Prescribing in Chronic Kidney Disease

Chronic kidney disease is abnormal kidney structure or function lasting over 3 months. It is graded by GFR category (G1 90 or over, G2 60 to 89, G3a 45 to 59, G3b 30 to 44, G4 15 to 29, G5 under 15 mL/min/1.73 m2) and by albuminuria (A1 under 30, A2 30 to 300, A3 over 300 mg/g). Prescribing has two tasks: protect the kidney and heart, and avoid harm from reduced clearance.

Adjustment thresholds. Renally cleared drugs need review once eGFR is under 60 and usually a firm dose change under 30. Narrow therapeutic index drugs need review earlier.

Pharmacokinetic changes. Hypoalbuminaemia and uraemia raise the free fraction of highly bound drugs such as phenytoin. Active metabolites accumulate (morphine-6-glucuronide, norpethidine, oxipurinol). Oedema enlarges the volume of distribution, and non-renal clearance may also fall.

Choice of estimate. Use eGFR for most drugs and Cockcroft-Gault clearance for narrow index drugs, anticoagulants and patients at extremes of body size.

Kidney and cardiovascular protection.

• ACE inhibitor or angiotensin receptor blocker for albuminuric, diabetic or hypertensive disease.

• SGLT2 inhibitor (dapagliflozin or empagliflozin) for most patients with albuminuria or diabetes.

• Finerenone for type 2 diabetes with albuminuria when potassium is 5.0 mmol/L or under.

• Statin therapy (atorvastatin 20 mg daily needs no adjustment).

Medicines to avoid or limit. NSAIDs; nitrofurantoin when eGFR is under 30; bisphosphonates when clearance is under 30 to 35 mL/min; sodium phosphate bowel preparations; magnesium and aluminium containing antacids and laxatives; and the highest-risk gadolinium agents when eGFR is under 30.

Special groups.

• Pregnancy: ACE inhibitors and angiotensin receptor blockers are contraindicated.

• Older adults: use Cockcroft-Gault clearance with caution and start low.

• HIV treatment in East Africa: tenofovir disoproxil 300 mg is given every 48 hours when clearance is 30 to 49 mL/min and avoided under 30. Dolutegravir raises creatinine by blocking tubular secretion without lowering true GFR.

• Herbal and over-the-counter NSAID use is common and should be asked about.

Monitoring. After starting or increasing an ACE inhibitor or angiotensin receptor blocker, check creatinine and potassium at 1 to 2 weeks. Accept a creatinine rise up to 30 percent. Reduce or stop if it rises more, or if potassium reaches 6.0 mmol/L.

Sick day advice. During vomiting, diarrhoea or fever, hold ACE inhibitors, angiotensin receptor blockers, SGLT2 inhibitors, metformin, diuretics and NSAIDs. Restart 24 to 48 hours after normal eating and drinking return.

Stop rules. Stop or reduce a renin-angiotensin system blocker for a creatinine rise over 30 percent or potassium 6.0 mmol/L or over after correcting reversible causes. Stop metformin when eGFR falls under 30 and SGLT2 inhibitors at dialysis.

Referral and escalation. Refer for eGFR under 30, a sustained fall of more than 25 percent with a change of category, heavy proteinuria, refractory hyperkalaemia, or an unclear cause of decline.

Common errors. Continuing metformin and NSAIDs through illness, using eGFR alone for a DOAC, stopping a renin-angiotensin blocker at a creatinine rise under 30 percent, and omitting dose review when eGFR crosses a category.