Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies

Chronic Kidney Disease Prognosis Consortium and Chronic Kidney Disease Epidemiology Collaboration, Josef Coresh, Hiddo J L Heerspink, Yingying Sang, Kunihiro Matsushita, Johan Arnlov, Brad C Astor, Corri Black, Nigel J Brunskill, Juan-Jesus Carrero, Harold I Feldman, Caroline S Fox, Lesley A Inker, Areef Ishani, Sadayoshi Ito, Simerjot Jassal, Tsuneo Konta, Kevan Polkinghorne, Solfrid Romundstad, Marit D Solbu & 12 others Nikita Stempniewicz, Benedicte Stengel, Marcello Tonelli, Mitsumasa Umesawa, Sushrut S Waikar, Chi-Pang Wen, Jack F M Wetzels, Mark Woodward, Morgan E Grams, Csaba P Kovesdy, Andrew S Levey, Ron T Gansevoort

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BACKGROUND: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies.

METHODS: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC.

FINDINGS: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0·83 (95% CI 0·74-0·94), decreasing to 0·78 (0·66-0·92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (pinteraction<0·0001). In individuals with baseline ACR of 300 mg/g or higher, a 30% decrease in ACR over 2 years was estimated to confer a more than 1% absolute reduction in 10-year risk of end-stage kidney disease, even at early stages of chronic kidney disease. Results were generally similar when we used change in PCR and when study populations from clinical trials were assessed.

INTERPRETATION: Change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change in albuminuria as a surrogate endpoint for end-stage kidney disease in clinical trials of progression of chronic kidney disease in the setting of increased albuminuria.

FUNDING: US National Kidney Foundation and US National Institute of Diabetes and Digestive and Kidney Diseases.

Original languageEnglish
Pages (from-to)115-127
Number of pages13
JournalThe lancet. Diabetes & endocrinology
Volume7
Issue number2
Early online date8 Jan 2019
DOIs
Publication statusPublished - Feb 2019

Fingerprint

Albuminuria
Chronic Kidney Failure
Observational Studies
Meta-Analysis
Creatinine
Albumins
Chronic Renal Insufficiency
Clinical Trials
National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)
Biomarkers
Urine
Renal Replacement Therapy
Glomerular Filtration Rate
Epidemiologic Studies
Proteins
Kidney

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Chronic Kidney Disease Prognosis Consortium and Chronic Kidney Disease Epidemiology Collaboration, Coresh, J., Heerspink, H. J. L., Sang, Y., Matsushita, K., Arnlov, J., ... Gansevoort, R. T. (2019). Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies. The lancet. Diabetes & endocrinology, 7(2), 115-127. https://doi.org/10.1016/S2213-8587(18)30313-9

Change in albuminuria and subsequent risk of end-stage kidney disease : an individual participant-level consortium meta-analysis of observational studies. / Chronic Kidney Disease Prognosis Consortium and Chronic Kidney Disease Epidemiology Collaboration; Coresh, Josef; Heerspink, Hiddo J L; Sang, Yingying; Matsushita, Kunihiro; Arnlov, Johan; Astor, Brad C; Black, Corri; Brunskill, Nigel J; Carrero, Juan-Jesus; Feldman, Harold I; Fox, Caroline S; Inker, Lesley A; Ishani, Areef; Ito, Sadayoshi; Jassal, Simerjot; Konta, Tsuneo; Polkinghorne, Kevan; Romundstad, Solfrid; Solbu, Marit D; Stempniewicz, Nikita; Stengel, Benedicte; Tonelli, Marcello; Umesawa, Mitsumasa; Waikar, Sushrut S; Wen, Chi-Pang; Wetzels, Jack F M; Woodward, Mark; Grams, Morgan E; Kovesdy, Csaba P; Levey, Andrew S; Gansevoort, Ron T.

In: The lancet. Diabetes & endocrinology, Vol. 7, No. 2, 02.2019, p. 115-127.

