Functional, histological and biochemical consequences of renal lymph disorder in mononephrectomized rats

OBJECTIVES: The lymphatic circulation forms an accessory pathway to return excess fluid and proteins from the tissue spaces back to the blood stream. The effects of blockage/leakage become problematic when the usual compensatory mechanisms are overwhelmed. However, our knowledge of renal lymphatics is very limited, and their importance is almost always neglected in kidney transplant surgery practice. Here, we show the time course of renal lesions caused by renal lymphatic disorder. METHODS: All animals underwent right nephrectomy and were divided into 2 groups: rats with left renal lymphatic vessel ligation (KL) and sham-operated rats (sham). Proteinuria, serum creatinine value and creatinine clearance (Ccr) were monitored. Renal histology was examined by light microscopy. Further biochemical analysis was provided using real-time PCR, immunostaining and Western blot techniques. RESULTS: The KL group developed progressive chronic renal failure. Severe proteinuria and reduced Ccr were observed from day 7 and day 14, respectively. Histomorphological changes appeared in ligated kidneys, characterized by tubular cell detachment, tubular cell necrosis, tubular atrophy or dilatation and deposition of extracellular matrix. Apoptosis index of ligated kidneys was increased from day 1. Overexpression of caspase-3 and increasing Bax to Bcl-2 ratio were detected in KL rats. CONCLUSIONS: Disturbance of renal lymph circulation induces severe chronic renal lesions, chronic renal failure and enhanced renal cell apoptosis. The Bax/Bcl-2 pathway mediates apoptosis in this disease.