AKI and CKD

Question 1

what is Glomerular Filtration Rate (GFR)

Answer 1

the rate at which the glomerulus is filtering the blood to form the filtrate

Males 90-140 ml/min
Females 80-125ml/min

Question 2

how do you estimate GFR?

Answer 2

To be able to measure GFR we need a substance that is:
- completely filtered
- not re-absorbed
- not secreted
- not metabolised by the nephron
(10ml of solution in blood - collect urine and there is 10ml)

Inulin fits this profile (100% gets filtered) BUT it requires an infusion into the blood therefore not practical - it takes a long time

In practice – creatinine clearance is measured

Question 3

what is creatinine?

what is it produced by?

Answer 3

It is a chemical waste molecule that is generated from muscle metabolism

Produced from creatine, a molecule of major importance for energy production in muscles

Released into the circulation at a constant rate
Removed from the circulation by filtration and excreted in urine

Question 4

Why is it important to check blood creatinine levels?

Answer 4

Measurement of creatinine concentration is used to:

- Determine sufficiency of kidney function
- Determine severity of kidney damage
- Monitor progression of kidney disease

Kidneys maintain blood creatinine at a specific levels

If creatinine levels in the blood are rising it could indicated that the kidneys are not functioning to their full ability to clear the creatinine

Problems with kidney function may lead to:
Loss of nutrients from the body
Failure to remove toxins
Affect drug treatments
Affect blood pressure

Question 5

what is creatinine clearance

Answer 5

It is a value which indicates the volume of creatinine (in millilitres) removed by the kidneys over a period of time (per minute)

Question 6

how is creatinine clearance measured?

Answer 6

24 hour urine collection = not practical

In practice: blood is taken from the patient. This is measuring the amount of creatinine in the blood plasma.

The higher the level of creatinine in the blood, the slower the kidneys are working = low creatinine clearance (mL/min)

Question 7

How can creatinine clearance be calculated?

Answer 7

Cockcroft & Gault equation:

```
CrCl = F(140-age) x weight / Serum Creatinine
F = 1.04 in females, F = 1.23 in males
Units = ml/min
~~~

Question 8

difference between eGFR and creatinine clearance

Answer 8

eGFR = estimated glomerlus filtration rate = which is measured via blood tests in labs = this has a chance of over estimating renal function

Question 9

when does creatinine clearance have to be calculated

Answer 9

DOACs
Nephrotoxic drugs
> 75 years
Extremes of muscle mass
Drugs that are ++renally excreted
Narrow therapeutic index drugs

Question 10

how can serum creatinine be affected?

Answer 10

1) The amount of muscle tissue you have
- Men tend to have higher levels of blood creatinine because they have more skeletal muscle tissues than women

2) High protein in diet
3) Exercise, particularly if muscle building

4) Any injuries involving damage to the muscles
- e.g. severe burns or conditions resulting in acute muscle wastage

5) Malnutrition leading to dramatic weight loss

Question 11

what is acute kidney injury (AKI)

Answer 11

AKI is NOT a disease but is the result of another clinical problem

AKI should be regarded as a spectrum of injury that may progress to organ failure

AKI occurs most commonly in patients who are at risk, who either are acutely ill or have had major surgery

Question 11

what is acute kidney injury (AKI)

Answer 11

AKI is NOT a disease but is the result of another clinical problem

AKI should be regarded as a spectrum of injury that may progress to organ failure

AKI occurs most commonly in patients who are at risk, who either are acutely ill or have had major surgery

Question 12

what are the risk factors of AKI?

