Rising Serum Uric Acid Level Is Negatively Associated with Survival in Renal Cell Carcinoma

Published on Apr 15, 2019in Cancers6.126
· DOI :10.3390/CANCERS11040536
Kendrick Yim7
Estimated H-index: 7
(UCSD: University of California, San Diego),
Ahmet Bindayi8
Estimated H-index: 8
(UCSD: University of California, San Diego)
+ 8 AuthorsIthaar H. Derweesh43
Estimated H-index: 43
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.
📖 Papers frequently viewed together
12 Citations
7 Citations
2 Citations
#1Hideo Yuki (Dokkyo Medical University)H-Index: 7
#2Takao Kamai (Dokkyo Medical University)H-Index: 15
Last. Ken-Ichiro Yoshida (Dokkyo Medical University)H-Index: 16
view all 11 authors...
// Hideo Yuki 1, * , Takao Kamai 1, * , Satoshi Murakami 1, 2 , Satoru Higashi 3 , Takahiro Narimatsu 1 , Tsunehito Kambara 1 , Hironori Betsunoh 1 , Hideyuki Abe 1 , Kyoko Arai 1 , Hiromichi Shirataki 3 and Ken-Ichiro Yoshida 1 1 Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan 2 Division of Field Application, Life Technologies, Tokyo, Japan 3 Department of Molecular and Cell Biology, Dokkyo Medical University, Mibu, Tochigi, Japan * These authors have contributed equally ...
8 CitationsSource
#1Caifeng Yue (SYSU: Sun Yat-sen University)H-Index: 5
#2Pinning Feng (SYSU: Sun Yat-sen University)H-Index: 5
Last. Min Liu (SYSU: Sun Yat-sen University)H-Index: 10
view all 9 authors...
Abstract Background Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. Methods A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56 months, survival was analysed using the Kaplan-Meier method. To further evaluate the progno...
9 CitationsSource
#1Sean Berquist (UC San Diego Health System)H-Index: 11
#2Hak J. Lee (UC San Diego Health System)H-Index: 18
Last. Ithaar H. Derweesh (UC San Diego Health System)H-Index: 43
view all 11 authors...
BACKGROUND: We evaluated the role of statins in patients who underwent surgery for renal cell carcinoma (RCC) and who had dyslipidemia, as use of statins has been suggested to improve outcomes in RCC. METHODS: Two-center retrospective study of patients with dyslipidemia who underwent surgery for RCC from 7/1995 to 6/2005. Patients were managed by statins or ezetimibe, fibrate agents, or cholestyramine. Analysis was conducted between patients who received statin therapy versus those that did not....
2 CitationsSource
#1Hiromi I. Wettersten (UCSD: University of California, San Diego)H-Index: 15
#2Omran Abu Aboud (UC Davis: University of California, Davis)H-Index: 10
Last. Robert H. Weiss (UC Davis: University of California, Davis)H-Index: 49
view all 4 authors...
Clear cell renal cell carcinoma is associated with reprogramming of metabolic pathways including glucose and fatty acid metabolism and the tricarboxylic acid cycle. Here, the authors discuss these reprogrammed pathways and the opportunities they provide for new therapies, imaging modalities and biomarkers.
108 CitationsSource
#1Ching-Wei Tsai (PRC: China Medical University (PRC))H-Index: 13
#2Shih-Yi Lin (PRC: China Medical University (PRC))H-Index: 15
Last. Chiu-Ching Huang (PRC: China Medical University (PRC))H-Index: 36
view all 4 authors...
Background Increasing evidence supports the association between hyperuricemia and incident chronic kidney disease (CKD); however, there are conflicting data regarding the role of hyperuricemia in the progression of CKD. This study retrospectively assessed the longitudinal association between uric acid (UA) level and CKD progression in a Chinese population lived in Taiwan. Methods Patients with physician diagnosis of hyperuricemia or receiving urate-lowering therapy between 2003 and 2005 were ide...
77 CitationsSource
#1Rana R. McKay (Harvard University)H-Index: 29
#2Xun Lin (Pfizer)H-Index: 22
Last. Daniel Y.C. HengH-Index: 29
view all 12 authors...
