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1

What happens when you have kidney failure?

Low GFR (glomerulus functions rate).

2

What is the terminology of renal failure?

Renal failure is the failure of the kidneys to work properly - always in terms of GFR. It is split up into two types of failure: acute kidney injury and chronic kidney disease.

3

What is the normal GFR?

100ml/min.

4

How do you know if someone has renal failure?

A lot of kidney failure is based on blood test.

5

What are the blood tests that you look for in renal failure?

1. Creatinine - comes from our muscles.
2. Urea.

6

Describe urea?

It is the main excretory product for waste nitrogen and it is formed in the liver from amino acids (urea cycle). 35g (600mmol) urea formed per day on average protein intake. Urea is the major solute in urine (main contributor to urine osmolality).

7

What is the amount of urea dependent on?

It depends on the dietary protein intake. Protein breakdown (catabolism) is increased by infections (septic), trauma and immobilisation. Bleeding into GIT (equivalent to high protein diet).

8

How does the kidney handle urea?

Urea is freely filtered. There is a variable fraction of filtered urea is reabsorbed in the tubules (back of diffusion). This fraction increases when the flow rate is slow (e.g. in a dehydrated patient, diffuse more urea back into the nephron, thus more urea in the blood.). Excretion rate depends on GFR, but relationship to GFR is not exact.

9

What happens to urea in kidney failure?

The urea rises, because the amount that is filtered has decreased due to the filtration rate decreasing. It is not nearly as good as creatinine. Urea is affected by factors other than renal function (e.g. protein diet, hydration status, intestinal bleeding).

10

Describe creatinine?

It is derived from creatine in the muscle. There is no biological function it is a purely a waste product. About 1% of muscle creatine converts spontaneously to creatinine per day (irreversible). The rate of creatinine formation is proportional to muscle mass (8-20mmol/day) - it is important to look at muscle mass. It is freely filtered and no tubular reabsorption or secretion therefore creatinine clearance rate is proportional to GFR. Plasma creatinine rises as GFR falls.

11

What is the relation between plasma creatinine and GFR?

Plasma creatinine rises as GFR falls. Plasma creatinine is an insensitive index of renal function (fails to detect early renal disease). Muscle mass varies widely in population. In an individual, serial plasma creatinine measurements can be used to monitor the course of renal disease.

Basically because the kidney is failing to get rid of waste product, so GFR decreases and creatinine increases as it is still in the blood.

12

Describe the effect of meat and fish intake on creatinine and eGFR?

Plasma creatinine rises by 10 to 30umol?l after a meat (or fish) meal. This is because creatinine formation occurs int he meat and fish, especially during cooking. This will result in a falsely low eGFR. Blood sample for creatinine should be taken after a meat and fish-free period of 12 hours (often doesn’t happen).

13

What is the most accurate measurement of GFR requires?

“Gold-standard” methods e.g. insulin clearance, 51Cr-EDTA clearance, these are impractical for everyday use. eGFR estimates the GFR using plasma creatinine.

14

What are the factors used in eGFR calculators?

Looking neither the blood test or things that measure muscle mass, so we use weight instead. Age is another factor. Older people have less muscle mass, so less creatinine. Creatinine tends to decrease with age. Women have less muscle mass then men.

15

Describe eGFR?

This is estimated glomerular filtration rate. The normal GFR is 100ml/min. It is the more accurate way of telling what kidney function is; accounts for muscle mass.

16

What are the limitations of eGFR?

It is inaccurate if muscle mass is unusually high or low (e.g. amputees, muscle wasting, body builders). eGFR is only valid for patients in steady-state i.e. with stable creatinine level. It is not valid if creatinine is rising (acute renal failure) or falling (recovery from acute kidney injury).

17

What are the two types of renal failure?

1. Acute - acute kidney injury.
2. Chronic - chronic kidney disease.

18

Describe acute kidney injury?

Rapid sudden reduction in GFR (days and weeks). It is usually eversible. 70% of these cases are due to “non-renal” causes.

19

What is the aetiology of AKI?

1. Pre-renal - problem with the blood supply getting to the kidney.
2. Renal - intrinsic to the nephrons.
3. Post-renal - blockage.

20

Describe pre-renal AKI?

There is decreased blood flow to the kidney so reduction in GFR.

21

What are the causes of pre-renal failure?

1. Low blood pressure.
2. Not enough blood to kidneys: dehydration, septic shock (huge cytokine release), haemorrhage, cardiogenic shock (heart not pumping properly, low CO) and severe renal artery stenosis.
Blood supply is sent to other important organs.

22

How is the history of a patient important?

80% of the diagnosis you can get from the diagnosis. What are the reasons for low BP: trauma or bleeding (GI bleeding); profoundly dehydrated (why might somebody be dehydrated); infection (hot and cold and shivery and coughing up green sputum); heart failure (breathless, angina, won’t be able to lie flat); recent surgery.

23

What else happens when you have an AKI?

Oliguric (less urine); generally patients have low urine output <1L/day.

24

What are the key blood tests results in AKI?

