6.8 Renal, Fluid, and Electrolyte Therapeutics
Key Takeaways
- Chronic kidney disease is staged by estimated glomerular filtration rate and albuminuria together, because albuminuria independently predicts progression and cardiovascular risk.
- Sodium-glucose cotransporter-2 inhibitors slow chronic kidney disease progression in patients with and without diabetes and cause an expected early dip in estimated glomerular filtration rate that is not a reason to stop.
- The 'triple whammy' of an ACE inhibitor or angiotensin receptor blocker plus a diuretic plus an NSAID is a leading avoidable cause of acute kidney injury.
- Severe hyperkalemia is managed by stabilising the myocardium with calcium, shifting potassium intracellularly with insulin and dextrose, and then removing potassium from the body.
- Correcting chronic hyponatremia faster than about 8 mmol/L in 24 hours risks osmotic demyelination syndrome.
6.8 Renal, Fluid, and Electrolyte Therapeutics
Exam Focus: Renal items on the Evaluating Examination test whether you can read a laboratory panel, recognise the drug regimen that caused the abnormality, and apply the correction rules safely. Electrolyte questions almost always hinge on a rate limit or a sequence.
Chronic Kidney Disease
Chronic kidney disease (CKD) is abnormality of kidney structure or function present for more than three months. Staging uses two axes, and both matter.
| eGFR category (mL/min/1.73 m2) | Description |
|---|---|
| G1: 90 or above | Normal or high, with other evidence of damage |
| G2: 60 to 89 | Mildly decreased |
| G3a: 45 to 59 | Mildly to moderately decreased |
| G3b: 30 to 44 | Moderately to severely decreased |
| G4: 15 to 29 | Severely decreased |
| G5: below 15 | Kidney failure |
Albuminuria categories run A1 (urine albumin-to-creatinine ratio below 3 mg/mmol), A2 (3 to 30), and A3 (above 30). A patient at G2/A3 carries higher risk than one at G3a/A1, which is why the two-axis grid, not eGFR alone, drives management.
Therapy that changes the trajectory
- Renin-angiotensin system blockade. An ACE inhibitor or angiotensin receptor blocker (never both together) titrated to the maximum tolerated dose in albuminuric CKD. Expect a creatinine rise of up to 30%; that is haemodynamic and acceptable. A larger rise, or hyperkalemia, prompts reassessment.
- Sodium-glucose cotransporter-2 (SGLT2) inhibitors. These slow progression in diabetic and non-diabetic CKD. Counsel that an early eGFR dip of a few mL/min is expected and reverses; it is not a signal to stop. Warn about genital mycotic infection and, in patients with diabetes, euglycemic ketoacidosis during illness or fasting.
- Blood pressure and glycemic control, statin therapy for cardiovascular risk, and a non-steroidal mineralocorticoid receptor antagonist such as finerenone in albuminuric diabetic kidney disease.
Complications of advancing CKD
| Complication | Mechanism | Management |
|---|---|---|
| Anemia | Reduced erythropoietin, functional iron deficiency | Replete iron to a transferrin saturation above 20% and ferritin above 100 to 200 mcg/L before starting an erythropoiesis-stimulating agent |
| Mineral and bone disorder | Phosphate retention, low calcitriol, secondary hyperparathyroidism | Dietary phosphate restriction, phosphate binders with meals, activated vitamin D, calcimimetics |
| Metabolic acidosis | Reduced acid excretion | Sodium bicarbonate when serum bicarbonate falls below about 22 mmol/L |
| Hyperkalemia | Reduced excretion, often drug-driven | Dietary review, potassium binders, drug reassessment |
Phosphate binders only work when taken with food, and calcium-based binders are limited by their calcium load. Erythropoiesis-stimulating agents are titrated to a hemoglobin around 100 to 110 g/L; normalising hemoglobin increases stroke and thrombosis risk.
