Relaxin decreases renal interstitial fibrosis and slows progression of renal disease.
BACKGROUND
Relaxin, a hormone of the insulin-growth factor family, promotes collagen remodeling. In rodent models of pulmonary and dermal fibrosis, relaxin reduced interstitial fibrosis. To study relaxin's effect in renal disease, we used the experimental bromoethylamine (BEA) model that leads to severe 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 osmotic pump delivering relaxin (2 microg/hour) or vehicle continuously for 28 days.


RESULTS
BEA caused a significant decrease in creatinine clearance, which was partially prevented by relaxin. In the relaxin-treated BEA rats, serum creatinine was normal, and albumin excretion was slightly decreased. By morphometric measurement, relaxin administration was associated with a significant decrease in interstitial fibrosis at the corticomedullary junction. This was accompanied by a decrease in the number of ED-1 positive cells (an index 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 groups.


CONCLUSIONS
Relaxin may have a useful application in decreasing interstitial fibrosis and thereby slowing the progression of renal disease.
Division of Nephrology, Cook County Hospital, Chicago, Illinois 60612, USA. SLGarber@aol.com
S L
SL
Garber
Y
Y
Mirochnik
C S
CS
Brecklin
E N
EN
Unemori
A K
AK
Singh
L
L
Slobodskoy
B H
BH
Grove
J A
JA
Arruda
G
G
Dunea
D000818:Animals; D003404:Creatinine / Q000378:metabolism; D018450:Disease Progression; D005021:Ethylamines; D005355:Fibrosis; D007668:Kidney / Q000473:pathology*; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D007679:Kidney Medulla / Q000187:drug effects / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012065:Relaxin / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D005021:Ethylamines; D016212:Transforming Growth Factor beta; C004504:2-bromoethylamine; D012065:Relaxin; D003404:Creatinine