TY - JOUR
T1 - 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
AU - Perrone, Ronald D.
AU - Mouksassi, Mohamad Samer
AU - Romero, Klaus
AU - Czerwiec, Frank S.
AU - Chapman, Arlene B.
AU - Gitomer, Berenice Y.
AU - Torres, Vicente E.
AU - Miskulin, Dana C.
AU - Broadbent, Steve
AU - Marier, Jean F.
N1 - Publisher Copyright:
© 2017 International Society of Nephrology
PY - 2017/5/1
Y1 - 2017/5/1
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.
KW - end-stage renal disease
KW - prognostic biomarker
KW - renal function decline
KW - total kidney volume
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U2 - 10.1016/j.ekir.2017.01.003
DO - 10.1016/j.ekir.2017.01.003
M3 - Article
AN - SCOPUS:85024892275
SN - 2468-0249
VL - 2
SP - 442
EP - 450
JO - Kidney International Reports
JF - Kidney International Reports
IS - 3
ER -