Knowing what to prescribe in kidney patients can frighten most doctors! Once you understand the principles and know how and where to look things up then it’s easy!! As a renal registrar, prescribing is one of our main reasons to be called….Here we will summarise the drugs that we most often get asked about with our ‘top tips’ to help you!
Remember, ALL drugs that are initiated in CKD/AKI patients should be looked up in the BNF or Renal Drug handbook/Database to check safety and dose adjustment. Your clinical pharmacistcan help with this and if you’re still unsure then you should contact the renal team….
In the tables below, are a summary of the most common medications we get asked about or we see complications from in AKI or CKD [1-3]…
Contrast
Iodinated contrast
Thought to cause CAN (Contrast Associated Nephropathy) through direct toxicity and medullary ischaemia Patients with CKD, proteinuria, diabetes and hypovolaemia are most at risk
Check ‘is there an alternative way to get the information I need without giving contrast?’ If the scan really needs to be done then do it CAN usually causes sCr rise 48-72 hours after contrastFourth, risk is 5-30% in arterial contrast and 2-10% in venous contrast To reduce risk – ensure any hypovolaemia is corrected and ACEi/ARBs withheld prior to the scan. You can give bicarbonate prior if there’s a renal tubular acidosis Ask radiology to give the most iso-osmolar contrast possible (risk increased with hyper-osmolar) If you have a dialysis patient who still has some residual renal function then you should try to preserve this by dialysing the contrast out after the scan
Contrast
Gadolinium
Thought to ‘rarely’ cause Nephrogenic Systemic Fibrosis (NSF) – a scleromyxodema type or hyperinflammatory disease in patients with reduced kidney function where the skin appears ‘woody’ and you get fibrosis of the connective tissues
>375 cases reported worldwide by the NSF registry A recent study showed no reported cases amongst 4931 patients who received gadolinium-based contrast for MRI I would still mention this in patients with CKD pre-MRI but quote the following study ‘Risk of Nephrogenic Systemic Fibrosis in Patients With Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent: A Systematic Review and Meta-analysis’ which reported no cases
Anti-hypertensives
ACE inhibitors and Angiotensin Receptor Blockers (ACEi/ARB)
These drugs markedly improve prognosis in HFrEF and slow the progression of proteinuric CKD They used to be thought of as a ‘nephrotoxin’ but this is NOT the case
Should not be continued in hyperkalaemia or hypovolaemia/sepsis as thought to exacerbate pre-renal AKI and hyperkalaemia Every discontinuation MUST also come with instructions as to when safe for re-initiation of the drug They are not ‘nephrotoxins’ as they do not cause kidney damage – they, in fact, concentrate blood flow to the kidney tubules which are an area very sensitive to hypoxia Temporary cessation of these drugs is unlikely to cause harm BUT they must be re-introduced as soon as clinically possible to avoid other potential harm from their absence It is normal for these drugs to cause an acute reduction in GFR once commenced due to altered glomerular haemodynamics caused by renal efferent arteriole relaxation Acute increases of sCr of up to 30% are normal in the first 2 months of treatment (only discontinue if rise exceeds this)
Anti-hypertensives
Alpha-blockers and calcium-channel blockers
Can exacerbate hypotension and worsen renal hypoperfusion
Withhold or reduce dose in AKI or at risk of hypotension e/g/ sepsis especially if BP low/low-normal
Anti-hypertensives
Beta blockers
Some patients who continue taking beta-blockers during an episode of AKI have developed complete heart block and required temporary pacing due to accumulation
Consider withholding or reducing dose depending on clinical signs in AKI In CKD – start at low dose and up-titrate wjth HR and BP monitoring
Diuretics
Loop diuretics (Furosemide/Bumetanide)
Diuretics are often necessary in CKD to help reduce extra-cellular volume and BP and the associated cardiovascular risk They should be used to reduce fluid overload and NOT be stopped due to an increase in sCr in the absence of hypovolaemia
Loop diuretics are the recommended diuretics for patients who have an eGFR <30 ml/min/1.73m2because other diuretics (such as thiazides) are less effective in advanced CKD They can be used in all stages of CKD These drugs are often stopped due to sCr increasing. If the patient is not hypovolaemic then this is not an indication to stop them as it will worsen their fluid overload – if in doubt then d/w the renal team Beware of complications such as over diuresis causing hypovolaemia and AKI and also hypokalaemic metabolic alkalosis
