Introduction

The kidneys are the two bean-shaped organs located just below the rib cage. They are each roughly the size of a fist, yet they play a crucial role in the body. Every day, about 200 litres of blood are filtered by the kidneys. While most of it is reabsorbed, or returned to the circulation, excess fluid and electrolytes, toxins, and metabolic waste products are excreted, forming the urine. The kidneys also produce a hormone named erythropoietin, which is essential to the production of red blood cells and a key site for controlling blood pressure.^1,2

Kidney cancer (KC) occurs when healthy kidney cells start exhibiting abnormal changes and growth, often leading to a cancerous tumour. Because cancer cells can grow out of control, early intervention is essential to keep them from spreading to the rest of the body. Recent studies have shown a concerning increase in the prevalence of KC worldwide,  particularly in Western countries. It is estimated that there are about 400,000 new cases of KC, and that it is the cause of 175,000 deaths every year. Awareness is a key element for early detection and improved outcomes.³

Understanding kidney cancer

What is kidney cancer?

In adults, KC arises from the uncontrolled growth of kidney cells in the renal parenchyma or the pelvis. The parenchyma is the main functional part of the kidney, while the pelvis is the funnel-shaped part of the ureter within the kidney where urine is initially collected, before moving down the thinner part of the ureter into the bladder.⁴

Source: AI-generated illustration, labels added by the author.

While it varies from country to country, the global incidence of KC ranges from 2.2% to 4% of all cancer diagnoses, with the UK at the top of this range according to Cancer Research UK. It is usually diagnosed later in life, is twice as likely to affect males assigned at birth as females assigned at birth, and the survival rate is highly dependent on the stage at which it is detected.^3,6

Different types of kidney cancers

KC can be classified into various types:^4,7

• Renal cell carcinoma (RCC): originates in the renal parenchyma and is by far the most common type of KC, accounting for roughly 9 out of 10 occurrences. It can be classified into 2 subtypes:
  • Clear cell RCC: the most common type of RCC. It is referred to as “clear cell” because when observed under a microscope, the cells appear very pale, or clear
  • Non-clear cell RCC:
    • Papillary RCC: the tumours form small finger-like projections called “papillae”. They can be slow-growing (type 1) or more aggressive and fast-growing (type 2)
    • Chromophobe RCC
    • Other rare subtypes

• Transitional cell carcinoma (TCC): originates in the renal pelvis, not the parenchyma
• Wilms’ tumour: a rare type of KC that mostly affects children

KC can grow and invade large blood vessels such as the renal vein (drains blood from the kidney) and the inferior vena cava (carries blood from the lower body to the heart). Unfortunately, this provides a quick route for the formation of metastases to the heart and lungs.⁸

Another unique characteristic of KC is that about 60% of patients remain asymptomatic, leading to late detection, giving the cancer time to spread and metastasise.⁹

Causes and risk factors

Genetic predisposition for KC

While about 95% of cases of KC are not inherited, the remaining 5% have been linked to a genetic predisposition. The first gene identified to have a link to KC was VHL (Von Hippel-Lindau), a tumour suppressor gene. Other genes involved in the development of KC include fumarate hydratase, folliculin, and BAP1.¹⁰

Lifestyle factors

Up to 40% of cases of KC could be linked to modifiable lifestyle factors. These can include:³

• Smoking
• Excess body weight accounts
• High blood pressure has a strong association with the frequency of KC
• Chronic use of NSAIDs (non-steroidal anti-inflammatory drugs), such as ibuprofen
• Occupational exposure to certain chemicals, such as cadmium, asbestos, and petroleum byproducts

Gender and race

Research has shown that gender plays a major role in the frequency and progression of KC. Men are twice as likely to develop and die from the disease compared to women. This disparity may be due to biological differences in hormone function, as well as lifestyle factors that tend to differ between men and women.³

Studies on racial differences in KC have mostly been conducted in the United States. These studies have shown that the frequency of RCC is about 10% higher in African Americans than in Caucasians. It is also important to note that clear cell RCC and papillary RCC are the most common types of KC observed in white populations and African Americans, respectively. 

