Green tea and coffee consumption and risk of kidney cancer in Japanese adults.

The study aimed to evaluate the association between green tea and coffee consumption and the risk of kidney cancer using data from a large prospective cohort study in Japan (the Japan Public Health Center-based Prospective Study: JPHC Study). A total of 102,463 participants aged 40-69 were followed during 1,916,421 person-years (mean follow-up period, 19 years). A total of 286 cases of kidney cancer (199 in men, 87 in women) were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) while adjusting for potential confounders. No statistically significant association between green tea intake and kidney cancer risk was found in the total population. Among women who consumed more than five cups of green tea per day, a statistically significant decreased risk was shown with a HR of 0.45 (95% CI: 0.23-0.89), compared to women who rarely consumed green tea. For coffee consumption, the association of kidney cancer risk was not statistically significant. This large prospective cohort study indicated green tea intake may be inversely associated with kidney cancer risk in Japanese adults, particularly in Japanese women.

Coffee consumption and risk of renal cancer: a meta-analysis of cohort evidence.

PURPOSE: There is increasing evidence that coffee consumption is related to reduced risks for some cancers, but the evidence for renal cancer is inconclusive. Therefore, we conducted a meta-analysis to summarize the cohort evidence of this relationship. METHODS: A literature search was performed in PubMed and Embase through February 2021. Meta-analyses using a random effects model were conducted for reported relative risk estimates (RRs) relating coffee intake and renal cancer incidence or mortality. We also performed a two-stage random effects exposure-response meta-analysis. Between-study heterogeneity was assessed. RESULTS: In a meta-analysis of the ten identified cohort studies, we found a summary RR of 0.88 [95% confidence interval (CI) 0.78-0.99] relating the highest vs. the lowest category of coffee intake and renal cancer, with no significant between-study heterogeneity observed (I2 = 35%, p = 0.13). This inverse association remained among studies of incident cancers (RR 0.85, 95% CI 0.76-0.96) and studies adjusting for smoking and body mass index (RR 0.87, 95% CI 0.77-0.99). CONCLUSIONS: Our findings from this meta-analysis of the published cohort evidence are suggestive of an inverse association between coffee consumption and renal cancer risk.

Coffee intake and trace element blood concentrations in association with renal cell cancer among smokers.

PURPOSE: To determine whether higher coffee intake may reduce the risk of renal cell cancer (RCC) associated with lead (Pb) and other heavy metals with known renal toxicity. METHODS: We conducted a nested case-control study of male smokers (136 RCC cases and 304 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cases diagnosed with RCC at 5 or more years following cohort enrollment were matched to controls on age (± 7 years) and whole blood draw date (± 30 days). Conditional logistic regression (using two-sided tests) was used to test for main effects and additive models of effect modification. RESULTS: After a mean follow-up of 16.3 years, coffee consumption was not significantly associated with renal cell cancer risk, when adjusting for blood concentrations of Cd, Hg, and Pb and RCC risk factors (age, smoking, BMI, and systolic blood pressure) (p-trend, 0.134). The association with above median blood Pb and RCC (HR = 1.69, 95% CI 1.06, 2.85) appeared to be modified by coffee consumption, such that RCC risk among individuals with both increased coffee intake and higher blood lead concentration were more than threefold higher RCC risk (HR = 3.40, 95% CI 1.62, 7.13; p-trend, 0.003). CONCLUSION: Contrary to our initial hypothesis, this study suggests that heavy coffee consumption may increase the previously identified association between higher circulating lead (Pb) concentrations and increased RCC risk. Improved assessment of exposure, including potential trace element contaminants in coffee, is needed.

Sugary drink consumption and risk of kidney and bladder cancer in Japanese adults.

Globally, sugary drinks are widely consumed, however, few epidemiologic studies have investigated the association between sugary drink consumption and risk of kidney and bladder cancer. We examined the association of sugary drinks with risk of kidney and bladder cancer in 73,024 participants from the Japan Public Health Center-based Prospective Study who reported no history of cancer. Sugary drink consumption was assessed using a validated food frequency questionnaire at study baseline (1995-1999). Individuals were followed to December 31, 2013. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs). During 1,069,815 person years of follow-up, 169 kidney cancer and 297 bladder cancer cases were documented. After adjusting for potential confounders, no greater risk of kidney and bladder cancer was observed. However, sugary drink consumption was positively associated with the risk of kidney cancer (HR for 100 ml/day increase in consumption was 1.11 [95% CI 1.01-1.22]) and bladder cancer (HR for 100 ml/d increase in consumption was 1.11 [95% CI 1.01-1.22]) among women after exclusion of cases diagnosed in the first three years of follow-up. In this large prospective cohort, consumption of sugary drinks was significantly associated with a small increase in hazard ratio for kidney and bladder cancer among women after exclusion of cases diagnosed within the first three years.

