14.1 Chronic Kidney Disease, Acute Kidney Injury & Electrolyte Disorders
Key Takeaways
CKD is staged by eGFR (G1 to G5) and albuminuria (A1 to A3); drug doses follow the CrCl or eGFR named in the product monograph.
ACE inhibitors or ARBs for albuminuria, SGLT2 inhibitors started at eGFR 20 or more, finerenone in type 2 diabetes, and statins slow CKD progression or reduce cardiovascular risk.
Sick-day rules (SADMANS) temporarily hold sulfonylureas, ACE inhibitors, diuretics, metformin, ARBs, NSAIDs and SGLT2 inhibitors during dehydrating illness.
Phosphate binders such as calcium carbonate are taken with meals, and ESA therapy for CKD anemia should not target a hemoglobin of 130 g/L or more.
Hyperkalemia with ECG changes is treated first with IV calcium gluconate, then insulin with dextrose and salbutamol, then potassium removal.
Chronic Kidney Disease, Acute Kidney Injury & Electrolyte Disorders
Kidney function affects dosing for a large share of the drugs pharmacists dispense. CKD also brings its own pharmacotherapy: slowing progression, and managing anemia, mineral and bone disorder, and potassium. PEBC sample cases include a patient with CKD whose rising phosphate and potassium must be managed.
1. Staging CKD (KDIGO)
CKD is kidney damage or an eGFR below 60 mL/min/1.73 m² for more than 3 months. It is staged by GFR category and albuminuria category, because both predict risk:
| GFR category | eGFR (mL/min/1.73 m²) |
|---|---|
| G1 | ≥ 90 |
| G2 | 60–89 |
| G3a | 45–59 |
| G3b | 30–44 |
| G4 | 15–29 |
| G5 | < 15 (kidney failure) |
| Albuminuria category | Urine albumin-to-creatinine ratio (mg/mmol) |
|---|---|
| A1 | < 3 |
| A2 | 3–30 |
| A3 | > 30 |
Use eGFR to stage disease. Use the CrCl or eGFR named in the product monograph for drug dosing; the PEBC formula sheet gives the Cockcroft-Gault equation (section 3.3).
2. Slowing CKD Progression
- Blood pressure control: systolic below 130 mmHg (Hypertension Canada 2025) if tolerated.
- ACE inhibitor or ARB (not both), titrated to the maximum tolerated dose in patients with albuminuria. A creatinine rise of up to about 30% after starting is expected.
- SGLT2 inhibitors (dapagliflozin, empagliflozin) slow eGFR decline and reduce kidney failure and cardiovascular events in CKD with or without diabetes, especially when albuminuria is present. They are started at an eGFR of 20 or above and continued until dialysis. Their glucose-lowering effect fades at low eGFR, but kidney protection does not.
- Finerenone, a non-steroidal mineralocorticoid receptor antagonist, for type 2 diabetes with albuminuric CKD already on a RAS inhibitor, when potassium is normal.
- Statin for most adults 50 years and older with CKD who are not on dialysis.
- Avoid nephrotoxins: NSAIDs, unnecessary contrast, and aminoglycosides where possible.
Important
Sick-day guidance ("SADMANS"): during vomiting, diarrhea or poor fluid intake, patients temporarily hold Sulfonylureas, ACE inhibitors, Diuretics, Metformin, ARBs, NSAIDs and SGLT2 inhibitors. They restart 24 to 48 hours after eating and drinking normally. This reduces the risk of acute kidney injury, lactic acidosis, euglycemic ketoacidosis and hypoglycemia.
3. Complications of CKD
Anemia
- Check iron status first: ferritin and transferrin saturation. Correct deficiency (oral, or IV in advanced CKD and dialysis) before starting erythropoiesis-stimulating agents (epoetin alfa, darbepoetin).
- ESA Hb target: about 100 to 115 g/L. Do not target 130 g/L or more; aiming that high increased stroke, thrombosis and cardiovascular events in trials. ESAs can also raise blood pressure.
Mineral and Bone Disorder
- Mechanism: falling phosphate excretion and reduced vitamin D activation lead to high phosphate, low calcium and secondary hyperparathyroidism.
- Dietary phosphate restriction comes first.
- Phosphate binders are taken with meals, so they bind dietary phosphate:
- calcium carbonate (inexpensive and first-line in many patients; avoid in hypercalcemia or vascular calcification);
- sevelamer (calcium-free; GI adverse effects);
- lanthanum.
