CHAPTER ONE

INTRODUCTION

• Background

Despite recent awareness and progress in health care, cancer still remains a societal and public health concern in Cameroon and the world at large. It is one of the leading causes of dead and mostly affects individuals from age 30 and above. The International Agency for Research on Cancer (IARC) in the year 2022, gave an estimated prevalence of 20milliion with an estimated dead of 9.7 million deaths in the world. The most diagnosed cancer in 2022 was cancer of the lung with a prevalence of 12.4%, followed by breast cancer with 11.6% prevalence, then colorectal cancer which was 9.6%, and lastly prostrate with 7.3% [1]. Also, the most common cancers among females include breast cancer with an estimation of 4,207 cases and cervical cancer (2,525 cases), while prostate cancer (2,050 cases) and Kaposi sarcoma (797 cases) are most prevalent among males [2]. Cancer is basically the abnormal growth of cells, whereby they grow without control in any tissue or organ beyond their usual boundaries and invade other parts of the body or organ and this phenomenon is known as metastasis. It is the main cause of death of cancer [3]. These tumor cells grow by utilizing Oxygen and supplements in the body, also by restricting other cells of their routine supplements and factors of their growth consequently the tumor cells mislead the immune system [4]. This increase in cancer incidence is associated with late-stage diagnoses and limited access to quality treatment services. The National Strategic Plan for Cancer Prevention and Control (2020–2024) underscores the need to strengthen diagnostic capacity, including renal function monitoring , during cancer therapy [2]. Chemotherapy has been recognized as the cornerstone in the management of cancer although frequently associated with adverse effects, including nephrotoxicity. Several chemotherapeutic agents such as cisplatin, methotrexate, and ifosfamide are known to induce acute kidney injury (AKI) or chronic renal impairment [5]. Therefore, monitoring kidney function in cancer patients undergoing chemotherapy is important so as to prevent drug-induced renal complications and improving therapeutic outcomes. The assessment of renal function in cancer patients undergoing chemotherapy is critical due to the potential nephrotoxicity of many chemotherapeutic agents. Traditional biomarkers, such as serum creatinine, have been widely used to for assessing renal function and estimating glomerular filtration rate (GFR); however, they have limitations, particularly in cancer patients who may experience muscle wasting owing to the fact that creatinine is muscle mass dependent as muscle atrophy, also several physiological and pathological variables including age, gender, muscle mass and dietary factors contributes as part of its limitation.

Hence, their limitations necessitate the exploration of novel biomarkers such as cystatin C. The standard filtration biomarkers are expected to have no influence on renal function after been readily excreted at the glomerular filtrates, reabsorbed, metabolized neither synthesized nor secreted by the kidney [6, 7].

Cystatin C has been proposed as a novel and sensitive biomarker. Cystatin C is a low molecular weight protein produced by all nucleated cells, freely filtered by the glomeruli, and reabsorbed by the renal tubules without it a potentially more sensitive indicator of early renal dysfunction [8]. Studies have demonstrated that Cystatin C can detect early renal impairment in cancer patients before changes in serum creatinine are evident [9]. Furthermore, some evidence suggests that elevated Cystatin C levels may correlate with disease severity and overall prognosis in oncology populations [10].

In Cameroon, and sub Saharan Africa as a whole, little has been studied on the comparative utility of these biomarkers in cancer management, despite an increase in cancer burdens and problem in chemotherapy usage. It is therefore worth assessing the performance of these renal markers in our local context, which offers the potential for improvement in chemotherapy, minimize nephrotoxicity   and optimize patient outcome.

1.2 Rationale

In the context of Cameroon, Cancer patients undergoing chemotherapy are frequently monitored using serum creatinine marker to determine their renal function. However, the reliability of this marker is not very certain in this population due to changes in nutrition, muscle mass and appetite loss. Nephrotoxicity has been identified as a vital risk determinant for oncological development leading to decreased probability of cancer survival. In addition to that , anticancer agents alters any part of the kidney nephron resulting to abnormal clinical presentations like Acute kidney Injury(AKI),and glomerular nephropathy thereby affecting the kidneys estimated glomerular filtration rate. Glomerular filtration rate is one of the ways apart of Blood Urea Nitrogen (BUN) and best parameter for assessing kidney function and chemotherapeutic nephrotoxicity, this is because it reveals an adequate correlation with renal mass and also to what extent the kidney has lost its function, hence the need for a sensitive, precise ,accurate and specific biomarker.

This study evaluates by assessing traditional biomarker, which is Creatinine with the novel cystatin C biomarker in detecting chemotherapy-induced nephrotoxicity in cancer patients. The aim is to identify the most accurate and reliable biomarker for monitoring renal function in this high risk population ,which can then help clinicians to make better informed clinical decisions about chemotherapy dosing and management which will certainly lead to  the improvement of  patients outcome and also the quality of life.

1.3 Research Questions

1. What are the levels of serum creatinine in cancer patients on chemotherapy at the Cameroon Oncology Center?
2. What are the levels of serum cystatin c in cancer patients on chemotherapy at the Cameroon Oncology Center?
3. Is there a correlation between serum creatinine and serum cystatin c in cancer patients on chemotherapy at the Cameroon Oncology Center?

1.4 Research Hypotheses

1. The levels of serum creatinine are abnormally high in cancer patients on chemotherapy at the Cameroon Oncology Center (COC)
2. The levels of serum cystatin c are abnormally high in cancer patients on chemotherapy at the Cameroon Oncology Center.
3. There’s a correlation between serum creatinine and cystatin c in cancer patients on chemotherapy at the Cameroon Oncology Center.

1.5 Objective                                                                                                                           

1.5.1 Main Objective                                                                                                              

The overall aim of this study was to assess renal function using traditional (Creatinine) and novel (Cystatin C) biomarkers and their correlations in cancer patients on chemotherapy at the Cameroon Oncology center.

1.5.2 Specific Objectives

1. To determine serum creatinine levels in cancer patients on chemotherapy at the the Cameroon Oncology Center.
2. To determine serum cystatin c levels in cancer patients on chemotherapy at the Cameroon Oncology Center.
3. To find out if there is a correlation between creatinine and cystatin c levels in cancer patients on chemotherapy at the Cameroon Oncology Center.