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

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.

Keywords: end-stage renal disease; prognostic biomarker; renal function decline; total kidney volume.

Figure 1

Summary of subjects included in the analysis, missing baseline characteristics, and disease endpoints. eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; TKV, total kidney volume.

Figure 2

Probability of avoiding a 30% decline in estimated glomerular filtration rate (eGFR) as a function of baseline total kidney volume (TKV) and baseline eGFR. Solid red line represents preserved eGFR (≥50 ml/min per 1.73 m²) and small TKV (<1000 ml). Dashed red line represents preserved eGFR (≥50 ml/min per 1.73 m²) and large TKV (≥1000 ml). Solid blue line represents reduced eGFR (<50 ml/min per 1.73 m²) and small TKV (<1000 ml). Dashed blue line represents reduced eGFR (<50 ml/min per 1.73 m²) and large TKV (≥1000 ml).

Figure 3

Probability of avoiding end-stage renal disease (ESRD) as a function of baseline total kidney volume (TKV) and baseline estimated glomerular filtration rate (eGFR). Solid red line represents preserved eGFR (≥50 ml/min per 1.73 m²) and small TKV (<1000 ml). Dashed red line represents preserved eGFR (≥50 ml/min per 1.73 m²) and large TKV (≥1000 ml). Solid blue line represents reduced eGFR (<50 ml/min per 1.73 m²) and small TKV (<1000 ml). Dashed blue line represents reduced eGFR (<50 ml/min per 1.73m²) and large TKV (≥ 1000 ml).

Figure 4

Effect of age, estimated glomerular filtration rate (eGFR), and total kidney volume (TKV) on hazard ratio (HR) of (a) 30% of decline of eGFR and (b) progression to ESRD for a reference autosomal dominant polycystic kidney disease subject (reference: 40 years, eGFR of 70 ml/min per 1.73 m² and TKV of 1000 ml, respectively). CI, confidence interval.