1. High creatinine.
2. Potassium: hyperkalaemia.
3. Phosphate: high.
4. Calcium: may be low.

25

What is the treatment for Pre-Renal AKI?

Fix the underlying problem: rehydrate, treat bleeding, fix heart, antibiotics for sepsis and ICU treatment for persistent low BP.

26

What happens after pre-renal AKI?

It either gets better or the person could get acute tubular necrosis (hypotensive for too long).

27

Describe renal AKI?

80% is from acute tubular necrosis (ATN) - mainly from pre-renal causes. Persistent oliguria and renal failure after correction of underlying pre-renal condition. It may take 4-6 weeks to recover, so in ATN creatinine will go up, low urine output an high potassium. During this 4-6 weeks period dialysis will occur [dialysis just keeps you alive while your kidneys are trying to get you better].

28

What is the treatment for ANT?

Maintain normal BP. Treat underlying problem. If kidneys keep getting worse, dialysis (usually when GFR <10ml/min).

29

What is the recovery of ANT?

95% get better. Polyuric phase int recovery: tubules can’t concentrate. Up to 20L urine/day (pee a lot). Need IV fluids till recovers.

30

What are the other things that can cause ANT?

Drugs and toxins (crack and gentamicin). Glomerulonephritis (inflammation of the glomerulus).

31

Describe rapidly progressive glomerulonephritis (RPGN)?

10% of acute injury in the renal form is RPGN. Acute renal failure is due to glomerular disease, it usually presents with blood and or protein in the urine. Diagnosis: renal biopsy to find out.

32

Describe post-renal AKI?

If you have a blockage from your kidneys to the outside, you will get back up. If there are stones in both ureters, or a great big tumour squashing the ureters.
1. Kidney stones.
2. Tumour.
3. Prostate hypertrophy.
4. Urinary retention.

33

What is the best way to sort out post-renal failure?

Do an ultrasound.

34

Describe chronic kidney disease?

It happens over months/years. It is the gradual decline in renal function, this decline in function is irreversible. There is elevated creatinine, urea and usually normal urine output. You want to stop the progression of the disease.

35

Describe the stages of chronic kidney disease?

1. Normal : >90ml/min (GFR). Normal kidney function but something else going on with their kidney that is intrinsic damage (leaking blood from the kidneys).
2. Early: 60-89ml/min (GFR) - there is an increased PTH. 50% of the population if they’re over the age of 50/60.
3. Moderate absorption: 30-59ml/min (GFR) - decreased calcium.
4. Severe: 15-29ml/min (GFR) - anaemia (low EPO), increased CV risk, high phosphate, acidosis, potassium may rise, and malnutrition.
5. ESRF: <15ml/min (GFR) - uraemia.

36

What are the causes of CKD?

1. Diabetes.
2. Glomerulonephritis.
3. Hypertension.
4. Loads of others.

37

What happens with an increase in CKD?

There is a gradual increase inc creatinine due to underlying disease. Scarring of glomeruli and interstitium.

38

What are the patient symptoms?

There are none in the early stages. Usually found on blood tests, the urine output is normal. Uraemia - symptoms of kidney failure.

39

What is the difference between signs and symptoms?

Symptoms are what people feel, signs are what you find with people.

40

What are the symptoms of uraemia?

1. Anorexia.
2. Nausea - like morning sickness.
3. Vomiting.
4. Itchiness (pruritus).
5. SOB (due to anaemia or fluid overload).
6. Cold intolerance.
7. Swelling.
8. Seizures.
9. Coma.

41

What are the signs of CKD?

No consistent signs early on. Most common is hypertension, oedema, pulmonary oedema and raised JVP.

42

How is CKD diagnoses?

Urea is increased so is creatinine and eGFR.

43

How are other blood tests helpful?

Kidneys produce erythropoietin, which tells the bone marrow to produce erythroid precursors (RBC precursors). If your kidneys aren’t working properly, then you won’t produce enough EPO, so you won’t produce enough RBC.

44

Describe bone disease?

Common in patients with CKD. Looks t their BP, Hb, symptoms, fluid overload and their bones.

45

Describe Vitamin D metabolism?

Vitamin D is stored in the liver, to make it active Vitamind D, there needs to be 1-alpha-hydroxylase (kidneys produce this).

46

Describe high serum phosphate in kidney failure?

You absorb phosphate in the gut, 2/3 is excreted in the urine. If your kidneys aren’t working then you excrete less phosphate in urine, so the serum phosphate will go up.

47

Describe parathyroid hormone?

PTH is a polypeptide hormone. They are there to try and make you deal with a low serum calcium or high phosphate.

48

Describe CKD findings?

1. High serum phosphate - due to decreased renal excretion.
2. Low 1,25 (OH) Vitamin D.
3. Low calcium.
4. High PTH - due to hypocalcaemia and hyperphoshatemia.
5. Excessive bone resorption of calcium.
6. Fractures.
7. Extra-osseous calcification.
8. Vascular calcification.

49

What happens if potassium is high?

Can get cardiac arrhythmias.

50

How do we prevent the deterioration of renal function?

The key thing is blood pressure, need to lower BP.