Abstract 4202: Kidney function and risk of renal cell carcinoma
Karine AlcalaNicolas AlcalaRichard M. MartinPaul BrennanDavid C. MullerHilary A. RobbinsMattias Johansson
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Abstract Background: The relationship between kidney function and risk of renal cell carcinoma (RCC) is not well understood. In this study, we evaluated the association between estimated glomerular filtration rate (eGFR) and risk of incident RCC, and assessed whether this association depends on time between eGFR measurement and RCC diagnosis. We also sought to evaluate if eGFR may be useful to predict RCC risk. Methods: We conducted this study in the UK Biobank cohort based on 440,983 participants of whom 984 were diagnosed with RCC during 4,552,747 person-years of follow-up. The temporal relation between kidney function and RCC was evaluated with flexible parametric survival models for eGFR calculated from creatinine, cystatin C and both, adjusted for C-reactive protein (CRP) and common RCC risk factors. We also assessed the benefit of combining CRP and eGFR with a published RCC risk prediction model by estimating calibration and discrimination using a resampling algorithm as internal validation. Results: We found that a lower eGFR - an indication of poor kidney function - was associated with higher RCC risk when measured up to five years prior to diagnosis. We estimated the RCC hazard ratio per standard deviation decrease in eGFR when measured one year before diagnosis at 1.22 (95% confidence interval [95% CI]: 1.11-1.34), and at 1.14 (95% CI: 1.05-1.19) when measured five years before diagnosis. The corresponding RCC HR for eGFR measured ten years before diagnosis was 1.03 (95% CI: 0.95-1.12). Adding eGFR to the RCC risk model provided a small improvement in risk discrimination 2 years before diagnosis with a C-index of 0.76 (95% CI: 0.71-0.81) compared to the published model (0.73, 95% CI: 0.68-0.79). Conclusion: This study demonstrated that markers of kidney function are robustly associated with RCC risk when measured within the last five years leading up to diagnosis. However, kidney function markers do not seem to provide important improvements in RCC risk discrimination beyond established risk factors. Citation Format: Karine Alcala, Nicolas Alcala, Richard Martin, Paul Brennan, David Muller, Hilary A. Robbins, Mattias Johansson. Kidney function and risk of renal cell carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4202.Keywords:
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Study Type – Diagnosis (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? For over 30 years it has been recognized that there is an association between end‐stage renal disease (ESRD) and the development of malignancy, particularly renal cortical tumour. Observational studies have consistently shown that patients with severely decreased glomerular filtration rate (GFR) develop cancer more frequently than their age‐ and exposure‐matched controls. This study is the first of its kind to look directly at the relationship between GFR and tumour size, in an effort to begin to examine the relationship between kidney function and oncogenesis. OBJECTIVE • To examine the relationship between tumour diameter and estimated GFR (eGFR) in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS • In total, 1009 patients undergoing partial or radical nephrectomy for unilateral RCC were identified in the Columbia Urologic Database. • eGFR was calculated using the modification of diet in renal disease equation using demographic data and preoperative serum creatinine values. • Data on patient demographics, tumour characteristics, and comorbidities were analyzed using univariate and multivariate regression analysis. RESULTS • Mean ( sd , range) tumour diameter was 5.29 (3.8, 0.3–29) cm. Mean ( sd , range) eGFR was 75 (23.4, 3–173) mL/min per 1.73 m 2 . • In multivariate regression analysis, tumour diameter independently predicted decreased preoperative eGFR (coefficient, −0.513; P = 0.008) when controlling for hypertension and race. • Consistent with this, decreased preoperative eGFR independently predicted increased tumour diameter (coefficient, −0.013; P = 0.007) when controlling for race, histology and smoking status. CONCLUSION • Tumour diameter and decreased preoperative eGFR are independently correlated in patients with RCC.
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Aim: To better evaluate the association between preoperative anemia and outcomes in patients following radical or partial nephrectomy for renal cell carcinoma (RCC). Materials and Methods: A meta-analysis of hazard ratios (HR) was conducted to measure the association between preoperative anemia and all-cause mortality (ACM), cancer-specific mortality (CSM), and disease recurrence (DR) in patients who underwent surgery for RCC. Results: A total of 14 studies (8,673 patients) met the eligibility criteria. All studies reported survival outcomes using the multivariable Cox proportional hazards model. Pooled results showed that preoperative anemia was associated with increased ACM [HR=2.13, 95% Confidence Interval (CI)=1.48-3.06], CSM (HR=1.91, 95% CI=1.26-2.90), and DR (HR=1.67, 95% CI=1.16-2.40). Conclusion: This meta-analysis indicates that preoperative anemia appears to be associated with earlier recurrence and shorter survival of patients undergoing radical or partial nephrectomy for RCC. Our findings, however, still need to be validated by well-designed prospective studies with larger sample sizes and well-controlled confounding factors.