Recent advances in upper tract urothelial carcinomas: From bench to clinics.

Urothelial carcinoma in the upper tract is rare and often discussed separately. Many established risk factors were identified for the disease, including genetic and external risk factors. Radiographic survey, endoscopic examination and urine cytology remained the most important diagnostic modalities. In localized upper tract urothelial carcinomas, radical nephroureterectomy with bladder cuff excision are the gold standard for large, high-grade and suspected invasive tumors of the renal pelvis and proximal ureter, whereas kidney-sparing surgeries should be considered in patients with low-risk disease. Advances in technology have given endoscopic surgery an important role, not only in diagnosis, but also in treatment. Although platinum-based combination chemotherapy is efficacious in advanced or metastatic disease, current established chemotherapy regimens are toxic and lack a sustained response. Immune checkpoint inhibitors have led to a new era of treatment for advanced or metastatic urothelial carcinomas. The remarkable results achieved thus far show that immunotherapy will likely be the future treatment paradigm. The combination of immune checkpoint inhibitors and other agents is another inspiring avenue to explore that could benefit even more patients. With respect to the high incidence rate and different clinical appearance of upper tract urothelial carcinomas in Taiwan, a possible correlation exists between exposure to certain external risk factors, such as arsenic in drinking water and aristolochic acid in Chinese herbal medicine. As more gene sequencing differences between upper tract urothelial carcinomas and various disease causes are detailed, this has warranted the era of individualized screening and treatment for the disease.

Low radon exposure and mortality among Jouac uranium miners: an update of the French cohort (1946-2007).

After the extension of the French cohort of uranium miners with the inclusion of workers employed in the Jouac mines, this article seeks to describe the new Jouac cohort and to estimate mortality risks, as well as to quantify their relation to radon exposure in this extended cohort. The Jouac cohort includes 458 miners hired by the Société des Mines de Jouac between 1957 and 2001. There is no measurement of radon exposure before 1978 and so no data were available. Consequently, only the post-1977 Jouac cohort (n = 314) has been included in the French cohort, creating an extended cohort of 5400 French uranium miners followed up from 1946 to 2007. Mortality analyses computed the standardised mortality ratios (SMRs). Excess relative risks (ERRs) were assessed using Poisson regression models. No evidence of a significant excess risk of overall mortality (n = 66, SMR = 0.93; 95% CI = 0.72-1.19) or any specific mortality was observed in the Jouac cohort. In the extended cohort, overall mortality did not increase, but a significant excess of deaths was observed for all cancers (SMR = 1.11, 95% CI = 1.03-1.19), lung cancer (SMR = 1.32, 95% CI = 1.14-1.51), and kidney cancer (SMR = 1.58, 95% CI = 1.01-2.35). Cumulative exposure to radon was 3.9 working level month (WLM) and 35.1 WLM in the post-1977 Jouac and extended cohorts, respectively. Cumulative radon exposure was significantly associated with an excess risk of death from lung cancer (ERR/100 WLM = 0.73, 95% CI = 0.32-1.33) and from cerebrovascular diseases (ERR/100 WLM = 0.42 95% CI = 0.04-1.04). In conclusion, the Jouac cohort is still a young cohort and its inclusion leads to slight modifications compared to previous analyses of the French cohort. The already known relation between radon exposure and lung cancer death as well as the excess risk of death from cerebrovascular diseases persisted in the extended cohort.

An Integrated View of Aristolochic Acid Nephropathy: Update of the Literature.

