Disturbance of lymph circulation develops renal fibrosis in rats with or without contralateral nephrectomy

BACKGROUND: The knowledge on renal lymphatics is very limited and their importance is often neglected in kidney transplantation surgery practice. Early papers demonstrated that acute ligation of hilar lymphatic ducts has a significant effect on sodium excretion and urine volume. However, the long-term effects of hilar lymphatic ducts ligation on renal function and histology were not mentioned. Here we show the time course of renal lesions caused by long-term ligation of renal hilar lymphatic vessels in rats with or without contralateral nephrectomy. METHODS: Animals were divided into three groups: rats with bilateral renal lymphatic ducts ligation (2KL); rats with one renal ligation and another nephrectomy (1KL); sham-operated rats (Sham). Proteinuria, serum creatinine value and creatinine clearance were monitored. Renal histology was examed by light microscopy. Further biochemical analysis was provided using real-time polymerase chain reaction, immunostaining and western blot techniques. RESULTS: From week 1 after ligation, both 1KL and 2KL rats developed severe proteinuria, whereas elevated serum creatinine and reduced creatinine clearance were observed from week 2. Histomorphological changes appeared in ligated kidneys at week 2, characterized by tubular damage, tubulointerstitial fibrosis and expansion of the mesangium. Overexpression of transforming growth factor-beta1 (TGF-beta1), Smad2/3, COL I genes and proteins were detected in 1KL and 2KL rats. Compared with 2KL rats, the changes in renal function and histology were more pronounced in 1KL rats. CONCLUSION: Disturbance of lymph circulation induced chronic renal failure and renal fibrosis, which were aggravated by lymphatic vessels ligation combined with contralateral nephrectomy. The effect of lymphatic ducts ligation on renal lesions may be explained by enhanced activation of the TGF-beta1/Smad signalling.