Collapse in advanced CKD: the triple whammy
A 74-year-old woman with type 2 diabetes, heart failure with reduced ejection fraction and stage 4 chronic kidney disease (baseline creatinine 180 micromol/L, eGFR 26 mL/min/1.73 m2) is brought to the emergency department with 3 days of vomiting and diarrhoea. Her regular medicines are metformin 1 g twice daily, ramipril 10 mg daily, furosemide 40 mg daily, spironolactone 25 mg daily and atorvastatin 20 mg at night. For knee pain she has been buying ibuprofen 400 mg three times daily over the counter for the past two weeks. Today her blood pressure is 96/58 mmHg, pulse 104 and regular, she is drowsy; potassium is 5.9 mmol/L, creatinine 268 micromol/L, lactate 2.1 mmol/L and blood glucose 6.8 mmol/L. The admitting team asks the pharmacist to review her therapy before she goes to the ward.
1. Which medicine-related problems explain this presentation, and how would you rank them in order of urgency?
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1. Acute kidney injury from the 'triple whammy' (most urgent driver). An ACE inhibitor (ramipril) plus a diuretic (furosemide) plus an NSAID (ibuprofen) in a volume-depleted patient collapses glomerular perfusion. The NSAID removes the prostaglandin-mediated afferent vasodilatation, the ACE inhibitor dilates the efferent arteriole, and the diuretic plus diarrhoea remove the volume. Creatinine rising from 180 to 268 micromol/L with a pulse of 104 fits this exactly; the NSAID is the single most removable cause.
2. Hyperkalaemia (K 5.9 mmol/L). Additive potassium retention from ramipril, spironolactone and the AKI itself, worsened by dehydration. This is the finding most likely to kill the patient in the next few hours, so in clinical terms it competes with item 1 for priority.
3. Metformin in a failing kidney plus acute illness. Contraindicated at eGFR below 30 and should be withheld during any acute illness with vomiting/diarrhoea and dehydration (sick-day rules) because of accumulation and lactic acidosis risk; lactate 2.1 is only mildly raised but does not exclude early metformin accumulation.
4. Spironolactone is both a potassium-retaining agent and volume-depleting in this setting, and should have been reconsidered at this eGFR.
Ranking for action: hyperkalaemia and AKI jointly first (same interventions), then metformin, then spironolactone, then review of statin (no dose change needed).
2. What immediate pharmacological actions would you recommend to the team, and which of her medicines should be withheld or stopped today?
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- Obtain an ECG immediately. Potassium 5.9 mmol/L with ECG changes (peaked T waves, widened QRS) is a cardiac emergency: give IV calcium gluconate or calcium chloride to stabilise the myocardium, then shift potassium intracellularly with insulin plus glucose and nebulised salbutamol, and remove potassium with a potassium binder. If the ECG is normal, shifting and removing therapy still start now because the rise is acute and ongoing.
- Stop ibuprofen permanently and document an NSAID allergy/intolerance flag with counselling not to buy it over the counter.
- Withhold ramipril and spironolactone while she is dehydrated and hyperkalaemic; both can be revisited after volume repletion and repeat biochemistry. Do not restart an ACE inhibitor and spironolactone together on the same day without a potassium check 3 to 5 days later.
- Withhold metformin during the acute illness and do not restart at an eGFR of 26; the drug should be stopped and diabetes managed another way.
- Review furosemide: she is volume depleted, so it should be held until she is euvolaemic; later, in CKD, a higher dose may be needed for effect, so the dose must follow her volume status, not habit.
- Treat the diarrhoea and dehydration with cautious fluid replacement and monitor urine output, potassium, creatinine and glucose at least daily, more often initially.
- Continue atorvastatin - no renal dose adjustment and no reason to interrupt it. The reasoning thread: every intervention targets either the potassium or the renal perfusion, and every drug stopped is one that either raises potassium, reduces renal perfusion, or accumulates in renal failure.
3. Design her discharge medication plan and the counselling you would give, with the specific numbers you would use for renal dosing at an eGFR that recovers to 35 mL/min/1.73 m2.
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If eGFR recovers to about 35 mL/min/1.73 m2:
- Metformin: do not restart if eGFR stays below 30; between 30 and 44 it may be continued only at a reduced maximum of 1000 mg daily, not started newly, and stopped again during any acute illness. At 35 she is in that band - involve the prescriber and explain the sick-day rule in writing.
- Ramipril: restart at a low dose (for example 2.5 mg daily) once she is euvolaemic and potassium is below 5.0 mmol/L; check potassium and creatinine 1 to 2 weeks after any dose change. A creatinine rise of up to 30 percent is acceptable; more than that warrants dose reduction.
- Spironolactone: generally avoided at this eGFR; if the heart failure team insists, use the lowest dose with potassium monitoring at 1 week and 1 month.
- Furosemide: keep the lowest dose that maintains euvolaemia; CKD patients often need higher doses, so titrate to weight, oedema and breathlessness rather than to a fixed number.
- Atorvastatin 20 mg unchanged.
Analgesia: paracetamol regularly, with topical NSAID only if strictly necessary and for short periods, and explicit advice to avoid all oral NSAIDs including over-the-counter ibuprofen and diclofenac.
Counselling points: what dehydration looks like and which drugs to pause; the phrase 'no anti-inflammatory painkillers, ever, without asking the pharmacist'; to tell every prescriber she has kidney disease; and to bring her medicine list to each visit. Arrange a repeat creatinine and potassium within 1 week of discharge and a follow-up with the renal or heart failure team.