Slide 1

Chronic Kidney
Disease
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Chronic Kidney Disease

 All conditions of the kidney

 Characterised by a slow and progressive loss

of kidney function

 Lasting at least 3 months

 Evidence of kidney damage and/or reduced

kidney function

 Undetected until kidney function less than 25%

 Kidney failure -> dangerous levels of waste

and fluid can build up in the body

Chronic kidney disease refers to all conditions of the kidney, characterised by a slow and
progressive loss of kidney function, lasting at least 3 months.
Where a person has had evidence of kidney damage and/or reduced kidney function,
regardless of the specific diagnosis of disease or condition causing the disease.
Evidence of kidney damage manifests as either urinary protein or albumin, a type of protein
that is a more sensitive and specific marker of kidney disease, blood in the urine, or scarring
detected by imaging tests.
Eventually, a person will develop permanent kidney failure.
Chronic kidney disease, also known as chronic renal failure, chronic renal disease, or chronic
kidney failure, is much more widespread than people realize; it often goes undetected and
undiagnosed until the disease is well advanced.
It is not unusual for people to realize they have chronic kidney failure only when their kidney
function is down to 25 percent of normal.
As kidney failure advances and the organ's function is severely impaired, dangerous levels of
waste and fluid can rapidly build up in the body.
Treatment is aimed at stopping or slowing down the progression of the disease - this is
usually done by controlling its underlying cause.
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Statistics
 Affects 1 in 10 Australians adults

 Contributing to 1 in 9 deaths

 Co-morbidities = cardiovascular disease and type 2 diabetes

 Risk factors = overweight and obesity, physical inactivity, poor diet,

tobacco smoking, and hypertension

CKD is more common than is widely known, affecting 1 in 10 Australians adults (1.7 million
people) and contributing to 1 in 9 deaths.
The elderly, Indigenous Australians and people living in remote and socioeconomically
disadvantaged areas are at an increased risk of CKD.
CKD closely co-exists with cardiovascular disease and type 2 diabetes, with these three
diseases accounting for around a quarter of the entire disease burden in Australia.
Accordingly, CKD shares a number of common risk factors with these other chronic diseases,
including: overweight and obesity, physical inactivity, poor diet, tobacco smoking,
hypertension, having family history of kidney disease and
being of Aboriginal or Torres Strait Islander origin.
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Stages of Chronis Kidney Disease

Diagnosis =
• Decline of kidney function for more than 3 months
• Evidence of kidney damage
• Declining GFR

GFR % of kidney Function

Stage 1 Kidney damage with normal >90ml/min 90-100%

function
Stage 2 Kidney damage with mild loss of 60-89ml/min 60-89%
kidney function
Stage 3 Moderate loss of kidney function 30-59 ml/min 30-59%

Stage 4 Severe loss of kidney function 15-29ml/min 15-29%

Stage 5 Kidney Failure <15ml/min < 15%

The diagnosis of CKD requires the following:

Decline of kidney function for 3 months or more AND

Evidence of kidney damage through either albuminuria or abnormal biopsy OR
Glomerular filtration rate less than 60 mL/min

Glomerular filtration rate is a test used to check how well the kidneys are working.
Specifically, it estimates how much blood passes through the glomeruli each minute.
Glomeruli are the tiny filters in the kidneys that filter waste from the blood

Chronic renal disease is categorised into 5 stages according to the level of reduced kidney
function and evidence of kidney damage.
Stages of CKD are measured by the glomerular filtration rate, which is the amount of blood
the kidneys clear of waste products in one minute.
An individual can move up and down through the first four stages of severity, but once they
reach stage 5, their kidney function does not usually improve.
In severe cases, kidney function may deteriorate to the extent that it is no longer sufficient
to sustain life and, if untreated, will most likely cause death.
This is called End-stage kidney disease and those affected by this disease require kidney
replacement therapy - either dialysis or kidney transplant - to survive.
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Pathogenesis of chronic Kidney Disease

 Causes:
 Glomerular disease - Glomerulonephritis

 Chronic infections

 Congenital anomalies

 Vascular diseases – hypertension

 Urinary tract obstructions

 Collagen diseases

 Nephrotic agents Glomerulonephritis Hypertensive

Nephropathy-
 Endocrine diseases - diabetes renal arterial
hyalinosis

Chronic renal disease typically results from:

Chronic glomerular disease, such as glomerulonephritis which affects the capillaries in the
glomeruli
Chronic infections such chronic pyelonephritis and tuberculosis
Congenital anomalies such as polycystic kidney disease
Vascular diseases such as hypertension and nephrosclerosis which causes hardening of the
kidneys
Obstructions such as renal calculi
Collagen diseases such as lupus
Nephrotoxic agents such as long term aminoglycoside therapy
And endocrine diseases such as diabetic nephropathy
Slide 6

Pathogenesis of Chronic Kidney Disease

Damage Nephron

Adaptive hyper filtration

↑ Glomerular ↑ Renin angiotensin

permeability aldosterone system

↑ filtration of proteins
Hypertension
and
macromolecules

inflammation and of the

glomerulus and tubules

Fibrosis and sclerosis of the

glomerulus and tubules

↓ GFR ↓ Urine output Systemic complications

Nephron damage is progressive

Damaged nephrons can no longer function

Healthy nephrons compensate for destroyed nephrons by enlarging, compensatory

hypertrophy, and increasing their clearance capacity, adaptive hyper filtration

Initial hyper filtration activates the renin angiotensin aldosterone system, which also further
increases hypertension, and increases glomerular permeability leading to proteinuria,
protein in the urine

The hyper filtration in the nephrons is so overwhelming, eventually causes inflammation and
subsequently fibrosis and sclerosis of the glomerulus and tubules, leading to their
destruction occurs

Progressively this leads to gradual decline in the glomerular filtration rate and decreased
urine output

If this condition continues unchecked, toxins accumulate in the body and produce fatal
changes in all major organ systems

The kidneys can maintain relatively normal function until about 75% of the nephrons are
non functional
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Vascular diseases – hypertension

 Damage blood vessels -> reduce

blood supply to the kidneys

 Damage glomerulus
 Focal segmental sclerosis – hardening
of sections of glomerulus

 Nephrosclerosis – hardening of entire

nephron

Hypertension is a leading cause of CKD.

Over time, high blood pressure can damage blood vessels throughout your body.
Elevated systemic blood pressures causes a hypertrophic response leading to intimal
thickening of the large and the small vasculature.
This can reduce the blood supply to important organs like the kidneys.

High blood pressure also damages the glomerulus.

Causing Focal segmental sclerosis, scarring of small sections of each glomerulus, only a
limited number of glomeruli are damaged at first.
Leading to Nephrosclerosis, hardening of the entire nephron

As a result, the kidneys may stop removing wastes and extra fluid from your blood.
The extra fluid in your blood vessels may build up and raise blood pressure even more.

Chronically these changes lead to tubular and glomerular loss causing nephrons loss.
Slide 8

Glomerular disease - Glomerulonephritis

 Inflammation of the glomeruli

 Post-streptococcal glomerulonephritis (type III

hypersensitivity)

 Immune complex forms – antibodies to

streptococcus

 Immune response

 Immune complex settles in glomeruli = inflammation

 Complement proteins = inflammation

 Recruit immune cells (oxidants and proteases) =

damage glomeruli

Glomerulonephritis is inflammation of the glomeruli.

Glomerulonephritis can come on suddenly (acute) or gradually (chronic).
Glomerulonephritis occurs on its own or as part of another disease, such as lupus or
diabetes.
Severe or prolonged inflammation associated with glomerulonephritis can damage your
kidneys.

Conditions that can lead to inflammation of the kidneys' glomeruli include Post-
streptococcal glomerulonephritis.
Glomerulonephritis may develop a week or two after recovery from a strep throat infection.
To fight the infection, the immune system produces extra antibodies that can eventually
settle in the glomeruli, causing inflammation.
Some members of the complement system such as C5a have been implicated in
inflammatory injury via inducing antibody deposition and activation and recruitment of
immune cells including neutrophil, macrophage/monocyte, platelets and T-cells.
These cells produce oxidants and proteases that cause fibrin deposition, capillary wall
damage and produce proteinuria.
This response is usually characterized by fibrosis and sclerosis of the glomerulus and tubules
or the nephron.
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Complications - Reduce renal function

Regulate Water
Remove wastes from your body (nitrogenous (urea,
balance
↑Na+ and H2O retention ammonia) and other toxins)

Generalised Oedema Retain waste products and toxins (uraemia)

