Fig. 6.

Schematic concept of CKD onset and progression. The kidney contains ∼1 million filtration units (glomeruli). From the initially healthy status (a), some glomeruli experience pathological molecular changes (yellow) reversibly compromising their function. Without treatment, additional glomeruli will be damaged (c), a few also beyond the point where effective treatment may be possible (red). As pressure on the remaining intact glomeruli increases, damage of individual glomeruli is further accelerated (d), with now detectable impact on kidney functional parameters (albuminuria and/or eGFR), and the first glomeruli are lost (black). The molecular mechanisms are identical at this later stage to the beginning, but irreversible damage has occurred to multiple glomeruli, which cannot be repaired. Progression from (d) to (e) (established CKD, most glomeruli damaged, many beyond repair or completely lost) and then to (f) (ESRD, very few glomeruli still functional) cannot be prevented because of the too high burden on the few remaining glomeruli. Prevention would have been possible with intervention at (b) or (c), stages where molecular changes displayed by CKD273 are evident but functional parameters are not yet affected.