Answer 12

Age >75 years
Previous AKI
Pre-existing CKD (eGFR <60ml/kg/1.73m2)
Heart failure
Atherosclerotic peripheral vascular disease (PVD)
Diabetes mellitus
Liver disease
Debility and dementia

Question 13

what are triggers for AKI

Answer 13

Sepsis or infection
Hypotension (Mean arterial pressure <65 mmHg, systolic pressure <90 mmHg)
Hypovolaemia (dehydration, bleeding)
Nephrotoxic medications e.g. gentamicin, NSAIDs, iodinated contrast
Anti-hypertensives e.g. ACE inhibitors, loop diuretics

Question 14

what are the three classifications of AKI

Answer 14

Pre renal - inadequate perfusion - not enough blood at sufficient pressure to allow filtering

renal - cellular damage/ intrinsic - damage to the cells that makes filtering mechanisms possible

post renal - obstruction - urine unable to drain adequately - system ‘backed up’

Question 15

Pre - renal

mechanism
causes

Answer 15

mechanism - Blood flow to the kidney reduced i.e. decreased perfusion. If not managed it can cause ischaemic injury.

cause :
- Intravascular volume depletion e.g. diarrhoea, vomiting or haemorrhage
- Decreased arterial pressure e.g. heart failure or sepsis
- Nephrotoxic medications e.g. ACEIs, ARBs, NSAIDs
- Kidney function typically returns to baseline after volume status established or nephrotoxic
medication discontinued

Question 16

post renal AKI

mechanism
causes

Answer 16

mechanism - Obstruction to outflow from the kidneys.

causes:
Causes waste (urine) to build up in the kidneys
Common causes include:
- kidney stones: mainly occurs in the ureters but may also develop in the urethra
- benign prostatic hyperplasia (BPH)
- CNS disorders that may affect outflow such as stroke, multiple sclerosis, spinal cord injury,
- blood clots in the ureters or urethra
- cancer of the prostate, cervix or colon
- nephrotoxic medications

Question 17

Renal/ intrinsic AKI

mechanism
causes

Answer 17

mechanism:
Damage to the functional tissues of the kidney

causes:
Can be categorised by the component of the kidney that is affected e.g.
- Glomerular: glomerulonephritis
- Tubular: acute tubular necrosis; rhabdomyolysis; myeloma
- Interstitial: interstitial nephritis

Acute tubular necrosis (ATN) is most common in hospitalised patients
In contrast to pre-renal causes, ATN does not improve with adequate repletion of intravascular volume
May resolve over time but temporary renal replacement therapy (i.e. dialysis) may be required
Common cause is usually ischaemic (prolonged hypotension) or due to nephrotoxic drugs

Question 18

what is the management for pre-renal AKI

Answer 18

hydration with IV fluids

Question 19

what is the management for post-renal AKI

Answer 19

refer patient to a urologist

Question 20

what is the management for intrinsic?

Answer 20

treat the damage…if treatable!

Question 21

what are other management options for AKI ( in terms of medication)

Answer 21

Hold all nephrotoxic medications

Adjust doses of all other medications that are prescribed

Question 22

what are possible further complications of AKI?

Answer 22

Hyperkalaemia  high potassium levels in blood
Metabolic acidosis  blood is too acidic; pH <7.25
Fluid overload  peripheral and/or pulmonary oedema
Uraemic encephalopathy  high urea levels in the blood

Question 23

what is the management of hyperkalemia?

Answer 23

AKI causes concentration of potassium in the blood stream to increase

Can have very severe consequences, in particular altering electrophysiology leading to cardiac arrhythmias

Acute treatment with Insulin or Salbutamol causes a shift of potassium from the blood stream into cells

Dietary potassium should be restricted

If potassium persistently high, patients may need to undergo urgent dialysis

Question 24

what is the management of acidosis?

Answer 24

In AKI acidosis occurs as the kidneys are no longer able to excrete H+ ions This rise causes the blood to become acidic Solution  to neutralise the pH of the blood IV Sodium bicarbonate is given and often these patients are admitted to HDU/ITU

Question 25

what is the management of odema?

