Renal dysfunction Flashcards
How many deaths each year are associated with acute kidney injury
100,000 deaths each year
How many people who are 16 years and above have chronic kidney disease
6%
What does think kidneys campaign do
- when to stop and re-start medicines
- guidance on sick days
- minimum data required to be communicated when a patient is discharged from hospital following an episode of AKI
Which drugs should not be given in kidney dysfunction
- NSAIDs
- strong opioids
- indapamide - direutics can cause hypvolaemia whcih can cause AKI
- amlodipine - not known to cause AKI but can cause hypotension and contribute to AKI
What are the three different classification of acute kidney injury
- Pre-renal
- renal
- post renal
Describe pre-renal AKI
- reversible impairment of renal function from relative hypovolaemia or hypoperfusion
- any condition reducing renal perfusion can potentially impair renal function
Describe renal AKI
- damage within the kidney could result from more severe ischaemia, sepsis, inflammation or toxicity ( renal cells are sensitive to inflammatory or ischaemic injury)
Describe post renal AKI
- Obstruction to urine outflow (e.g. enlarged prostate in men) causes a damaging back pressure within the kidney
Describe the 3 stages of severity of AKI
Stage 1
- creatine rise of 26 micromol/litre or more within 48 hours or
- creatine rise of greater than or equal to x 1.5 from baseline in 7 days or
- reduced urne output of less than 0.5 ml/kg/hour for more than 6 hours
Stage 2
- creatine rise of greater than and equal to x2 from the baseline or
- reduced urine output of less than 0.5ml/kg/hour for 12 hours or more
stage 3
- creatine rise of greater than or equal to x3 fro baseline within 7 days or
- creatine rise to greater than or equal to 354 micromol/litre with either - acute rise in creatine of greater than or equal to 26 micromol/litre within 48 hours or a 50% rise from baseline within 7 days
or
- urine output of less than 0.3 ml/kg/hour for 24 hours
or
- anuria for 12 hours
or
- any requirement for renal replacement therapy
What should prescribing in AKI do
- correct hypovolaemia
- minimise renal hypoperfusion
- treat other causes such as sepsis
- avoid the use of (or withdraw) nephrotoxic agents
- consider drugs that are renally excreted and may need adjustment
what drugs can induce nephrotoxicity
- aminoglycosides
- amphotericin
- cytotoxic chemotherapy
- diuretics
- immunosuppressants
- lithium salts
- NSAIDs/COX-2 inhibitors
- radiocontrast media
describe how aminoglycosides nephrotoxicity
- they are directly nephrotoxic
- causes acute tubular necrosis
describe how amphotericin causes nephrotoxicity
- directly nephrotoxic
Describe how cytotoxic chemotherapy can cause nephrotoxicity
- e.g. cisplatin which has been associated with renal tubular damage
How does diuretics cause nephrotoxicity
lead to volume depletion
How do immunosuppressants cause nephrotoxicity
- ciclosporin and tacrolimus cause renal vasoconstriction producing ischaemia
How do lithium salts cause neprhotoxicity
- can cause tubulo-interstitial damage and chronic kidney disease with long term use
- should only be suspended if there is known lithium overdose or toxic levels
How can NSAIDs/COX-2 inhibitors cause nephrotoxicity
- renal blood flow often relies on prostaglandins
- NSAIDs and cycooxygenase-2 inhibitors reduce prostaglandin synthesis and cause renal hypoperfusion and AKI
How does radiocontrast media cause nephrotoxicity
- high ionic load can produce renal vasoconstriction leading to ischaemia
Name some synthetic and naturally occurring agents that cause nephrotoxic
Synthetic agents
- insecticides
- herbicides
Naturally occurring agents
- alkaloids from plants/fungi
- reptile venoms
- cocaine
Name pathological states that are nephrotoxic
- hypoperfusion
- sepsis
- rhabdomyolysis
- hepatorenal syndrome
describe the pathological states that are nephrotoxic
- hypoperfusion = reduces oxygen and nutrient supply to the kidney
- sepsis = endotoxins and inflammatory mediators from infection can damage the renal vascular endothelium resulting in thrombosis
- rhabdomyolysis = myoglobin released from damaged muscles precipitates in renal tubules and also reduces blood flow in the outer medulla
