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Flashcards in Renal - Drugs and the kidney Deck (22):

What are the 3 stages of AKI?

Stage 1:
- creatinine rise of 26 micromol/L or more within 48 hours
- creatinine rise of > 1.5 x baseline in last 7 days
- urine output of < 0.5 ml/kg/hr for more than 6 hours

Stage 2:
- creatinine rise of >2 x baseline within 7 days

Stage 3:
- creatinine rise of >3 x baseline within 7 days, or
- creatinine rise to >354 micromol/ L or more
- urine output of < 0.3 ml/kg/hr for 24 hours


Nephrotoxic drugs that can precipiate AKI?

Avoiding or withdrawing these drugs in AKI is helpful
Aminoglycosides (directly nephrotoxic)
Amphotericin B
Cytotoxic chemotherapy
Diuretics (lead to volume depletion)
Immunosuppressants (tacrolimus and ciclosporin cause renal vasoconstriction producing ischaemia)
Lithium salts
Radio contrast media


Nephrotoxic pathological states

These states are toxic to the kidney and can cause AKI
1) Hypoperfusion - reduces oxygen and nutrient supply
2) Sepsis - endotoxins and inflammatory mediators can damage renal vascular endothelium causing thrombosis and increase capillary permeability causing hypoperfusion
3) Rhabdomyolysis - myoglobin released from damaged muscles
4) Hepato-renal syndrome - patients with end stage liver disease have renal vasoconstriction


When should the eGFR be used to assess renal function?

GFR is the best indication of renal function, but it is not easy to measure/ estimate. Renal function is estimated from the MDRD formula

But most of the information about drug pharmacokinetics in renal disease is calculated based on creatinine clearance from the Cockcroft-Gault equation

MDRD should not be used to assess renal function in patients with extremes of weight, children, pregnancy or catabolic states. May also not be suitable in old patients with low muscle mass


When the creatinine clearance a preferred method to assess renal function?

Creatinine clearance is used to estimate GFR but it is not strictly interchangeable with eGFR. In patients at the extremes of weight or using drugs with a narrow therapeutic windows then the creatinine clearance should be used to measure doses, rather than the eGFR


How do ACEi and NSAIDs affect glomerular filtration?

Angiotensin II constricts the efferent arteriole, which maintains pressure within the glomerulus if blood flow changes within the afferent arteriole so ACEi cause efferent arteriolar dilatation. This increases outflow from the glomerulus and reduces pressure

NSAIDs inhibit prostaglandin synthesis. These are vasodilators and dilate the afferent arteriole to maintain hydrostatic pressure in the glomerulus


Pharmacokinetic changes in kidney disease

All stages of drug kinetics can potentially be altered by renal impairment, but luckily not all of these result in clinically important consequences

Remember, "ADME"
- Absorption - most drug absorption is unaffected by renal disease
- Distribution - protein binding of some drugs is affected in renal disease
- Metabolism - some hepatic processes are affected by renal dysfunction but only at severe levels
- Elimination - water soluble drugs are particularly affected

Elimination half life is the time it takes for half the plasma concentration of the drug to be removed. Half life is prolonged in renal impairment if the drug is removed by the kidney. Extent of drug accumulation is proportional to the prolongation of the half life


How should fluid balance be monitored in AKI?

Pulse - supine and upright (where possible)
Blood pressure - supine and upright
Arterial oxygen saturations

These are especially useful if you suspect hypovolaemia. A rise in pulse from sitting to standing of more than 30 bpm is a very sensitive indicator of hypovolaemia

Look for signs of:
- pulmonary oedema - examine for tachypnoea, coarse bibasal inspiratory crackles, chest x ray signs
- fluid overload - check for pitting and ankle oedema, check the patients weight daily


What is the best choice of fluids for volume repletion in AKI?

Sodium chloride 0.9% is an appropriate fluid in AKI. Avoid Hartmann's due to the high potassium. Sodium bicarbonate 1.26% is a good alternative if the patient has AKI with hypovolaemia and a metabolic acidosis (serum bicarbonate of less than 20 mmol/L)

Volume repletion:
- repeated fluid "challenges" with 250 to 500ml of 0.9% sodium chloride may be beneficial
- monitor vital signs including urinary output


What is the best choice of fluids for a maintenance regime?

Reduce rate of infusion if patient remains oliguric
- iatrogenic fluid overload is associated with pulmonary oedema
0.9% sodium chloride remains a good option, but should be tailored to a patients fluid and volume status


How is CKD staged?

CKD is classified based on 2 parameters - the eGFR and the albumin = Albumin: Creatinine (ACR)

Note that CKD cannot be diagnosed unless there are markers of kidney damage


When should diuretics be considered in CKD?

Loop diuretics - reduce fluid overload and hyperkalaemia in CKD
- ONLY consider diuretic therapy in fluid overload or hyperkalaemia
- if used in other patients then they could cause dehydration and pre renal AKI

For severe fluid overload requiring urgent treatment:
- use an infusion of a loop diuretic (e.g. up to 250 mg of furosemide given via a syringe driver over 1 hour, at a rate not exceeding 4 mg/min)
- do not give bolus injections of loop diuretics. Higher infusion rates can cause deafness

- avoid using combined loop and thiazide diuretics (because of volume depletion)
- thiazides are ineffective if the eGFR <30
- potassium sparing diuretics should not be used because of the risk of hyperkalaemia
- ACEi and spironolactone can reduce proteinuria but risks hyperkalaemia


Why can ACEi be dangerous in CKD? When should they be used with caution?

