Renal - Drugs and the kidney Flashcards
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 NSAIDs 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
Hints:
- 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)