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Objective. To investigate whether radical nephrectomy (RN) and nephron-sparing surgery (NSS) for T1 renal cell carcinoma influence renal function, oncological outcome or survival rate. Material and methods. A retrospective study was performed, including 290 nephrectomies for tumours of a diameter of less than 7 cm; 174 radical nephrectomies were compared to 116 nephron-sparing surgeries. Preoperative and pathological data were compared between the two groups. The glomerular filtration rate was estimated using the abbreviated Modification of Diet and Renal Disease (MDRD4) study equation. The evolution of renal function was analysed from 6 months to 4 years after surgery, and the oncological outcomes were evaluated by means of cancer and non-cancer survival curves. Results. The results showed a major impairment in renal function in the RN group compared to those who underwent NSS (25 vs 7 ml/min/1.73 m2, 6 months after surgery), a difference that was maintained over time. Moreover, patients undergoing RN had a greater chance of developing renal failure. Overall, the survival curves showed a higher mortality rate for the RN group (p = 0.034), although the cancer-specific mortality rate did not show any statistically significant differences (p = 0.079). Conclusions. For stage T1 renal cortical tumours, NSS should, whenever possible, be regarded as the primary therapeutic option, given that it obtains similar oncological outcomes to RN and preserves renal function, which seems to translate into a lower overall mortality rate.
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Introduction: The relationship between estimated-glomerular filtration rate (eGFR) and acute ischemic stroke outcomes remains controversial. Hypothesis: We aimed to evaluate the impact of eGFR on all-cause mortality, recurrent stroke, and vascular events in patients with acute ischemic stroke. Methods: 4036 patients with acute ischemic stroke recruited from 26 hospitals across China from August 2009 to May 2013 were included in our study. GFR was estimated by CKD-EPI equations based on serum creatinine and/or cystatin C (CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys). The Cox proportional hazards models were used to examine the relationship between declined eGFR and 1-year all-cause mortality, recurrent stroke, and vascular events. Declined eGFR was defined as <60 mL/min /1.73 m2. Results: Declined eGFR was present in 7.22% (n=281) of patients based on the CKD-EPIcr equation, 3.43% (n=119) based on the CKD-EPIcys equation, and 5.67% (n=170) based on the CKD-EPIcr-cys equation. Compared to patients with an eGFR ≥90 mL/min /1.73 m2, adjusted hazard ratios (95% confidence interval) for all-cause mortality associated with eGFR<60 mL/min /1.73 m2 were 1.68 (1.06 to 2.66, p=0.026), 2.29 (1.29 to 4.06, p=0.005), and 1.79 (1.08 to 2.98, p=0.024) using CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys equations, respectively. For recurrent stroke, adjusted hazard ratios (95% confidence interval) were 0.90 (0.49 to 1.66, p=0.743), 0.60 (0.19 to 1.93, p=0.393), and 0.89 (0.40 to 1.95, p=0.762), respectively. For vascular events, adjusted hazard ratios (95% confidence interval) were 1.33 (0.81 to 2.19, p=0.266), 1.07 (0.46 to 2.47, p=0.880), and 1.31 (0.70 to 2.43, p=0.403), respectively. Conclusion: Our study indicates that declined eGFR is a strong independent risk factor for total mortality among patients with acute ischemic stroke. However, there is no association between low eGFR and recurrent stroke or vascular events among patients with acute ischemic stroke. In addition, the association of eGFR with all-cause mortality among patients with acute ischemic stroke is stronger when eGFR was calculated based on the CKD-EPIcys equation compared to CKD-EPIcr and CKD-EPIcr-cys equations.
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Renal cell carcinoma (RCC) accounts for 90-95% of all neoplastic lesions of the kidney. In Russia in 2008 defined 17 563 new cases of RCC. In this common tumor found in 45.6 % of cases. A metastatic forms are still a significant part of RCC – 28-32%. In the last decade the proportion of localized tumors increased to 55.4% and the 5-year cancer survival for local forms of RCC is 86-98%. However, it is not accompanied by a significant increase in overall survival. This situation is definitely needed in the analysis. First of all, to assess the impact of surgical treatment on survival . Radical nephrectomy remains the gold standard for surgical treatment of RCC, including the treatment of small tumors and produced more than 80% of cases. Assessing the impact of surgery on renal function is necessary also due to the fact that in 26% of patients with localized tumors , the opposite kidney healthy and normal preoperative serum creatinine glomerular filtration rate (GFR ) less than 60 ml/min . Even at baseline GFR from 60 to 90 ml/min, patients subjected to radical nephrectomy have 58% risk reduction of its <60 ml/min. In this group of patients in the 2-fold increased risk of cardiovascular complications and 4.5 times the risk of death. Within three years after radical nephrectomy in 21.6% of patients have progression of cardiovascular disease and 6.0% of patients die from complications associated with them.