Answer 25

In AKI oedema occurs as the kidneys are no longer able remove water or sodium as efficiently Give a loop diuretic e.g. furosemide; often needs to be given IV at a high dose Monitor serum creatinine as there is a risk of worsening pre-renal AKI through dehydration Not all patients will be responsive If persistently fluid overloaded, patients may need to undergo urgent dialysis

Question 26

what is the management of uraemic encephalothopy

Answer 26

In AKI uraemia occurs as the kidneys are no longer able remove urea as efficiently Urea is toxic and able to cross the blood brain barrier causing encephalopathy Encephalopathy can range in severity from mild confusion to coma Patients with uraemic encephalopathy must undergo urgent renal replacement therapy (dialysis) to remove the toxic urea from the blood

Question 27

what are nephrotoxic medications

Answer 27

``` Medications with nephrotoxic potential which must be reviewed in patients with AKI (or those at risk of AKI) include: ACEIs ARBs NSAIDs Diuretics Aminoglycosides Iodinated contrast agents ```

Question 28

what does the afferent and efferent arterioles do when there is low blood pressure.

Answer 28

deliver more blood to glomerlus and prevent blood from leaving the glomerlus keep blood in glomerlus to improve perfusion When renal perfusion is low (i.e. decreased blood pressure) the body does the following in the blood vessels of the glomerulus: - vasoconstricts the efferent blood vessels - vasodilates the afferent blood vessels

Question 29

what does prostaglandins do?

Answer 29

produced by macular densa cells | causes vasodilation of the affarent arteriole

Question 30

what does angiotensin 2 do?

Answer 30

vasoconstriction of the efferent arteriole | -concentrates the blood in the glomerlus

Question 31

what does NSAIDs do? | in regards to AKI

Answer 31

inhibit prostaglandins - prevents vasodilation of the afferent arteriole = preventing maximum blood entering the glomerlus

Question 32

what does ACEi do? | in regards to AKI?

Answer 32

inhibits conversion of angiotensin I to angiotensin II causes vasoconstriction on the efferent arteriole to increase resistance of the blood leaving the glomerulus - more concentrate blood in the glomerulus preventing reperfusion Paradoxically, ACEIs are also renoprotective but can cross over into being nephrotoxic - patients with stable kidney even if they have kidney disease poor renal function but is stable = fine to continue acei acute kidney problem = stop acei

Question 33

things to bear in mind before starting medications for people with AKI

Answer 33

Do not initiate in patients that are at a higher risk of AKI  always consider risk Vs benefit Hold drugs if patient is pre-op Discontinue drugs immediately if patient has an AKI

Question 34

what is chronic kidney disease?

Answer 34

“abnormalities of kidney function or structure present for more than 3 months, with implications for health” Common, frequently unrecognised and often exists with other conditions e.g. CV disease or diabetes 200-9/10 £1.5billion (1.3% of NHS spend) 2% of the above was for renal replacement therapy ~30% of people with advanced kidney disease are referred late to nephrology, causing increased mortality and morbidity Risk increases with age Asymptomatic

Question 35

what are the risk factors of CKD?

Answer 35

``` Diabetes mellitus Hypertension Cardiovascular disease Hypercholesterolaemia Obesity Metabolic syndrome Age and race AKI Malignancy Family history of CKD Kidney stones Infections like Hep C and HIB Autoimmune disease ``` Long-term & regular use of nephrotoxic medications e.g. NSAIDs or lithium Glomerulonephritis: kidney inflammation Polycystic Kidney Disease: an inherited condition where growth called cysts develop in the kidneys Blockages in the flow of urine: recurrent kidney stones or an enlarged prostate

Question 36

how does diagnosing CKD work?

Answer 36

Diagnosing CKD is done according to the classifications however there are certain prompts or findings that will lead to checking the GFR. These can be: Persistent microalbuminuria Persistent proteinuria Persistent haematuria (after excluding other causes) OR, it could be as a result of imaging e.g. Ultrasound or biopsy

Question 37

what are clinical complications of CKD

Answer 37

``` There are multiple complications with CKD result in the majority of renal patients being on long-term medications: Chronic anaemia Hypertension Hypercalcaemia Hyperphosphataemia Chronic vitamin D deficiency Pulmonary oedema Acidosis ``` ``` Other clinical complications include: Renal osteodystrophy Hyperparathyroidism resulting in bone changes Uraemic encephalopathy Peripheral neuropathy Coagulopathy ```