Acute Kidney Injury and Sick-Day Management
Acute kidney injury is classified as prerenal (hypoperfusion), intrinsic (tubular, glomerular, or interstitial injury), or postrenal (obstruction). Drug-induced injury spans all three: NSAIDs and contrast media reduce perfusion, aminoglycosides, vancomycin, amphotericin B, and cisplatin injure tubules, proton pump inhibitors and beta-lactams cause acute interstitial nephritis, and anticholinergics precipitate retention.
The triple whammy — an ACE inhibitor or angiotensin receptor blocker, plus a diuretic, plus an NSAID — is one of the most preventable causes of hospital admission for acute kidney injury. The diuretic depletes volume, the NSAID blocks afferent arteriolar vasodilation, and the renin-angiotensin blocker removes efferent vasoconstriction, so glomerular filtration collapses.
Sick-day guidance is a defined pharmacist intervention. During vomiting, diarrhea, or fever with reduced intake, temporarily hold: sulfonylureas, angiotensin-converting enzyme inhibitors, diuretics and direct renin inhibitors, metformin, angiotensin receptor blockers, non-steroidal anti-inflammatory drugs, and SGLT2 inhibitors. Restart once the patient is eating and drinking normally for 24 to 48 hours.
Electrolyte Disorders
Potassium
Hyperkalemia with electrocardiographic changes is a medical emergency treated in a fixed sequence:
- Stabilise the membrane: intravenous calcium gluconate or chloride. This does not lower potassium; it protects the myocardium.
- Shift potassium intracellularly: intravenous insulin with dextrose, plus nebulised salbutamol. Sodium bicarbonate is used in acidosis.
- Remove potassium: loop diuretics, potassium binders such as sodium zirconium cyclosilicate or patiromer, or dialysis.
Review contributing drugs: renin-angiotensin blockers, spironolactone, trimethoprim-sulfamethoxazole, potassium supplements, and non-selective beta-blockers.
Hypokalemia must be corrected alongside magnesium, because hypomagnesemia causes renal potassium wasting that makes potassium replacement futile until magnesium is restored.
Sodium
Assess hyponatremia by volume status: hypovolemic (vomiting, diuretics), euvolemic (syndrome of inappropriate antidiuretic hormone secretion, often drug-induced by selective serotonin reuptake inhibitors, carbamazepine, or thiazides), or hypervolemic (heart failure, cirrhosis).
The rate limit is the examinable point: correct chronic hyponatremia by no more than about 8 mmol/L in 24 hours. Faster correction risks osmotic demyelination syndrome, an irreversible neurological injury. Acute symptomatic hyponatremia with seizures is the exception and is treated with hypertonic saline under close monitoring.
Calcium and magnesium
Ionised calcium is the physiologically active fraction; in hypoalbuminemia, correct total calcium by adding 0.02 mmol/L for every 1 g/L that albumin falls below 40 g/L. Hypercalcemia of malignancy is treated with saline hydration followed by a bisphosphonate. Proton pump inhibitors, loop diuretics, and alcohol use are common causes of hypomagnesemia.
Dialysis and Drug Therapy
Dialysis removes drugs that are small, water-soluble, minimally protein-bound, and have a low volume of distribution — the profile of aminoglycosides, vancomycin, lithium, and metformin. Highly protein-bound or widely distributed drugs such as amiodarone and digoxin are not meaningfully cleared. Doses of dialysable drugs are given after the session so the dose is not removed.
A 74-year-old on ramipril and hydrochlorothiazide starts naproxen for back pain. Two weeks later her creatinine has risen from 78 to 190 micromol/L. What is the most likely mechanism?
A patient with potassium of 7.2 mmol/L has peaked T waves on the electrocardiogram. Which intervention should be given first?
A patient with chronic hyponatremia of 116 mmol/L is admitted. Over the first 24 hours the sodium should not rise by more than approximately:
A patient with type 2 diabetes and chronic kidney disease starts empagliflozin. Two weeks later the eGFR has fallen from 48 to 43 mL/min/1.73 m2 and the patient feels well. What is the most appropriate action?