Valentin Arnoux

External validation of the RENAL nephrometry score in renal tumours treated by partial nephrectomy

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.

High-grade renal injury: non-operative management of urinary extravasation and prediction of long-term outcomes.

Study Type – Therapy (outcomes)

High Grade Blunt Renal Trauma: Predictors of Surgery and Long-Term Outcomes of Conservative Management. A Prospective Single Center Study

PURPOSE The management of major renal trauma has shifted in the last decade in favor of a nonoperative approach. Our level 1 trauma center promotes this approach with the objective of renal function preservation. However, certain situations still require surgery. In this study we analyze predictors of surgery and long-term outcomes after conservative management. MATERIALS AND METHODS From January 2004 to March 2015 we prospectively collected data from all patients admitted to our institution for high grade blunt renal trauma (grades IV and V). Nonoperative management was considered successful when patients did not undergo surgical exploration, regardless of angioembolization or endoscopic treatment. RESULTS Of 306 patients with renal trauma 151 presented with major injuries, including 124 grade IV and 27 grade V. Nonoperative management was successful in 110 (89%) cases of grade IV and 14 (52%) cases of grade V lesions. Deceleration mechanism (p=0.03), associated lesions (p=0.001), percentage of devitalized parenchyma (p=0.012), angioembolization (p <0.001), hemodynamic instability (p <0.001) and low hemoglobin (p=0.001) were more frequent in patients treated surgically. On multivariate analysis grade (OR 7.36, p=0.01) and hemodynamic instability (OR 4.18, p=0.04) were the only independent predictors of surgical treatment. Long-term followup of preserved kidneys revealed a remaining 40% and 0% relative renal function after grade IV and V injuries, respectively. Only devascularized parenchyma greater than 25% predicted the decline of long-term renal function. CONCLUSIONS 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.

Long-term renal function assessment with dimercapto-succinic acid scintigraphy after conservative treatment of major renal trauma.

PURPOSE The management of high grade blunt renal injury has evolved with time to become increasingly conservative with the ultimate objective of renal preservation. We evaluated relative renal function with dimercapto-succinic acid renal scintigraphy 6 months after major renal trauma (grade IV or V). MATERIALS AND METHODS This prospective observational study was done between January 2004 and April 2010. All patients who presented with grade IV or V renal trauma and were treated conservatively were included in analysis. Patient and trauma characteristics, and initial management were recorded. Relative renal function was evaluated by dimercapto-succinic acid renal scintigraphy 6 months after trauma. RESULTS A total of 88 patients were included in the study. Conservative management was possible in 79 patients (90%), including 69 and 10 with grade IV and V trauma, respectively. Dimercapto-succinic acid renal scintigraphy was done at 6 months for 22 patients (28%). Mean relative renal function for grade IV and V injuries was 39% and 11%, respectively (p=0.0041). The percent of devascularized parenchyma (p=0.0033) and the vascular subtype of grade IV injuries (p=0.0194) also correlated with decreased renal function. No complication or de novo arterial hypertension was noted. CONCLUSIONS Conservative treatment achieves the objective of renal function preservation for grade IV lesions. Grade V and specific subtypes of grade IV injury have a poor functional outcome. Further study must be performed to determine which patients will benefit from conservative treatment vs early nephrectomy to avoid a longer hospital stay and useless procedures.

Dysregulated Expression of Protein Kinase CK2 in Renal Cancer

Renal cell carcinomas (RCCs) have notoriously been shown to be refractory to traditional therapies including radiation and cytokine therapies. The use of molecularly targeted therapies against mTOR, VEGF, and other angiogenic factors has significantly improved the standards of care of this disease. Yet, improvements are still required as many of the current therapies are limited by acquired resistance. However, the recent development of molecular targeted therapies involving kinase inhibitors has changed the clinical management of RCCs. Protein kinase CK2 is critical for the activation of multiple pro-survival signaling pathways, and its catalytic activity is invariably elevated in various types of tumors. However, the precise role of CK2 has never been addressed in RCCs. In this study, we have analyzed the activity of CK2 and the expression of its subunits in a small cohort of RCC tumors. This analysis revealed, in the majority of tumor samples, an upregulation of the CK2 catalytic subunits that was not correlated with mRNA abundance in the majority of tumor samples. Moreover, relative levels of the three CK2 subunits varied significantly between tumor samples, and a positive correlation was observed between low CK2β expression and an upregulation of the ZEB2 mesenchymal marker in a subset of tumor samples. Using the CK2 inhibitor CX-4945 to downregulate the CK2 catalytic activity in 786-O cells as a model of VHL-deficient renal cancer cell line, we showed that CK2 represents a potential promising therapeutic target in RCCs.