Aldosterone as a mediator of progressive renal disease: pathogenetic and clinical implications

Am J Kidney Dis. 2001 Apr;37(4):677-88. doi: 10.1016/s0272-6386(01)80115-3.


End-stage renal disease is an enormous public health burden with an increasing incidence and prevalence. This escalating prevalence suggests that newer therapeutic interventions and strategies are needed to complement current antihypertensive approaches. Although much evidence shows that angiotensin II mediates progressive renal disease, recent evidence also implicates aldosterone as an important pathogenetic factor in progressive renal disease. Several lines of experimental evidence show that selective blockade of aldosterone, independent of renin-angiotensin blockade, reduces proteinuria and nephrosclerosis in the spontaneously hypertensive stroke-prone rat model and reduces proteinuria and glomerulosclerosis in the subtotally nephrectomized rat model (ie, remnant kidney). Although pharmacological blockade with angiotensin II-receptor blockers and angiotensin-converting enzyme inhibitors reduces proteinuria and nephrosclerosis and/or glomerulosclerosis, selective reinfusion of aldosterone restores these abnormalities despite continued renin-angiotensin blockade. Based on this theoretic construct, randomized clinical studies will be initiated to delineate the potential renal-protective effects of antihypertensive therapy using aldosterone-receptor blockade. This is a US government work. There are no restrictions on its use.

Publication types

  • Review

MeSH terms

  • Aldosterone / physiology*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Captopril / therapeutic use
  • Eplerenone
  • Humans
  • Hypertension / complications
  • Hypertension / physiopathology
  • Kidney Failure, Chronic / drug therapy
  • Kidney Failure, Chronic / physiopathology*
  • Kidney Failure, Chronic / prevention & control*
  • Mineralocorticoid Receptor Antagonists* / therapeutic use
  • Rats
  • Rats, Inbred SHR
  • Spironolactone / analogs & derivatives
  • Spironolactone / therapeutic use


  • Angiotensin-Converting Enzyme Inhibitors
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Aldosterone
  • Eplerenone
  • Captopril