What medications are used to manage Chronic Kidney Disease (CKD) stage 5?

Medication Management in CKD Stage 5

For patients with CKD Stage 5, the medication regimen should prioritize cardiovascular protection with statins, management of secondary hyperparathyroidism with vitamin D analogs like paricalcitol, blood pressure control with loop diuretics and ACE inhibitors/ARBs (with careful hyperkalemia monitoring), and treatment of complications including anemia, hyperkalemia, and metabolic bone disease.

Cardiovascular Risk Reduction

Statin Therapy

• All patients aged ≥50 years with CKD Stage 5 (not yet on chronic dialysis) should receive treatment with a statin or statin/ezetimibe combination to reduce cardiovascular mortality, which is the leading cause of death in this population 1.
• Choose statin-based regimens to maximize absolute reduction in LDL cholesterol to achieve the largest treatment benefits 1.
• High-dose statins are indicated for secondary prevention regardless of contrast-induced nephropathy risk 1.
• Cardiovascular complications are the most common causes of death in patients with kidney failure (stage G5) maintained on regular dialysis treatment 2.

Antiplatelet Therapy

• Low-dose aspirin is recommended for secondary prevention of recurrent ischemic cardiovascular disease events in CKD patients with established ischemic cardiovascular disease 1.
• For CKD Stage 5 (eGFR <15 mL/min/1.73 m²), there are insufficient safety and efficacy data for P2Y12 receptor inhibitors 1.

Blood Pressure Management

Loop Diuretics as First-Line

• Loop diuretics (furosemide 20-80 mg twice daily or torsemide 5-10 mg once daily) are the preferred diuretic class in CKD Stage 5 because thiazide and thiazide-like diuretics lose effectiveness when GFR falls below 30 mL/min 3.
• Volume overload is the primary driver of hypertension in advanced CKD 3.
• Dietary sodium restriction to no more than 2 grams daily is essential 4.

ACE Inhibitors or ARBs

• ACE inhibitors or ARBs should be added or optimized at maximal tolerated doses if not contraindicated by hyperkalemia or symptomatic hypotension 3.
• ACE inhibitor use has been associated with decreased mortality in CKD Stage 5 patient cohorts 3.
• Close monitoring for hyperkalemia is mandatory when using ACE inhibitors or ARBs in CKD Stage 5 1, 5.
• Check serum potassium within 2-4 weeks of initiating or dose-adjusting ACE inhibitors/ARBs 3.
• Monitor serum creatinine within 2-4 weeks of initiating or dose-adjusting these agents 3.

Blood Pressure Targets

• Target blood pressure of 140/90 mmHg for most CKD Stage 5 patients, provided there is no substantial orthostatic hypotension or symptomatic intradialytic hypotension 3.
• An alternative acceptable range is SBP 130-139 mmHg 3.

Critical Contraindications

• Never combine ACE inhibitor + ARB, as this increases adverse events (hyperkalemia, acute kidney injury) without additional benefit 3.
• Avoid any combination of ACE inhibitor, ARB, and direct renin inhibitor 3.

Secondary Hyperparathyroidism Management

Paricalcitol (Vitamin D Analog)

• Paricalcitol capsules are FDA-approved for prevention and treatment of secondary hyperparathyroidism in CKD Stage 5 patients on hemodialysis or peritoneal dialysis 6.
• Initial dose: Administer orally three times a week, no more frequently than every other day, using the formula: Dose (micrograms) = baseline iPTH (pg/mL) divided by 80 6.
• Treat patients only after baseline serum calcium has been adjusted to 9.5 mg/dL or lower to minimize hypercalcemia risk 6.
• Titrate dose based on iPTH, serum calcium, and phosphorus levels using the formula: Dose (micrograms) = most recent iPTH level (pg/mL) divided by 80 6.
• If serum calcium is elevated, decrease dose by 2 to 4 micrograms 6.

Hyperkalemia Management

Dietary and Pharmacologic Interventions

• Implement an individualized approach in CKD Stage 5 patients with emergent hyperkalemia that includes dietary and pharmacologic interventions 1.
• Provide advice to limit intake of foods rich in bioavailable potassium (e.g., processed foods) for patients with history of hyperkalemia 1.
• Assessment and education through a renal dietitian or accredited nutrition provider are advised 1.
• Be aware of local availability or formulary restrictions regarding potassium exchange agents 1.

