Amyloid and the Kidneys

The kidneys are the most common organs involved in the systemic amyloidoses

Types of Amyloid in which the kidneys may be affected:

  • AL amyloidosis
  • AA amyloidosis
  • Hereditary Amyloidosis mutations:
  • ATTR mutation
  • Apolipoprotein A1
  • Afib
  • AApoA
  • Agel
  • Dialysis related Amyloidosis. Rarely seen now with improved dialysis filtering system.

The Normal Kidney

Normal Kidneys

The kidneys are vital organs that keep the body healthy. Without them, the body cannot remove toxins, and this would have a serious impact on health.

Location and Structure

Kidneys sit in the middle of the back, on either side of the spine. They are well protected by a layer of fat, the lower ribs, and back muscles. Each kidney is bean-shaped, about the size of a fist, and weighs around 150 grams. Most people are born with two kidneys, but about one in 750 people have only one. Even so, one kidney alone can provide up to 75% of normal function. Inside each kidney are about one million tiny filters called nephrons. Blood enters through the renal artery and leaves through the renal vein after being cleaned.

What do the kidneys do?

The kidneys perform four main jobs:

  1. Clean the blood – They filter and refresh the blood around 12 times every hour, which adds up to about 200 litres a day. Nephrons remove waste and extra water, turning it into urine.
  2. Remove waste and extra fluid – They produce one to two litres of urine each day to clear unwanted chemicals and toxins from the body.
  3. Control blood pressure – They help blood vessels know when to tighten or relax, keeping blood pressure steady.
  4. Support bones and blood health – They activate vitamin D to keep bones strong and release hormones that help the body make red blood cells, which carry oxygen around the body.

How do the kidneys work?

How Urine Leaves the Body

The remaining waste fluid passes through a process to become urine. The urine then flows from the kidneys through tubes called ureters into the bladder, where it is stored. When the bladder empties, the urine flows out through a tube called the urethra. In healthy people, about two litres of urine are produced every day.

More information on what your kidneys do at Kidney.org.au

What happens when the deposition of amyloid in the kidneys damages them?

Renal amyloid occurs when the abnormal amyloid protein fibrils, deposit and accumulate in the kidneys over time.

The amyloid protein can be deposited in any part of the kidney but is predominately seen in the nephron. This interferes with kidney function. The speed of progression of deposition varies depending on the type of amyloidosis.

Symptoms

Symptoms of kidney involvement can be very non-specific. Some people may have significant kidney damage, even up to 80%, yet notice very few problems. Because the symptoms are often vague and resemble other kidney or medical conditions, diagnosis is sometimes delayed.

  • Tiredness
  • Fluid retention(edema) resulting in swelling usually in legs, feet and ankles and sometimes in the hands
  • Breathlessness due to fluid retention
  • Sudden increase in weight
  • Headaches
  • Nausea and loss of appetite
  • Loss of concentration
  • Becoming irritable
  • Poor sleep
  • Weight loss
  • Changed sexual function
  • Itch
  • A reduction in the volume of urine
  • Protein (Bence Jones) or blood in the urine
  • Frothy urine
  • Anaemia
  • Raised Cholesterol
  • Low blood pressure
  • Enlarged kidneys because of the deposition of amyloid
  • Renal failure.

NB Many of these symptoms are also common in other types of kidney disease.

In about three out of four people with renal amyloidosis, the amyloid proteins build up in the tiny filters of the kidney. This gradually damages the kidney’s ability to filter the blood and manage fluid balance.

As a result, several problems can occur:

  • Waste buildup in the blood: The kidneys cannot clear toxins effectively, so waste products accumulate.
  • Protein in the urine (proteinuria): Damaged filters allow protein to leak into the urine. Losing protein, especially a key blood protein called albumin, causes changes in blood chemistry.
  • Swelling (oedema): Albumin normally helps pull extra fluid back into the blood to be removed by the kidneys. When albumin is lost in the urine, fluid builds up in tissues, leading to swelling in the ankles, feet, hands, or elsewhere. Fluid in the lungs can cause shortness of breath.
  • Salt and water imbalance: The kidneys struggle to keep the right balance of salt and water, which can make swelling worse.
  • Changes in blood chemistry: Potassium and other important blood chemicals may fall outside safe limits.
  • Anaemia: Kidneys produce less of a hormone called EPO, which helps make red blood cells, leading to tiredness and weakness.
  • High cholesterol: Kidney damage can raise blood cholesterol levels.
  • Scarring of kidney blood vessels: Over time, this further reduces kidney function.

