Key Facts

Prescribing in renal impairment is one of the most important aspects of safe drug therapy. Renal impairment affects all aspects of pharmacokinetics and increases sensitivity to many drugs. The BNF provides essential guidance on dose adjustment.

Epidemiology

• CKD affects ~13% of UK population (stages 3–5)
• ADRs more common in renal impairment — drug accumulation is a leading cause
• AKI affects ~20% of emergency hospital admissions; often drug-related

Pharmacokinetic Changes in Renal Impairment

• Absorption: may be altered by nausea, GI oedema; rarely significant
• Distribution: reduced protein binding (uraemia + hypoalbuminaemia) → increased free drug → increased effect/toxicity (e.g. phenytoin)
• Metabolism: generally preserved; some renal metabolism reduced (e.g. insulin degradation in kidneys)
• Excretion: most important change — reduced GFR and tubular secretion → drug accumulation

Pharmacodynamic Changes

• Increased sensitivity to sedatives, opioids, anticoagulants
• Altered electrolyte handling → hyperkalaemia risk with ACE-i/ARBs/K-sparing diuretics
• Impaired platelet function in uraemia → increased bleeding risk
• Impaired immune function → increased infection risk

Pathophysiology

• Reduced nephron mass → reduced GFR → decreased filtration/secretion of drugs
• Accumulation of uraemic toxins → altered drug binding and receptor sensitivity
• Fluid overload → altered volume of distribution for water-soluble drugs

Signs of Drug Accumulation in Renal Impairment

• Digoxin: nausea, visual disturbance (yellow vision), bradycardia, arrhythmia
• Lithium: tremor, confusion, polyuria, renal tubular damage
• Opioids: excessive sedation, respiratory depression (especially morphine → M6G accumulation)
• Metformin: lactic acidosis — abdominal pain, tachypnoea, confusion, raised lactate
• Aminoglycosides: ototoxicity (vestibular/cochlear), nephrotoxicity
• Methotrexate: pancytopenia, mucositis — especially with concurrent NSAIDs

Red Flags

• AKI in patient on nephrotoxic drugs — immediate review and stop/hold
• 'Triple whammy' combination (NSAID + ACE-i + diuretic) in any patient
• Hyperkalaemia (K+ >6.0 mmol/L) in patient on RAAS inhibitors
• Lactic acidosis in patient on metformin with deteriorating renal function
• Opioid toxicity (pinpoint pupils, reduced GCS, RR <8) — naloxone

Renal Function Assessment

• eGFR (CKD-EPI equation): standard reporting by UK labs; used for CKD staging
• Cockcroft-Gault creatinine clearance: used by BNF for drug dose adjustments; accounts for age, weight, sex, creatinine
• Serum creatinine: trend more useful than single value
• Cystatin C: alternative GFR marker — less affected by muscle mass

Drug Monitoring

• TDM: essential for renally cleared narrow TI drugs — gentamicin, vancomycin, digoxin, lithium
• U&Es: monitor closely when starting/adjusting ACE-i, ARBs, diuretics, NSAIDs
• K+: monitor with ACE-i, ARBs, K-sparing diuretics, co-trimoxazole
• Drug levels: adjust and recheck after renal function changes

Bloods

• FBC: anaemia of CKD, drug-induced cytopenias
• Calcium, phosphate, PTH: CKD-mineral bone disease
• Albumin: affects protein binding of drugs
• LFTs: combined hepatorenal impairment further complicates dosing

General Principles

• Check eGFR/CrCl before prescribing any new drug in at-risk patients
• Consult BNF renal appendix: provides specific dose adjustments for each CrCl/eGFR range
• Use minimum effective dose: titrate cautiously
• Loading dose: usually unchanged (depends on Vd); maintenance dose adjusted
• Avoid nephrotoxins: where possible (NSAIDs, aminoglycosides, contrast)
• Monitor regularly: renal function + drug levels when indicated

Key Drug Adjustments

• Metformin: eGFR 30–45 → reduce to 500 mg BD; eGFR <30 → stop
• Digoxin: reduce dose; lower target range; monitor levels
• Morphine: avoid in severe CKD (M6G accumulation) → use fentanyl, buprenorphine, or oxycodone (lower active metabolite risk)
• DOACs: apixaban 2.5 mg BD if CrCl 15–29 mL/min; dabigatran avoid if CrCl <30; rivaroxaban 15 mg OD if CrCl 15–49
• Gentamicin: once-daily dosing with TDM; avoid if possible in CKD
• Lithium: reduce dose; monitor levels closely (aim lower end of range)
• Allopurinol: start 100 mg OD; increase slowly based on eGFR
• Gabapentin/pregabalin: significant dose reduction required

Sick Day Rules

• Temporarily STOP: ACE-i/ARBs, diuretics, metformin, NSAIDs during acute illness, vomiting, diarrhoea, dehydration
• Resume when eating/drinking normally and renal function stable
• Patient education card available from NHS/Renal Association

Dialysis Considerations

• Some drugs removed by dialysis — supplementary doses needed post-dialysis (e.g. gentamicin, vancomycin)
• Others not significantly removed (e.g. digoxin — large Vd, high protein binding)
• Consult renal pharmacist for dialysis drug dosing

Referral Criteria

• Renal pharmacist: complex drug dosing in CKD/dialysis
• Nephrology: progressive CKD, AKI, drug-induced nephrotoxicity
• Clinical pharmacology: complex interactions in renal impairment

• Appropriate dose adjustment prevents drug accumulation and toxicity
• AKI: often reversible if nephrotoxins stopped promptly
• Drug-induced CKD (e.g. chronic NSAID use, lithium): may be irreversible
• Sick day rules: simple intervention that significantly reduces AKI risk
• Medication errors in renal impairment are common and preventable — a priority area for patient safety

Drugs Requiring Dose Adjustment in CKD

'Sick Day Rules' — Drugs to Temporarily Stop