Anemia: A potent modulator of renal hemodynamics in models of progressive renal disease

The results of these studies demonstrate that, albeit by different mechanisms, induction of anemia prevents the development of glomerular capillary hypertension in three models of progressive renal disease, and retards progression of structural renal injury in the two models in which it has thus far been assessed. While the mechanism underlying the differential effect of anemia on renal resistance vessels in different disease states is unclear, the demonstrated ability of anemia to favorably modulate glomerular capillary hydraulic pressure, and thus retard the progression to structural glomerular injury, renders moderate anemia a potentially useful therapeutic tool for patients with progressive renal disease. Further work is clearly needed to assess the effect of anemia in other models of progressive renal disease, to assess the level of anemia needed to lower glomerular capillary pressure, and to provide insight into mechanisms responsible for this effect. In addition, clinical studies in patients with varying degrees of renal insufficiency are needed to assess the effect of induction of anemia on systemic and renal hemodynamics and the progression of renal disease. However, induction of moderate anemia may, via its effect on glomerular capillary hydraulic pressure, retard the pace of progression of diverse renal diseases in humans. Furthermore, the experimental observation that anemia has a favorable, and raising hematocrit an unfavorable, effect on systemic and glomerular capillary hydraulic pressure, would suggest that caution be exercised regarding the use of rHu-Epo to raise hematocrit in patients with residual renal function. Short-term studies to date have not systematically disclosed support for this caution, but longer studies are necessary for this purpose. Worsening of systemic hypertension has been noted in patients on hemodialysis after hematocrit has been raised with erythropoietin. Aggravation of hypertension, in combination with potentially unfavorable effects of the higher hematocrit on glomerular capillary hydraulic pressure, could hasten the progression to end-stage renal failure in these patients with residual renal function. Future studies are therefore needed to more clearly define the potential role of modulation of hematocrit in retarding the progression of diverse renal diseases.