Estimating renal insufficiency in breast cancer patients using ultrasound determined resistive index: A cross-sectional study of a Nigerian Cohort

Oluwagbemiga Oluwole Ayoola; Olusegun A Alatise; Olalekan Olasehinde; Tewogbade A Adedeji; Adewale O Adisa; Bukola B Olagbaju; Olurotimi O Komolafe; Fatiu A Arogundade

doi:10.4103/jrmt.jrmt_27_21

ORIGINAL ARTICLE

Year : 2022 | Volume : 3 | Issue : 1 | Page : 8-12

Estimating renal insufficiency in breast cancer patients using ultrasound determined resistive index: A cross-sectional study of a Nigerian Cohort

Oluwagbemiga Oluwole Ayoola¹, Olusegun A Alatise², Olalekan Olasehinde², Tewogbade A Adedeji³, Adewale O Adisa², Bukola B Olagbaju¹, Olurotimi O Komolafe¹, Fatiu A Arogundade⁴
¹ Department of Radiology, Obafemi Awolowo University, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
² Department of General Surgery, Obafemi Awolowo University, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
³ Department of Chemical Pathology, Obafemi Awolowo University, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
⁴ Department of Internal Medicine, Obafemi Awolowo University, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria

Date of Submission	30-Nov-2021
Date of Decision	10-Jun-2022
Date of Acceptance	13-Jun-2022
Date of Web Publication	07-Jul-2022

Correspondence Address:
Oluwagbemiga Oluwole Ayoola
Department of Radiology, Obafemi Awolowo University Teaching Hospitals Complex, PMB 5538, Ile-Ife
Nigeria

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrmt.jrmt_27_21

Abstract

Purpose: The purpose of this study was to investigate if the renal arterial resistive index (RRI) is impaired in women with breast cancer and correlate these values with estimated glomerular filtration rate (eGFR) as determined by the Chronic Kidney Disease Epidemiology Collaboration equation. Materials and Methods: This was an observational study of fifty chemotherapy-naïve women with histologically confirmed breast carcinoma recruited consecutively over a 1-year period. All women had a Doppler ultrasonography done to determine their RRI and eGFR. Results: Fifty women with breast cancer were evaluated. Their ages ranged from 28 to 85 years, with a mean age of 48.6 ± 13.8 years. The mean RRI in the study was 0.7 ± 0.07. There were thirty subjects (60%) with abnormal resistive index (RI) (>0.7), whereas twenty subjects (40%) had normal RRI. The mean eGFR in the study cohort was 62.6 ± 17. eGFR was abnormal in 96% of the women. About half (n = 24, 48%) had severe renal insufficiency (stages 3 and 4). The majority had advanced breast disease (stages 3 and 4), with 23 patients (46%) presenting with stage 3 disease and 17 (34%) stage 4 disease. Pearson's correlation done between RRI and eGFR showed a mild but statistically significant correlation between RI and eGFR (r = −0.28, P = 0.04). Conclusions: Renal artery RI is raised in most subjects with breast cancer and correlates significantly with the eGFR as determined by cystatin C alone.

Keywords: Breast cancer, cystatin C, glomerular filtration rate, kidney, renal artery resistivity index

How to cite this article:
Ayoola OO, Alatise OA, Olasehinde O, Adedeji TA, Adisa AO, Olagbaju BB, Komolafe OO, Arogundade FA. Estimating renal insufficiency in breast cancer patients using ultrasound determined resistive index: A cross-sectional study of a Nigerian Cohort. J Radiat Med Trop 2022;3:8-12

How to cite this URL:
Ayoola OO, Alatise OA, Olasehinde O, Adedeji TA, Adisa AO, Olagbaju BB, Komolafe OO, Arogundade FA. Estimating renal insufficiency in breast cancer patients using ultrasound determined resistive index: A cross-sectional study of a Nigerian Cohort. J Radiat Med Trop [serial online] 2022 [cited 2023 Jan 30];3:8-12. Available from: http://www.jrmt.org/text.asp?2022/3/1/8/350090

