What medications are recommended for a patient with stage 4 Chronic Kidney Disease (CKD) and Impaired renal function?

Medications for Stage 4 CKD with Impaired Renal Function

For patients with stage 4 CKD, ACE inhibitors or ARBs are the cornerstone of therapy, with blood pressure targets of <130 mmHg systolic, and additional medications should include phosphate binders, vitamin D supplementation, and erythropoiesis-stimulating agents when indicated, while avoiding nephrotoxic drugs and adjusting all medication doses for reduced kidney function. 1

Blood Pressure Management

First-Line Antihypertensive Therapy

• ACE inhibitors (such as lisinopril) or ARBs are recommended as initial treatment for stage 4 CKD patients, particularly those with moderate to severely increased urine albumin excretion. 1, 2
• Target systolic blood pressure should be <130 mmHg based on evidence from patients with CKD stages 1-3b, though data for stage 4 specifically are limited. 1
• For lisinopril specifically in stage 4 CKD, reduce the initial dose to 5 mg daily (half the usual dose) and titrate up to a maximum of 40 mg daily as tolerated. 2

Additional Antihypertensive Options

• When ACE inhibitors or ARBs alone are insufficient, add thiazide diuretics, calcium channel blockers, or loop diuretics depending on volume status. 1
• Loop diuretics are particularly useful in stage 4 CKD patients with volume overload or nephrotic-range proteinuria. 1
• Multiple medications are typically required to achieve blood pressure targets in advanced CKD. 1

Mineral and Bone Disorder Management

Phosphate Control

• Initiate or increase phosphate binders when serum phosphorus exceeds 4.6 mg/dL (1.49 mmol/L). 1
• Monitor serum calcium and phosphorus every 3-6 months in stage 4 CKD. 1
• Monitor PTH levels every 6-12 months in stage 4 CKD. 1

Vitamin D Therapy

• Measure 25-hydroxyvitamin D levels at first encounter; if <30 ng/mL, initiate ergocalciferol (vitamin D2) supplementation. 1
• Active vitamin D sterols (calcitriol, alfacalcidol, or doxercalciferol) should be initiated when 25(OH)D levels are >30 ng/mL and intact PTH is above target range for stage 4 CKD. 1
• Only prescribe active vitamin D sterols when serum calcium is <9.5 mg/dL (2.37 mmol/L) and serum phosphorus is <4.6 mg/dL (1.49 mmol/L). 1
• Monitor calcium and phosphorus monthly for the first 3 months after initiating active vitamin D therapy, then every 3 months thereafter. 1

Anemia Management

Erythropoiesis-Stimulating Agents (ESAs)

• Initiate epoetin alfa at 50-100 Units/kg three times weekly (adults) or 50 Units/kg three times weekly (pediatric patients) when anemia is present. 3
• Use the lowest dose sufficient to reduce the need for red blood cell transfusions; do not target hemoglobin levels >11 g/dL as this increases mortality, myocardial infarction, stroke, and thromboembolism risk. 3
• The intravenous route is recommended for patients on hemodialysis. 3
• Evaluate and maintain iron repletion before and during ESA therapy. 3

Glycemic Control in Diabetic Patients with Stage 4 CKD

Safe Antidiabetic Medications

• Metformin should be reevaluated when GFR reaches 45 mL/min/1.73 m² and stopped when GFR is 30 mL/min/1.73 m² or below. 1
• DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin) can be used but require dose adjustments in stage 4 CKD. 1
• Thiazolidinediones (pioglitazone) can be used as they are metabolized by the liver, but avoid in advanced heart failure due to fluid retention risk. 1

Medications to Avoid

• Exenatide is not recommended when GFR <30 mL/min/1.73 m². 1
• Liraglutide should be avoided when GFR <60 mL/min/1.73 m² per manufacturer recommendations. 1
• Pramlintide is not recommended for stage 4 CKD or greater. 1
• Acarbose and miglitol should not be used when GFR <25 mL/min/1.73 m². 1

Pain Management in Stage 4 CKD

First-Line Analgesics

• Acetaminophen is recommended as first-line therapy for mild pain, with a maximum daily dose of 3000 mg/day (650 mg every 6 hours). 4
• For moderate to severe pain, fentanyl and buprenorphine (transdermal or IV) are the safest opioids in stage 4 CKD. 4

Opioid Management

• All other opioids require significant dose reduction and careful monitoring due to accumulation of active metabolites. 4
• Prescribe analgesics on a regular schedule rather than "as required" for chronic pain. 4
• Always include rescue doses for breakthrough pain episodes. 4
• Proactively prescribe laxatives for prophylaxis of opioid-induced constipation. 4

Medications to Avoid

• NSAIDs should generally be avoided or used only for very short durations with careful monitoring due to risk of worsening kidney function. 4

Medications to Avoid in Stage 4 CKD

Nephrotoxic Agents

• Avoid aminoglycoside antibiotics and tetracyclines due to nephrotoxicity. 5
• Avoid allopurinol in patients receiving azathioprine. 1
• Avoid NSAIDs and COX-2 inhibitors whenever possible. 1

General Dosing Principles

Dose Adjustment Requirements

• All medications require careful consideration in stage 4 CKD as diminished renal function changes volume of distribution, metabolism, elimination rate, and bioavailability. 5
• Even liver-metabolized drugs can lead to increased toxicity risk in renal failure, necessitating dose adjustments or extended intervals between doses. 5
• Consultation with a nephrologist is recommended before initiating any new medication in advanced kidney disease. 5

Monitoring and Follow-Up

Laboratory Monitoring Schedule

• Complete blood count should be monitored regularly to assess for anemia, neutropenia, and thrombocytopenia. 1
• Serum calcium and phosphorus every 3-6 months. 1
• PTH levels every 6-12 months. 1
• Alkaline phosphatase annually or more frequently if PTH is elevated. 1

Critical Pitfalls to Avoid

• Do not target hemoglobin >11 g/dL with ESAs as this significantly increases cardiovascular mortality and stroke risk. 3
• Do not continue metformin when GFR falls below 30 mL/min/1.73 m² due to lactic acidosis risk. 1
• Do not use active vitamin D sterols when serum calcium is ≥9.5 mg/dL or phosphorus is ≥4.6 mg/dL. 1
• Do not assume standard drug dosing is safe; nearly all medications require adjustment or avoidance in stage 4 CKD. 5, 2