A comparison of iothalamate-GFR and serum creatinine-based outcomes: Acceleration in the rate of GFR decline in the African American Study of Kidney Disease and Hypertension

Julia Lewis, Tom Greene, Lawrence Appel, Gabriel Contreras, Janice Douglas, Jim Lash, Robert Toto, Fredrick Van Lente, Xuelei Wang, Jackson T. Wright

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

In renal clinical trials, both slope-based and time-to-event renal outcomes have been used. These outcomes are typically based on estimates of GFR obtained using creatinine or iothalamate GFR (iGFR). The African American Study of Kidney Disease and Hypertension (AASK) was a trial in 1094 African Americans with hypertensive nephrosclerosis, which examined the effects of two levels of BP control and three antihypertensive regimens. This study compared the effects of the AASK interventions on outcomes based on serum creatinine with corresponding outcomes based on iGFR using 9742 matched pairs of iGFR and serum creatinine measurements. The iGFR-based outcomes included (1) a time-to-event composite outcome including a 50% GFR decline, ESRD, or death; (2) a composite outcome including a 50% GFR decline or ESRD; (3) mean decline in GFR in the first 3 mo after randomization (acute slope); (4) mean decline in GFR starting 3 mo after randomization (chronic slope); and (5) mean decline in GFR from baseline (total slope). The corresponding creatinine-based outcomes were (1) a composite of doubling of serum creatinine, ESRD, or death and (2) a composite of doubling of serum creatinine or ESRD and acute, chronic, and total slopes defined by the mean change in estimated GFR (eGFR), where eGFR was estimated from a regression equation for GFR depending primarily on serum creatinine and developed in AASK enrollees. Mean changes in iGFR and eGFR were also compared under extended models that allowed for the possibility that the rate of GFR decline may change over time during the chronic phase, an apparent acceleration in rate of decline of renal function over time was found. Subtle differences were observed between effects of the interventions on some of the creatinine and iGFR slope-based outcomes, but the main conclusions of the trial were similar for the serum creatinine and iothalamate-based measurements. This has important implications for the design of clinical trials with renal outcomes.

Original languageEnglish (US)
Pages (from-to)3175-3183
Number of pages9
JournalJournal of the American Society of Nephrology
Volume15
Issue number12
DOIs
StatePublished - Dec 2004

Fingerprint

Iothalamic Acid
Kidney Diseases
African Americans
Creatinine
Hypertension
Serum
Chronic Kidney Failure
Kidney
Random Allocation
Nephrosclerosis
Clinical Trials
Antihypertensive Agents

ASJC Scopus subject areas

  • Nephrology

Cite this

A comparison of iothalamate-GFR and serum creatinine-based outcomes : Acceleration in the rate of GFR decline in the African American Study of Kidney Disease and Hypertension. / Lewis, Julia; Greene, Tom; Appel, Lawrence; Contreras, Gabriel; Douglas, Janice; Lash, Jim; Toto, Robert; Van Lente, Fredrick; Wang, Xuelei; Wright, Jackson T.

In: Journal of the American Society of Nephrology, Vol. 15, No. 12, 12.2004, p. 3175-3183.

Research output: Contribution to journalArticle

Lewis, Julia ; Greene, Tom ; Appel, Lawrence ; Contreras, Gabriel ; Douglas, Janice ; Lash, Jim ; Toto, Robert ; Van Lente, Fredrick ; Wang, Xuelei ; Wright, Jackson T. / A comparison of iothalamate-GFR and serum creatinine-based outcomes : Acceleration in the rate of GFR decline in the African American Study of Kidney Disease and Hypertension. In: Journal of the American Society of Nephrology. 2004 ; Vol. 15, No. 12. pp. 3175-3183.
@article{7345fd0b44eb4ba5854aa29a4ac33549,
title = "A comparison of iothalamate-GFR and serum creatinine-based outcomes: Acceleration in the rate of GFR decline in the African American Study of Kidney Disease and Hypertension",
abstract = "In renal clinical trials, both slope-based and time-to-event renal outcomes have been used. These outcomes are typically based on estimates of GFR obtained using creatinine or iothalamate GFR (iGFR). The African American Study of Kidney Disease and Hypertension (AASK) was a trial in 1094 African Americans with hypertensive nephrosclerosis, which examined the effects of two levels of BP control and three antihypertensive regimens. This study compared the effects of the AASK interventions on outcomes based on serum creatinine with corresponding outcomes based on iGFR using 9742 matched pairs of iGFR and serum creatinine measurements. The iGFR-based outcomes included (1) a time-to-event composite outcome including a 50{\%} GFR decline, ESRD, or death; (2) a composite outcome including a 50{\%} GFR decline or ESRD; (3) mean decline in GFR in the first 3 mo after randomization (acute slope); (4) mean decline in GFR starting 3 mo after randomization (chronic slope); and (5) mean decline in GFR from baseline (total slope). The corresponding creatinine-based outcomes were (1) a composite of doubling of serum creatinine, ESRD, or death and (2) a composite of doubling of serum creatinine or ESRD and acute, chronic, and total slopes defined by the mean change in estimated GFR (eGFR), where eGFR was estimated from a regression equation for GFR depending primarily on serum creatinine and developed in AASK enrollees. Mean changes in iGFR and eGFR were also compared under extended models that allowed for the possibility that the rate of GFR decline may change over time during the chronic phase, an apparent acceleration in rate of decline of renal function over time was found. Subtle differences were observed between effects of the interventions on some of the creatinine and iGFR slope-based outcomes, but the main conclusions of the trial were similar for the serum creatinine and iothalamate-based measurements. This has important implications for the design of clinical trials with renal outcomes.",
author = "Julia Lewis and Tom Greene and Lawrence Appel and Gabriel Contreras and Janice Douglas and Jim Lash and Robert Toto and {Van Lente}, Fredrick and Xuelei Wang and Wright, {Jackson T.}",
year = "2004",
month = "12",
doi = "10.1097/01.ASN.0000146688.74084.A3",
language = "English (US)",
volume = "15",
pages = "3175--3183",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "12",