- hepatorenal syndrome = patients with end-stage liver disease often have renal vasoconstriction
What is the best indicator of function of the kidney
- Glomerular filtration rate (GFR)
What is the eGFR derived from
- CKD-EPI formula
- MDRD formula
In the UK what is the eGFR derived from
CKD-EPI
what is used as an estimate of eGFR
- creatine clearance
What formula can be used to measure creatine clearance
- The Cockcroft-Gault formula can be used to calculate estimated creatine clearance
when is the cockcroft-gault formula/creatine clearance used
- estimating renal function or calculating drug doses in patients with renal impairment
- older adults
- patients at extremes of muscle mass
- patients on a medicine with a low therapeutic index
if you are overweight …
eGFR is not an accurate reflection of the renal function
in what case do you not use the MDRD, CKD-EPI (or eGFR)
- extremes of weight
- children
- pregnancy
- catabolic states
- reduced muscle mass - such as extreme old age, malnutrition, amputation and other muscle disorders
what can you use if you dont use the MDRD, CKD-EPI
= serum creatine
describe glomerular filtration
- for filtration to occur the pressure within the capillary must be maintained at a fairly high level
- the afferent enters the glomerulus and the efferent arteriole leaves the glomerulus
- prostaglandins produced within the kidney maintain renal blood flow and GFR especially under conditions of reduced effective circulating volume
- angiotensin II is produced by the renin angiotensin system in response to hypovolaemia or reduced renal perfusion
- it causes effernet arteriolar vasoconstriction
what does inhibition of prostaglandin production do
- inhibition of prostaglandin production or angiotensin II can compromise glomerular filtration and lead to AKI
What are the stages of pharmacokinetics
ADME
- absorption
- distribution
- metabolism
- elimination
Describe how renal impairment affects the pharmacokinetic stages
- absorption = most drug absorption is unaffected by reduced renal function
- distribution = protein binding of some drugs are affected in renal impairment
- metabolism = some hepatic processes are affected by renal impairment but only at severe levels
- elimination = water soluble drugs are particularly affected
What happens to half life in renal impairment
- half life is prolonged in renal impairment if the drug is significantly removed by the kidney
what is the elimination half life
- The elimination half life is the time taken for the plasma concentration of a drug to fall by half
How can drug doses by adjusted in renal impairment
- reducing the amount of the regular dose given
- extending the interval between regular doses (better for maintaining specific peak and trough concentrations)
What is the ideal drug in renal impairment
- no active metabolites
- disposition unaffected by changes in fluid balance
- disposition unaffected by changes in protein binding
- pharmacodynamics unaffected by altered tissue sensitivity
- a wide therapeutic window therefore safe as doses/serum concentrations increase
- not inherently nephrotoxic
what do you need to monitor in AKI
fluid balance
How do you monitor patients in AKI
- pulse - supine and upright
- blood pressure - supine and upright
- arterial oxygen saturation
What should you do if you suspect hypovolaemia in AKI
- check the supine heart rate and blood pressure
- a rise of heart rate on standing of more than or equal to 30 beats per minute
What should you look for signs in AKI
- pulmonary oedema - examine for tachypnoea, fine bilateral basal inspiratory crackles, chest x ray signs
- fluid overload - check for pitting ankle and sacral oedema - check the patients weight daily
What fluids should you prescribe in AKI
- sodium chloride 0.9% is an appropriate IV fluid in AKI over 1 hour
- sodium bicarbonate 1.26% is a good alternative if the patient has AKI with hypovolemia and a metabolic acidosis
What are the two successive phases of AKI fluid replacement
Volume repletion
- repeated fluid challenges with infusion of 250 to 500ml or more of sodium chloride 0.9% may best regimen
- monitor vital signs, including urine output, in an acute or high dependency environment