The term "aristolochic acid nephropathy" (AAN) is used to include any form of toxic interstitial nephropathy that is caused either by ingestion of plants containing aristolochic acids (AA) as part of traditional phytotherapies (formerly known as "Chinese herbs nephropathy"), or by the environmental contaminants in food (Balkan endemic nephropathy). It is frequently associated with urothelial malignancies. Although products containing AA have been banned in most of countries, AAN cases remain regularly reported all over the world. Moreover, AAN incidence is probably highly underestimated given the presence of AA in traditional herbal remedies worldwide and the weak awareness of the disease. During these two past decades, animal models for AAN have been developed to investigate underlying molecular and cellular mechanisms involved in AAN pathogenesis. Indeed, a more-in-depth understanding of these processes is essential to develop therapeutic strategies aimed to reduce the global and underestimated burden of this disease. In this regard, our purpose was to build a broad overview of what is currently known about AAN. To achieve this goal, we aimed to summarize the latest data available about underlying pathophysiological mechanisms leading to AAN development with a particular emphasis on the imbalance between vasoactive factors as well as a focus on the vascular events often not considered in AAN.

Psychological Disorders and Psychosocial Resources of Patients with Newly Diagnosed Bladder and Kidney Cancer: A Cross-Sectional Study.

PURPOSE: Psychological disorders have been proven to be associated with poor physiological, psychological and immune outcomes in cancer patients. However, despite of many challenges of the changed self-image/body image and the altered sexual/urinary function, relatively little is known about psychological disorders of patients with newly diagnosed bladder and kidney cancer. We aimed to investigate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD) and the associated psychosocial factors among bladder/kidney cancer patients. METHODS: A cross-sectional study was conducted of consecutive inpatients with bladder/kidney cancer in the First Affiliated Hospital of China Medical University in Liaoning Province, northeast China. A total of 489 early-stage cancer patients eligible for this study completed questionnaires on demographic and clinical variables, depression, anxiety, PTSD, perceived social support and positive psychological variables (hope, optimism and resilience) anonymously during October 2013 and August 2014. Hierarchical regression analysis was used to examine the relationships between psychosocial resources and psychological disorders, while controlling for possible covariates. RESULTS: The prevalence of depression, anxiety and PTSD was 77.5%, 69.3% and 25.2%, respectively, while 24.9% of patients had psychological co-morbidity. Psychosocial resources together explained more than one-third of the variance on psychological disorders. Under standardized estimate (ß) sequence, patient's perception of social support from family was significantly associated with depression, anxiety and PTSD (p < 0.01). Optimism and resilience showed integrated and independent effects on psychological disorders, and hope represented the significant association with PTSD only (p < 0.01). CONCLUSIONS: The high prevalence of psychological disorders in newly diagnosed patients with early-stage bladder/kidney cancer should receive more attention in Chinese medical settings. Additionally, in consideration of the different protective effects of psychosocial resources, the present study demonstrated that one complete psychological intervention integrating the associated psychosocial factors are necessary to ameliorate psychological disorders so as to provide patients with a more holistic cancer care.

Vitamin C intake and risk of renal cell carcinoma: a meta-analysis.

Studies have showed that vitamin C intake is linked to renal cell carcinoma risk, however, the results were inconsistent. Hence, the present meta-analysis was to examine the association between vitamin C intake and RCC risk. We searched the published studies that reported the relationship between vitamin C intake and RCC risk using PubMed and Embase up to January 2015. Based on a fixed effects model, RR and the corresponding 95% CI were used to assess the pooled risk. 3 prospective cohort studies and 7 case-control studies were included. The overall RR (95% CI) of RCC for the highest vs. the lowest levels of vitamin C intake was 0.78(0.69,0.87). Little evidence of heterogeneity was found. In the subgroup analyses, we found an inverse association between vitamin C intake and RCC risk in the case-control studies but not in the prospective cohort studies. Additionally, this association between vitamin C intake and RCC risk was not differed by population distribution. Our study provides evidence that vitamin C intake is associated with a reduced RCC risk. However, our conclusion was just based on ten including studies, so more high-quality of case-control studies or cohort studies which report this topic are needed.

One-Carbon Metabolic Factors and Risk of Renal Cell Cancer: A Meta-Analysis.

