A model to predict disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD): the ADPKD Outcomes Model.

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

Additional file 1: of A model to predict disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD): the ADPKD Outcomes Model

Variance covariance matrices for TKV and eGFR progression equation coefficients. Table S1. Variance covariance matrix for the TEMPO 3:4 TKV equation coefficients. Table S2. Variance covariance matrix for the TEMPO 3:4 eGFR equation coefficients. Example of using the TKV and eGFR progression equations to predict annual ADPKD progression. Applying the ADPKD-OM to alternative patient populations. Using CKD-Epi measurements to model eGFR progression. Table S3. Comparison of eGFR progression equation coefficient estimates. Table S4. Variance covariance matrix for the TEMPO 3:4 eGFR equation coefficients. Validation against CRISP I-derived progression equations. CRISP I-derived equations for TKV (Equation S1) and eGFR (Equation S2) progression. Table S5. TKV progression equation coefficient estimates, as derived from CRISP I. Table S6. eGFR progression equation coefficient estimates, as derived from CRISP I. Validation against HALT-PKD trial data. Validation against THIN data. Validation against Thong and Ong [40]. Equation S3. eGFR progression equation, derived by Thong and Ong [40]. Table S7. eGFR progression equation coefficient estimates, as derived from Thong and Ong [40]. (DOCX 51 kb