Maintenance of fluid regimen
- adjust prescribed regimens to take account of fluid balance if the patient requires continuing IV fluid therapy
- reduce the rate of infusion so patient remains oliguric
What should you be careful with fluid replacement
- iatrogenic fluid overload risk pulmonary oedema and has recently been associated with increased mortality in AKI
- reflex prescirbing of up to 3 to 4 litres of IV fluids per day wihtout proper fluid balance assessment is wrong and risks disaster
- IV colloids do not provide any additional benefit for volume expansion and renal recovery compared with sodium chloride 0.9%
What two parameters classify CKD
- eGFR
- albumin:creatine ratio
Name the stages of CKD
- G1 - greater than 90
- G2 - 60-90
- G3a - 45-59
- G3b - 30-44
- G4 - 15-29
- G5 - less than 15
What is the most severe levels of CKD
G5
who should you only use loop diuretic therapy in CKD
- only consider diuretic therapy in fluid overload and or hyperkalaemia or hypertension in CKD
What should you do for severe fluid overload requiring urgent treatment
- use an infusion of a loop diuretic (e.g. up to 250mg of furosemide given neat via a syringe driver over 1 hour at a rate not exceeding 4mg/minute)
- do not give bolus injections of loop diuretics - high infusion rates can cause deafness
- infusions should be given with the benefit of specialist advice
Why is combination diuretic regimes not recommended
- intravascular volume depletion can occur rapidly and make renal dysfunction worse
What diuretics should not be used with CKD
- potassium sparing diuretics should not be used due to risk of hyperkalaemia
- most thiazides are ineffective in severe renal impairment
- metolazone does remain effective if the eGFR is less than 30ml/min/1.73m2 although it is associated with a risk of excessive diuresis - metolazone should only be inititiated under specialist supervision
what two combination of medicines can reduce proteinuria
- ACE inhibitors and spironolactone can reduce proteinuria
- but the risk of hyperkalaemia with this combination means it should only be used on specialist advice in renal impairment
what do you have to be careful of when prescribing ACE inhibitors to patients with CKD
- serious hypotension can occur on initiation in susceptible patients with renal impairment - those prescribed high dose diuretic treatment for fluid overload are at particular risk due to dehydration and poor renal perfusion
When prescribing ACE inhibitors with patients with CKD what should you do
- monitor blood pressure closely
- carefully titrate the dose and monitor renal function
What patients with CKD should you not use ACE inhibitors in
- Bilateral renal stenosis
- renal artery stenosis in a patient with a single functioning kidney
- known wide spread vascular disease such as renovascular disease is likely to be present compromising blood flow
describe how RAAS system causes rapid deterioration of renal function with AKI
- RAAS system is stimulated in patients with poorly perfused kidneys
- this produced angiotensin II which causes renal vasoconstriction in the efferent arterioles
- this constriction of the outflow from the glomerulus creates a back pressure which maintains filtration at the glomerulus depsite overal poor kidney perfusion
- blocking angiotensin II will lead to dilatation in efferent arterioles
- leading to loss of back pressure and failure of filtration
what is the target blood pressure for patients with
- CKD
- CKD and diabetes
- CKD = 140/90mmHg
- CKD and diabetes and those with an ACR of greater than 70mg/mmol = 130/80mmHg
How do you manage patients with hypertension
- non drug therapy = important but unlikely to provide blood pressure control to target when used alone
- Multiple antihypertensive agents = likely to be needed to provide BP control - this is particularly the case in hypertension owing to CKD
- When ACE inhibitor/ARB therapy is used titrate this to the maximum tolerated dose before adding another agent
Who should ACE/ARB inhibitors be offered to patients with CKD and..
- diabetes mellitus and an ACR of 3 mg/mmol or more (ACR A2 or A3)
- Hypertension and an ACE or 30 mg/mmol or more (ACE A3).