BACKGROUND: Nutrients related to one-carbon metabolism were previously shown to be significantly associated with the risk of cancer. The aim of this meta-analysis was to evaluate potential relationships between one-carbon metabolic factors and renal cell cancer (RCC) risk. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched through March 2015 for observational studies of quantitative RCC risk estimates in relation to one-carbon metabolic factors. The relative risks (RRs) with 95% confidence intervals (CIs) measured the relationship between one-carbon metabolic factors and RCC risk using a random-effects model. RESULTS: Of the 463 citations and abstracts identified by database search, seven cohorts from five observational studies reported data on 133,995 individuals, and included 2,441 RCC cases. Comparing the highest with the lowest category, the pooled RRs of RCC were 0.72 (95%CI: 0.52-1.00; P = 0.048) for vitamin B12. In addition, an increase in folic acid supplementation of 100 µg/day was associated with a 3% lower risk of RCC (RR, 0.97; 95%CI: 0.93-1.00; P = 0.048). Similarly, an increase of 5 nmol/L of vitamin B2 was associated with a reduced risk of RCC 0.94 (95%CI: 0.89-1.00; P = 0.045). Sensitivity analyses suggested that a higher serum vitamin B6 might contribute to a reduced risk of RCC (RR, 0.83; 95%CI: 0.77-0.89; P < 0.001). CONCLUSIONS: Higher levels of serum vitamin B2, B6, B12, and folic acid supplementation lowered the risk of RCC among the study participants.

Comparative Analysis of Smoking as a Risk Factor among Renal Cell Carcinoma Histological Subtypes.

PURPOSE: Smoking is the best established modifiable risk factor for renal cell carcinoma. However, the risks of individual renal cell carcinoma histological subtypes are unknown. Therefore, we investigated the relationship between smoking and renal cell carcinoma subtype. MATERIALS AND METHODS: Cigarette smoking data were prospectively collected from 816 consecutive patients with nonfamilial renal cell carcinoma (705) or benign pathology (111) undergoing nephrectomy at a single National Comprehensive Cancer Network® cancer center, and were retrospectively tested for an association with histological diagnosis on univariable and propensity adjusted analyses. RESULTS: Smoking was reported by 51% of patients, including 21% active smokers and 30% former smokers. Active smoking was more common with clear cell (23%) or papillary (26%) renal cell carcinoma than benign histology (14%, p <0.05 each), yet strikingly less common with chromophobe renal cell carcinoma (6%, p <0.05 vs clear cell or papillary). Any smoking history (active or former) was also relatively uncommon with chromophobe (26%) vs clear cell (53%, p = 0.003) or papillary (58%, p = 0.001) histology. Smoking extent based on mean pack-years was significantly greater with clear cell (15.3 mean pack-years) or papillary (15.2 mean pack-years) renal cell carcinoma but not chromophobe renal cell carcinoma (9.4 mean pack-years) compared to benign histology (9.4 mean pack-years, p ≤0.05, p <0.05, p = 1.0, respectively). On propensity analyses adjusting for multiple variables, clear cell (OR 2.2, p <0.05) and papillary (OR 2.4, p <0.05) histologies but not chromophobe histology remained independently associated with active smoking. CONCLUSIONS: Traditional understanding of smoking as a renal cell carcinoma risk factor applies to clear cell and papillary renal cell carcinoma but not the chromophobe subtype. These findings underscore distinct carcinogenic mechanisms underlying the various renal cell carcinoma subtypes.

Mortality analyses in the updated French cohort of uranium miners (1946-2007).

PURPOSE: The objectives are to analyze mortality risks in the extended follow-up of the French uranium miners' cohort and to examine their potential relation to occupational exposure to ionizing radiation (IR). METHODS: The total cohort includes 5,086 uranium miners employed in the CEA-COGEMA group and followed up from 1946 to 2007. Vital status, causes of death, and cumulative radon exposures were recorded. The post-55 subcohort includes 3,377 miners first employed after 1955, for whom long-lived radionuclides (LLR) and external gamma-ray exposure were also recorded. External mortality analyses were performed by computing standardized mortality ratios (SMR). Excess relative risks (ERRs) due to IR exposures were estimated from Poisson regression models. RESULTS: The miners included in the total cohort were followed up for 35.4 years and exposed to 36.6 working level months (WLM) on average. There was no evidence of a difference in overall mortality between miners and the general French male population. Miners had a statistically significant excess mortality rate from lung cancer (SMR = 1.34 [95% CI 1.16-1.53]) and from kidney cancer (SMR = 1.60 [1.03-2.39]). Cumulative radon exposure was significantly associated with lung cancer risk (ERR/100 WLM = 0.71 [0.31-1.30]) and cerebrovascular risk (ERR/100 WLM = 0.41 [0.04-1.03]). In the post-55 subcohort, this excess mortality from lung cancer remained associated with exposure to radon, and also with exposure to LLR and external gamma rays. CONCLUSIONS: The analyses in the extended follow-up strengthen the results previously observed among French uranium miners about their excess risk of mortality and its association with their occupational IR exposure.