}

TY - JOUR

T1 - A comparison of iothalamate-GFR and serum creatinine-based outcomes

T2 - Acceleration in the rate of GFR decline in the African American Study of Kidney Disease and Hypertension

AU - Lewis, Julia

AU - Greene, Tom

AU - Appel, Lawrence

AU - Contreras, Gabriel

AU - Douglas, Janice

AU - Lash, Jim

AU - Toto, Robert

AU - Van Lente, Fredrick

AU - Wang, Xuelei

AU - Wright, Jackson T.

PY - 2004/12

Y1 - 2004/12

N2 - In renal clinical trials, both slope-based and time-to-event renal outcomes have been used. These outcomes are typically based on estimates of GFR obtained using creatinine or iothalamate GFR (iGFR). The African American Study of Kidney Disease and Hypertension (AASK) was a trial in 1094 African Americans with hypertensive nephrosclerosis, which examined the effects of two levels of BP control and three antihypertensive regimens. This study compared the effects of the AASK interventions on outcomes based on serum creatinine with corresponding outcomes based on iGFR using 9742 matched pairs of iGFR and serum creatinine measurements. The iGFR-based outcomes included (1) a time-to-event composite outcome including a 50% GFR decline, ESRD, or death; (2) a composite outcome including a 50% GFR decline or ESRD; (3) mean decline in GFR in the first 3 mo after randomization (acute slope); (4) mean decline in GFR starting 3 mo after randomization (chronic slope); and (5) mean decline in GFR from baseline (total slope). The corresponding creatinine-based outcomes were (1) a composite of doubling of serum creatinine, ESRD, or death and (2) a composite of doubling of serum creatinine or ESRD and acute, chronic, and total slopes defined by the mean change in estimated GFR (eGFR), where eGFR was estimated from a regression equation for GFR depending primarily on serum creatinine and developed in AASK enrollees. Mean changes in iGFR and eGFR were also compared under extended models that allowed for the possibility that the rate of GFR decline may change over time during the chronic phase, an apparent acceleration in rate of decline of renal function over time was found. Subtle differences were observed between effects of the interventions on some of the creatinine and iGFR slope-based outcomes, but the main conclusions of the trial were similar for the serum creatinine and iothalamate-based measurements. This has important implications for the design of clinical trials with renal outcomes.

AB - In renal clinical trials, both slope-based and time-to-event renal outcomes have been used. These outcomes are typically based on estimates of GFR obtained using creatinine or iothalamate GFR (iGFR). The African American Study of Kidney Disease and Hypertension (AASK) was a trial in 1094 African Americans with hypertensive nephrosclerosis, which examined the effects of two levels of BP control and three antihypertensive regimens. This study compared the effects of the AASK interventions on outcomes based on serum creatinine with corresponding outcomes based on iGFR using 9742 matched pairs of iGFR and serum creatinine measurements. The iGFR-based outcomes included (1) a time-to-event composite outcome including a 50% GFR decline, ESRD, or death; (2) a composite outcome including a 50% GFR decline or ESRD; (3) mean decline in GFR in the first 3 mo after randomization (acute slope); (4) mean decline in GFR starting 3 mo after randomization (chronic slope); and (5) mean decline in GFR from baseline (total slope). The corresponding creatinine-based outcomes were (1) a composite of doubling of serum creatinine, ESRD, or death and (2) a composite of doubling of serum creatinine or ESRD and acute, chronic, and total slopes defined by the mean change in estimated GFR (eGFR), where eGFR was estimated from a regression equation for GFR depending primarily on serum creatinine and developed in AASK enrollees. Mean changes in iGFR and eGFR were also compared under extended models that allowed for the possibility that the rate of GFR decline may change over time during the chronic phase, an apparent acceleration in rate of decline of renal function over time was found. Subtle differences were observed between effects of the interventions on some of the creatinine and iGFR slope-based outcomes, but the main conclusions of the trial were similar for the serum creatinine and iothalamate-based measurements. This has important implications for the design of clinical trials with renal outcomes.

UR - http://www.scopus.com/inward/record.url?scp=9644268179&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9644268179&partnerID=8YFLogxK

U2 - 10.1097/01.ASN.0000146688.74084.A3

DO - 10.1097/01.ASN.0000146688.74084.A3

M3 - Article

C2 - 15579521

AN - SCOPUS:9644268179

VL - 15

SP - 3175

EP - 3183

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 12

ER -