Introduction

Renal insufficiency is a well-known complication of cancer and cancer treatment. Various mechanisms have been implicated in the causal pathway of cancer-induced nephropathy. The direct effect of cancer on kidney function resulting from tumor infiltration, postrenal obstruction, paraneoplastic nephropathies, and other cancer-related events such as sepsis and hypovolemia has been described. Cancer treatment, particularly chemotherapy, exerts an indirect effect on the kidney by causing tumor lysis syndrome which may sometimes overwhelm the function of the kidney.^[1],[2] Patients with preexisting compromised kidney function are particularly at risk for developing cancer-related renal insufficiency^[3] giving the role of the kidneys in excreting the metabolic by-products of rapid cell death.

Renal insufficiency is often characterized by a progressive decrease in glomerular filtration rate (GFR) and subsequent rise in blood urea nitrogen and serum creatinine levels and an eventual compromise in renal function. It is a serious complication which has important ramifications in terms of choice of therapy and patients' overall outcome.^[4] Studies evaluating the prevalence and the impact of renal insufficiency among cancer patients have reported a high prevalence and a substantial impact on survival.^[5] The global rise in cancer incidence and the development of several systemic and targeted therapies, therefore, raises concerns about the increased potentials for cancer-related nephropathies.

For these reasons, evaluating the renal status of cancer patients before commencement of therapy is not only pragmatic but rational. Such evaluation should, however, be done using adequate and reliable methods of estimating renal function. It is well understood that traditional metrics such as serum creatinine are a relatively late marker of renal injury. This is because a significant amount of renal compromise would have occurred before a rise in creatinine level is apparent. GFR estimation using more sensitive markers of renal impairment is advocated for this reason.^[6],[7]

Renal Doppler ultrasonography has also been described as a noninvasive adjunct to biochemical methods in estimating renal function. Ultrasound-derived renal artery resistive index (RRI) has been shown to negatively correlate with GFR in a variety of clinical areas.^[8] Over the years, it has been used in a number of settings such as the management of renal artery stenosis, chronic kidney disease, and assessment of chronic renal allograft rejection.^{[9],[10],[11],[12]} It has gained increased applicability in other clinical areas such as in hypertension and diabetes mellitus where it serves as a useful tool for evaluation and prognostication.^[13],[14] Such evaluation has not been done in cancer patients. As there are differences in the pathomechanism of renal dysfunction in various disease conditions, it is important to verify if RRI may find applicability in the management of cancer patients. The use of RRI in evaluating renal impairment in cancer patients as done in this study is novel. In a cohort of newly diagnosed breast cancer patients, renal function was evaluated using ultrasound determined RRI and its correlation with GFR determined.

Materials and Methods

This was an observational study of fifty subjects with histologically confirmed, chemotherapy-naive breast carcinoma, recruited in a consecutive manner over a 1-year period from the surgical outpatient clinic of a tertiary health-care institution. Excluded from the study were subjects with congenital urogenital anomalies, hypertension, diabetics, urinary tract infection, human immunodeficiency virus, sickle cell disease, dyslipidemias, subjects on oral contraceptive pills and adrenergic drugs, smokers, subjects on dialysis or with massive edema, and patients on medications that may interfere with renal function such as cimetidine, probenecid, and angiotensin-converting enzyme inhibitors. Approval was obtained from the research and ethics committee of the hospital, and the study was carried out in compliance with the Declaration of Helsinki of 1964, as revised in 2013. Written informed consent was obtained from all the study participants.

Clinical evaluation/staging

Details of all subjects including demographic data, blood pressure, anthropometry, and other clinical examination findings were noted. Body mass index (BMI) was calculated using the standard formula, BMI = weight (kg) ÷ height² (m). Eligible patients were staged using clinical evaluation and radiological assessment based on findings on X-ray and abdominopelvic ultrasound. Staging was carried out according to the American Joint Committee on Cancer version VI. Patients with stage 1 and 2 diseases were further subcategorized as early, whereas those with stage 3 and 4 diseases were classified as advanced.