If amyloid build-up continues, kidney function gets worse and can lead to kidney failure. At this stage, patients may need dialysis or, in some cases, a kidney transplant.

When the eGFR is around 15 and falling, the kidneys can find it harder to clear waste products and extra fluid from the body. This does not always mean dialysis needs to start straight away, but it is usually the time when your kidney team will discuss dialysis and other treatment options with you. Dialysis is a treatment that helps remove waste and excess fluid when the kidneys can no longer do this well enough.

More information about dialysis can be found here.

Terms you may hear during treatment

Albuminuria

This means there is too much albumin, a type of protein, in the urine. It can be a sign that the kidneys are leaking protein. Some doctors may also call this “proteinuria”, which means protein in the urine.

Hypoalbuminaemia

This means there is a lower than normal level of albumin in the blood. This can happen when the kidneys leak too much protein into the urine.

Diagnosis

Suspicions (not diagnostic) that someone may have renal amyloidosis:

  • Oedema
  • Low Blood pressure
  • Lots of Protein in the urine
  • Abnormal kidney function
  • Enlarged kidney because of amyloid deposition

Amyloidosis can be hard to diagnose. There is no specific diagnostic blood test and symptoms vary greatly from patient to patient.

If amyloid has already been definitively diagnosed information about the kidney function learnt through the blood and urine tests may be enough to diagnose amyloidosis in the kidney.

A kidney biopsy is often the best way to confirm whether amyloidosis is affecting the kidneys. During a biopsy, a very small sample of kidney tissue is taken and examined under a microscope.

In some people, a kidney biopsy may not be needed. For example, if amyloid has already been found in another part of the body and the kidney tests strongly suggest kidney involvement, your specialist may be able to make the diagnosis without doing a kidney biopsy.

How the biopsy is done

Most kidney biopsies are done using local anaesthetic and ultrasound guidance. This means the area is numbed, and an ultrasound scan is used to help guide the biopsy needle safely.

Step by step:

  • You will usually lie on your stomach for a biopsy of your own kidney. If the biopsy is from a transplanted kidney, you will usually lie on your back.
  • The doctor uses an ultrasound scan to find the kidney and choose the safest spot for the biopsy.
  • The skin is cleaned, and local anaesthetic is injected to numb the area. This can sting briefly.
  • A biopsy needle is passed through the skin into the kidney using ultrasound guidance. You may feel pressure, but you should not feel sharp pain.
  • You may be asked to take a deep breath and hold it for 5 to 10 seconds while the sample is taken.
  • Usually, 2 to 3 small samples are taken.
  • A dressing is placed over the biopsy site after the procedure.
  • The procedure commonly takes about 30 to 60 minutes.

After the biopsy, you will be monitored for several hours. Your blood pressure, pulse and urine will be checked, as bleeding is the main risk after a kidney biopsy.

Blood tests, taking blood from a vein:

  • To measure the number of red and white blood cell and platelets
  • To measure the serum(blood fluid) free light chains and serum protein electrophoresis
  • Measure the body’s clotting function
  • Identify markers to indicate kidney, heart and liver function.

Tests to assess kidney function

These tests help your healthcare team understand how well your kidneys are working and monitor any changes over time.

Serum creatinine

Creatinine is a waste product that comes from the normal wear and tear of muscles.

The kidneys usually remove creatinine from the blood. When kidney function gets worse, the level of creatinine in the blood often rises.

Creatinine levels can vary between people depending on age, body size, muscle mass and other factors. For this reason, creatinine is usually used together with other information to estimate kidney function.

Estimated glomerular filtration rate, or eGFR

The estimated glomerular filtration rate, usually called eGFR, is a blood test result that gives an estimate of how well your kidneys are filtering waste and extra fluid from your blood.

The eGFR is calculated using your blood creatinine level, age and sex. In some situations, other factors may also be considered.

A lower eGFR generally means the kidneys are not filtering as well. Your healthcare team will interpret your eGFR together with your urine tests, symptoms, medical history and overall health.

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Treatment

Treatment for kidney amyloidosis usually has three main aims:

  • To stop or slow down the production of the amyloid-forming protein
  • To support and protect the organs affected by amyloid, including the kidneys
  • To maintain wellbeing and quality of life

Your healthcare team

People with kidney amyloidosis are usually cared for by a team of health professionals. This team may not all be in the same clinic or hospital, and you may not see everyone at the same time.

