01Principles and purposeThe professional or clinical skill and the decisions it supports.
Kidney and liver disease change prescribing through more than reduced elimination. An impaired kidney may accumulate a medicine or an active metabolite, alter electrolyte tolerance and make further haemodynamic disturbance more dangerous. Liver disease may reduce metabolism or protein binding while also increasing susceptibility to bleeding, sedation and renal injury. These effects do not all move in parallel. A person can have a modest enzyme abnormality with preserved synthetic function, or serious cirrhosis without strikingly high transaminases. Begin with the disease and its stability, then ask how that state changes the particular medicine’s exposure and effects.
The correct response can be a lower dose, a longer interval, a different agent, more monitoring or a temporary interruption. The choice depends on the medicine’s therapeutic purpose and pharmacology. Reducing a maintenance dose proportionally is not always appropriate for a loading dose, and extending an interval can produce different peak and trough concentrations from reducing each administration. Some medicines become ineffective rather than primarily toxic as kidney function declines. Others retain a protective indication despite reduced glucose-lowering effect. A safe plan therefore links a defined clinical aim to a medicine-specific recommendation, with enough information for the next clinician to reproduce the reasoning.
Key points
- Use the renal measure required by the specific medicine: laboratory eGFR and Cockcroft–Gault creatinine clearance are not interchangeable for every dosing decision, particularly with DOACs.
- Check the age, current weight, creatinine value, units and clinical stability before accepting a calculated clearance. Creatinine-based estimates become unreliable during rapidly changing acute kidney injury.
- For stable renal function using creatinine in micromol/L, Cockcroft–Gault clearance in mL/min is (140 − age) × weight × 1.23 / creatinine for men, or × 1.04 for women; extremes of body composition need careful interpretation.
- Do not equate a raised ALT with a quantified loss of drug clearance. Assess the liver disease, bilirubin, albumin, coagulation context and features of decompensation as well as liver enzymes.
- Metformin prolonged-release dosing illustrates a product-specific renal rule: GFR 30–44 mL/min limits the daily total to 1 g, while GFR below 30 is a contraindication; acute dehydration or hypoxia may require interruption before a chronic threshold is reached.
- In cirrhosis, consider susceptibility to bleeding, encephalopathy, kidney injury and fluid retention in addition to drug accumulation. A normal routine test does not establish universal medicine safety.
- Every hold or reduction needs a reason, monitoring and a restart or reassessment plan. Check dialysis modality and timing explicitly when they are relevant; dialysis is not a single dosing category.
02Situations and prioritiesThe context, relevant information and actions that matter most.
Compare previous results, recent illness, intake and urine output. A creatinine value that has been stable for months can support a chronic dosing category; the same value during a rapid rise may underestimate the severity of current loss of function. Ask whether the patient is dehydrated, septic, obstructed or receiving a new nephrotoxic medicine.
Look for new sedation, confusion, myoclonus, bleeding, hypoglycaemia or arrhythmia after a dose change or organ deterioration. The relevant problem may be an active metabolite rather than the parent medicine. A prescription tolerated for years can become unsafe during a short episode of illness without any change in the written dose.
Ascites, encephalopathy, jaundice, gastrointestinal bleeding and worsening renal function identify a higher-risk clinical state. Consider alcohol exposure and the reason for liver disease. Do not use a single albumin or INR value as a stand-alone severity label when inflammation, malnutrition or anticoagulant treatment may contribute to the result.
Record actual body size, amputation, marked muscle wasting, oedema and dialysis details where relevant. Low creatinine in a sarcopenic person can obscure impaired filtration. Medicine administration may also be affected by swallowing difficulty, nausea or an altered feeding route, so a mathematically reduced dose can still be impractical or incorrectly delivered.
03Assessment and interpretationHow to gather information, assess the situation and recognise uncertainty.
Consider the information, its meaning and its limitations before deciding what follows.
- 01
Serial kidney function and urine output - Why
- Assess the degree and trajectory of renal impairment.
