Relaxin decreases renal interstitial fibrosis and slows progression of renal disease

Background. Relaxin, a hormone of the insulin-growth factor family, promote s collagen remodeling. In rodent models of pulmonary and dermal fibrosis, r elaxin reduced interstitial fibrosis. To study relaxin's effect in renal di sease, we used the experimental bromoethylamine (BEA) model that leads to s evere renal interstitial fibrosis, a decrease in glomerular filtration rate , and albuminuria at one month. Methods. Rats were injected with BEA one week prior to implantation of an o smotic pump delivering relaxin (2 mug/hour) or vehicle continuously for 28 days. Results. BEA caused a significant decrease in creatinine clearance, which w as partially prevented by relaxin. In the relaxin-treated BEA rats, serum c reatinine was normal, and albumin excretion was slightly decreased. By morp hometric measurement, relaxin administration was associated with a signific ant decrease in interstitial fibrosis at the corticomedullary junction. Thi s was accompanied by a decrease in the number of ED-1 positive cells tan in dex of macrophage infiltration) and in the intensity of immunohistochemical staining for transforming growth factor-beta. This antifibrotic effect of relaxin did not appear to be mediated by systemic hemodynamic changes since the mean arterial pressure was not significantly different among the group s. Conclusions. Relaxin may have a useful application in decreasing interstiti al fibrosis and thereby slowing the progression of renal disease.