Your team may include:

  • a kidney specialist, also called a nephrologist
  • a haematologist, especially for AL amyloidosis
  • other specialists, depending on which organs are affected, such as a cardiologist, neurologist or gastroenterologist
  • a pharmacist
  • a specialist nurse
  • a dietitian
  • a psychologist, social worker or counsellor
  • an exercise physiologist or physiotherapist

The treatment recommended will depend on the type of amyloidosis, which organs are affected, and your overall health.

AL amyloidosis

Treatment aims to reduce the abnormal light chains made by cells in the bone marrow. These light chains are the proteins that form amyloid in AL amyloidosis. Treatment often uses medicines similar to those used for myeloma, including combinations of chemotherapy, targeted therapy and antibody treatments. If treatment reduces light chain production, kidney function and protein leakage may stabilise or improve.

AA amyloidosis

Treatment focuses on controlling the underlying inflammatory condition that is causing the body to produce too much serum amyloid A protein. If the inflammation is well controlled, amyloid production can fall, and kidney function may stabilise or gradually improve.

ATTR amyloidosis

ATTR amyloidosis is caused by changes in a protein called transthyretin, or TTR. This may be hereditary or age-related. Some treatments aim to stabilise the TTR protein, while others reduce the amount of TTR made by the liver. Your specialist will discuss whether any of these treatments are suitable or available for your type of ATTR amyloidosis.

For more information, see the sections on the individual types of amyloidosis.

Supportive treatments are very important. They help manage symptoms, protect kidney function where possible, and improve day-to-day wellbeing.

Supportive treatment may include:

  • Blood pressure management. Good blood pressure control can help protect the kidneys. In amyloidosis, blood pressure may be high, normal or sometimes low, so treatment needs to be individualised.
  • Managing fluid balance. Some people retain extra fluid, causing ankle swelling, weight gain or shortness of breath.
  • Diuretics, also called fluid tablets. These medicines help the body pass extra salt and water in the urine.
  • Reducing salt intake. A lower-salt diet can help reduce fluid retention and blood pressure.
  • Avoiding medicines that may harm the kidneys. This includes non-steroidal anti-inflammatory drugs, often called NSAIDs, such as ibuprofen, naproxen or diclofenac, unless your doctor specifically advises otherwise.
  • Dietitian support. A dietitian can help with salt, fluid, protein, cholesterol and weight management.
  • Managing cholesterol and heart risk. Kidney amyloidosis can cause high cholesterol, especially when there is heavy protein leakage in the urine.
  • Maintaining strength and activity. Exercise advice may help with fatigue, muscle strength and general wellbeing.

People with amyloidosis may also have symptoms from other organs, or side effects from treatment. Your healthcare team can help manage these symptoms and adjust treatment as needed.

If the eGFR is at 15 and dropping the body will have increasing difficulty getting rid of waste products and excess water.
Dialysis, which means the removal of excess water and waste products, will probably be discussed.

There are several things you can do to help manage kidney amyloidosis and support your overall wellbeing.

  • Learn about your type of amyloidosis. Understanding which type of amyloidosis you have, and how it is affecting your kidneys and other organs, can help you feel more confident in your care.
  • Work with your healthcare team on fluid and salt intake. Some people with kidney amyloidosis need to limit salt or fluid, especially if they have swelling or fluid retention. Your team will guide you on what is right for you.
  • Monitor your weight. Weigh yourself regularly and keep a record. A sudden increase in weight may mean your body is holding on to extra fluid. Let your nurse or doctor know if this happens.
  • Stay active where possible. Gentle, regular activity can help maintain strength, circulation, energy levels and wellbeing. Ask your healthcare team what type of exercise is safe for you.
  • Avoid medicines that may harm the kidneys. Non-steroidal anti-inflammatory drugs, also called NSAIDs, can sometimes worsen kidney function. These include medicines such as ibuprofen, naproxen and diclofenac. Check with your doctor or pharmacist before using them.
  • Tell your healthcare team about all medicines and supplements. This includes over-the-counter medicines, vitamins, herbal products and other supplements.
  • Stay connected. Keeping in touch with family, friends and your community can help support your emotional wellbeing.
  • Consider writing things down. Some people find it helpful to keep a diary of symptoms, questions, appointments, test results or their personal story.
  • Connect with others. Joining a support group, either online or in person, can help you share experiences, learn from others and feel less alone.

See section “Living with amyloidosis”

More useful information from Kidney health Australia. Dialysis and travel. Knowing your kidneys