On World Kidney Day, we examine the diseases that impair the function of the kidneys such as chronic kidney disease (CKD) and kidney cancer and their impact on Southeast Asia.
The 9th most common type of cancer in men worldwide kidney cancer or renal cancer accounts for more than 131,000 deaths each year and places a significant economic burden on society. The economic burden of metastatic kidney cancer is estimated to be US$1.6 billion in some countries.
An increased risk of kidney cancer has been observed in many Asian countries, with the incidence and mortality of this cancer increasing by 2% to 3% per decade worldwide. In 2012, a total of 121,099 kidney cancer cases were recorded in Asian countries, with 66.12% cases being male.
Renal cell carcinoma (RCC)
Renal cell carcinoma (RCC), a solid tumour cancer, is the most common form of kidney cancer that typically affects the elderly, over the age of 65. In Singapore, kidney cancer is the 8th most common cancer among men and accounts for 1 to 2% of all cancers.
Dr Toh Chee Keong, Consultant Medical Oncologist at Curie Oncology, Farrer Park Medical Centre says, “Roughly two-thirds of RCC occur in males. Other than being male, there are other risk factors – some of which can be addressed with lifestyle changes, or modifiable risk factors – such as obesity, smoking and hypertension. Non-modifiable risk factors include gender, age, and genetics. Having advanced renal disease that requires dialysis, is another risk factor too.”
Compared to the early 1990s when most RCC was not diagnosed until it was symptomatic, advanced Stage III or IV, today far more are being discovered earlier. Associate Professor Marniza Saad, Clinical Oncologist, University Malaya Specialist Centre (UMSC), says,"This is because diagnostic imaging is not only better today, but also far more common and increasingly used for evaluating patients with other abdominal conditions, leading to more kidney masses being discovered."
Although 30% of RCC is detected at a late stage, advanced kidney cancer is not as aggressive as some other late-stage cancers such as pancreatic or liver cancer. Compared to the early 1990s when the only treatment options for RCC were surgery and radiation therapy, today there are many more treatment options for RCC. Life expectancy, even for advanced RCC have doubled or even tripled from then. With the right treatment, RCC patients can have a good quality of life and comparatively good prolongation of life too.
In early-stage kidney cancer (Stage I and II) when the tumour is within the kidney and has not metastasised, surgery can remove the tumour, although some patients experience a recurrence of the cancer after a period of time.
Says Dr Ravindran Kanesvaran, Senior Consultant and Deputy Head of the Department of Medical Oncology, National Cancer Centre, “For advanced RCC, there was little hope prior to 2005. Because it responded poorly to traditional chemotherapy, the prognosis was just 1 to 1.5 years after being diagnosed. However, significant advances have been made in the last decade with novel treatments such as targeted therapies (TTs) and immunotherapy becoming the mainstay of cancer treatment. These treatments used individually or in combination have improved the prognosis and landscape for the treatment of kidney cancer.”
Targeted therapy consists of drugs such as tyrosine kinase inhibitors (TKI) which target and inhibit particular pathways that promote cancer growth. For instance, they might switch off the signals to grow new blood vessels to feed the tumour and thus prevent or slow its growth. Side effects may include high blood pressure, heart problems and diarrhoea.
Immunotherapy is a form of treatment that involves the stimulation of the patient’s immune system to recognise the cancer cells and kill them. Side effects include flu-like symptoms but these can be controlled with medication. Many clinical trial studies show that immunotherapy agents are well tolerated with minimal side effects. Because of this, immunotherapy is a reasonable option in older kidney cancer patients too.
Unfortunately, cancers can evolve and adapt to drugs over time and start growing or progressing again but now that we have more immunotherapy and targeted therapy options, when the first-line treatment begins to fail, we can try a second-line treatment and so on.
The current prognosis of advanced kidney cancer with targeted therapy and immunotherapy is more encouraging, between 3 to 3.5 years. There is ongoing research into new drugs and different combinations of existing immunotherapy and targeted drugs so that might improve in the future.
Chronic kidney disease (CKD)
Chronic kidney disease (CKD), a progressive condition where the kidney function deteriorates over time, is a leading cause of death and disability globally. Non-communicable diseases, such as diabetes mellitus, hypertension, dyslipidemia, and obesity, as well as infectious diseases like malaria, severe dengue and hepatitis B are risk factors for CKD.
