Total Kidney Volume Is a Prognostic Biomarker of Renal Function Decline and Progression to End-Stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease

Ronald D. Perrone, Mohamad Samer Mouksassi, Klaus Romero, Frank S. Czerwiec, Arlene B. Chapman, Berenice Y. Gitomer, Vicente Torres, Dana C. Miskulin, Steve Broadbent, Jean F. Marier

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Introduction Autosomal dominant polycystic kidney disease is the most common hereditary kidney disease. TKV is a promising imaging biomarker for tracking and predicting the natural history of autosomal dominant polycystic kidney disease. The prognostic value of TKV was evaluated, in combination with age and eGFR, for the outcomes of 30% decline in eGFR and progression to ESRD. Observational data including 2355 patients with TKV measurements were available. Methods Multivariable Cox models were developed to assess the prognostic value of age, TKV, height-adjusted TKV, eGFR, sex, race, and genotype for the probability of a 30% decline in eGFR or ESRD. Results TKV was the most important prognostic term for 30% decline in eGFR in autosomal dominant polycystic kidney disease patients with and without preserved baseline eGFR. For a 40-year-old subject with preserved eGFR (70 ml/min per 1.73 m2), the adjusted hazard ratios for a 30% decline in eGFR were 1.86 (95% CI, 1.65–2.10) for a 2-fold larger TKV (600 vs. 1200 ml) and 2.68 (95% CI, 2.22–3.24) for a 3-fold larger TKV (600 vs. 1800 ml), respectively. Hazard ratios for progression to ESRD for 2- and 3-fold larger TKV were 1.72 (95% CI, 1.49–1.99) and 2.36 (95% CI, 1.88–2.97), respectively. Discussion The capability to predict 30% decline in eGFR is a novel aspect of this study. TKV was formally qualified, both by FDA and EMA, as a prognostic enrichment biomarker for selecting patients at high risk for a progressive decline in renal function for inclusion in interventional clinical trials.

Original languageEnglish (US)
Pages (from-to)442-450
Number of pages9
JournalKidney International Reports
Volume2
Issue number3
DOIs
StatePublished - May 1 2017

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Autosomal Dominant Polycystic Kidney
Chronic Kidney Failure
Inpatients
Biomarkers
Kidney
Inborn Genetic Diseases
Kidney Diseases
Proportional Hazards Models
Genotype
Clinical Trials

Keywords

  • end-stage renal disease
  • prognostic biomarker
  • renal function decline
  • total kidney volume

ASJC Scopus subject areas

  • Nephrology

Cite this

Total Kidney Volume Is a Prognostic Biomarker of Renal Function Decline and Progression to End-Stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease. / Perrone, Ronald D.; Mouksassi, Mohamad Samer; Romero, Klaus; Czerwiec, Frank S.; Chapman, Arlene B.; Gitomer, Berenice Y.; Torres, Vicente; Miskulin, Dana C.; Broadbent, Steve; Marier, Jean F.

In: Kidney International Reports, Vol. 2, No. 3, 01.05.2017, p. 442-450.

Research output: Contribution to journalArticle

Perrone, Ronald D. ; Mouksassi, Mohamad Samer ; Romero, Klaus ; Czerwiec, Frank S. ; Chapman, Arlene B. ; Gitomer, Berenice Y. ; Torres, Vicente ; Miskulin, Dana C. ; Broadbent, Steve ; Marier, Jean F. / Total Kidney Volume Is a Prognostic Biomarker of Renal Function Decline and Progression to End-Stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease. In: Kidney International Reports. 2017 ; Vol. 2, No. 3. pp. 442-450.
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abstract = "Introduction Autosomal dominant polycystic kidney disease is the most common hereditary kidney disease. TKV is a promising imaging biomarker for tracking and predicting the natural history of autosomal dominant polycystic kidney disease. The prognostic value of TKV was evaluated, in combination with age and eGFR, for the outcomes of 30{\%} decline in eGFR and progression to ESRD. Observational data including 2355 patients with TKV measurements were available. Methods Multivariable Cox models were developed to assess the prognostic value of age, TKV, height-adjusted TKV, eGFR, sex, race, and genotype for the probability of a 30{\%} decline in eGFR or ESRD. Results TKV was the most important prognostic term for 30{\%} decline in eGFR in autosomal dominant polycystic kidney disease patients with and without preserved baseline eGFR. For a 40-year-old subject with preserved eGFR (70 ml/min per 1.73 m2), the adjusted hazard ratios for a 30{\%} decline in eGFR were 1.86 (95{\%} CI, 1.65–2.10) for a 2-fold larger TKV (600 vs. 1200 ml) and 2.68 (95{\%} CI, 2.22–3.24) for a 3-fold larger TKV (600 vs. 1800 ml), respectively. Hazard ratios for progression to ESRD for 2- and 3-fold larger TKV were 1.72 (95{\%} CI, 1.49–1.99) and 2.36 (95{\%} CI, 1.88–2.97), respectively. Discussion The capability to predict 30{\%} decline in eGFR is a novel aspect of this study. TKV was formally qualified, both by FDA and EMA, as a prognostic enrichment biomarker for selecting patients at high risk for a progressive decline in renal function for inclusion in interventional clinical trials.",
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AU - Mouksassi, Mohamad Samer

