Figure 4 The theoretical contribution of genetic and environmental factors to polycystin protein dosage explains the rate of cyst progression in patients with autosomal dominant polycystic kidney disease (ADPKD) Figure 4 | The theoretical contribution of genetic and environmental factors to polycystin protein dosage explains the rate of cyst progression in patients with autosomal dominant polycystic kidney disease (ADPKD). Bars represent the relative loss of functional polycystin protein dosage and contribution of genetic and environmental factors to subsequent cyst growth and increase in total kidney volume (TKV). The upper horizontal orange line indicates a growth rate consistent with reaching end-stage renal disease (ESRD) at 50 years of age, whereas the lower horizontal red line indicates a growth rate consistent with ESRD at 70 years of age. Patient 1 has a missense mutation in PKD2 (encoding polycystin 2), which has less severe consequences for disease progression than other mutations, but has had environmental exposures that increase the rate of cyst growth. Patients 2 and 3 have similar main genetic effects, a missense mutation in PKD1, but patient 2 has also had a 'second-hit' somatic mutation, whereas patient 3 also has other genetic modifiers. Patient 4 has a nonsense mutation in PKD1, resulting in early-onset ESRD. Lanktree, M. B. & Chapman, A. B. (2017) New treatment paradigms for ADPKD: moving towards precision medicine Nat. Rev. Nephrol. doi:10.1038/nrneph.2017.127