They should be used to reduce fluid overload and NOT be stopped due to an increase in sCr in the absence of hypovolaemia Spironolactone and Eplerenone antagonise aldosterone which have prognostic benefits in HF
Use with caution in CKD as risk hyperkalaemia especially when also taking an ACEi/ARB
Analgesics
NSAIDS
People with CKD are generally advised to avoid NSAIDs (with the exception of aspirin for CVS disease)
NSAIDs inhibit the normal prostaglandin-induced dilatation of the renal afferent arteriole. This can result in pre-renal kidney damage (especially in the elderly). Cases of kidney failure often present to the renal ward due to the combination of NSAIDs with an ACEi/ARB so do NOT prescribe these drugs together ACEi/ARBs cause renal efferent arteriole relaxation and when combined with the NSAID-induced reduction of efferent arteriole dilation – can result in kidney failure due to lack of blood perfusion to the glomerulus and tubules Quality of life should be weighed against risk of kidney function progression (e.g. if benefits in inflammatory arthritis etc.) Less commonly, NSAIDs can cause drug-induced interstitial nephritis (allergic-type inflammation) which can result in kidney failure. Treatment is drug withdrawal +/- steroids Even less commonly, NSAIDs can cause nephrotic-range proteinuria kidney-damage or nephrotic syndrome
Analgesics
Opiates
The active metabolites of opiates accumulate in renal failure (CKD/AKI) resulting in opiate toxicity
If toxicity occurs then naloxone can be used as you would in a non-renal patient Ideally chose more renal friendly methods of analgesia such as paracetamol, lignocaine patches, TENS machines etc. Codeine and Morphine especially should be avoided Tramadol immediate release can be used in some cases but often causes toxicity All other opiates should be used with caution but if necessary the following can be used in small doses with close monitoring for toxicity – oxycodone hydrochloride, hydromorphone, fentanyl patch/lollipop, alfentanyl
Anticonvulsants
Gabapentin, Pregabalin, Levetiracetam
These drugs are mostly excreted renally and therefore accumulate in patients with renal impairment
These drugs result in significant GCS suppression when they accumulate in renal impairment so remember adjust the dose based on BNF/renal drug database advice
Anticonvulsants
Phenytoin
If low serum albumin – phenytoin toxicity is a risk Can cause interstitial nephritis
Monitor levels Correct levels for uraemia and low serum albumin or, if assay available, measure salivary phenytoin
Benzodiazepines
Benzodiazepines
Can easily accumulate (along with its active metabolites) leading to confusion and GCS reduction
Reduce dose and monitor closely for sedative effects
Baclofen
Baclofen
Can cause encephalopathy in patients with renal impairment due to accumulation which can occur quickly even with the lowest doses
Reduce dose and use cautiously in patients with moderately impaired kidney function (eGFR <60) and avoid
Digoxin
Digoxin
Can aggravate hyperkalaemia Also accumulates commonly in renal impairment resulting in bradycardia, visual disturbances and confusion
Reduce dose and monitor drug levels
Anti-anginals
Nitrates and Nicorandil
Can cause hypotension and renal hypoperfusion in excessive doses resulting in AKI
Start low and cautiously increase dose whilst monitoring BP
Gout Medications
Allopurinol
Accumulation in renal impairment can cause aplastic anaemia, agranulocytosis and thrombocytopaenia Can cause interstitial nephritis
Use low dose to start with and up titrate aiming to normalise serum urate levels (maximum dose of 300mg OD)
Gout Medications
Colchisine
Can accumulate in larger doses causing diarrhoea, nausea and vomiting, bone marrow suppression, and in rare cases, multi-organ failure, cardiac toxicity, neuropathy and myopathy Can exacerbate hypoperfusion when given with an NSAID
Safe to use (often used in gout) but at a reduced dose of 500 micrograms BD or TDS For acute gout – use colchisine at low doses or prednisolone
Methotrexate
Methotrexate
Accumulation can cause bone marrow suppression, mucositis, acute hepatic toxicity and acute interstitial pneumonitis Can also induce acute kidney injury from a crystal nephropathy Can exacerbate hyperkalaemia
Avoid if at risk of hyperkalaemia Avoid hypovolaemia as can precipitate a crystal nephropathy Monitor levels and if toxicity develops – can be rescued using folinic acid
Lithium
Lithium
Can cause hypernatraemia and diabetes insipidus (especially if unwell which can risk hypovolaemic AKI) Can exacerbate AKI if also hypovolaemic or in combination with ACEi/ARB/NSAIDs Can cause a chronic interstitial nephritis resulting in AKI/progressive CKD Accumulates causing N+V, diarrhoea, weakness, reduced GCS, confusion, blackouts, myoclonic jerks, hyperreflexia, choreoathetoid movements and incontinence
