Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease

A Post Hoc Analysis From the HALT-PKD Trials

HALT-PKD Trial Investigators

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Previous clinical studies of autosomal dominant polycystic kidney disease (ADPKD) reported that loss of kidney function usually follows a steep and relentless course. A detailed examination of individual patterns of decline in estimated glomerular filtration rate (eGFR) has not been performed. Study Design: Longitudinal post hoc analysis of data collected during the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trials. Setting & Participants: 494 HALT-PKD Study A participants (younger; preserved eGFR) and 435 Study B participants (older; reduced eGFR) who had more than 3 years of follow-up and 7 or more eGFR assessments. Measurements: Longitudinal eGFR assessments using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation. Predictors: Demographic, clinical, laboratory, and imaging features of participants. Outcomes: Probability of linear and nonlinear decline patterns or of stable eGFR calculated for each participant from a Bayesian model of individual eGFR trajectories. Results: Most (62.5% in Study A and 81% in Study B) participants had a linear decline in eGFR during up to 8 years of follow-up. A proportion (22% in Study A and 13% in Study B) of progressors had a nonlinear pattern. 15.5% of participants in Study A and 6% in Study B had a prolonged (≥4.5 years) period of stable eGFRs. These individuals (Study A) had significantly smaller total kidney volumes, higher renal blood flows, lower urinary albumin excretion, and lower body mass index at baseline and study end. In Study B, participants with reduced but stable eGFRs were older than the progressors. Two-thirds of nonprogressors in both studies had PKD1 mutations, with enrichment for weak nontruncating mutations. Limitations: Relatively short follow-up of a clinical trial population. Conclusions: Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD.

Original languageEnglish (US)
Pages (from-to)666-676
Number of pages11
JournalAmerican Journal of Kidney Diseases
Volume71
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Autosomal Dominant Polycystic Kidney
Polycystic Kidney Diseases
Glomerular Filtration Rate
Kidney
Body Mass Index
Mutation
Renal Circulation
Chronic Renal Insufficiency
Longitudinal Studies
Albumins
Creatinine
Epidemiology
Demography
Clinical Trials

Keywords

  • Autosomal dominant polycystic kidney disease (ADPKD)
  • Bayesian models
  • eGFR slope
  • eGFR trajectory
  • end-stage renal disease (ESRD)
  • estimated glomerular filtration rate (eGFR)
  • kidney disease progression
  • mutation analysis
  • total kidney volume

ASJC Scopus subject areas

  • Nephrology

Cite this

Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease : A Post Hoc Analysis From the HALT-PKD Trials. / HALT-PKD Trial Investigators.

In: American Journal of Kidney Diseases, Vol. 71, No. 5, 01.05.2018, p. 666-676.

Research output: Contribution to journalArticle

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abstract = "Background: Previous clinical studies of autosomal dominant polycystic kidney disease (ADPKD) reported that loss of kidney function usually follows a steep and relentless course. A detailed examination of individual patterns of decline in estimated glomerular filtration rate (eGFR) has not been performed. Study Design: Longitudinal post hoc analysis of data collected during the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trials. Setting & Participants: 494 HALT-PKD Study A participants (younger; preserved eGFR) and 435 Study B participants (older; reduced eGFR) who had more than 3 years of follow-up and 7 or more eGFR assessments. Measurements: Longitudinal eGFR assessments using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation. Predictors: Demographic, clinical, laboratory, and imaging features of participants. Outcomes: Probability of linear and nonlinear decline patterns or of stable eGFR calculated for each participant from a Bayesian model of individual eGFR trajectories. Results: Most (62.5{\%} in Study A and 81{\%} in Study B) participants had a linear decline in eGFR during up to 8 years of follow-up. A proportion (22{\%} in Study A and 13{\%} in Study B) of progressors had a nonlinear pattern. 15.5{\%} of participants in Study A and 6{\%} in Study B had a prolonged (≥4.5 years) period of stable eGFRs. These individuals (Study A) had significantly smaller total kidney volumes, higher renal blood flows, lower urinary albumin excretion, and lower body mass index at baseline and study end. In Study B, participants with reduced but stable eGFRs were older than the progressors. Two-thirds of nonprogressors in both studies had PKD1 mutations, with enrichment for weak nontruncating mutations. Limitations: Relatively short follow-up of a clinical trial population. Conclusions: Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD.",
keywords = "Autosomal dominant polycystic kidney disease (ADPKD), Bayesian models, eGFR slope, eGFR trajectory, end-stage renal disease (ESRD), estimated glomerular filtration rate (eGFR), kidney disease progression, mutation analysis, total kidney volume",
author = "{HALT-PKD Trial Investigators} and Brosnahan, {Godela M.} and Abebe, {Kaleab Z.} and Moore, {Charity G.} and Rahbari-Oskoui, {Frederic F.} and Bae, {Kyongtae T.} and Grantham, {Jared J.} and Schrier, {Robert W.} and Braun, {William E.} and Chapman, {Arlene B.} and Flessner, {Michael F.} and Harris, {Peter C.} and Hogan, {Marie C.} and Perrone, {Ronald D.} and Miskulin, {Dana C.} and Steinman, {Theodore I.} and Torres, {Vicente E.} and Theodore Steinman and Jesse Wei and Peter Czarnecki and Ivan Pedrosa and William Braun and Saul Nurko and Erick Remer and Arlene Chapman and Diego Martin and Frederic Rahbari-Oskoui and Pardeep Mittal and Vicente Torres and Hogan, {Marie C.} and Ziad El-Zoghby and Peter Harris and James Glockner and Bernard King and Ronald Perrone and Neil Halin and Dana Miskulin and Robert Schrier and Godela Brosnahan and Berenice Gitomer and Cass Kelleher and Amirali Masoumi and Nayana Patel and Franz Winklhofer and Jared Grantham and Alan Yu and Connie Wang and Louis Wetzel and Moore, {Charity G.} and Bost, {James E.} and Sharon Moe",
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TY - JOUR

T1 - Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease

T2 - A Post Hoc Analysis From the HALT-PKD Trials

AU - HALT-PKD Trial Investigators

AU - Brosnahan, Godela M.