Abstract Background A growing body of evidence has demonstrated the anti-neoplastic activity of statins. The objective of this study was to investigate the effect of statin use on survival in patients with metastatic renal cell carcinoma (mRCC) treated in the modern therapy era. Patients and methods We conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Statistical analyses were performed using Cox regression and the Kaplan–Meier method. Results We identifie...
26 CitationsSource
#1Prakash Deedwania (UCSF: University of California, San Francisco)H-Index: 85
#2Peter H. Stone (Brigham and Women's Hospital)H-Index: 118
Last. Daniel J. WilsonH-Index: 72
view all 5 authors...
Background Improvement in renal function and decreases in serum uric acid (SUA) have been reported following prolonged high-intensity statin (HMG-CoA reductase inhibitor) therapy. This post hoc analysis of the SAGE trial examined the effect of intensive versus less intensive statin therapy on renal function, safety, and laboratory parameters, including SUA, in elderly coronary artery disease (CAD) patients (65–85 years) with or without chronic kidney disease (CKD).
11 CitationsSource
#1Shushan Yan (Nanjing Medical University)H-Index: 6
#2Peng-jun ZhangH-Index: 2
Last. Beicheng Sun (Nanjing Medical University)H-Index: 38
view all 10 authors...
SUA is a potent antioxidant and thus may play a protective role against cancer. Many epidemiological studies have investigated this hypothesis but provided inconsistent and inconclusive findings. We aimed to precisely elucidate the association between SUA levels and cancer by pooling all available publications. Totally, 5 independent studies with 456,053 subjects and 12 with 632,472 subjects were identified after a comprehensive literature screening from PubMed, Embase, and Web of Science. The p...
22 CitationsSource
#1Samuel D. Kaffenberger (VUMC: Vanderbilt University Medical Center)H-Index: 14
#2Opal Lin-Tsai (Vandy: Vanderbilt University)H-Index: 5
Last. Peter E. Clark (VUMC: Vanderbilt University Medical Center)H-Index: 62
view all 10 authors...
Abstract Purpose To determine whether statin use at time of surgery is associated with survival following nephrectomy or partial nephrectomy for renal cell carcinoma (RCC). Statins are thought to exhibit a protective effect on cancer incidence and possibly cancer survival in a number of malignancies. To date, no studies have shown an independent association between statin use and mortality in RCC. Methods A retrospective cohort study of 916 patients who underwent radical or partial nephrectomy f...
27 CitationsSource
#1Qiang Geng (PKU: Peking University)H-Index: 10
#2Jingyi Ren (PKU: Peking University)H-Index: 10
Last. Hong Chen (PKU: Peking University)H-Index: 14
view all 5 authors...
Statins can significantly improve the lipid profile and reduce cardiovascular events. However, beneficial effects of statins on renal function are still controversial. PubMed, the Cochrane Central Register of Controlled Trials, Web of Knowledge, and ClinicalTrials.gov Web sites were searched for randomized controlled trials. The selected studies reported renal function during treatment with statins and control. Forty-one studies with a total of 88,523 participants were included in this analysis....
42 CitationsSource
Cited By3
#1Shuyi MiH-Index: 1
#2Liang GongH-Index: 1
Last. Ziqi SuiH-Index: 1
view all 3 authors...
In recent years, metabolic syndrome (Mets) has been a hot topic among medical scientists. Mets has an intimate relationship with the incidence and development of various cancers. As a contributory factor of Mets, hyperuricemia actually plays an inseparable role in the formation of various metabolic disorders. Although uric acid is classically considered an antioxidant with beneficial effects, mounting evidence indicates that a high serum uric acid (SUA) level may serve as a pro-oxidant to genera...
3 CitationsSource
OBJECTIVE Epidemiological evidence investigating serum uric acid and kidney cancer risk remains unclear. We conducted this study to examine the relationship between serum uric acid and the incidence and mortality of kidney cancer. METHODS This is a prospective analysis of 444 462 participants without any cancer from the UK Biobank. Serum uric acid was measured at baseline and the incidence and mortality of kidney cancer was determined through contact with the cancer and death registry. Cox regre...
#1Claudia ManiniH-Index: 5
#2José I. López (UPV/EHU: University of the Basque Country)H-Index: 33
Renal cell carcinoma (RCC) ranks in the top‐ten list of malignancies both in males and females [...]
8 CitationsSource