Research output: Contribution to journalArticle

Chronic Kidney Disease Prognosis Consortium and Chronic Kidney Disease Epidemiology Collaboration, Coresh, J, Heerspink, HJL, Sang, Y, Matsushita, K, Arnlov, J, Astor, BC, Black, C, Brunskill, NJ, Carrero, J-J, Feldman, HI, Fox, CS, Inker, LA, Ishani, A, Ito, S, Jassal, S, Konta, T, Polkinghorne, K, Romundstad, S, Solbu, MD, Stempniewicz, N, Stengel, B, Tonelli, M, Umesawa, M, Waikar, SS, Wen, C-P, Wetzels, JFM, Woodward, M, Grams, ME, Kovesdy, CP, Levey, AS & Gansevoort, RT 2019, 'Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies' The lancet. Diabetes & endocrinology, vol. 7, no. 2, pp. 115-127. https://doi.org/10.1016/S2213-8587(18)30313-9
Chronic Kidney Disease Prognosis Consortium and Chronic Kidney Disease Epidemiology Collaboration, Coresh J, Heerspink HJL, Sang Y, Matsushita K, Arnlov J et al. Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies. The lancet. Diabetes & endocrinology. 2019 Feb;7(2):115-127. https://doi.org/10.1016/S2213-8587(18)30313-9
Chronic Kidney Disease Prognosis Consortium and Chronic Kidney Disease Epidemiology Collaboration ; Coresh, Josef ; Heerspink, Hiddo J L ; Sang, Yingying ; Matsushita, Kunihiro ; Arnlov, Johan ; Astor, Brad C ; Black, Corri ; Brunskill, Nigel J ; Carrero, Juan-Jesus ; Feldman, Harold I ; Fox, Caroline S ; Inker, Lesley A ; Ishani, Areef ; Ito, Sadayoshi ; Jassal, Simerjot ; Konta, Tsuneo ; Polkinghorne, Kevan ; Romundstad, Solfrid ; Solbu, Marit D ; Stempniewicz, Nikita ; Stengel, Benedicte ; Tonelli, Marcello ; Umesawa, Mitsumasa ; Waikar, Sushrut S ; Wen, Chi-Pang ; Wetzels, Jack F M ; Woodward, Mark ; Grams, Morgan E ; Kovesdy, Csaba P ; Levey, Andrew S ; Gansevoort, Ron T. / Change in albuminuria and subsequent risk of end-stage kidney disease : an individual participant-level consortium meta-analysis of observational studies. In: The lancet. Diabetes & endocrinology. 2019 ; Vol. 7, No. 2. pp. 115-127.
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abstract = "BACKGROUND: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies.METHODS: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC.FINDINGS: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80{\%}] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30{\%} decrease in ACR during a baseline period of 2 years was 0·83 (95{\%} CI 0·74-0·94), decreasing to 0·78 (0·66-0·92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (pinteraction<0·0001). In individuals with baseline ACR of 300 mg/g or higher, a 30{\%} decrease in ACR over 2 years was estimated to confer a more than 1{\%} absolute reduction in 10-year risk of end-stage kidney disease, even at early stages of chronic kidney disease. Results were generally similar when we used change in PCR and when study populations from clinical trials were assessed.INTERPRETATION: Change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change in albuminuria as a surrogate endpoint for end-stage kidney disease in clinical trials of progression of chronic kidney disease in the setting of increased albuminuria.FUNDING: US National Kidney Foundation and US National Institute of Diabetes and Digestive and Kidney Diseases.",
author = "{Chronic Kidney Disease Prognosis Consortium and Chronic Kidney Disease Epidemiology Collaboration} and Josef Coresh and Heerspink, {Hiddo J L} and Yingying Sang and Kunihiro Matsushita and Johan Arnlov and Astor, {Brad C} and Corri Black and Brunskill, {Nigel J} and Juan-Jesus Carrero and Feldman, {Harold I} and Fox, {Caroline S} and Inker, {Lesley A} and Areef Ishani and Sadayoshi Ito and Simerjot Jassal and Tsuneo Konta and Kevan Polkinghorne and Solfrid Romundstad and Solbu, {Marit D} and Nikita Stempniewicz and Benedicte Stengel and Marcello Tonelli and Mitsumasa Umesawa and Waikar, {Sushrut S} and Chi-Pang Wen and Wetzels, {Jack F M} and Mark Woodward and Grams, {Morgan E} and Kovesdy, {Csaba P} and Levey, {Andrew S} and Gansevoort, {Ron T}",
note = "US National Kidney Foundation and US National Institute of Diabetes and Digestive and Kidney Diseases.",
year = "2019",
month = "2",
doi = "10.1016/S2213-8587(18)30313-9",
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pages = "115--127",
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TY - JOUR