Overall, a higher risk of mortality is observed in racial minorities, and these differences correlate with socioeconomic factors such as access to healthcare, delayed diagnosis and treatment, the presence of commorbidities such as hypertension and chronic kidney disease and quality of care received.^3,11,12

Acute kidney injury, chronic, and end-stage kidney disease

Acute kidney injury (AKI), chronic (CKD) and end-stage kidney disease (ESKD) strongly correlate with a higher incidence of KC. People who survived childhood cancer have a higher risk of developing KC, particularly if their treatment involved kidney-toxic medications, which could have led to AKI.³

Symptoms and early warning signs

A large proportion of KC patients do not develop symptoms, leading to late diagnoses. Only about 10 to 15% will develop symptoms. There are 3 most common symptoms:

• Flank pain
• Hematuria (blood in the urine) 
• Flank fullness (lump, or swelling)

Even though less frequent, other symptoms include fatigue, unintended weight loss, high blood pressure, and anaemia. Because symptoms of kidney cancer (KC) are uncommon, it is essential to consult a healthcare provider if any of these develop, as early detection significantly improves the chances of survival.¹³

Diagnosis and screening

Because symptoms are rare in the early stages of KC, it is often detected “by accident” while running tests for another condition. A proper diagnosis usually involves a combination of laboratory tests, imaging, and clinical evaluation. Once a healthcare provider has evaluated the medical history and symptoms of the patient, they will usually start with blood work and urine analysis to determine kidney function, testing for anaemia, platelets, and electrolyte levels. These establish a baseline before performing imaging tests, central to diagnosing KC.

Imaging studies such as renal ultrasound, computerised tomography (CT) scan, and magnetic resonance imaging (MRI) are important to characterise the type of tumour present, as well as the stage of the cancer. A biopsy may be performed for suspicious lesions. Although biomarker research is ongoing, imaging remains the primary method for diagnosing, monitoring, and planning treatment for RCC. Genetic testing can also occasionally be recommended when the patient has a family history of KC.¹³

Treatment options

Treatment for KC depends on the stage of the cancer. In the early stages, surgery is the most common approach. If the tumour is small enough, it can be removed while preserving the rest of the organ. However, if the tumour has invaded too much of the kidney and possibly surrounding tissues, the whole organ is removed.

For patients who cannot undergo surgery, thermal ablation (freezing or heating the tumour) or active surveillance may be options for small tumours. If the cancer is more advanced and has spread to other parts of the body, systemic treatments are often required. These can include drugs that are immune checkpoint inhibitors and targeted therapies, which block cancer growth pathways. 

These therapies are frequently used in combination to improve outcomes. Emerging treatments such as stereotactic body radiation therapy (SBRT) and adjuvant immunotherapy are being explored to limit the chances of recurrence after surgery.^13,14

Summary

The kidneys are two important bean-shaped organs located below the rib cage. Each kidney is about the size of a fist and filters around 200 litres of blood daily. While most blood is reabsorbed, excess fluid, toxins, and waste are turned into urine. Kidney cancer (KC) happens when healthy kidney cells grow abnormally, possibly forming a tumour. KC typically develops in the renal parenchyma or the pelvis. The global incidence of KC varies but is around 2. 2% to 4% of cancer cases, with men being twice as likely to be affected as women. KC is classified into several types, the most common being renal cell carcinoma (RCC). Other types include transitional cell carcinoma (TCC) and Wilms’ tumour, which mostly affects children. Lifestyle factors like smoking, obesity, and high blood pressure may be linked to 40% of KC cases. Differences in gender, race, and socioeconomic factors can also affect KC incidence and outcomes. Symptoms of KC are often rare, with common signs being flank pain, hematuria, and flank fullness. Many cases are diagnosed unexpectedly during tests for other conditions. Diagnosis typically requires blood work, urine analysis, and imaging tests. Treatment depends on the cancer stage and may include surgery, thermal ablation, or systemic therapies. Emerging treatments are being explored to enhance outcomes after surgery.