Regional geographic variations in kidney cancer incidence rates in European countries.

CONTEXT: Marked unexplained national variations in incidence rates of kidney cancer have been observed for decades in Europe. OBJECTIVE: To investigate geographic variations at the regional level and identify European regions with high incidence rates of kidney cancer. EVIDENCE ACQUISITION: Regional- and national-level incidence data were extracted from the Cancer Incidence in Five Continents databases, local cancer registry databases, and local published reports. World population age-standardised rates (ASRs) were calculated for the periods 2003-2007 and 1988-1992. Rates by period and sex were compared using map visualisation. EVIDENCE SYNTHESIS: During 2003-2007, the highest ASR was found in the Plzen region, Czech Republic (31.4/100,000 person-years in men). Other regions of the Czech Republic had ASRs of 18.6-27.5/100,000 in men, with a tendency for higher rates in regions south of Prague. Surrounding regions, including eastern Germany and regions of Slovakia and Austria, had medium-to-high incidence rates (13.0-16.8/100,000 in men). Three other areas in Europe showed higher incidence rates in men compared with the rest of the continent: Lithuania, Estonia, Latvia, and Belarus (15.0-17.6/100,000); Iceland (13.5/100,000), and northern Italy (up to 16.0/100,000). Similar regional differences were observed among women, with rates approximately half of those observed in men in the same region. In general, these regional geographic variations remained stable over the periods 1988-1992 and 2003-2007, although higher incidence rates were detected in the Baltic countries in 2003-2007. CONCLUSIONS: Several European regions show particularly high rates of kidney cancer incidence. Large variations were observed within countries covered by national health-care systems, implying that overdetection is not the major factor. PATIENT SUMMARY: We present regional geographic variations in kidney cancer incidence rates in Europe. We highlight several regions with high incidence rates where further studies should be conducted for cancer control and prevention.

[Nutritional prevention of urological tumours]. / Alimentäre Prävention urologischer Tumoren.

Through the last decade considerations on the role of vitamins and antioxidants in the primary prevention of genitourinary tumors have changed dramatically. In spite of all efforts, the efficacy of a specific compound has not been proven so far. In consequence, recommendations to use vitamins or other supplements for the primary prevention of urological tumors should be avoided. However, there is some evidence that moderate food consumption, reduction of dairy products and an Asian or Mediterranean diet may not only prevent prostate cancer (PCA) but also harbour additional beneficial effects on general health. Although quantification of these findings may be difficult, it becomes evident that these measures will have additional synergistic effects on cardiovascular diseases. Considering the large number of PCA patients dying not cancer-related but from concomitant diseases, primary prevention in particular of PCA should always also consider the general health of the target population. More recent studies suggest a potential effect of nutritional compounds on biochemical tumour recurrence in PCA patients after definite therapy. These observations may serve as a starting point for validation within controlled clinical trials.

Kidney cancer mortality and ionizing radiation among French and German uranium miners.

The investigation of potential adverse health effects of occupational exposures to ionizing radiation, on uranium miners, is an important area of research. Radon is a well-known carcinogen for lung, but the link between radiation exposure and other diseases remains controversial, particularly for kidney cancer. The aims of this study were therefore to perform external kidney cancer mortality analyses and to assess the relationship between occupational radiation exposure and kidney cancer mortality, using competing risks methodology, from two uranium miners cohorts. The French (n = 3,377) and German (n = 58,986) cohorts of uranium miners included 11 and 174 deaths from kidney cancer. For each cohort, the excess of kidney cancer mortality has been assessed by standardized mortality ratio (SMR) corrected for the probability of known causes of death. The associations between cumulative occupational radiation exposures (radon, external gamma radiation and long-lived radionuclides) or kidney equivalent doses and both the cause-specific hazard and the probability of occurrence of kidney cancer death have been estimated with Cox and Fine and Gray models adjusted to date of birth and considering the attained age as the timescale. No significant excess of kidney cancer mortality has been observed neither in the French cohort (SMR = 1.49, 95 % confidence interval [0.73; 2.67]) nor in the German cohort (SMR = 0.91 [0.77; 1.06]). Moreover, no significant association between kidney cancer mortality and any type of occupational radiation exposure or kidney equivalent dose has been observed. Future analyses based on further follow-up updates and/or large pooled cohorts should allow us to confirm or not the absence of association.

