NephrologyTier 2Topic

Prescribing in kidney disease

Four questions for every drug

Four separate questions for every drug in CKD:
- 1. Is it nephrotoxic?
- 2. Is it (or an active metabolite) renally cleared?
- 3. Does CKD change what it does? (altered protein binding, volume of distribution, receptor sensitivity)
- 4. Should it be withheld when the patient is sick?
*The commonest prescribing error in CKD is dosing by BSA-normalised eGFR instead of absolute clearance*

Adverse drug events are 2-3x more common in CKD; a leading cause of avoidable admission
~50% of patients with eGFR <60 receive at least one inappropriately dosed medication
Polypharmacy: dialysis patients take a median of 10-12 medicines

Absorption - gastroparesis (diabetes), phosphate binders and calcium chelate other drugs, raised gastric pH from PPIs and urea
Distribution
- Oedema increases Vd for water-soluble drugs
- Hypoalbuminaemia and uraemic displacement increase the free fraction of highly protein-bound drugs (phenytoin, warfarin) - the total level looks normal while the patient is toxic
Metabolism - reduced hepatic CYP activity in uraemia; reduced renal metabolism (insulin, vitamin D)
Excretion - reduced filtration, secretion and reabsorption; active metabolites accumulate even when the parent drug does not

Morphine -> morphine-6-glucuronide: renally excreted, more potent than morphine
- -> accumulation in advanced CKD -> sedation, myoclonus, respiratory depression
- *Avoid morphine in advanced CKD* - use an opioid with inactive or non-renally-cleared metabolites
Pethidine -> norpethidine: neurotoxic, seizures. Never in CKD
Codeine and tramadol - unpredictable; avoid or reduce substantially
Allopurinol -> oxypurinol: renally cleared - start at 50-100 mg and titrate by urate, do not dose by eGFR alone
Sulfonylureas - active metabolites; glibenclamide is the worst

Purpose	Use
Staging CKD, monitoring	eGFR (CKD-EPI creatinine), mL/min/1.73m2
Drug dosing of narrow-therapeutic-index drugs	Absolute clearance in mL/min - Cockcroft-Gault CrCl, or eGFR de-indexed for BSA
Confirming a borderline eGFR	Cystatin C-based eGFR

*The two differ most at the extremes of body size* - a 45 kg 85-year-old with an eGFR of 55 may have an absolute CrCl of 30
DOACs, digoxin, aminoglycosides, vancomycin, LMWH, methotrexate, lithium - dose on absolute clearance
Creatinine-based estimates overestimate function in the frail, sarcopenic and elderly - reduced muscle mass means reduced creatinine production, so the creatinine sits in the 'normal' range despite a substantially reduced GFR
eGFR is invalid in AKI (not at steady state), pregnancy, amputation, extreme muscle mass, and on creatine supplements

Drug	Issue
NSAIDs	Avoid entirely - haemodynamic AKI, AIN, hyperkalaemia, HTN
Metformin	eGFR >=30; reduce dose below 45; withhold when sick (lactic acidosis)
SGLT2i	Continue for renal benefit to dialysis; withhold in acute illness or fasting (euglycaemic DKA); hold 3 days pre-op
ACEi/ARB/MRA	Hyperkalaemia; withhold in acute illness; never dual-block
Aminoglycosides	Once-daily, shortest course, level monitoring; avoid with vancomycin
Vancomycin	AUC-guided dosing (AUC/MIC 400-600)
Trimethoprim	Hyperkalaemia; raises creatinine without changing GFR
Lithium	Narrow index, nephrogenic DI, chronic interstitial nephritis; dialysable
Digoxin	Reduce dose ~50%; toxicity worsened by hypokalaemia and hypomagnesaemia
DOACs	Dabigatran ~80% renal - avoid if CrCl <30; apixaban and rivaroxaban dose-reduce
LMWH	Accumulates below CrCl 30 - dose-reduce, monitor anti-Xa, or use UFH
Gadolinium	Nephrogenic systemic fibrosis if eGFR <30 - use group II agents and only if essential
Bisphosphonates	Avoid if eGFR <30; risk of adynamic bone
Denosumab	Not renally cleared but *severe prolonged hypocalcaemia in advanced CKD* - correct vitamin D and calcium first, monitor
Sodium picosulfate / phosphate bowel preparations	Acute phosphate nephropathy - use PEG-based preparation
Herbal medicines	Aristolochic acid; unquantified potassium loads

Paracetamol - first-line, no dose change
Avoid NSAIDs
Opioids
- Preferred: fentanyl, buprenorphine, methadone - hepatic metabolism, inactive metabolites
- Use with caution and reduced dose: oxycodone, hydromorphone
- Avoid: morphine (M6G), pethidine (norpethidine), codeine, tramadol
Neuropathic: gabapentin and pregabalin are renally cleared - reduce dose substantially (sedation, myoclonus, falls; a very common error)

Dose-reduce: beta-lactams (except ceftriaxone and flucloxacillin), aciclovir (neurotoxic if unadjusted), fluconazole, ciprofloxacin, cotrimoxazole, ethambutol
No change: rifampicin, doxycycline, azithromycin, ceftriaxone, metronidazole (reduce in severe CKD), moxifloxacin, linezolid
Nitrofurantoin ineffective and toxic below eGFR ~45
Loading doses are usually unchanged (Vd) - it is the maintenance dose or interval that changes

Time doses after dialysis for dialysable drugs (many beta-lactams, aciclovir, levetiracetam, gabapentin)
Avoid ESAs, phosphate binders and calcium supplements with interacting drugs - separate doses
Preserve residual renal function: avoid nephrotoxins even on dialysis

Withhold during acute illness with volume depletion: ACEi/ARB/ARNI, MRA, diuretics, metformin, SGLT2i, NSAIDs
Restart when eating and drinking normally, and check UEC

Polypharmacy and older age; frailty and sarcopenia (creatinine misleads)
AKI - the commonest consequence of a prescribing error in CKD
Hyperkalaemia - RAS blockade, trimethoprim, heparin, NSAIDs, calcineurin inhibitors
Hypoglycaemia - sulfonylureas and insulin as eGFR falls (reduced renal insulin clearance)
Bleeding - DOAC and LMWH accumulation, uraemic platelet dysfunction
Neurotoxicity - aciclovir, gabapentinoids, pethidine, cefepime, lithium
Contrast and gadolinium exposure
Transplant recipients - CYP3A4 interactions with calcineurin inhibitors (azoles, macrolides, rifampicin, diltiazem)

A prescribing error in CKD usually presents as AKI, hyperkalaemia, hypoglycaemia, bleeding or neurotoxicity - not as an obvious drug reaction
eGFR changes over time, so the dose that was right last year may not be right now - review at every significant change in function
AKI is the commonest reason a chronic prescription becomes dangerous - which is why sick-day rules matter more than any single dose adjustment
Discharge is the highest-risk moment: withheld drugs are either restarted too early or never restarted. Document explicitly what was stopped, why, and when to restart
Reconcile the medication list at every transition of care, including OTC analgesics, complementary medicines and salt substitutes

11 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.