ACEi and ARBs are not directly nephrotoxic but can cause severe hypotension (esp those prescribed diuretic)
- check BP regularly
- titrate dose and check renal function

Hint: serum creatinine can rise after starting an ACEi, a rise of <20% is acceptable and the drugs do not need to be stopped

ACEi/ ARBs should not be used in:
- bilateral renal artery stenosis
- renal artery stenosis in a patient with a single functioning kidney
- known widespread vascular disease


Management of hypertension in CKD

Control of hypertension important in CKD. Targets are:
- CKD target BP <140/90 mmHg
- CKD + diabetes + ACR > 70 mg/mmol target BP is <130/80 mmHg

Counsel the patient that:
- non drug therapy (especially salt restriction) is important
- multiple antihypertensive agents are likely to be needed to control BP
- when ACEi/ ARB used, titrate to maximum tolerated dose before adding another


Practical points about using ACEi or ARBs to treated hypertension in CKD

ACEi/ARBs are first line for HTN in renal disease, but avoid them in known renovascular disease (or patients with widespread vascular disease)

Check K+ and eGFR before starting and again about 7 days later; re check after 7 days if any dose increases are made

Do not start if K+ is above upper limit of normal (>5)


Are beta blockers, calcium channel blockers or alpha blockers useful in CKD?

CCBs - very useful in CKD and HTN
- produce oedema, resistant to diuretics and can be confused with volume overload

Beta blockers - limited management
- only used for resistant hypertension; HTN accompanied by IHD, or HTN with heart failure (uncommon)
- in CKD use beta blockers with significant non renal elimination (e.g. bisoprolol or metoprolol)

Alpha blockers - 4th line


What is acute on chronic CKD?

Acute decline in renal function due a precipitating cause (e.g. arrhythmia, pneumonia etc) there is an acute fall in eGFR, the patient may be in pulmonary oedema

In these patients:
- check obs
- full cardiovascular, respiratory and abdo exam
- urinalysis
- FBC, U&E, renal function


Guidelines for cardioversion in AF

Treatment of AF involves either rate or rhythm control:
- rate control: accept that the pulse is irregular but reduce the heart rate so it no longer causes haemodynamic comrpomise
- rhythm control: return the patient back to sinus rhythm

Different drugs are used:
- rate control = beta blockers, calcium channel blockers, and digoxin (this is not usually first line, but is the preferred choice in patients with co-existing heart failure)
- rhythm control = sotalol, amiodarone, flecainide

Different factors may sway your decision to do one or the other:
- factors favouring rate control: older than 65, history of ischaemic heart disease
- factors favouring rhythm control: younger than 65, symptomatic, first presentation, lone AF or AF secondary to a known precipitant, congestive heart failure

Duration of AF is another important factor:
- onset < 48 hours: if definitely less than 48 hours, patients should be heparinised an cardiovert using either electrical DC cardioversion or chemical cardioversion using rhythm control drugs
- onset > 48 hours: patients require anticoagulation for at least 3 weeks prior to elective cardioversion, which is favoured in this scenario


Diuretic regimes that can be used in CKD

Avoid diuretic combinations that use K+ sparing agents as these increase the risk of hyperkalaemia
Remember that thiazide diuretics require a minimum eGFR of 30 to work effectively
Loops and thiazides can be used by watch for dehydration
i.v. loop diuretics are preferred to the oral route


What drugs can precipitate hyperkalaemia?

Contain potassium - e.g. laxatives (Movicol, Fybogel)
Act to retain potassium in the serum - e.g. ACEi, ARBs, potassium sparing diuretics, NSAIDs
Prevent intracellular buffering of potassium - e.g. beta blockers, digoxin

These drugs should be stoped in uncontrolled hyperkalaemia, especially ACEi and ARBs


ECG changes associated with hyperkalaemia

Potassium should be treated urgently if it reaches 6.5 mmol/L - do an ECG first. ECG changes include:
- tall tented T waves
- ST segment depression
- widened QRS
- reduced or absent P waves
- sine wave signals immediate cardiac arrest


Management of hyperkalaemia

1) Protect the heart
- stabilise the myocardium with i.v. calcium gluconate 10%, 10-20 ml over 5-10 minutes

2) Reduce serum potassium concentration
i) nebulised salbutatmol (5-10 mg over 20-30 mins)
- will reduced potassium by up to 1 mmol/L for up to 2 hours
- not effective for all patients
ii) 50 ml of 50% glucose together with 5-10 units of soluble fast acting insulin (e.g. actrapid)
- can be a one off or used as a continuous infusion
- starts to work after 15-30 mins
- omit exogenous glucose if serum is > 15 mmol/L
- monitor glucose to avoid hypoglycaemia

3) Get rid of excess potassium
i) stop an drugs that raise serum potassium
ii) correct metabolic acidosis
- CKD oral sodium bicarbonate 1-6 g/day
- AKI i.v. 1.26% sodium bicarb 250-500 mls
(bicarbonate increases intracellular Na which reduces the activity of the Na+/K+ ATPase --> increased intracellular K+)
- if patient fluid overloaded then dialysis is the best option not sodium bicarb

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