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

The kidneys are extremely important organs for the daily workings of the body.
Most people have 2 bean shaped kidneys located either side of the spine below the rib cage.
Some people are born with one kidney or lose a kidney through illness or accident. The body can manage very well with one kidney.
If neither kidney is functioning death will occur quickly.

What do the kidneys do?

  • Act as a filtration unit clearing waste products from the body produced during the body’s metabolism.
  • Regulate body fluids and salt levels regardless of the environment a person is living in.
  • Clear medications/drugs from the body.
  • Regulate the body’s salt, potassium and acid content.
  • Release hormones which help to control blood pressure and control calcium metabolism.
  • Activate vitamin D, produced in the skin, and produce Erythropoietin (EPO) a hormone that promotes the formation of red blood cells by the bone marrow.

How do the kidneys work?

The kidneys, Ureters and bladder are part of the Urinary system.
The nephron is the functional unit of filtration and collection in the kidney.
Each kidney has over a million nephrons/ filtering units.
Each nephron includes a tiny filter called a glomerulus attached to a tubule.

All the blood from the body passes through the kidneys many times each day. The kidneys filter approximately 140 quarts of blood a day.

  • Blood enters the kidney through the right renal artery. This large blood vessel then branches into many smaller vessels.
  • Blood flows into the nephron under pressure and enters a cluster of tiny blood vessels—the glomerulus, (the filter system).
  • The thin walls of the glomerulus allow smaller molecules, wastes, and fluid—mostly water—to pass into the tubule.
  • In the tubule water and chemicals are added to and removed from the filtered fluids according to the body’s needs.
  • Larger molecules, such as proteins and blood cells cannot get through the barrier and stay in the blood vessel.
  • The blood leaves the kidney and enters the body by the renal vein.
  • The remaining waste fluid in the tubule become pre-urine which then 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 approximately 2 liters of urine are produced every day.

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

Watch: How do your kidneys work? By Emma Bryce

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 glomerulus.
  • Amyloid deposition and accumulation disrupts tissue architecture which then interferes with kidney function.
  • The speed of progression of deposition varies depending on the type of amyloidosis.

Symptoms

Symptoms vary between patients and can be very vague.
Even when there is considerable kidney damage (up to 80%) some people experience few symptoms.
Many of the symptoms mimic other types of kidney disease and other diseases. This can result in delayed diagnosis.

  • 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.

The amyloid targets the glomeruli in approximately 75% of those with renal amyloidosis.

The build of the amyloid proteins in the glomeruli will slowly damage kidney’s filtration and collection system.

This damage can result in:

  • Interference with the clearance of waste products by the kidneys with the result that waste products build up in the blood.
  • Kidneys start leaking protein into the urine (proteinuria). This loss of protein causes changes in the blood which result in fluid buildup in the body tissues. (Nephrotic syndrome).
  • When the body loses large amounts of protein, the blood protein called albumin can became low.
    Albumin acts like a sponge drawing extra fluid from the body into the blood stream where it remains until the kidneys can remove it.
    When albumin leaks into the urine the blood loses its capacity to absorb fluid from the body and it can accumulate in the ankles feet, hands and other areas causing swelling/oedema.
    If fluid builds up in the lungs this can result in breathlessness.
  • The kidneys ability to handle salt and water balance becomes impaired.
  • Difficulty keeping the body’s blood chemistry with in safe limits especially potassium levels.
  • A drop in the EPO which can result in anaemia.
  • Scarring or hardening of the tiny blood vessels with in the kidney.
  • A breakdown in kidney function can cause blood cholesterol to rise to high levels.
  • If the deposition of the amyloid protein into the kidneys continues for too long the kidney function will worsen, leading to kidney failure.
  • Kidney failure can lead to the need to consider dialysis and in some patients a kidney transplant.

Read more on dialysis and types of dialysis

Albuminuria. An increased amount of the protein albumin in the urine.
Hyperlipidemia. A person’s blood has more than normal amounts of blood and cholesterol.
Hypoalbuminemia. When a person’s blood contains less than the normal albumin.

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 definitive diagnosis of amyloidosis can only be made through a biopsy.

  • A biopsy can be taken from the fat pad on the stomach or from the symptomatic organ such as the kidney.
  • A kidney biopsy will involve taking a small piece of tissue from the kidney. https://www.healthline.com/health/renal-biopsy.
  • This tissue is then stained with Congo red dye and examined under a microscope using polarized light. If amyloid is present, the stained tissue shows up as red, turning to apple green birefringence,
  • If a diagnosis of amyloidosis is proven other tests will then be performed on the biopsy using special stains and laser microdissection followed by mass spectrometry (LMD-MS) to work out the type of amyloidosis. It is imperative that the “type” of is known as treatments vary between types.

Other tests may be performed at this time to help with the diagnosis, establish the level of kidney damage and ascertain whether other organs involved.

Some tests will then be run routinely to monitor disease and treatment.

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.

Serum creatinine
Creatinine is a waste product that comes from the normal wear and tear on muscles of the body.
Creatinine levels in the blood vary depending on age, race and body size.
As kidney disease progresses creatinine in the blood usually rises.

