Progrès dans les traitements des cancers du rein

Partial nephrectomy is the gold standard for the renal tumours less than 7 to 10 cm whenever feasible in order to preserve renal function. The extension of nephron-sparing surgery using a mini-invasive approach is possible by robotic surgery. Radical nephrectomy is mandatory in the other situations and especially in case of locally advanced renal carcinoma. The place of cytoreductive nephrectomy in metastatic renal cell carcinoma is the purpose of the CARMENA trial. Tyrosine kinase inhibitors are currently the first line treatment; but in the near future new immunotherapy by checkpoints molecules could crucially change the treatment of metastatic renal cell carcinoma. Numerous trials in a neoadjuvant or adjuvant settings are ongoing.     

Small renal masses in the era of personalized medicine: Tumor heterogeneity,growth kinetics,and risk of metastasis

Small renal masses (SRMs) represent a heterogeneous group showing a variety of clinical and biological behaviors. The best treatment for SRMs has been the focus of much debate over the past decades. Present strategies include surgery (partial or radical nephrectomy), local treatments (radiofrequency and cryoablation), or active surveillance. The choice among these therapeutic options is based on patient clinical features such as age or comorbidities rather than on tumor characteristics. Several studies have recently focused on the molecular behavior of SRMs. They showed that SRMs present histotype and nuclear grading heterogeneity, together with not unvarying growth kinetics and risk of recurrence or metastasis, suggesting that personalized approaches should be designed to optimize the management of these patients. At present, several studies are in course to identify predictive biomarkers to guide the decision-making process in this subpopulation. In this review, we summarized the data on growth kinetics, tumor heterogeneity, and risk of metastasis in patients with SRMs, with focus on the current role of biopsies and imaging in the management of these patients.     

Protective effect of resveratrol on 5/6 nephrectomized rats and its mechanism

Objective To investigate the protective effect of resveratrol (RSV) on 5/6 nephrectomized rats and its mechanism. Methods Fifty male SD rats were randomly divided into three groups: sham operated (Sham, n＝10）, 5/6 nephrectomy (Nx, n＝20), and 5/6 nephrectomy＋RSV 20 mg/kg (Nx＋RSV, n＝20). RSV or normal saline was administered one week after 5/6 nephrectomy. Proteinuria was detected every 4 weeks. Serum creatinine and the renal pathological changes were measured after 12 weeks. Immunohistochemisty staining of fibronectin (FN), collagenⅠ, transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) were used to analyze the changes of renal fibrosis. Western blotting was used to measure the expression of Smad3, phospho-Smad3, and acety-Smad3. Immunoprecipitation was used to detect the interaction between Sirt1 and Smad3. Results Compared with the sham operated rats, subtotal nephrectomy significantly increased proteinuria [(152.14±30.49) mg/24 h vs (25.34±7.54) mg/24 h], serum creatinine[(111.60±21.50) μmol/L vs (53.90±11.59) μmol/L], glomerular sclerosis index (1.56±0.34 vs 0.35±0.08) and the expressions of fibronectin, collagenⅠ, TGF-β and CTGF in renal tissue at 12 weeks after operation (all P＜0.01), and RSV treatment significantly inhibited the above up-regulations (all P＜0.01). Compared with the sham operated rats, subtotal nephrectomy increased the expression of phospholylation and acetylation of Smad3. RSV treatment significantly reduced the expression of acety-Smad3, but had no effect on the phospho-Smad3. Immunoprecipitation revealed a binding effect of Smad3 with Sirt1. Conclusions RSV treatment can attenuate proteinuria, protect renal function and inhibit renal fibrosis in 5/6 nephrectomized rats. This renal protective effect is associated with reduced Smad3 acetylation and activation of Sirt1, which suggesting that Sirt1 may be a potential therapeutic target of CKD.     