T1 - Change in albuminuria and subsequent risk of end-stage kidney disease

T2 - an individual participant-level consortium meta-analysis of observational studies

AU - Chronic Kidney Disease Prognosis Consortium and Chronic Kidney Disease Epidemiology Collaboration

AU - Coresh, Josef

AU - Heerspink, Hiddo J L

AU - Sang, Yingying

AU - Matsushita, Kunihiro

AU - Arnlov, Johan

AU - Astor, Brad C

AU - Black, Corri

AU - Brunskill, Nigel J

AU - Carrero, Juan-Jesus

AU - Feldman, Harold I

AU - Fox, Caroline S

AU - Inker, Lesley A

AU - Ishani, Areef

AU - Ito, Sadayoshi

AU - Jassal, Simerjot

AU - Konta, Tsuneo

AU - Polkinghorne, Kevan

AU - Romundstad, Solfrid

AU - Solbu, Marit D

AU - Stempniewicz, Nikita

AU - Stengel, Benedicte

AU - Tonelli, Marcello

AU - Umesawa, Mitsumasa

AU - Waikar, Sushrut S

AU - Wen, Chi-Pang

AU - Wetzels, Jack F M

AU - Woodward, Mark

AU - Grams, Morgan E

AU - Kovesdy, Csaba P

AU - Levey, Andrew S

AU - Gansevoort, Ron T

N1 - US National Kidney Foundation and US National Institute of Diabetes and Digestive and Kidney Diseases.

PY - 2019/2

Y1 - 2019/2

N2 - BACKGROUND: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies.METHODS: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC.FINDINGS: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0·83 (95% CI 0·74-0·94), decreasing to 0·78 (0·66-0·92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (pinteraction<0·0001). In individuals with baseline ACR of 300 mg/g or higher, a 30% decrease in ACR over 2 years was estimated to confer a more than 1% absolute reduction in 10-year risk of end-stage kidney disease, even at early stages of chronic kidney disease. Results were generally similar when we used change in PCR and when study populations from clinical trials were assessed.INTERPRETATION: Change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change in albuminuria as a surrogate endpoint for end-stage kidney disease in clinical trials of progression of chronic kidney disease in the setting of increased albuminuria.FUNDING: US National Kidney Foundation and US National Institute of Diabetes and Digestive and Kidney Diseases.

AB - BACKGROUND: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies.METHODS: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC.FINDINGS: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0·83 (95% CI 0·74-0·94), decreasing to 0·78 (0·66-0·92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (pinteraction<0·0001). In individuals with baseline ACR of 300 mg/g or higher, a 30% decrease in ACR over 2 years was estimated to confer a more than 1% absolute reduction in 10-year risk of end-stage kidney disease, even at early stages of chronic kidney disease. Results were generally similar when we used change in PCR and when study populations from clinical trials were assessed.INTERPRETATION: Change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change in albuminuria as a surrogate endpoint for end-stage kidney disease in clinical trials of progression of chronic kidney disease in the setting of increased albuminuria.FUNDING: US National Kidney Foundation and US National Institute of Diabetes and Digestive and Kidney Diseases.

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JO - The lancet. Diabetes & endocrinology

JF - The lancet. Diabetes & endocrinology

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