Glomerular Filtration Rate. eGFR
Estimated Glomerular Filtration Rate (eGFR) is a key indicator of renal function.
GFR is a mathematically derived entity based on a patient’s serum creatinine level, age, sex and race.

GFR Stages

  1. Normal – 100/120
  2. Damage becoming obvious – 60 and below
  3. Symptomatic – 30 and below
  4. Kidney Failure – 15 and below
  5. Dialysis needed – 7/8

Blood urea nitrogen (BUN)
Urea nitrogen comes from the breakdown of protein in the foods we eat.
Normal BUN level is between 7 and 20. As kidney function decreases, the BUN level rises.

Normal BUN level is between 7 and 20. As kidney function decreases, the BUN level rises.

Urine analysis. The testing of a urine sample

  • Dip stick test. This consists of a chemically treated strip being dipped into a urine sample. This test can show excesses amount of protein, blood and bacteria in the urine. If an excessive amount of protein is detected this is called proteinuria.
  • This test does not show whether the protein is amyloid protein.
  • A special test will be done to measure any free light chains in the urine known as Bence Jones Proteins

Microalbuminuria

  • A sensitive dipstick test can detect albumin in the urine.
  • Albumin is a protein found in the blood. Albumin does not pass into the urine in healthy kidneys
  • A damaged kidney lets some albumin pass into the urine.

Creatinine Clearance

Creatinine is a chemical waste molecule that is generated from muscle metabolism. This test compares the creatinine in a 24 hour urine sample to the creatinine in the blood to show how much waste the kidneys are filtering each minute.

Kidney ultrasound is a noninvasive diagnostic exam that produces images, which are used to assess the size, shape, and location of the kidneys.

Ultrasound may also be used to assess blood flow to the kidneys.

Go to the section on “What is Amyloidosis?” and separate section on the different types of amyloidosis

Treatment

Aims of treatment are three fold:

  • To stop or slow the amyloid production.
  • To care for the damaged organs/supportive treatment.
  • To maintain and improve quality of life.

Medical care for those with renal amyloidosis will usually be given by a multidisciplinary team (not necessarily under one roof and not always seen at the same time) consisting of a renal physician/kidney specialist and a haematologist.

Other medical specialists on the team will vary according to which other organs are involved.

Other members of the team:

  • Pharmacist
  • Specialized nurse
  • Dietician
  • Psychologist/social worker/counselor
  • Exercise physiologist

There is no “approved” amyloidosis treatment at this time anywhere in the world to stop the production of the abnormal protein amyloid, which deposits in the organs and tissues in all type of amyloidosis.

Present treatments in AL amyloidosis have been borrowed from those which have been shown to work in myeloma, also a bone marrow disease. If the treatment reduces the production of the “light chains” there is a chance that kidney function may improve.

In AA amyloidosis if the underlying inflammatory disease is successfully controlled the production of the amyloid protein SAA may eventually reduce slowly improving organ function including kidney function.

In both hereditary and wild type ATTR a number of treatments are being trialed to stop the production of the protein in the liver, to stabilize the protein TTR in the blood or to remove the deposited protein in the organs. At this stage TTR stabilizing drugs have been introduced to therapy but these are not available in Australia as yet.

Go to section on the individual types of amyloidosis.

Supportive treatments are very important.

Patients with kidney disease due to amyloid involvement may have other organ damage due to the amyloid deposition.
This fact as well as side effects from any treatments may produce a variety of other symptoms and need other supportive treatments not mentioned below.

  • Controlling blood pressure. Well controlled blood pressure may help to slow the progression of kidney disease.
    Blood pressure in people with kidney disease for other reasons is often high, however in amyloidosis patients it may be low.
  • Controlling fluid intake.
  • Diuretics to help reduce fluid retention by promoting the excretion of fluids by increasing urine production.
  • Controlling salt input.
  • Avoiding NSAIDs non-steroidal and anti-inflammatory drugs which may damage the kidneys
  • Working with a dietician.
  • Weight control.

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.

Kidney transplant may occasionally be considered in AL patients when the patient is completely in remission but their kidney function is still failing
In AA amyloidosis a kidney transplant may be considered if the underlying chronic infection causing the diseases is completely under control.

Some tips for patient’s self-management

  • Understand your own unique type of amyloidosis disease and how this is affecting your kidneys and other organs of your body.
  • Work with your treatment team to satisfactorily control fluid and salt intake.
  • Monitor weight. Keep a diary and note weight changes. A sudden weight gain may indicate that the body is retaining too much fluid and should be reported to the nurse or doctor.
  • Taking gentle regular exercise to improve circulation and muscle tone and enhance well-being.
  • Avoiding NSAIDs non-steroidal and anti-inflammatory drugs which may damage the kidneys. Talk with you medical team about this.
  • Always inform the medical team about non-prescription drugs, vitamins and other supplements you may be taking or wish to take.
  • Keep up your outside friendships as much as possible.
  • Write your story
  • Join in a support group, on line or in person.

See section “Living with amyloidosis”

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

Amyloid and the Kidney

Meet the kidneys! (video) | Khan Academy