Avoid if possible or can an alternative be given? Monitor levels and serum sodium
Diabetes Drugs
Metformin
Accumulates in renal impairment resulting in hypoglycaemia Can cause lactic acidosis
Avoid in eGFR <30 Avoid in AKI Avoid for 48 hours post-contrast and can be restarted if no CAN develops
Diabetes Drugs
Insulin and other hypoglycaemic agents
Accumulate leading to hypoglycaemia
Insulin doses will usually need to be reduced in AKI and as CKD progresses Avoid MR preparations of hypoglycaemic agents Monitor glucose levels and reduce doses appropriately
Anticoagulants
Low-molecular-weight heparins
Can accumulate resulting in an increased bleeding risk
Reduce dose and monitor anti-Xa levels or switch to an alternative anticoagulant
Anticoagulants
DOACs
Can accumulate resulting in an increased bleeding risk
Dose adjust based on creatinine clearance for each type Reduced dose or contraindicated in renal impairment based on type of DOAC and CrCl
Anticoagulants
Warfarin
INR can rise due to warfarin displacement from binding sites from an acute rise in urea
Monitor INR in AKI, reduce dose if necessary and withhold depending on indication for use
Antibiotics
Gentamycin and Vancomycin (aminoglycosides)
Can cause ototoxcity resulting in deafness if accumulation Are also true ‘nephrotoxics’ – cause tubular cell toxicity Vancomycin (like many antibiotics) can cause interstitial nephritis
Avoid if possible If unable to avoid then reduce dose/alter interval Drug levels must be carefully monitored
Antibiotics
Teicoplanin
Accumulates in renal impairment resulting in confusion, seizures and coma
Reduce dose based on renal function
Antibiotics
Trimethoprim and Co-Trimoxazole
Increases hyperkalaemia risk (especially in elderly) Can make AKI diagnosis difficult as interferes with tubular creatinine secretion so sCr goes up without genuine fall in GFR Can cause interstitial nephritis Co-Trimoxazole can cause a crystal nephropathy
Try to avoid or reduce dose if already on a potassium sparing diuretic or ACEi/ARB (risk of life-threatening hyperkalaemia is 7 x higher when on Spironolactone and sudden death risk is 1.5 x higher when already on ACEi/ARB) Correct hypovolaemia in Co-Trimoxazole use to avoid crystal nephropathy
Antibiotics
Penicillins
Can accumulate causing confusion, reduced GCS and seizures Can cause interstitial nephritis
Reduce dose based on renal function
Antibiotics
Tetracyclines
Accumulates causing further renal impairment, benign intracranial hypertension, jaundice and hepatitis Can cause interstitial nephritis
Avoid in AKI
Acyclovir
Acyclovir
Accumulates causing confusion and seizures Also can cause a crystal nephropathy
Use a reduced dose Avoid hypovolaemia as can precipitate a crystal nephropathy
Antifungals
Amphotericin-B
Another one of the few true nephrotoxics – causes tubular cell toxicity Can cause hypokalaemia
Like gentamycin, avoid if possible If unable to avoid then reduce dose/alter interval Drug levels must be carefully monitored
Antifungals
Fluconazole
Accumulates causing confusion, seizures and coma
Reduce dose Be wary in transplant recipients as can increase tacrolimus levels Withhold statin as can increase rhabdomyolysis risk
Antifungals
Valganciclovir and Ganciclovir
Accumulates resulting in bone marrow suppression Ganciclovir can cause a crystal nephropathy
Reduce dose Monitor renal function and dose adjust as it changes Monitor FBC Correct hypovolaemia in Ganciclovir to reduce chance of crystal nephropathy
Calcineurin Inhibitors
Tacrolimus and Ciclosporin
Increase hyperkalaemia risk Can be nephrotoxic and neurotoxic in high doses
Monitor levels and liaise with the patient’s transplant or renal team to adjust dose accordingly as different patients have different therapeutic ranges
Lipid lowering Agents
Statins and Fibrates
Increases risk of rhabdomyolysis
Stop whilst taking Clarithromycin to prevent rhabdomyolysis Stop of rhabdomyolysis for another reason Stop if myalgia
5-ASA
Mesalasine
Causes tubular and glomerular damage. Also interstitial nephritis.
Avoid ideally
Bisphosphonates
Bisphosphonates
Can cause renal impairment often when doses are high or during short infusions
Reduce dose and infusion duration accordingly As hypercalcaemia can cause renal impairment – balance risks against benefits of bisphosphonate administration
There are many pitfalls and tricks to dealing with drugs in renal transplant patients…we will cover these tips in ‘Tales of a Transplant Patient – clinical pearls and pitfalls!’
References
Hartmann, B. et al. Drug Therapy in Patients with Chronic Renal Failure. Dtsch Arztebl Int (2010). 107(37): 647-656.
Gallieni, M., Cancarini, G. Drugs in the elderly with chronic kidney disease: beware of potentially inappropriate medications. Neph Dial Transpl (2014). 30(3): 342-344.
URINE GOOD HANDS 