Abstract
Aim and Background: To investigate the association of serum uric acid (SUA) levels along with statin use in Renal Cell Carcinoma (RCC), as statins may be associated with improved outcomes in RCC and SUA elevation is associated with increased risk of chronic kidney disease (CKD). Methods: Retrospective study of patients undergoing surgery for RCC with preoperative/postoperative SUA levels between 8/2005–8/2018. Analysis was carried out between patients with increased postoperative SUA vs. patients with decreased/stable postoperative SUA. Kaplan-Meier analysis (KMA) calculated overall survival (OS) and recurrence free survival (RFS). Multivariable analysis (MVA) was performed to identify factors associated with increased SUA levels and all-cause mortality. The prognostic significance of variables for OS and RFS was analyzed by cox regression analysis. Results: Decreased/stable SUA levels were noted in 675 (74.6%) and increased SUA levels were noted in 230 (25.4%). A higher proportion of patients with decreased/stable SUA levels took statins (27.9% vs. 18.3%, p = 0.0039). KMA demonstrated improved 5- and 10-year OS (89% vs. 47% and 65% vs. 9%, p < 0.001) and RFS (94% vs. 45% and 93% vs. 34%, p < 0.001), favoring patients with decreased/stable SUA levels. MVA revealed that statin use (Odds ratio (OR) 0.106, p < 0.001), dyslipidemia (OR 2.661, p = 0.004), stage III and IV disease compared to stage I (OR 1.887, p = 0.015 and 10.779, p < 0.001, respectively), and postoperative de novo CKD stage III (OR 5.952, p < 0.001) were predictors for increased postoperative SUA levels. MVA for all-cause mortality showed that increasing BMI (OR 1.085, p = 0.002), increasing ASA score (OR 1.578, p = 0.014), increased SUA levels (OR 4.698, p < 0.001), stage IV disease compared to stage I (OR 7.702, p < 0.001), radical nephrectomy (RN) compared to partial nephrectomy (PN) (OR 1.620, p = 0.019), and de novo CKD stage III (OR 7.068, p < 0.001) were significant factors. Cox proportional hazard analysis for OS revealed that increasing age (HR 1.017, p = 0.004), increasing BMI (Hazard Ratio (HR) 1.099, p < 0.001), increasing SUA (HR 4.708, p < 0.001), stage III and IV compared to stage I (HR 1.537, p = 0.013 and 3.299, p < 0.001), RN vs. PN (HR 1.497, p = 0.029), and de novo CKD stage III (HR 1.684, p < 0.001) were significant factors. Cox proportional hazard analysis for RFS demonstrated that increasing ASA score (HR 1.239, p < 0.001, increasing SUA (HR 9.782, p < 0.001), and stage II, III, and IV disease compared to stage I (HR 2.497, p < 0.001 and 3.195, p < 0.001 and 6.911, p < 0.001) were significant factors. Conclusions: Increasing SUA was associated with poorer outcomes. Decreased SUA levels were associated with statin intake and lower stage disease as well as lack of progression to CKD and anemia. Further investigation is requisite.
Highlights
There is increasing evidence that renal cell carcinoma (RCC) is a metabolically driven disease.Many of the known genes associated with the development of RCC are involved in regulating cellular metabolism within nutrient-deprived tumor microenvironments [1,2,3]
Levels, stage IV disease compared to stage I, radical nephrectomy (RN) compared to partial nephrectomy (PN), and de novo chronic kidney disease (CKD)
Our suggest that changes in serum uric acid (SUA) levels can predict postoperative renal function, CKD sequelae, and survival findings suggest that changes in SUA levels can predict postoperative renal function, CKD sequelae, in the context of RCC treated with nephrectomy
Summary
There is increasing evidence that renal cell carcinoma (RCC) is a metabolically driven disease.Many of the known genes associated with the development of RCC are involved in regulating cellular metabolism within nutrient-deprived tumor microenvironments [1,2,3]. Recent studies have identified components of the metabolic syndrome (hypertension, hyperglycemia, hyper-triglyceridemia, and obesity) as independent risk factors for developing RCC [4,5,6]. These same metabolic derangements are risk factors for developing chronic kidney disease (CKD) [7,8], with higher morbidity and mortality in CKD patients undergoing extirpative surgery for RCC [9]. Hyperuricemia, defined as serum uric acid (SUA) elevation, is correlated with development of atherosclerosis, metabolic syndrome, and of CKD after surgery for renal tumors [10,11]
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