- Aluminum binders are avoided long term (toxicity), and magnesium-based antacids are avoided in CKD.
- Separate binders from levothyroxine, fluoroquinolones, tetracyclines and iron.
- Active vitamin D (calcitriol, alfacalcidol) and cinacalcet treat secondary hyperparathyroidism.
4. Hyperkalemia
| Situation | Management |
|---|---|
| ECG changes or K⁺ about 6.5 mmol/L or higher (emergency) | 1) IV calcium gluconate to stabilize the heart membrane: acts within minutes, does not lower potassium. 2) Shift potassium into cells: regular insulin IV with dextrose, and nebulized salbutamol. 3) Remove potassium: binders, loop diuretics, or dialysis |
| Mild, asymptomatic, no ECG change (about 5.5 to 6.0 mmol/L) | Review diet and potassium-raising drugs, then add a potassium binder |
- Drugs that raise potassium: ACE inhibitors, ARBs, MRAs, potassium supplements and salt substitutes (KCl), trimethoprim, NSAIDs, heparin, and calcineurin inhibitors.
- Potassium binders:
- Sodium polystyrene sulfonate: slow onset. Separate other oral drugs by at least 3 hours. Rare intestinal necrosis risk.
- Patiromer and sodium zirconium cyclosilicate: allow many patients to continue renin-angiotensin blockers.
- PEBC sample items choose sodium polystyrene sulfonate for asymptomatic mild hyperkalemia in CKD.
5. Acute Kidney Injury (AKI) and Other Electrolytes
- Pre-renal AKI: dehydration, heart failure, and the "triple whammy" of an ACE inhibitor or ARB plus a diuretic plus an NSAID.
- Intrinsic AKI: aminoglycosides, vancomycin (higher trough levels), IV contrast, cisplatin, and drug-induced interstitial nephritis (PPIs, beta-lactams, NSAIDs).
- Post-renal AKI: urinary retention, often from anticholinergics or decongestants in men with BPH.
- Hyponatremia:
- Common drug causes: thiazides, SSRIs and SNRIs, carbamazepine and oxcarbazepine, desmopressin.
- Correct chronic hyponatremia slowly, generally no more than 8 to 10 mmol/L in 24 hours, to avoid osmotic demyelination.
- Hypokalemia from loop or thiazide diuretics: replace potassium chloride, and correct magnesium, or potassium will not normalize.
Dosing Pearls in Reduced Kidney Function
- Metformin: reduce the dose at an eGFR of 30 to 45; stop below 30.
- Nitrofurantoin: limited by renal function (section 11.2).
- Gabapentin and pregabalin: reduce the dose (sedation and falls).
- DOACs and enoxaparin: adjust by CrCl.
- Avoid in severe CKD: meperidine, codeine and morphine (metabolite accumulation), and phosphate enemas, magnesium laxatives and antacids (phosphate or magnesium toxicity).
A patient on hemodialysis has a potassium level of 7.1 mmol/L, with peaked T waves and a widened QRS on the ECG. Which medication should be given first?
Sodium polystyrene sulfonate orally
Patiromer orally
Furosemide intravenously
Intravenous calcium gluconate
A patient with stage 4 CKD has a persistently high phosphate level despite dietary counselling. Calcium is normal and there is no vascular calcification. The prescriber starts calcium carbonate as a phosphate binder. Which counselling point is most important?
Take it once weekly with a full glass of water, remaining upright for 30 minutes.
Take it with meals, and separate it from levothyroxine and ciprofloxacin.
Take it only on days when phosphate-rich foods are eaten.
Take it at bedtime on an empty stomach for best absorption.
A 66-year-old with type 2 diabetes and CKD (eGFR 48) takes metformin, empagliflozin, ramipril and hydrochlorothiazide. She calls the pharmacy with vomiting and diarrhea since yesterday and cannot keep fluids down. What is the best advice?
Temporarily hold metformin, empagliflozin, ramipril and hydrochlorothiazide, try to maintain fluids, restart them 24 to 48 hours after eating and drinking normally, and seek care if she cannot keep fluids down.
Stop all medications permanently, because they have caused her symptoms.
Continue all medications and add ibuprofen for abdominal cramps until the diarrhea settles.
Double the hydrochlorothiazide to prevent fluid retention while she is ill and eating less.
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