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Nonoperative management can and should be performed safely in cases of grade IV injuries whenever possible, with valuable long-term renal function. It can also be initiated in grade V cases. However, surgeons should consider nephrectomy with the onset of any suspicious symptoms.

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Background. Tacrolimus trough concentrations (mean/variability), as well as concentration-to-dose ratio (C/D ratio), affect kidney allograft outcomes. We investigated the link between the C/D ratio and death-censored kidney graft survival (DCGS). Methods. We performed a retrospective study on 1029 kidney transplant patients (2004–2016) with the following criteria: tacrolimus-based immunosuppression, >1-year graft survival, no initial use of everolimus, and available anti–human leukocyte antigen antibody data. We analyzed the impact of the time-varying C/D ratio on DCGS. Fast metabolizers were defined by a C/D ratio < 1.05. We also investigated the effect of an early (mo 3 to mo 6 post transplantation) C/D ratio below 1.05. Cox survival analyses were performed, adjusting for potential confounders (tacrolimus trough, variability of tacrolimus trough, de novo donor-specific antibody development, cytochrome P450 3A5 genotype, pregraft sensitization, mo 3 glomerular filtration rate). Results. Time-varying C/D ratio was significantly associated with DCGS (hazard ratio [HR], 2.35; P < 0.001) in a univariate model, on the full analysis set comprising 1029 patients. In the multivariate time-varying model, based on 666 patients with available cytochrome P450 3A5 genotypes, the effect of the C/D ratio remained significant (HR, 2.26; P = 0.015); even when glomerular filtration rate at month 3 < 30 mL/min/1.73 m2 (HR, 2.61; P = 0.011), de novo donor-specific antibody development (HR, 4.09; P < 0.001) and continued steroid prescription (HR=2.08, P = 0.014) were taken into account (other covariates, including tacrolimus trough concentrations, were nonsignificant). In the same multivariate model, the effect of early C/D ratio (median at mo 3 and mo 6) remained significantly associated with DCGS (HR, 2.25; P = 0.041). Conclusions. C/D ratio is an independent and early predictor of DCGS. Identification of fast metabolizers could be a strategy to improve graft survival, for example, by optimizing tacrolimus formulation. Mechanistic studies to understand the C/D ratio effect are required.

What's known on the subject? and What does the study add?• Using a standardized classification for renal tumours is a major step towards an objective comparison of the indications and expected outcomes of partial nephrectomy (PN).• Several scores have been described, including the RENAL nephrectomy score (RNS), to evaluate the anatomical features of a renal tumour and predict the surgical challenges with particular regard to PN. Previous studies show discrepancies with regard to the effectiveness of using the RNS to predict postoperative outcomes. Although we showed that conversion to radical nephrectomy was predicted by the RNS, the occurence of complications was more difficult to predict. Objective• To evaluate the RENAL nephrometry score (RNS) as a predictor of the perioperative outcomes of a partial nephrectomy. Patients and Methods• A retrospective review of 177 consecutive patients who were candidates for an open partial nephrectomy (OPN, n = 159) or a laparoscopic partial nephrectomy (LPN, n = 18) from August 2008 to January 2011 was undertaken.• Tumour complexity was stratified into three categories:low (4-6), moderate (7-9) and high (10-12) complexity.• Complications, and surgical and renal outcomes were recorded and analysed.• Predictors of conversion to radical nephrectomy (RN) and complications were assessed using univariate and multivariate logistic regression. Multiple linear regression was used to evaluate the prediction of postoperative estimated glomerular filtration rate (eGFR) and warm ischaemia time (WIT). Results• The median RNS was 7 (interquartile range 6-9).• Tumour complexity was assessed as low in 72 (40.6%), moderate in 87 (49.2%) and high in 18 patients (10.2%).• There were no significant differences among the three groups with respect to demographic characteristics, operating time, estimated blood loss, transfusion, length of stay, complications and positive surgical margins. Conversion to RN occurred in 29 patients (16.3%).• RNS was significantly associated with an increased risk of conversion to RN (odds ratio [OR] = 3.5, P = 0.01 and OR = 6.7, P = 0.005, respectively, for moderate vs low, and high vs low complexity groups).• On multivariate analysis, RNS was the only independent predictor of WIT (P = 0.03) and conversion to RN (P = 0.008), but failed to predict postoperative eGFR (P = 0.84) and the occurrence of major complications (P = 0.91). Conclusions• In the present series, RNS predicted an increased risk of conversion to RN and prolonged WIT.• RNS was not a predictor of complications and postoperative renal function.

Clear cell renal cell carcinoma (ccRCC) is the third type of urologic cancer. At time of diagnosis, 30% of cases are metastatic with no effect of chemotherapy or radiotherapy. Current targeted therapies lead to a high rate of relapse and resistance after a short-term response. Thus, a major hurdle in the development and use of new treatments for ccRCC is the lack of good pre-clinical models that can accurately predict the efficacy of new drugs and allow the stratification of patients into the correct treatment regime. Here, we describe different 3D cultures models of ccRCC, emphasizing the feasibility and the advantage of ex-vivo treatment of fresh, surgically resected human tumor slice cultures of ccRCC as a robust preclinical model for identifying patient response to specific therapeutics. Moreover, this model based on precision-cut tissue slices enables histopathology measurements as tumor architecture is retained, including the spatial relationship between the tumor and tumor-infiltrating lymphocytes and the stromal components. Our data suggest that acute treatment of tumor tissue slices could represent a benchmark of further exploration as a companion diagnostic tool in ccRCC treatment and a model to develop new therapeutic drugs.

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E 2 4 9What ' s known on the subject? and What does the study add? High-grade renal trauma seems to be eligible for conservative management. Ureteric stent placement raises issues about its usefulness and its timing. Predictive factors of post-trauma function and surgery need to be known.Urinary extravasation is not associated with poor functional outcome. Ureteric stenting is needed only in case of sepsis and ureteric clot retention. The only independent predictor of long-term renal function is the importance of devascularised renal fragments. OBJECTIVE• To predict the outcomes of a nonoperative approach to managing urinary extravasation after blunt renal trauma. PATIENTS AND METHODS• A prospective observational study was conducted between January 2004 and October 2011. First-line non-operative management was proposed for 99 patients presenting with a grade IV blunt renal injury according to the revised American Association for the Surgery of Trauma (AAST) classifi cation. Among them, 72 patients presented with a urinary extravasation.• Management and outcomes were recorded and compared between patients presenting and those who did not present with urinary leakage. Relative postoperative renal function was assessed 6 months after the trauma using dimercapto-succinic acid renal scintigraphy.• Predictors of the need for endoscopic or surgical management and long-term renal function were evaluated on multivariate analysis. RESULTS• Among patients with urinary leakage, endoscopic ureteric stent placement and open surgery were required in 37% and 15%, respectively.• On multivariate analysis, fever of > 38.5 ° C and ureteric clot obstruction were independent predictors of the need for ureteric stent placement. The only predictor of open surgery was the percentage of devitalised parenchyma.• Long-term renal function loss was correlated to the percentage of devitalised parenchyma and associated visceral lesions. Urinary extravasation did not predict surgical intervention or long-term renal function loss. CONCLUSIONS• Urinary extravasation after blunt renal trauma can be successfully managed conservatively and does not predict long-term decreased renal function or surgery requirement.• A devascularised parenchyma volume of > 25% predicts a higher rate of surgery and poorer renal function. KEYWORDSkidney trauma , kidney injury , non-operative trauma , urinary extravasation , renal function Study Type -Therapy (outcomes) Level of Evidence 2b