Bad breath, things taste different
Urine production
Urinate frequently and at Nausea and viomiting

night (nocturia) Neuropathy – fatigue, cant think clearly

Foamy or bubbly
Electrolyte (phosphorus and
Respiratory symptoms calcium)
Electrolyte shortness of breath Synthesize active form of
Synthesize
(potassium) Reduced oxygen vitamin D
erythropoietin to ↑RBC
↑K+ blood ↓Ca absorption
production
(hyperkalaemia) ↓calcification of bones
Anaemia
arrhythmias
Fatigue

As a result of chronic renal disease, the kidneys are less able to do the following jobs to help
maintain health:
Remove wastes from your body
Release hormones that help to:
Control blood pressure
Promote strong bones
Prevent anaemia by increasing the number of red blood cells in your body
Keep the right balance of important electrolytes in your blood, including sodium, potassium,
phosphorus and calcium, and maintain water balance
Maintain the body’s balance of acid and base

The kidneys are remarkable in their ability to compensate for problems in their function.
That is why chronic kidney disease may progress without symptoms for a long time until only
very minimal kidney function is left.
Patients with stages 1-3 ([GFR] >30 mL/min) of CKD are generally asymptomatic;
water/electrolyte imbalances or endocrine/metabolic derangements are not clinically
evident.
Signs and symptoms are most evident at stages 4-5, when GFR is les than 30 mL/min.

Because the kidneys perform so many functions for the body, kidney disease can affect the
body in a large number of different ways.
Symptoms vary greatly. Several different body systems may be affected.
Notably, most patients have no decrease in urine output even with very advanced chronic
kidney disease.

Signs and symptoms of chronic kidney disease include:

Change in Urine
Kidneys make urine, so when the kidneys are failing, the urine may change.
Need to urinate frequently, especially at night (nocturia);
Need to urinate more often, or in lesser amounts than usual, with pale urine
Or may feel pressure or have difficulty urinating.
Urine may be foamy or bubbly, this can lead to an above-normal amount of protein in the
urine.

Generalized oedema or Swelling, due to Water retention.

Loss of GFR leads to sodium and water retention. Fluid moves into the extravascular space,
due to increased hydrostatic pressure, causing pitting oedema in the lower extremity
Fluid movement could also be due to hypoalbuminemia, in some diseases, leading to a low
oncotic pressure.
Failing kidneys don't remove extra fluid, which builds up in your body causing swelling in the
legs, ankles, feet, and/or hands.

Anaemia, indicated by Fatigue or reduced exercise capacity

Healthy kidneys make a hormone called erythropoietin that tells your body to make oxygen-
carrying red blood cells.
As the kidneys fail, they make less EPO.
With fewer red blood cells to carry oxygen, your muscles and brain tire very quickly.

Respiratory symptoms,
Being short of breath can be related to the kidneys in two ways.
First, extra fluid in the body can build up in the lungs. This leads to pulmonary crackles or
shortness of breath due to fluid accumulation causes pulmonary oedema and loss of air
space causing ventilation-perfusion mismatch.
This leaves less area for oxygen diffusion form the blood vessels.
And second, anaemia (a shortage of oxygen-carrying red blood cells) can leave your body
oxygen-starved and short of breath.

Hyperkalemia, or high levels of potassium, indicated by malaise or life threatening

arrhythmias, due to the inability of the kidneys to secrete potassium in the urine

Damaged kidneys fail to regulate phosphate (Hyperphosphatemia), calcium (hypocalcemia)

and produce Vitamin D.
In early stages of CKD, low levels of calcium, hypocalcemia, are due to hyperphosphatemia
(negative feedback).
When kidneys fail, their ability to activate vitamin D is lost.
Without the activated vitamin D to control calcium and phosphorus levels in the blood, PTH
will try to overcompensate.
This leads to a high bone turnover, always attempting to normalize the low calcium levels in
the blood.
Over time, this becomes leads to increased adsorption of calcium from bone, weakening the
bone structure, and as a consequence of over activation the parathyroid undergoes
hyperplasia.

Urea and other toxins accumulate in the blood, called uremia and cause life threatening
issues.
Kidneys remove wastes from the bloodstream.
When the kidneys fail, the build-up of wastes in your blood can cause severe itching, can
make food taste different and cause bad breath.
You may also notice that you stop liking to eat meat, or that you are losing weight because
you just don't feel like eating.
A severe build-up of wastes in the blood can also cause nausea and vomiting. Loss of
appetite can lead to weight loss.
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