Initial evaluation using podometrics requires both a recent biopsy (to determine podocyte number, density and glomerular volume) as well as the current rate of podocyte loss. These two measures together will define progression risk and time to ESKD. For subsequent decision-making to determine treatment efficacy the urine podocyte loss rate alone would usually be adequate.
Glomerular volume (GV): GV enlargement is a major driver of progression. GV is impacted by nutrition and growth factors. If reduced podocyte density is due to increased glomerular volume, then reducing the growth factor/nutrient milieu by diet, medications, bariatric surgery and related strategies (targeting BMI) would be projected to effectively prevent progression. Exposing patients to steroids would be expected to be counterproductive. Systematic implementation of this strategy is projected to be a major largely unrecognized opportunity to reduce progression prevalence.
Reduced podocyte number: If podocyte number per tuft is decreased and urine assay shows that the rate of podocyte detachment is increased then that patient will be projected to continue to progress unless effective treatment to reduce further podocyte detachment is implemented. On the other hand if the urine assay shows that the rate of podocyte detachment has returned to baseline then management can focus on determining what therapeutic strategies are needed to maintain a normal rate of podocyte detachment.
Podocytes too small: New strategies for facilitating podocyte adaption to hypertrophic stress will need to be developed and tested.
Podocytes are dysfunctional: The most common dysfunctional phenotype is effaced foot processes that predominate in Minimal Change Disease but are also present to lesser extents in other glomerular diseases where foot process effacement may account for some proportion of the total proteinuria. Steroid therapy can be expected to return effaced foot processes to the mature phenotype. Podocyte dysfunctional phenotypes may also occur in genetic glomerular diseases, but in each case podocyte number, size and density should be evaluated to determine the most effective therapeutic approach.
Projected time to ESKD: As described above rate of podocyte detachment data (expressed as fold × normal) combined with estimation of the remaining podocyte number per glomerulus can potentially be used to project the time to ESKD (80% podocyte loss) for an individual person (if treatment was not modified). Further studies are required to validate this concept for individual people.
Progression risk: If the rate of podocyte detachment is increased above the normal median then the risk for progression is expected to be directly related to the degree of increased rate of podocyte detachment. On the other hand if the rate of podocyte detachment is not increased then that person will not be at risk for progression, even if they have abnormal eGFR.