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There is an increase in the number of patients with renal cell carcinoma (RCC) every year. At the same time radical nephrectomy (RN) remains the standard treatment of renal malignancies and the most common surgical procedure for this pathology. A considerable number of patients with kidney cancer have diminished renal function that worsens after removal of functioning kidney tissue together with a tumor. This promotes retained low overall survival rates in patients with RCC, by improving cancer-specific survival. Renal function was studied in 48 patients with RCC prior to and 1 year after RN. In all the patients, glomerular filtration rate (GFR) was estimated using the Cockroft-Gault equation with and without protein load. Renal parenchyma volume was calculated by spiral computed tomography. Patients aged over 60 years had decreased baseline renal function as compared to those aged under 60 years (GFR 77.4 versus 103.6 ml/min/1.73 m2). The postoperative reduction in female renal function was more pronounced (GFR, 84.92 versus 92.54 ml/min/1.73 m2). Patients with metastatic RCC had lower baseline renal function and its significant postoperative loss than those with the non-metastatic forms of a tumor. A load test showed a substantially decreased renal reserve in patients with RCC.
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Epithelial ovarian cancer is the most lethal gynecologic cancer worldwide and chemoresistance is one of the major causes of treatment failure. We investigated whether ERCC1, TAU, TOPO2A, TOPO1, P53, and C-MYC expression could be used as predictors for treatment outcomes. Immunohistochemical staining was used to examine the expression of these biomarkers in resected tumor specimens from 38 patients treated in our institute. Clinicopathological data including demographics, staging, histological type, treatment response, expression of the biomarkers, and patient outcomes were analyzed. The median follow-up period was 47.5 months (range, 10–135 months) and the median overall survival was 56.0 months. Patients who did not have expression of ERCC1, and those who had expression of TOPO1 had significantly better overall survival. Cox regression analysis also confirmed that these two biomarkers were significant independent factors predicting survival (ERCC1, hazard ratio 5.51, 95% confidence interval: 2.02–14.00, p = 0.001; TOPO1, hazard ratio 0.22, 95% confidence interval: 0.06–0.77, p = 0.017). We concluded that poor overall survival was significantly associated with positive ERCC1 and negative TOPO1 expression. The results might be the consequence of chemoresistance to platinum and camptothecins, both of which are commonly used regimens in the treatment of epithelial ovarian cancer.
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Height loss that occurs with aging is a common phenomenon associated with musculoskeletal abnormalities, such as osteoporosis and sarcopenia. Notably, such height loss is also associated with poor outcomes, including cardiovascular disease and mortality. In this study, we investigated the relationship between height loss and kidney outcome.This longitudinal study includes data from the Japan Specific Health Checkups Study from 2008 to 2014. Height loss was estimated using the first three visits (visits 1-3), and kidney outcomes were evaluated using data from the following visits (visit 3 to the last visit). The annual height change for each participant was estimated using mixed-effects model, and participants were divided into five groups according to the quintile of the rate. The association between height change and the incidence of 1.5-fold increase in serum creatinine level from baseline was analyzed using Cox regression analysis. The decline rates of estimated glomerular filtration rate among the groups were compared using a mixed-effects model.In total, 187 682 participants were included in the analyses. The median rate of height change was -0.11 cm/year. The adjusted hazard ratio (95% confidence interval) for 1.5-fold increase in serum creatinine level in participants with the steepest category of height decline (Q1; Quintile 1) was 1.45 (1.26-1.67) compared with the reference (Q4; Quintile 4). The decline of the estimated glomerular filtration rate in Q1 (-1.25 mL/min/1.73 m2 /year) was significantly higher than that of the reference: Q4 (-0.92 mL/min/1.73 m2 /year) (P for interaction <0.001).Height loss is associated with a rapid decline in kidney function. Geriatr Gerontol Int 2023; 23: 282-288.
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Many studies have evaluated the usefulness of creatinine- (eGFRcr) and cystatin C-based estimated glomerular filtration rate (eGFRcys) at specific time points in predicting renal outcome. This study compared the performance of both eGFR changing slopes in identifying patients at high risk of end-stage renal disease (ESRD). From 2012 to 2017, patients with more than three simultaneous measurements of serum creatinine and cystatin C for 1 year were identified. Rapid progression was defined as eGFR slope < − 5 mL/min/1.73 m2/year. The primary outcome was progression to ESRD. Overall, 1323 patients were included. The baseline eGFRcr and eGFRcys were 39 (27–48) and 38 (27–50) mL/min/1.73 m2, respectively. Over 2.9 years (range, 2.0–3.8 years) of follow-up, 134 subjects (10%) progressed to ESRD. Both the eGFRcr and eGFRcys slopes were associated with a higher risk of ESRD, independently of baseline eGFR (hazard ratio [HR] = 0.986 [0.982–0.991] and HR = 0.988 [0.983–0.993], respectively; all p < 0.001). The creatinine- and cystatin C-based rapid progressions were associated with increased risk of ESRD (HR = 2.22 [1.57–3.13], HR = 2.03 [1.44–2.86], respectively; all p < 0.001). In the subgroup analyses, the rapid progression group, defined on the basis of creatinine levels (n = 503), showed no association between the eGFRcys slope and ESRD risk (p = 0.31), whereas the eGFRcr slope contributed to further discriminating higher ESRD risk in the subjects with rapid progression based on eGFRcys slopes (n = 463; p = 0.003). Both eGFR slopes were associated with future ESRD risk. The eGFRcr slope was comparable with the eGFRcys slope in predicting kidney outcome.
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