The Study On Influencing Factors Associated With Declines In Renal Function After Unilateral Nephrectomy And The Susceptibility And Intervention Of Cisplatin-induced Renal Injury

Background and objective:?To study the changes of renal function after unilateral radical nephrectomy, and to explore the influencing factors associated with declines in renal function. ?We seted up cisplatin-induced acute kidney injury in rats by using uninephrectomy rats. To study the susceptibility of cisplatin-induced renal injury between uninephrectomy and sham groups and the role of oxidative stress in cisplatin-induced renal injury.?Cisplatin-induced kidney injury is associated with oxidative stress and inflammation, while baicalein has strong antioxidant and anti-inflammation activity. The aim of this study was to explore the protective effect of baicalein on cisplatin-induced renal injury.Methods: ? All the patients who were treated with unilateral radical nephrectomy for renal malignant neoplasms in Chinese PLA General Hospital from January 2011 to December 2015 were retrospectively analyzed. Patients with the data of estimated glomerular filtration rates [eGFR?60ml/(min·1.73m2)] before the operation and patients who were followed up for more than 3 months after the operation were enrolled into the study. According to the last eGFR, patients were divided into two groups [eGFR<60ml/(min·1.73m2) and eGFR?60ml/(min·1.73m2)].The rate of descent of the post-operation eGFR was measured and the demographics,tumor types and operative methods were analyzed. The univariate and multivariate analyses were performed to show influencing factors. ?The renal function of the contralateral kidney was stable after 4 weeks of unilateral nephrectomy. we built cisplatin-induced renal injury model in rats. The experiment was divided into 4 groups (UN,sham,UN+cis, sham+cis). Serum biochemical markers and urinary protein were measured in each group 72 hours after intraperitoneal injection of cisplatin (3mg/kg body weight). The kidney tissues were collected for pathology. The renal pathological changes were observed under light microscope. E method was used to detect the expression of renal injury markers (KIM-1 and NGAL) and the expression of oxidative stress markers (MDA, SOD and GSH) in in renal tissue. ?The rats were divided into three groups: control; cisplatin: received normal saline through per oral route for 7 consecutive days and a single intraperitoneal injection of cisplatin (3mg/kg body weight) on 5th day; cis+bai: received baicalein (100mg/kg body weight) through per oral route for 7 consecutive days and a single intraperitoneal injection of cisplatin (3mg/kg body weight) on 5th day. Serum biochemical markers and urinary protein were measured in each group 72 hours after injection of cisplatin. The changes of renal injury were observed under light microscope. The oxidative stress markers( MDA, SOD, GSH, gp91phox and p47phox)and inflammatory markers (TNF-a and NF-KB(p65)) in renal tissue were measured by ELISA and Western Blot.Results: ?94 patents were enrolled into the study. Before the operation, the eGFR of 55 (58.5%) patients were more than 90ml/(min·1.73m2), and the other 39(41.5% ) patients were at 60?89 ml/(min·1.73m2). After the operation and following up for 3-50 months, the eGFR of 33 patients dropped below 60 ml/(min·1.73m2).Univariate analyses showed that there were no significant differences in gender(P=0.718) , follow-up time (p=0.592) , body mass index (BMI) (P=0.769),complicated with diabetes (P=0.959), tumor pathological types (P=0.826) and tumor sides(P=0.084) between these two groups. There were significant differences in age(P<0.001) , preoperative eGFR (P<0.001) , complicated with hypertension(P=0.002) and operative methods (P=0.024). Multivariate analyses showed that age(OR=1. 195, P<0.001 ) and preoperative eGFR (OR=0.952, P=0.047) were associated with the declines in renal function. ?Compared with the UN group (sham+cis vs sham), the rats in UN+cis group showed decreased body weight, the Scr, BUN and urinary protein were significantly higher (P<0.05),the pathological results showed that the renal injury was obvious at the kidneys, kim-1 and NGAL were significantly increased (P<0.05). Compared with the sham+cis group, renal function index increased (P<0.05), the renal tubule injury was more severe (P<0.05) and the expression of KIM-1 and NGAL in renal tissue was significantly up-regulated(P<0.05) in UN+cis group. At the same time, the lipid peroxidation product MDA of renal tissue was higher and the expression of antioxidant SOD and GSH decreased in UN+cis group ( sham+cis group) when compared with the UN group (sham group)respectively (P<0.05). ?Compared with cisplatin group, the values of Scr, BUN and urinary protein was significantly lower (P<0.05), the renal pathology showed less renal tubular damage (P<0.05) and the expression of KIM-1 and NGAL in urine was significantly decreased (P<0.05) in cis+bai group after 72 hours of cisplatin injection.The content of MDA, gp91phox, p47phox, TNF-? and NF-?B (p65) in renal tissue was decreased (P<0.05) and the expression of SOD, GSH was increased in cis+bai group compared with that in cisplatin group.Conclusion:? The renal function should be monitored before and after unilateral radical nephrectomy. Older age and lower preoperative eGFR were two independent risk factors associated with declines in renal function after unilateral nephrectomy. ?Kidney injury induced by cisplatin in unilateral nephrectomy rats was more obvious than that in sham group. Cisplatin-induced renal injury may be related to oxidative stress. ?Baicalein relieves cisplatin-induced kidney injury via reduction of oxidative stress and inflammatory response.