- Interpretation and limitations
- Use a result recent enough for the clinical situation. The creatinine lags behind a sudden change, so urine output and physiology can identify deterioration before a new steady state exists. Repeat testing should be timed to the risk and linked to a clear plan for handling doses while the trajectory remains uncertain.
- 02
A reproducible creatinine-clearance calculation - Why
- Apply the product-required renal estimate using verified inputs.
- Interpretation and limitations
- Write age in years, weight in kilograms and serum creatinine in micromol/L when using the UK Cockcroft–Gault factors. The output is mL/min, not indexed mL/min/1.73 m². In unusual body composition, compare plausible weight assumptions and obtain pharmacy advice when they cross a consequential dose boundary.
- 03
Liver blood tests and synthetic-function context - Why
- Characterise hepatic injury and severity relevant to treatment.
- Interpretation and limitations
- ALT and AST suggest hepatocellular injury, while bilirubin, albumin and clotting context add different information. Clinical decompensation and the underlying diagnosis remain important. A product restriction referring to Child–Pugh class requires a properly assessed class rather than an approximate conversion from an isolated ALT elevation.
- 04
Drug concentrations and targeted safety tests - Why
- Investigate exposure or physiological effects when the result will change care.
- Interpretation and limitations
- Use therapeutic drug monitoring only with a defined question, correct sample timing and knowledge of recent doses. Electrolytes, glucose, ECG or coagulation assessment may be more immediately useful for some toxic effects. A concentration inside the laboratory range cannot rule out increased clinical sensitivity in a vulnerable patient.
04Worked approachesCases with ordered reasoning, an action and a check of the outcome.
01Worked caseResolve a renal estimate before prescribingA 79-year-old woman weighs 50 kg and has stable creatinine of 100 micromol/L; the laboratory eGFR is 51 mL/min/1.73 m². A proposed medicine requires Cockcroft–Gault clearance for dosing, and its supplied dose table changes below 40 mL/min.+
- 1Confirm that creatinine is stable and the measured 50 kg weight is a reasonable input for this patient. Identify the required output as creatinine clearance in mL/min; the reported indexed eGFR cannot simply be copied into the product table.
- 2Calculate the age term: 140 − 79 = 61 years. Multiply 61 × 50 × 1.04 = 3,172, then divide by creatinine 100 micromol/L to obtain an estimated clearance of 31.72 mL/min.
- 3Compare 31.72 with the supplied 40 mL/min boundary and use the below-40 dosing category for the next product-specific decision. Do not invent a dose from the clearance alone: the exact agent, indication and complete dose table remain necessary.
- 4Independently check by estimating 61 × 50 is about 3,000 and division by about 100 should yield roughly 30, not 300. Record the inputs, method, result and final action to use the lower-clearance category, then verify the actual product regimen before signing.
02Acute illnessManage medicines during evolving kidney injuryA patient with a previously stable regimen develops dehydration and rising creatinine.+
- 1Assess urgency, perfusion, urine output and the cause of illness. Review the complete medicine list for accumulating agents, nephrotoxins, potassium-raising treatment and medicines unsafe during hypoxia or volume depletion; do not wait for a perfect renal estimate before addressing instability.
- 2Prioritise changes by likely harm and treatment necessity. Some medicines require a temporary hold, others an adjusted regimen or an alternative route, while essential treatment may need specialist continuation with monitoring. Avoid an undifferentiated instruction to stop every long-term medicine.
- 3Use the relevant acute-care and medicine-specific guidance to decide the next doses and laboratory schedule. Explain what the patient should take tonight and tomorrow; a general phrase such as review renal drugs does not supply an actionable administration plan.
- 4When physiology recovers, reassess each interrupted medicine deliberately. Record renal recovery, oral intake, relevant electrolytes and indication before restart, and communicate the updated list to the patient and the team that will issue future supplies.
03Hepatic reviewChoose treatment in clinically significant liver diseaseA patient with known cirrhosis needs a new medicine or has a possible adverse effect.+
- 1Characterise the liver disease and look for decompensation, renal dysfunction, bleeding risk and encephalopathy. Clarify alcohol use, nutrition and concurrent medicines, including sedatives and non-prescription pain treatment that may compound vulnerability.
