert L
O’Brien, Alicia
Russell, Gregory B
Sattar, Abdus
Iyengar, Sudha K
Thomas, Charles
Sedor, John R
Schelling, Jeffrey R
Diabetic nephropathy in a sibling and albuminuria predict early GFR decline: a prospective cohort study
title Diabetic nephropathy in a sibling and albuminuria predict early GFR decline: a prospective cohort study
title_full Diabetic nephropathy in a sibling and albuminuria predict early GFR decline: a prospective cohort study
title_fullStr Diabetic nephropathy in a sibling and albuminuria predict early GFR decline: a prospective cohort study
title_full_unstemmed Diabetic nephropathy in a sibling and albuminuria predict early GFR decline: a prospective cohort study
title_short Diabetic nephropathy in a sibling and albuminuria predict early GFR decline: a prospective cohort study
title_sort diabetic nephropathy in a sibling and albuminuria predict early gfr decline: a prospective cohort study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703258/
https://www.ncbi.nlm.nih.gov/pubmed/23773264
http://dx.doi.org/10.1186/1471-2369-14-124
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