Chronic Kidney Disease #3: Advancements in Medication

Doctor's Insight.

Chronic kidney disease or CKD affects an estimated 850 million people worldwide.

CKD is often caused by lifestyle diseases.

In such cases, the basic way to manage the condition is making lifestyle changes such as improving your diet and exercising.

If this alone cannot control the decline in kidney function, it becomes necessary to get medical treatment.

Up until now, the most commonly used medications were drugs for conditions that cause kidney disease, such as diabetes and high blood pressure.

In 2021, however, the first ever drug that works on CKD itself, was approved in Japan, the US and in Europe.

As the drug acts directly on the kidneys, they are expected to be effective in treating many patients regardless of the cause or the type of CKD.

Today, we'll focus on the major shift in the treatment of chronic kidney disease.

Today's expert is Dr. Masaomi Nangaku, President of the International Society of Nephrology.

He is a world renowned nephrologist who has spent decades conducting research on the cause and the treatment of kidney disease.

Dr. Nangaku, welcome back to our show.

Thank you for having me.

Doctor, please tell us about the new drug for CKD.

How is it different from previous drugs?

The drug is called "SGLT2 inhibitor" and it's actually used for treating diabetes.

It was discovered that this drug has the effect of suppressing the decline of kidney function regardless of whether the patient had diabetes or not.

Clinical trials have shown that this drug clearly reduced the decline in kidney function in many CKD patients.

And now, it is available for treating CKD under insurance coverage.

That's wonderful.

It is said that the number of CKD patients is increasing worldwide.

This new drug will make a great impact for patients around the world.

By 2017, it affected 1 in every 11 people.

SGLT2 inhibitor is expected to slow the progression of the disease and save the lives of many people.

It looks like we have entered a new era in the drug treatment for Chronic Kidney Disease.

Now, let's find out more about how the new drug, SGLT2 inhibitor works on our kidenys.

When you take a close look at a kidney you will see small tissue such as glomeruli and renal tubules.

SGLT2 is a protein found in the cells of the tubules and is closely linked to the glomerulus.

The glomerulus is about 0.1 to 0.2 mm in diameter, in which capillaries are bundled together like a ball of thread.

There are approximately 1 million glomeruli in each kidney.

The glomerulus functions like a sieve which filters excess water, salt, and waste products from the blood.

The filtered substances are then released into the renal tubules.

SGLT2 reabsorbs sodium and glucose from the tubules, which are necessary for the body, and releases them back to the blood vessels.

In CKD, glomerular hypertension occurs and cause excessive filtration.

In other words, it is an overactive state.

This condition puts strain on the glomerulus and consequently on the kidneys, leading to the progressive decline in kidney function.

So how do SGLT2 inhibitors work?

SGLT2 inhibitors suppress the function of SGLT2 and prevent the reabsorption of sodium and glucose.

When the glomerulus detects this, the internal pressure in the glomerulus decreases.

This normalizes the filtration and reduces the strain on the kidneys, slowing the decline of kidney function.

SGLT2 inhibitors also protect the kidneys in other ways.

Among them, one that I was able to discover after many years of research is the relationship between CKD and hypoxia.

Hypoxia and CKD... how are they related?

The kidneys consume large amounts of oxygen during reabsorption, which requires a lot of energy.

For reasons including this, the kidneys become chronically hypoxic in CKD patients.

As a result, the tissue in the kidneys become increasingly hard.

This is called fibrosis and is a major factor in the progression toward end-stage kidney disease.

SGLT2 inhibitors reduce the kidney's energy demand by inhibiting reabsorption, which in turn eliminates hypoxia.

As a result, the drug slows the decline of kidney function.

I understand that the great advantage of SGLT2 inhibitor is that many CKD patients can use them.

But is the drug for everyone?

SGLT2 inhibitors are an important option for many CKD patients.

However, it cannot be used on patients who have started dialysis.

What's important is to start using the drug at an early stage.

The sooner a patient starts using it, the easier it is to maintain sufficient kidney function.

If the drug can prevent the progression toward end-stage kidney disease, the patient could be hopeful about living a full life without dialysis.

And even if that were not the case, the drug still can greatly delay the start of dialysis.

Patients can benefit greatly if the drug can significantly delay the start of dialysis.

Yes, and the new drug can also greatly reduce the risk of death from complications such as heart failure.

The results of clinical trials have shown that the incidence of such complications was reduced by an average of about 30 to 40% of all patients at various stages of the disease.

That's quite a decrease.

With so many benefits, CKD patients would want to start using SGLT2 inhibitors as soon as they can.

Yes, but of course, there is also the risk of side effects.

It is important that doctors offer the drug as a treatment option as soon as the patient qualifies for the treatment.

Dr. Nangaku, do CKD patients take other types of drugs?

Often times, yes.

As CKD progresses, patients may experience various symptoms.

Medications are prescribed as needed to control such symptoms.

In particular, major progress has been made in recent years for anemia medications.

Can you tell me how anemia drugs have advanced?

In the past, anemia medications were only available through injections and patients had to go to the hospital for it.

But now, an oral medication called "HIF-PH inhibitors" has become available which could be taken at home.

Also, it is said that oral medications can work on patients who were unable to get results with injectable drugs.

When did this become available in Japan?

HIF-PH inhibitors were first approved in Japan and China in 2019, followed by European countries.

In Japan, there are five types of approved drugs, making it easier for patients to use one that's right for them.

In the future, more types are expected to become available around the world.

This is really good news for CKD patients suffering from anemia.

The drugs for treating chronic kidney disease are continuing to advance.

Yes.

Several other drugs for CKD are currently undergoing research, development, and clinical trials.

There are many things CKD patients could do to try to slow the progression of the disease; eating healthy, exercising and taking drugs that are currently available.

This will increase the chance of using new drugs when they become available in the future.

Dr. Nangaku, thank you for your time today.

Thank you.