- an ACR of 70 mg/mmol or more, irrespective of whether the patient is hypertensive or has cardiovascular disease
What should you consider when prescribing ACE inhibitors/ARBs
- avoid them in renovascular disease patients
- avoid then in widespread vascular disease
- check the potassium concentration and eGFR before treatment and 7 days later
- do not start treatment if ACE.ARB is above the upper limit of normal - greater than 5 mmol/l
- choose a cost effective ACE/ARB that allows once daily regimen
- if the patients eGFR falls by 25% or more or serum creatinine increases by 30% or more at 7 day check look for other factors that may be causing the acute change, but if no others stop the ACE/ARB
- if a dry cough causes problems with an ACE inhibitor switch to the ARB
How can calcium channel blockers be used in hypertension in patients with CKD
- agents are useful in CKD and hypertension
- they can produce oedema which is resistance to diuretics and can be confused with a volume overload
How are diuretics used in patients with CKD and hypertension
- crucial for blood pressure control in patients with salt and volume overload particularly in CKD stage G4/G5
- and or when oedematous
How are beta blockers used in patients with CKD and hypertension
- have a limited role in hypertension management
- now mainly used in resistant hypertension, hypertension accompanied by ischaemic heart disease or hypertension with heart fialure
- use beta blockers such as bisoprolol or metoprolol as these have non renal elimination
- start with a low dose and be aware of pharmacodynamic changes
What beta blockers should you use in CKD
bisoprolol or metoprolol
why is hyperkalaemia a particular problem in AKI
- urinary excretion of potassium is reduced
- intracellular potassium may be released
what causes an increase in extracellular potassium
- rise rapidly following tissue damage such as burns, crash injuries, sepsis and ischaemia
What increase the hyperkalaemia
- hyperkalaemia is exacerbated by acidosis which causes potassium loss from cells
what drugs affect potassium levels
- Contain potassium = such as laxatives
- act to retain potassium in serum = ACE inhibitors, ARBs, potassium sparing diuretics, NSAIDs
- prevent intracellular buffering of potassium - beta blockers digoxin
What drug should you stop straight away in uncontrolled hyperkalameia
- ACE inhibitors and ARBs
what level of potassium concentration should be treated straight away
- Treat hyperkalaemia urgently if the serum potassium concentration reaches 6.5 mmol/k
what are the aims of the treatment of hyperkalaemia
- protect the heart - stabilise the myocardium
- reduce the serum potassium concentration - drive potassium into the cells
- rid the body of excess potassium - stop the drugs contributing to hyperkalaemia and reduce potassium intake
How do you protect the heart in hyperkalaemia
- stablilise the heart with IV calcium gluconate 10%, 10-20ml (2.25-4.5) over 5-10 minutes
- this stabilises the myocardium
- protective effect begins in minutes but is short lived (less than 1 hour)
- calcium chloride 10% in 10ml syringes provides 6.8 mmol of calcium is given by slow intravenous injection
Name two drugs that can be used to reduce serum potassium concentration
- nebulised salbutamol
- soluble insulin
describe nebulised salbutamol reduces serum potassium concentration
- glucose drive potassium into the cells
- in those patients where an effect is obtained it will reduce serum potassium by up to 1mmol/l and last for 2 hours
- not effective for all patients and will not lower the potassium permanently
- it is to be seen as a temporary emergency measure if used
describe how soluble insulin reduces serum potassium concentration
- 50ml of 50% glucose together with 5-10 units of soluble insulin over 10 minutes
- insulin promotes intracellular potassium uptake so reducing serum levels
- the effect becomes apparent after 15-30 minutes and peaks after about 1 hour and lasts for 2-3 hours
- it will decrease potassium by around 1mmol/l
- omit exogenous glucose if the serum glucose is more than 15mmol/l
- monitor the glucose after 30 minutes then hourly for 6 hours to check for delayed hypoglycaemia which is a common problem - the hypoglycemia effects lasts longer than the potassium lowering effect
What drugs should you stop that promote hyperkalaemia in hyperkalameia
- ACE inhibitors
- ARBs
- NSAIDS
- oral potassium supplements
- potassium-sparing diuretics
- metformin - risk of lactic acidosis
How do you correct the metabolic acidosis that develops in hyperkalaemia
- in CKD - correct acidosis with oral sodium bicarbonate 1-6g day in divided doses
- in AKI correct acidosis with 50-100mmol of IV bicarbonate ions - 1.4 to 1.26%,2 50-500mls over 15 to 60 minutes
- do not mix bicarboante and calcium in the same line as an insoluble precipitate will form
- bicarbonate activates the cell membrane Na/H exchanger producing an increase in intracellular sodium which promotes increased activity of Na-K-ATPase resulting in increased intracellular sequestration of potassium
- if the patient is fluid overload, IV sodium bicarbonate can exacerbate this - in this case dialysis may be the only viable action
What drug do you use to restrict dietary potassium
- calcium polystyrene sulphonate - 15-30g two to four times a day
How does calcium polystyrene sulphonate work
- the ion exchange resin binds potassium in the GI tract releasing calcium in exchange, thus physically removing potassium from the body
- give it in conjunction with lactulose to reduce the risk of faecal impaction
- monitor potassium closely especially as the therapeutic effect of calcium resoium can continue to work for some time even after treatment has stopped
What are the signs of hyperkalaemia in an ECG
- loss of P waves
- Prolonged PR interval
- QRS widening
