Cell Hypertrophy: A “Biophysical Roadblock” to Reversing Kidney Injury

In anamniotes cell loss can typically be compensated for through proliferation, but in amniotes, this capacity has been significantly diminished to accommodate tissue complexity. In order to cope with the increased workload that results from cell death, instead of proliferation highly specialised post-mitotic cells undergo polyploidisation and hypertrophy. Although compensatory hypertrophy is the main strategy of repair/regeneration in various parenchymal tissues, the long-term benefits and its capacity to sustain complete recovery of the kidney has not been addressed sufficiently. In this perspective article we integrate basic principles from biophysics and biology to examine whether renal cell hypertrophy is a sustainable adaptation that can efficiently regenerate tissue mass and restore organ function, or a maladaptive detrimental response.