后腹腔镜单纯肾切除术治疗良性无功能肾的疗效分析

目的:探讨后腹腔镜单纯肾切除术治疗良性无功能肾的临床疗效。方法:回顾分析2009年8月至2013年2月为20例良性无功能肾患者行后腹腔镜单纯肾切除术的临床资料。其中肾盂输尿管结合部狭窄4例,肾盂结石2例,输尿管结石10例,肾结核4例。肾动静脉均用Hem-o-lok夹闭后切断。结果:20例手术均获成功,无中转开放手术及严重并发症发生,术中均未输血。镜下操作时间平均(74.10±19.98)min,术中出血量平均(35.85±40.18)ml,术后平均住院(5.55±0.94)d。结论:后腹腔镜单纯肾切除术治疗良性无功能肾安全、有效,具有患者创伤小、康复快的优点,值得推荐使用。     

Interleukin 1 Receptor Antagonist and Tumor Necrosis Factor-α Gene Polymorphism in Patients with End-Stage Renal Failure

Urea and creatinine are not generally considered to be important uremic toxins despite evidence from dialysis experiments to the contrary, and despite striking elevations of these nitrogenous waste products in uremia. In order to study this problem in acute uremia, we used a new dietary method for prolonging the survival of bilaterally nephrectomized rats. Urea or creatinine were injected on three successive days starting one day after the inception of uremia. Urea or creatinine injections shortened the survival time of acutely uremic rats, and increased the involution of thymus and spleen. The extra urea, but not creatinine, increased the serum osmolality. These data indicate that urea and creatinine are toxic in the acutely uremic rat. Hypertonicity of the serum may contribute to the toxicity of urea. Additional mechanisms of toxicity and additional toxins are not excluded.     

BILATERAL NEPHRECTOMY DELAYS GASTRIC EMPTYING OF A LIQUID MEAL IN AWAKE RATS

Aims: This study evaluates the effect of bilateral nephrectomy on the gastric emptying of a liquid meal. Methods: Male rats were submitted under anesthesia to cervical vessels cannulation and bilateral lumbar incision, followed or not by nephrectomy. Next day, they were gavage fed (1.5 mL) with phenol red (0.5 gmL^?1) in 5% glucose solution and sacrificed 0, 10, 20, 30 or 45 min later. A blood sample was obtained for biochemical analysis while gastric dye retention was determined by spectrophotometry. Data (mean ± SEM) were compared by ANOVA and Student–Newman–Keuls tests. Results: Gastric emptying values from nephrectomy group at 10, 20, 30 and 45 min were lower (P<0.05) than those of sham-operated animals (22.0 ± 4.0 vs. 38.9 ± 6.1%, 34.1 ± 1.4 vs. 66.9 ± 1.3%, 45.5 ± 6.1 vs. 64.9 ± 5.4% and 59.7 ± 2.4 vs. 81.5 ± 4.0%, respectively). Mean arterial pressure, blood volume, serum osmolarity, urea, creatinine and potassium values were higher (P < 0.05) in nephrectomy group than in sham-operated animals (143.3 ± 2.7 vs. 100.5 ± 4.1 mmHg, 15.7 ± 0.9 vs. 8.9 ± 1.1 mL 100 g^?1, 344.0 ± 10.8 vs. 299.4 ± 1.3 mOsm KgH₂O^?1, 344.0 ± 33.7 vs. 47.0 ± 2.8 mg dL^?1, 3.6 ± 0.3 vs. 1.1 ± 0.1 mg dL^?1, 6.4 ± 0.7 vs. 3.7 ± 0.2 mEq L^?1, respectively). The plasmatic Na⁺ values did not change (139.3 ± 2.0 in sham-operation vs. 123.0 ± 7.5 mEq L^?1 in nephrectomy). Conclusion: Acute loss of kidney function markedly delays the gastric emptying rates, which could be involved in gastrointestinal dysmotility complaints seen after renal failure.     

Laboratory Study Atrial Natriuretic Peptide Inhibits Mesangial Cell Proliferation Induced by Early Postnephrectomy Serum

Rat kidney mesangial or tubular cells were grown in tissue culture medium supplemented with sera of 20 sham-operated vs. 20 nephrectomized Charles River rats. Each cell sample was grown with or without addition of atrial natriuretic peptide (ANP) to the medium. ANP completely abolished the growth stimulatory effect of postnephrectomy serum [i.e., effect of renotropic factor(s) present in the serum] on mesangium cells. Tubular cell proliferation was unchanged. We propose that interaction between renotropin and atrial natriutetic peptide activity might be one of the possible mechanisms regulating compensatory renal growth following nephrectomy.