No association between tea consumption and risk of renal cell carcinoma: a meta-analysis of epidemiological studies.

OBJECTIVE: To evaluate the association between tea consumption and the risk of renal cell carcinoma. METHODS: We searched PubMed,Web of Science and Scopus between 1970 and November 2012. Two evaluators independently reviewed and selected articles based on predetermined selection criteria. RESULTS: Twelve epidemiological studies (ten case-control studies and two cohort studies) were included in the final analysis. In a meta-analysis of all included studies, when compared with the lowest level of tea consumption, the overall relative risk (RR) of renal cell carcinoma for the highest level of tea consumption was 1.03 (95% confidence interval [CI] 0.89-1.21). In subgroup meta-analyses by study design, there was no significant association between tea consumption and renal cell carcinoma risk in ten case-control studies using adjusted data (RR=1.08, 95% CI 0.84-1.40). Furthermore, there was no significant association in two cohort studies using adjusted data (RR=0.95, 95% CI 0.81-1.12). CONCLUSION: Our findings do not support the conclusion that tea consumption is related to decreased risk of renal cell carcinoma. Further prospective cohort studies are required.

Risk factor for clear cell renal cell carcinoma in Chinese population: a case-control study.

BACKGROUND: Risk factors for clear cell renal cell carcinoma (ccRCC) differ among populations and remain controversial. We carried out a hospital-based case-control study to examine the effects of health status, lifestyle, and some genetic polymorphisms on ccRCC risk in Chinese subjects. METHODS: Between 2007 and 2009, 250 newly diagnosed, histologically confirmed ccRCC cases and 299 sex-, age-matched healthy controls provided complete information including consumption of tea and alcohol, smoking, occupational exposure, body mass index (BMI), hypertension, diabetes, and urolithiasis by face-to-face interview in Shanghai. Genetic polymorphisms of cytochrome P450 mono-oxygenase (CYP1A1: 6235T>C, 4889A>G, and 4887C>A), glutathione S-transferase (GSTP1: 342A>G), and N-acetyltransferase (NAT2: 481C>T, 590G>A, and 857G>A) were identified by PCR-RFLP and DNA sequencing. Adjusted odds ratio (AOR) and 95% confidence interval (CI) were derived through multivariate logistic regression. RESULTS: Green tea intake (≥500 ml/d) was inversely associated with ccRCC risk, with an AOR of 0.34 (95% CI 0.21-0.55). BMI (≥25 kg/m(2)), hypertension, and urolithiasis were independently associated with an increased risk of ccRCC, with AOR (95% CI) of 2.10 (1.32-3.34), 2.49 (1.57-3.93), and 3.33 (1.12-9.89), respectively. No association was observed between smoking, alcohol consumption, or occupational exposure with ccRCC risk. The polymorphisms and their interactions with the environmental exposures were mostly not associated with ccRCC risk. CONCLUSION: BMI (≥25 kg/m(2)), hypertension, and urolithiasis are independently associated with an increased risk, whereas green tea intake (≥500 ml/d) is independently associated with a decreased risk of ccRCC. The polymorphisms of the xenobiotic-metabolizing enzymes are weakly associated with ccRCC risk in Chinese subjects.

New therapeutic strategies for renal cell carcinoma.

Treatment options for renal cell carcinoma have changed dramatically since 2005 when the U.S. Food and Drug Administration approved six new therapies. These agents inhibit pathways relevant in the pathogenesis of renal cell carcinoma, interfering with tumor angiogenesis, cell progression, and metastasis. Understanding the pharmacology of these agents is necessary for clinicians to provide appropriate patient education, assure adherence with the treatment plan, and facilitate early identification and intervention for side effects. These activities will provide positive clinical outcomes.