Citrate Attenuates Tubulointerstitial Fibrosis in 5/6 Nephrectomized Rats by Decreasing Transforming Growth Factor-(cid:31)1
Krissanapong Manotham MD*, Somchai Eiam-Ong MD**, Somchit Eiam-Ong PhD***, Pongsak Wannakrairot MD****, Kearkiat Praditpornsilpa MD**, Saowaluck Chusil MD**, Kriang Tungsanga MD**
Affiliation : * Nephrology Unit, Medicine, Lerdsin General Hospital ** Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University Hospital *** Department of Physiology, Faculty of Medicine, Chulalongkorn University Hospital **** Department of Pathology, Faculty of Medicine, Chulalongkorn University Hospital
Objective : Tubulointerstitial fibrosis plays an essential role in progression to end stage renal disease (ESRD)
in various chronic renal failure (CRF) models including the 5/6 nephrectomy (5/6). The present study exam-
ines the renoprotective effect of citrate in the renal ablative model that is quite similar to CRF in human.
Materials and Methods : Male Wistar rats underwent 5/6 and were fed with tap water (5/6tap) or tap water
containing 67 mEq/L citrate solution (5/6cit). Sham-operated rats (S) were divided into Stap and Scit groups.
Renal function, renal histopathology, renal α-Smooth muscle actin (SMA), and renal transforming growth
factor (TGF) - (cid:31)1 were determined immediately and at the 8th week after operation.
Results : Following the surgery, the values of glomerular filtration rate (GFR) in the 5/6tap and the 5/6cit groups
were 2.39 + 0.25 and 2.35 + 0.25 (mL/kg/min), respectively, both were significantly lower than sham groups
(p < 0.05). At the eighth week, the 5/6tap group had progressively decreased GFR and had higher fibrosis
score, increased α-SMA positive cells, and renal tissue TGF- (cid:31)1 when compared with the sham groups. The 5/
6cit group, when compared with the 5/6tap group, had higher GFR (2.51 + 0.22 vs 1.17 + 0.33 mL/kg/min; p <
0.05), lower fibrosis score (1.83 + 0.88 vs 3.0 + 0.4, p < 0.001), lower (cid:31)-SMA activity (159 + 2.9 vs 187 + 12.3
cells per 1000 interstitial cells, p < 0.05), and lower renal TGF- (cid:31)1 levels (1771.3 + 239.5 vs 4716.9 + 871.2
pg/mg protein, p < 0.005).
Conclusion : As such, in 5/6 nephrectomized rats, citrate therapy for eight weeks could decrease
tubulointerstitial fibrosis mainly by reducing the heightened renal TGF-(cid:31)1 levels and additionally by attenu-
ating the increased myofibroblast activity.
Keywords : Citrate, 5/6 nephrectomy, Tubulointerstitisl fibrosis, TGF-(cid:31)1