Lipid Management Beyond Statins

• Consider prescribing PCSK-9 inhibitors to CKD patients who have an indication for their use 1.
• Consider a plant-based "Mediterranean-style" diet in addition to lipid-modifying therapy to reduce cardiovascular risk 1.

Hyperuricemia and Gout Management

Symptomatic Hyperuricemia

• Patients with CKD and symptomatic hyperuricemia should be offered uric acid-lowering intervention 1.
• Consider initiating uric acid-lowering therapy after the first episode of gout, particularly where there is no avoidable precipitant or serum uric acid concentration is >9 mg/dL (535 mmol/L) 1.
• Prescribe xanthine oxidase inhibitors in preference to uricosuric agents 1.

Acute Gout Treatment

• For symptomatic treatment of acute gout in CKD, low-dose colchicine or intra-articular/oral glucocorticoids are preferable to NSAIDs 1.
• Nonpharmacological interventions include limiting alcohol, meats, and high-fructose corn syrup intake 1.

Asymptomatic Hyperuricemia

• Do not use agents to lower serum uric acid in patients with CKD and asymptomatic hyperuricemia to delay CKD progression 1.

Diabetes Management in CKD Stage 5

Sulfonylurea Considerations

• First-generation sulfonylureas should be avoided in CKD Stage 5 due to prolonged half-lives and increased risk of hypoglycemia 7.
• If a sulfonylurea is necessary, glipizide is the preferred agent because it lacks active metabolites that accumulate in renal impairment 7.
• Start glipizide conservatively at 2.5 mg once daily with slow titration 7.
• For CKD Stage 5 (eGFR <15 mL/min/1.73 m²), there are insufficient safety and efficacy data for P2Y12 receptor inhibitors, and similar caution applies to many oral hypoglycemic agents 1.

Contemporary Diabetes Management

• SGLT2 inhibitors and GLP-1 receptor agonists are now fully emerged as drugs that substantially reduce cardiovascular complications in CKD patients already treated with adequate doses of renin-angiotensin system inhibitors 2.

Anemia Management

• Recent clinical trials have shown potential benefits of hypoxia-inducible factor prolyl hydroxylase inhibitors, especially as oral agents in CKD patients 2.
• The value of proactively administered intravenous iron for safely treating anemia in dialysis patients has been demonstrated 2.

Medications to Avoid

Nephrotoxic Agents

• Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) 1, 8.
• Aminoglycoside antibiotics and tetracyclines should be avoided due to nephrotoxicity 9.
• Nephrotoxic drugs should be avoided entirely in CKD Stage 5 patients 9.

Drug Dosing Adjustments

• All medications in CKD Stage 5 require careful consideration as diminished renal function changes volume of distribution, metabolism, rate of elimination, and bioavailability 9.
• Even for drugs metabolized by the liver, renal failure can lead to increased risk of toxicity, necessitating dose adjustments or extended intervals between doses 9.
• Many antibiotics and oral hypoglycemic agents require dosing adjustments 8.

Monitoring for CKD Complications

Patients require monitoring for:

• Hyperkalemia 8
• Metabolic acidosis 8
• Hyperphosphatemia 8
• Vitamin D deficiency 8
• Secondary hyperparathyroidism 8
• Anemia 8

Multidisciplinary Care

• The creation of multidisciplinary ACKD units including a nephrologist, nephrology nurse, dietitian, and social worker allows an integrated approach to management and is cost-effective 10.
• Consultation with a nephrologist is recommended before initiating any new medication in patients with advanced kidney disease to determine appropriate dosing 9.

Common Pitfalls to Avoid

• Do not use dual RAAS-blockade (ACE inhibitor + ARB) due to safety issues 3, 5.
• Avoid full-dose sulfonylureas without dose reduction in CKD Stage 5 7.
• Do not prescribe thiazide diuretics as they are ineffective when GFR <30 mL/min 3.
• Avoid NSAIDs for pain management; use alternatives 1.
• Be cautious with antimicrobials (fluoroquinolones and sulfamethoxazole-trimethoprim) that interact with sulfonylureas to increase hypoglycemia risk 7.