Laboratory methods, accuracy, and precision controls

Sample collection and laboratory analysis

All blood samples taken from participants were collected in the morning and centrifuged (3500 g for 5 min). The supernatant serum was separated, and samples were frozen at −80°C until assayed within the time limit of analyte stability as specified in the assay standard operating procedures. Quantitative enzyme-linked immunosorbent assay based on competitive immunoassay principles was used to determine cystatin C concentrations according to the manufacturer's instructions (assay kits were procured from Aviscera Bioscience, Inc., 2348 Walsh Ave., Suite C, Santa Clara, CA 95051, USA). Estimated glomerular filtration rate (eGFR) was determined using cystatin C alone by the Chronic Kidney Disease Epidemiology Collaboration equation. eGFR was classified into stages 1–5 based on the severity of kidney disease.^[15],[16]

Ultrasound technique

Renal Doppler ultrasound was performed with a color flow Doppler machine (Mindray DC-7, Shenzhen Mindray Bio-Medical Electronics Co. Ltd, Shenzhen, China), using 3.5-MHz curvilinear transducer. All subjects were examined in the supine position: left lateral decubitus for the right kidney and right lateral decubitus for the left kidney to exclude renal anomalies. Doppler sonography was performed using the noncompression technique on the right kidney. RRI was obtained on all the subjects. All subjects were normotensive at the time of renal sonography. Doppler parameters were obtained for segmental or interlobar arteries. Three readings from the arteries in the upper pole, interpolar, and lower pole regions were taken, and average values of parameters were recorded. RRI >0.7 was considered abnormal.^[17] The average of 3 readings was obtained from each subject by a single radiologist, with over 10-year experience to minimize intra-observer variability.

Data analysis

Sociodemographic data, disease characteristics, radiological findings, and laboratory parameters were presented as descriptive statistics in the form of mean and frequency distribution. The mean values of RRI and eGFR were compared across the various stages of the disease. Pearson's correlation was used to determine the relationship between RRI and eGFR. For all statistical analyses, P < 0.05 was considered significant. The Statistical Package for Social Sciences (SPSS) (IBM, Chicago, IL, USA) was used to carry out the data analysis.

Results

Over the study period, fifty women with breast cancer were evaluated. Their ages ranged from 28 to 85 years, with a mean age of 48.6 ± 13.8 years. The majority had normal BMI with a mean of 24.9 ± 5.4 kg/m². The majority had advanced disease (stages 3 and 4), with 23 patients (46%) presenting with stage 3 disease and 17 (34%) stage 4 disease. Ten patients (20%) presented with stage 2 disease and none with stage 1 disease.

Biochemical assessment

The mean eGFR in the study cohort was 62.6 ± 17. eGFR was abnormal in 48 patients (96%) with only 2 patients having eGFR >90. About half (n = 24, 48%) had severe renal insufficiency (stages 3 and 4). eGFR was not related to age, BMI, or stage of disease.

Sonologic assessment

The mean RRI for the entire cohort was 0.7 ± 0.07. There were thirty subjects (60%) with abnormal RI (>0.7), whereas twenty subjects (40%) had normal RRI. There was a progressive increase in the mean resistive index (RI) with increasing age, although this was not statistically significant [P = 0.1, [Figure 1]]. Similarly, obese patients had higher RI compared to nonobese patients, but this was not statistically significant [P = 0.2, [Figure 2]]. Cancer stage had no significant relationship with RRI [P = 0.4, [Figure 3]].

Figure 1: Boxplot showing renal artery resistive index data based on age

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Figure 2: Boxplot showing renal artery resistive index data based on body mass index

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Figure 3: Boxplot showing renal artery resistive index data based on cancer stage

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Relationship between resistive index with estimated glomerular filtration rate

Correlation of RRI with eGFR done using the Pearson's correlation technique showed a mild but statistically significant correlation between RI and eGFR [r = −0.28, P = 0.04, [Figure 4]].