- 2Check the exact product restrictions and specialist guidance for this indication. Separate a pharmacokinetic dose recommendation from a contraindication caused by bleeding or hepatic coagulopathy; a smaller dose does not necessarily overcome the latter.
- 3Select a regimen with a defined clinical aim, cautious introduction where appropriate and a practical review interval. Seek specialist pharmacy or hepatology advice when severity categories, limited evidence or narrow therapeutic margins make the decision uncertain.
- 4Monitor both response and organ-related harm, including mental state, fluid status and renal trajectory when relevant. If an adverse effect emerges, reassess causality and the whole regimen rather than attributing every new symptom to progression of cirrhosis.
05Relevant medicines and safetySpecific regimens and precautions when the skill involves prescribing.
Metformin prolonged release in stable renal impairment
At GFR 30–44 mL/min, the selected product permits no more than 1,000 mg orally per day and an initial dose no higher than 500 mg daily; it is contraindicated below GFR 30.Review dehydration, sepsis, hypoxia, hepatic insufficiency and excess alcohol as separate lactic-acidosis risks. A stable chronic category cannot justify continuing unchanged through serious acute illness; formulation and total daily exposure must be checked.
Amlodipine when kidney and liver function differ
The ordinary adult oral starting regimen is 5 mg once each day, with 10 mg daily as the usual ceiling. Renal impairment alone does not require dose adjustment; liver impairment calls for cautious selection and slow titration.Monitor pressure, dizziness and oedema, with particular care in older adults and hepatic impairment. Severe hypotension or shock remains a contraindication regardless of the numerical kidney-function estimate.
06Feedback, follow-up and evidenceReview outcomes, seek feedback and identify what to improve.
- Choose repeat testing according to both current organ function and the medicine’s risk. A stable low-risk regimen and a narrow-therapeutic-index drug during acute illness should not share an arbitrary annual monitoring interval.
- When a result crosses a dosing boundary, confirm the inputs, trend and clinical context promptly. Avoid excessive rounding near a threshold, and document whether the change is persistent, uncertain or caused by a transient illness.
- After a dose reduction, check that benefit is preserved as well as that toxicity improves. Under-treatment can be serious for infection, thrombosis or seizure control; achieving a lower drug concentration is not itself the therapeutic objective.
- At discharge after organ deterioration, list stopped, reduced and restarted medicines with their reasons and next review dates. Confirm that the receiving prescriber has the latest renal or hepatic context and knows which decisions remain conditional.
07Special situationsVariants, exceptions and circumstances that change the usual approach.
Indexed and absolute values differ
Laboratory eGFR is usually normalised to a standard body surface area, while Cockcroft–Gault estimates creatinine clearance in absolute mL/min. Their numerical similarity in some adults should not conceal the different methods and product requirements.
Creatinine reflects more than filtration
Muscle mass influences creatinine generation. Frailty, amputation and unusual body composition can make an apparently reassuring value misleading. Recognise the limitation before using a calculator’s decimal places as evidence of clinical precision.
Contraindication is not a dose suggestion
A product may be unsuitable because organ disease creates a physiological bleeding or metabolic risk. Halving the dose cannot be assumed to convert a contraindicated medicine into an acceptable choice.
Loading and maintenance have different determinants
A loading dose aims to establish a concentration, while maintenance replaces eliminated drug. Organ impairment may affect these components differently, so use the specific regimen rather than automatically applying the same percentage reduction to every dose.
08Common pitfallsFrequent interpretation and management errors.
- 01
Copying an indexed laboratory eGFR into a DOAC dosing decision without checking the required method can select the wrong renal category.
- 02
Interpreting a rapidly changing creatinine as a steady-state clearance can underestimate acute accumulation risk and delay a necessary medicine hold.
- 03
Using an isolated transaminase result to calculate an invented percentage dose reduction confuses hepatic injury with a measured drug-clearance capacity.
- 04
Restarting every pre-admission medicine automatically after kidney injury can reintroduce a dose that no longer fits the patient’s recovered baseline.