Effect of relaxin in two models of renal mass reduction.
BACKGROUND
Relaxin (Rlx), a 6-kD protein hormone, belongs to the insulin growth factor family. We have previously shown that Rlx reduces interstitial fibrosis in a model of chronic papillary necrosis.


OBJECTIVE
The purpose of this study was to extend these observations to a model of renal injury induced by mass reduction.


METHODS
Renal mass was reduced by either infarction or surgical excision of both poles, with removal of the contralateral kidney. Two weeks later, creatinine clearance was done and animals from both groups implanted with osmotic pumps delivering either Rlx (2 microg/h) or vehicle (Veh). Treatment was continued for 4 weeks. The severity of the glomerular injury was quantified by planimetric measurements. Renal function was assessed by creatinine clearance and plasma creatinine.


RESULTS
Rlx significantly decreased systolic blood pressure in animals with infarction. This was accompanied by a decrease in serum creatinine and a slight improvement in creatinine clearance. The severity of the glomerular lesion was reduced by Rlx (sclerosis index, Veh 1.16 +/- 0.13 vs. Rlx 0.74 +/- 0.16, p = 0.037). In the excision group the animals were normotensive. In this group, Rlx treatment was accompanied by a decrease in serum creatinine (Veh 1.01 +/- 0.03 vs. Rlx 0.81 +/- 0.05 mg/dl, p = 0.02) and an increase in GFR (Veh 0.90 +/- 0.14 vs. Rlx 1.33 +/- 0.11 ml/min, p = 0.03). The sclerosis index was also reduced.


CONCLUSIONS
Rlx decreases renal injury by at least two mechanisms, one by lowering blood pressure as seen in the infarction model, the other independent of blood pressure as seen in the normotensive excision model where there was also a significant functional improvement.
Garber
Sandra L
SL
Division of Nephrology at Cook County Hospital, Chicago, Ill 60612, USA. SLGarber@AOL.com
Mirochnik
Yelena
Y
Brecklin
Carolyn
C
Slobodskoy
Leonid
L
Arruda
Jose A L
JA
Dunea
George
G
D000818:Animals; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012065:Relaxin / Q000494:pharmacology*
D012065:Relaxin