Compensatory Glomerulopathy

  • Compensatory Glomerulopathy is a pathologic change observed in glomeruli that are hyperfunctioning in an attempt to compensate for the loss other glomerulo-nephronic units.
  • Initial Insult
    • A diverse variety of primary insults, acute or chronic, can initiate compensatory glomerulopathy. However, all do so by destroying sufficient numbers of glomerulo-nephronic units to cause a decline in the total renal Glomerular Filtrate Rate (GFR). Experimentally, it has been shown that nearly 80% of total renal tissue must be removed to precipitate pathogenic progression of compensatory glomerulopathy.
  • Compensation
    • To maintain sufficient total GFR, the individual GFR of each remaining glomerulus must increase. This is accomplished by a variety of still murky factors which together cause hypertrophy of the glomerular capillary tuft and increase the glomerular capillary hydrostatic pressure] of the remaining glomeruli, thus causing higher filtration in each individual glomerulus (See: Glomerular Filtration Rate).
  • Decompensation
    • Chronic hyperfiltration ultimately results in injury to the cells of the glomerulus. It appears that hypertrophy and hyperfiltration of the glomerular capillary tuft is not compensated by expansion of the podocytes. This mismatch ultimately results in dysregulation of podocytes which are a key component of selective glomerular filtration. With the loss of glomerular barrier selectivity, plasma proteins leak into the mesangium, causing mesangial sclerosis and proliferation of mesangial cells. Ultimately, the progressive glomerulosclerosis (sometimes very similar to Focal Segmental Glomerulosclerosis) leads to collapse of the glomerular capillaries and eventually the affected glomerulus is completely destroyed. This only serves to place further functional pressure on the remaining glomeruli which accelerates their eventual demise.
Clinical Consequences
  • Initially, proteinuria is observed consistent with a loss of selectivity of the glomerular barrier. However, with progressive disease chronic renal failure is the ultimate result. Indeed, compensatory glomerulopathy is thought to be the mechanistic basis for the pathogenic sequence of chronic renal failure.