Regular Article
Chronic kidney disease in patients with cancer and its association with occurrence of venous thromboembolism and mortality

https://doi.org/10.1016/j.thromres.2014.04.002Get rights and content

Abstract

Introduction

The risk for occurrence of venous thromboembolism (VTE) in cancer patients has been the aim of numerous investigations. Chronic kidney disease (CKD) is a frequent comorbidity in cancer patients and has been found to be a risk factor for VTE in the general population. We investigated the association of CKD with VTE and mortality in cancer patients.

Methods

Patients were recruited into the prospective cohort study, Vienna Cancer and Thrombosis Study (CATS). CKD was estimated with equations for glomerular filtration rate (eGFR) based on serum creatinine by Modification of Diet in Renal Disease (MDRD), CKD Epidemiology collaboration (CKD-EPI) and Cockcroft-Gault equation (C-G). Patients were subsequently classified to stages of CKD according to the Kidney Diseases Outcomes Quality Initiative. Primary endpoint was occurrence of VTE and secondary endpoint was death.

Results

The cohort of 1100 patients was prospectively followed over a median of 723 days. CKD with an eGFR of under 90 ml/min was common with a prevalence of 71.1%, 67.0% or 51.5% of patients calculated with MDRD, CKD-EPI and C-G equations, respectively, but severe CKD (eGFR < 30 ml/min) was rare. Patients with a moderately decreased eGFR (90-60 ml/min/1.73 m2) based on CKD-EPI had a subdistribution hazard ratio of 0.68 (95% confidence interval 0.43-1.06). An association between CKD and occurrence of VTE or mortality could also not be shown with the other equations.

Conclusions

In our investigation of a large cohort of cancer patients with a high prevalence of CKD, a reduced eGFR was not an independent risk factor for occurrence of VTE or death.

Introduction

Patients with cancer have an increased risk of venous thromboembolism (VTE) compared to the general population, an association which is well recognized [1], [2]. Renal insufficiency is a common comorbid disease in cancer patients [3], [4], which can result in chronic kidney disease (CKD) [5]. The prevalence of CKD in cohort studies of cancer patients with a diversity of solid tumors was between 12 and 57% depending on severity of CKD [3], [4].

Serum creatinine (Scr), is the most universally used marker of renal function, although it is poorly reliable especially in elderly, sarcopenic patients [6]. An improved measure of kidney function is the estimated glomerular filtration rate (eGFR) based on Scr. A widely used equation for calculating eGFR is the Crockcoft-Gault equation (C-G) [7], but also the Kidney Diseases Outcomes Quality Initiative (K/DOQI) [8] recommended Modification of Diet in Renal Disease (MDRD) equation [9] and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) [10] have shown to offer valuable clinical estimates of GFR. Using these estimates of GFR, patients with CKD can be classified into different stages of CKD according to K/DOQI [8].

Patients with CKD have an increased risk of cardiovascular events, hospitalization, and mortality [11]. In recent studies also an association between CKD and risk of VTE was reported in the general population [12], [13]. In the cancer patient population, data on the association of CKD and VTE is scarce, because these patients are not comprehensively represented in most prospective observational studies and interventional trials [14], [15], [16]. The association of kidney disease and VTE was investigated in one retrospective cohort study based on ICD 10 coding [1]. Kidney disease was found to increase the risk for VTE 1.5-fold compared to patients without kidney disease [1].

As patients with cancer require a precise risk assessment, the association of CKD with VTE has to be elucidated. In addition, cancer patients with CKD may also have poor overall survival compared to patients with good kidney function [17]. Thus, we aimed at investigating the association of CKD reflected by eGFR, with risk of VTE and mortality in a prospective observational cohort study of cancer patients.

Section snippets

Study Design and Patient Population

Patients were recruited to the Vienna Cancer and Thrombosis Study (CATS), a single-center, ongoing, prospective cohort study with the aim to investigate parameters for prediction of VTE risk in cancer patients. A thorough description of the study design has been previously published elsewhere [18], [19] and a brief outline is given here. The study was conducted at the Vienna General Hospital of the Medical University of Vienna, Austria in accordance with the declaration of Helsinki and the

Patient Population

The total study population consisted of 1100 cancer patients who were prospectively followed over a median observation time of 723 days ([25th-75th percentile]: 319–731). The median age was 62 years (53–68) and 451 of patients were female (41.0%). Median BMI was 25.2 kg/m2 (95%CI, 22.4–28.3). Over the course of the observation time 94 VTE events occurred (8.5%) and 478 patients died (43.5%). Cancer entities included in the study are listed in declining frequency: Lymphoma (16.7%), lung cancer

Discussion

Patients with active cancer are at increased risk for occurrence of VTE. The risk of VTE is further modulated by presence of comorbidities [25], [26]. CKD is a disease with increasing prevalence in the general population [11], [27] as well as a frequent comorbidity in cancer patients [1], [3]. In our current investigation, we found a prevalence of 71.1%, 67.0% and 51.5% of patients with eGFR < 90 ml/min/1.73 m2, based on MDRD, CKD-EPI and C-G equation. However, we did not find an increased risk for

Conclusion

CKD is a comorbid disease with high prevalence in patients with cancer. In our investigation of predictive parameters for the occurrence of VTE events in cancer patients, we were not able to confirm that patients with moderate CKD, based on equation for estimating GFR, are at increased risk of VTE or mortality compared to patients without CKD. Conclusions for the group of patients with severe CKD were limited by the low prevalence of severe CKD in the cohort. None of the equations used for

Funding

This work was supported by funds of the “Oesterreichische Nationalbank” [Anniversary Fund, project number 14744]; by a grant from the “Hochschuljubiläumsstiftung der Stadt Wien.”

Conflict of Interest Statement

The authors have declared no conflicts of interest.

Acknowledgements

We thank all persons who have supported in recruiting patients for the Vienna Cancer and Thrombosis Study.

We are also thankful to the members of the adjudication committee: Renate Koppensteiner, and Andrea Willfort-Ehringer (Department of Angiology, Medical University of Vienna); Sylvia Metz-Schimmerl (Department of Diagnostic Radiology, Medical University of Vienna); and Robert Dudczak (Department of Nuclear Medicine, Medical University of Vienna).

Furthermore, we would like to thank Florian

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