Role of heparin as a protective agent following reduction of renal mass.

To determine the mechanism by which heparin affords protection from damage to the remnant kidney following reduction of renal mass, either whole heparin or a low molecular weight fraction of heparin was administered to Munich-Wistar rats which had had 90% ablation of renal mass. The low molecular weight fraction differed from the whole heparin in that it had greatly decreased anticoagulant activity as measured by the United States Pharmacopoeia (USP) assay, and increased antifactor Xa activity. The morphological alterations were examined and various physiological features were studied. The administration of whole heparin to rats with reduction of renal mass resulted in prolonged clotting time, reduced BP elevation, elimination of albuminuria, and lessening of renal damage. No such differences were observed in the rats receiving the fraction of heparin or the control group to which no therapy was given. The inability of the fraction of heparin to prolong clotting time suggested that it was unable to inactivate the serine proteases of the coagulation cascade. It is probable that the protective effect of whole heparin in this model is due to its ability to inhibit serine proteases such as kallikrein and components of the coagulation cascade resulting in a beneficial alteration in glomerular hemodynamics, lowering of systemic BP, and anticoagulation.