Figure 4: Scatterplot showing correlation between renal artery resistive index and glomerular filtration rate

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Discussion

This rising incidence of cancer and the abysmally poor outcomes, particularly in resource-poor settings, necessitates interventions targeting all aspects of cancer care. The increasing role of chemotherapy and other systemic targeted therapies in the treatment of cancer, and the potential impact on the kidney which is the main excretory pathway, justifies a closer look at the subject. This study which examines the pattern of renal insufficiency in a Nigerian cohort provides important data on a subject that has only been scantily reported in our population of patients. The use of ultrasound-derived RI for assessing renal function in cancer patients as evaluated in this study is novel and provides evidence on its usefulness in assessing renal function in cancer patients. The overwhelming majority of patients in this study had abnormal renal function based on eGFR. The majority also had high RI above the 0.7 threshold with a statistically significant correlation with eGFR.

The patients evaluated in this study were predominantly women with locally advanced or metastatic disease which by itself is a poor prognostic indicator. These categories of patients often require chemotherapy either for neoadjuvant therapy in locally advanced cases or for palliation in the metastatic setting. The need for thorough evaluation of their renal status, therefore, becomes imperative. While advanced stage is perhaps the most important contributor to poor outcomes observed in this setting, the high prevalence of renal insufficiency as observed in this study suggests that such comorbidities if undetected may contribute in no small ways to poor outcomes.

The initial evidence on the prevalence of renal insufficiency in cancer patients came from the French IRMA studies (Renal Insufficiency and Anticancer Medications). In two different studies with about 5000 adult patients with solid tumors, predominantly breast, colorectal, and lung cancers, 52.9% and 50.2% of the patients in the IRMA-1 and IRMA-2 studies, respectively, had reduced GFR (lower than 90 mL/min/1.73 m²), and 12.0% and 11.8% had stage 3 or 4 (lower than 60 mL/min/1.73 m²). Specifically, among those with breast cancer, only about 38.6% of the patients with breast cancer had normal eGFR (≥90 mL/min/1.73 m²).^[18],[19] Similar findings were also reported in the BIRMA study which was the Belgian counterpart of the IRMA study.^[20] In the current study, however, none of the patients had normal eGFR, with the majority (76%) having stage 3 eGFR. The prevalence of deranged renal function observed in this study exceeds findings from these earlier studies. This may reflect the disease severity in this cohort or the differences in the methods of GFR estimation in the various studies. This study deployed the use of cystatin C for estimating eGFR while the earlier studies employed the use of the “Modification of Diet in Renal Disease” formula.

The finding of deranged renal function in the cohort of patients in this study has important ramifications on their management. It prompts the need to adopt more rigorous methods of evaluating renal function in this category of patients. It also raises the need for a stronger interdisciplinary approach to the management of cancer patients, particularly as it relates to the choice of therapy and dosage adjustment based on renal function as depicted by earlier studies.

This study highlights the potential usefulness of RI as a noninvasive adjunct to biochemical assays in the assessing renal function among cancer patients. RRI has been previously identified as a noninvasive modality for assessing renal hemodynamics. An elevated RRI is often indicative of increased systemic vascular resistance and worse outcomes.^[10] Its usefulness has been described in patients with renal vascular disease, chronic kidney disease, hypertension, and diabetes mellitus by providing important diagnostic, therapeutic, and prognostic information.^[13],[21] Although this study only shows an association between RRI and eGFR, it does serve as a basis for further evaluating the potential usefulness of Doppler-derived RRI in making therapeutic decisions and for monitoring patients on treatment for cancer. Being a cross-sectional study, this study was unable to evaluate the biochemical and sonographic parameters over time to see how these change with disease progression. This study also did not evaluate the effect of chemotherapy on renal function and the relationship between renal function and outcomes. These are potential areas for further evaluation.

Within these limits, however, this study clearly shows a high prevalence of renal insufficiency in the study population and identifies RRI as a possible sonographic marker.

Conclusion

RRI is elevated in several patients with breast cancer and is positively correlated with eGFR. It may prove to be a useful noninvasive marker of renal function in patients with breast cancer.

Acknowledgments

Special thanks goes to Mr. Idowu Omisile who was supportive with the data analysis

Financial support and sponsorship

This study was financially supported by the Tertiary Education Trust Fund (TETFUND).

Conflicts of interest

There are no conflicts of interest.

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