AU - Romero, Klaus

AU - Czerwiec, Frank S.

AU - Chapman, Arlene B.

AU - Gitomer, Berenice Y.

AU - Torres, Vicente

AU - Miskulin, Dana C.

AU - Broadbent, Steve

AU - Marier, Jean F.

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N2 - Introduction Autosomal dominant polycystic kidney disease is the most common hereditary kidney disease. TKV is a promising imaging biomarker for tracking and predicting the natural history of autosomal dominant polycystic kidney disease. The prognostic value of TKV was evaluated, in combination with age and eGFR, for the outcomes of 30% decline in eGFR and progression to ESRD. Observational data including 2355 patients with TKV measurements were available. Methods Multivariable Cox models were developed to assess the prognostic value of age, TKV, height-adjusted TKV, eGFR, sex, race, and genotype for the probability of a 30% decline in eGFR or ESRD. Results TKV was the most important prognostic term for 30% decline in eGFR in autosomal dominant polycystic kidney disease patients with and without preserved baseline eGFR. For a 40-year-old subject with preserved eGFR (70 ml/min per 1.73 m2), the adjusted hazard ratios for a 30% decline in eGFR were 1.86 (95% CI, 1.65–2.10) for a 2-fold larger TKV (600 vs. 1200 ml) and 2.68 (95% CI, 2.22–3.24) for a 3-fold larger TKV (600 vs. 1800 ml), respectively. Hazard ratios for progression to ESRD for 2- and 3-fold larger TKV were 1.72 (95% CI, 1.49–1.99) and 2.36 (95% CI, 1.88–2.97), respectively. Discussion The capability to predict 30% decline in eGFR is a novel aspect of this study. TKV was formally qualified, both by FDA and EMA, as a prognostic enrichment biomarker for selecting patients at high risk for a progressive decline in renal function for inclusion in interventional clinical trials.

AB - Introduction Autosomal dominant polycystic kidney disease is the most common hereditary kidney disease. TKV is a promising imaging biomarker for tracking and predicting the natural history of autosomal dominant polycystic kidney disease. The prognostic value of TKV was evaluated, in combination with age and eGFR, for the outcomes of 30% decline in eGFR and progression to ESRD. Observational data including 2355 patients with TKV measurements were available. Methods Multivariable Cox models were developed to assess the prognostic value of age, TKV, height-adjusted TKV, eGFR, sex, race, and genotype for the probability of a 30% decline in eGFR or ESRD. Results TKV was the most important prognostic term for 30% decline in eGFR in autosomal dominant polycystic kidney disease patients with and without preserved baseline eGFR. For a 40-year-old subject with preserved eGFR (70 ml/min per 1.73 m2), the adjusted hazard ratios for a 30% decline in eGFR were 1.86 (95% CI, 1.65–2.10) for a 2-fold larger TKV (600 vs. 1200 ml) and 2.68 (95% CI, 2.22–3.24) for a 3-fold larger TKV (600 vs. 1800 ml), respectively. Hazard ratios for progression to ESRD for 2- and 3-fold larger TKV were 1.72 (95% CI, 1.49–1.99) and 2.36 (95% CI, 1.88–2.97), respectively. Discussion The capability to predict 30% decline in eGFR is a novel aspect of this study. TKV was formally qualified, both by FDA and EMA, as a prognostic enrichment biomarker for selecting patients at high risk for a progressive decline in renal function for inclusion in interventional clinical trials.

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