A large part of the disease burden is in Asia, with approximately 434.3 million people afflicted with CKD across the eastern, southern, and south-eastern regions. Socioeconomic status is highly correlated with common risk factors for chronic diseases, making low to middle income countries particularly vulnerable to the burden of chronic diseases like CKD. Regions of low socioeconomic status are also less likely to have early detection and proper disease management.
With the rising prevalence of diabetes and hypertension in Southeast Asia, the incidence of the disease is only projected to increase in the near future, posing a significant financial and economic burden on low-to-middle-income countries in the region.
Diabetes and CKD
The incidence of diabetes mellitus, or type 2 diabetes, is on the rise in Southeast Asia. Studies show diabetics are 3.5 times more likely to develop CKD as well as being at higher risk of developing other associated disorders like cardiovascular disease.
In Singapore, 11% of patients with CKD were diabetic, and about 430,000 (14%) of the population aged 18 to 19 years have been identified as having pre-diabetes, putting them at higher risk of developing diabetes as they age. Meanwhile, studies show that in Malaysia, the prevalence of diabetes is on the rise, with about 3.65 million Malaysians living with diabetes in 2020.
“In individuals who have had diabetes for many years, the constant high glucose levels in the blood causes damage to the blood vessels and tissues in the kidneys, affecting the organ’s filtrating functions,” explains Professor Lim Soo Kun, Consultant Nephrologist, University Malaya Medical Center (UMMC).
“In a healthy individual, the GFR (glomerular filtration rate) or efficiency of the kidney in filtering out blood and albumin, naturally declines with age, from about our mid-30s, by about 0.5mL/min per year to about 1.0mL/min per year by our late 50s or 60s. In patients with comorbidities such as diabetes, CKD can progress very quickly, causing their GFR to drop by as much as 12 mL/min/ to 20 mL/min/ each year. By Stage V CKD, GFR is below 10 (GFR <10mL/min) and the patient would require dialysis to survive,” explains Professor Lim.
Dialysis is usually required to help with blood filtration to remove excess water, solutes and toxins. The most recent data available from 2018 shows that among the over 8,400 new dialysis patients reported in the country, a staggering 69.2% of them had diabetes.
Managing early- and end-stage kidney disease
Starting treatment as early as possible to slow down the progression of the disease is crucial to limit further damage to the kidney and minimise associated complications. The end-goal of treatment in CKD patients is typically to reduce or delay the need to undergo dialysis within a patient’s lifetime as well as improve the patient’s quality of life.
“When kidney disease is detected and managed with lifestyle changes and treatments early, it changes the trajectory of the disease progression. This benefits patients in the long run by increasing life expectancy and quality of life. From my clinical experience, the earlier we start the patient on aggressive therapy, the better the chances of slowing down progression and extending the time before patients reach end-stage kidney disease (ESKD), i.e., putting off the patient’s need for dialysis for as long as possible,” advises Professor Lim.
Conventional management includes controlling risk factors such as controlling blood sugar levels for diabetics and maintaining optimal blood pressure for those who are hypertensive, combined with certain medications.
“Treatments like angiotensin-converting enzyme (ACE) inhibitors or angiotensin blockers have been used for over 20 years which do provide some kidney protection. However, they do not prevent CKD from worsening,” says Professor Lim.
“Fortunately, there have been some exciting developments in the treatment of CKD recently with the introduction of SGLT2 (sodium-glucose co-transporter-2) inhibitors, a new drug class that can potentially change the way we manage and treat CKD, even ESKD, and diabetes,” he adds.
Lifestyle modifications should not be underestimated
In managing kidney disease or any other chronic disease, experts confirm lifestyle modifications should go hand-in-hand with medications.
Doctors often stress that improving heart health can improve kidney function, and vice versa, because there is a relationship between kidney and heart disease. Data collected over a period of nine years from over 3,900 heart failure patients found that almost 11% of patients had Stage IV (severe) CKD, indicating that lifestyle modifications that benefit the heart, will also benefit the kidneys.
“It is also common to see obese patients having a higher risk of heart and kidney disease, which underlines the importance of making lifestyle changes that help manage weight. Patients are often recommended a CKD diet, which consists of foods that are fresh, low in salt (sodium), phosphorus and fat, and have only small portions of protein. It is also wise to moderate alcohol intake,” advises Professor Lim.