Background: Autosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage
renal disease (ESRD); however, the natural course of disease progression is heterogeneous between patients. This study
aimed to develop a natural history model of ADPKD that predicted progression rates and long-term outcomes in patients
with differing baseline characteristics.
Methods: The ADPKD Outcomes Model (ADPKD-OM) was developed using available patient-level data from the placebo
arm of the Tolvaptan Efficacy and Safety in Management of ADPKD and its Outcomes Study (TEMPO 3:4; ClinicalTrials.gov
identifier NCT00428948). Multivariable regression equations estimating annual rates of ADPKD progression, in terms of
total kidney volume (TKV) and estimated glomerular filtration rate, formed the basis of the lifetime patient-level simulation
model. Outputs of the ADPKD-OM were compared against external data sources to validate model accuracy and
generalisability to other ADPKD patient populations, then used to predict long-term outcomes in a cohort matched to
the overall TEMPO 3:4 study population.
Results: A cohort with baseline patient characteristics consistent with TEMPO 3:4 was predicted to reach ESRD at a mean
age of 52 years. Most patients (85%) were predicted to reach ESRD by the age of 65 years, with many progressing to
ESRD earlier in life (18, 36 and 56% by the age of 45, 50 and 55 years, respectively). Consistent with previous research and
clinical opinion, analyses supported the selection of baseline TKV as a prognostic factor for ADPKD progression, and
demonstrated its value as a strong predictor of future ESRD risk. Validation exercises and illustrative analyses confirmed
the ability of the ADPKD-OM to accurately predict disease progression towards ESRD across a range of clinically-relevant
patient profiles.
Conclusions: The ADPKD-OM represents a robust tool to predict natural disease progression and long-term outcomes in
ADPKD patients, based on readily available and/or measurable clinical characteristics. In conjunction with clinical
judgement, it has the potential to support decision-making in research and clinical practice