AU - Abebe, Kaleab Z.

AU - Moore, Charity G.

AU - Rahbari-Oskoui, Frederic F.

AU - Bae, Kyongtae T.

AU - Grantham, Jared J.

AU - Schrier, Robert W.

AU - Braun, William E.

AU - Chapman, Arlene B.

AU - Flessner, Michael F.

AU - Harris, Peter C.

AU - Hogan, Marie C.

AU - Perrone, Ronald D.

AU - Miskulin, Dana C.

AU - Steinman, Theodore I.

AU - Torres, Vicente E.

AU - Steinman, Theodore

AU - Wei, Jesse

AU - Czarnecki, Peter

AU - Pedrosa, Ivan

AU - Braun, William

AU - Nurko, Saul

AU - Remer, Erick

AU - Chapman, Arlene

AU - Martin, Diego

AU - Rahbari-Oskoui, Frederic

AU - Mittal, Pardeep

AU - Torres, Vicente

AU - Hogan, Marie C.

AU - El-Zoghby, Ziad

AU - Harris, Peter

AU - Glockner, James

AU - King, Bernard

AU - Perrone, Ronald

AU - Halin, Neil

AU - Miskulin, Dana

AU - Schrier, Robert

AU - Brosnahan, Godela

AU - Gitomer, Berenice

AU - Kelleher, Cass

AU - Masoumi, Amirali

AU - Patel, Nayana

AU - Winklhofer, Franz

AU - Grantham, Jared

AU - Yu, Alan

AU - Wang, Connie

AU - Wetzel, Louis

AU - Moore, Charity G.

AU - Bost, James E.

AU - Moe, Sharon

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Background: Previous clinical studies of autosomal dominant polycystic kidney disease (ADPKD) reported that loss of kidney function usually follows a steep and relentless course. A detailed examination of individual patterns of decline in estimated glomerular filtration rate (eGFR) has not been performed. Study Design: Longitudinal post hoc analysis of data collected during the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trials. Setting & Participants: 494 HALT-PKD Study A participants (younger; preserved eGFR) and 435 Study B participants (older; reduced eGFR) who had more than 3 years of follow-up and 7 or more eGFR assessments. Measurements: Longitudinal eGFR assessments using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation. Predictors: Demographic, clinical, laboratory, and imaging features of participants. Outcomes: Probability of linear and nonlinear decline patterns or of stable eGFR calculated for each participant from a Bayesian model of individual eGFR trajectories. Results: Most (62.5% in Study A and 81% in Study B) participants had a linear decline in eGFR during up to 8 years of follow-up. A proportion (22% in Study A and 13% in Study B) of progressors had a nonlinear pattern. 15.5% of participants in Study A and 6% in Study B had a prolonged (≥4.5 years) period of stable eGFRs. These individuals (Study A) had significantly smaller total kidney volumes, higher renal blood flows, lower urinary albumin excretion, and lower body mass index at baseline and study end. In Study B, participants with reduced but stable eGFRs were older than the progressors. Two-thirds of nonprogressors in both studies had PKD1 mutations, with enrichment for weak nontruncating mutations. Limitations: Relatively short follow-up of a clinical trial population. Conclusions: Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD.

AB - Background: Previous clinical studies of autosomal dominant polycystic kidney disease (ADPKD) reported that loss of kidney function usually follows a steep and relentless course. A detailed examination of individual patterns of decline in estimated glomerular filtration rate (eGFR) has not been performed. Study Design: Longitudinal post hoc analysis of data collected during the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trials. Setting & Participants: 494 HALT-PKD Study A participants (younger; preserved eGFR) and 435 Study B participants (older; reduced eGFR) who had more than 3 years of follow-up and 7 or more eGFR assessments. Measurements: Longitudinal eGFR assessments using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation. Predictors: Demographic, clinical, laboratory, and imaging features of participants. Outcomes: Probability of linear and nonlinear decline patterns or of stable eGFR calculated for each participant from a Bayesian model of individual eGFR trajectories. Results: Most (62.5% in Study A and 81% in Study B) participants had a linear decline in eGFR during up to 8 years of follow-up. A proportion (22% in Study A and 13% in Study B) of progressors had a nonlinear pattern. 15.5% of participants in Study A and 6% in Study B had a prolonged (≥4.5 years) period of stable eGFRs. These individuals (Study A) had significantly smaller total kidney volumes, higher renal blood flows, lower urinary albumin excretion, and lower body mass index at baseline and study end. In Study B, participants with reduced but stable eGFRs were older than the progressors. Two-thirds of nonprogressors in both studies had PKD1 mutations, with enrichment for weak nontruncating mutations. Limitations: Relatively short follow-up of a clinical trial population. Conclusions: Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD.

KW - Autosomal dominant polycystic kidney disease (ADPKD)

KW - Bayesian models

KW - eGFR slope

KW - eGFR trajectory

KW - end-stage renal disease (ESRD)

KW - estimated glomerular filtration rate (eGFR)

KW - kidney disease progression

KW - mutation analysis

KW - total kidney volume

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U2 - 10.1053/j.ajkd.2017.10.023

DO - 10.1053/j.ajkd.2017.10.023

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EP - 676

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

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