How to manage shortness of breath (SOB) in a patient with Chronic Kidney Disease (CKD)?

Management of Shortness of Breath in Chronic Kidney Disease

Systematically identify and treat the underlying cause of dyspnea in your CKD patient, prioritizing volume overload, cardiac complications, anemia, and pulmonary pathology—as breathlessness in CKD is multifactorial and rarely resolves with dialysis alone. 1

Initial Diagnostic Approach

The pathophysiology of dyspnea in CKD involves multiple co-existing mechanisms that require targeted evaluation 1:

Assess Volume Status First

• Determine absolute and relative fluid overload using clinical examination (jugular venous pressure, peripheral edema, pulmonary crackles) combined with technological methods if available 2
• Volume expansion and iso-osmotic sodium retention are non-traditional risk factors that accelerate cardiovascular disease in CKD 3
• Critical caveat: Hemodialysis often fails to significantly improve breathlessness despite addressing fluid overload, indicating alternative pathologies must be sought 1

Evaluate Cardiac Complications

• Screen for heart failure, which has 70-80% prevalence in kidney failure patients and occurs early in CKD progression 3
• Obtain 12-lead ECG, check thyroid and kidney function, serum electrolytes, full blood count, and transthoracic echocardiography to assess left ventricular size/function, left atrial size, valvular disease, and right heart function 4
• Screen for atrial fibrillation using opportunistic pulse-based screening when measuring blood pressure, followed by wearable device or Holter ECG if indicated 4
• Consider pulmonary hypertension as a contributing factor 1

Check for Pulmonary Pathology

• Evaluate for unrecognized chronic lung disease, lung fibrosis, and air microembolism 1
• Systemic inflammation in CKD contributes to endothelial dysfunction and lung fibrosis 1

Laboratory Assessment

• Measure hemoglobin to identify anemia, which is a major contributor to dyspnea in CKD 3, 1
• Check serum ferritin (target >100 mcg/L) and transferrin saturation (target >20%) before considering erythropoiesis-stimulating agents 5

Treatment Algorithm Based on Etiology

For Volume Overload

• Use high-dose and combination diuretic therapy, which has been successfully used in CKD stages 3 and 4, though monitor closely for worsening kidney function and electrolyte imbalances 6
• Consider peritoneal dialysis in patients with symptomatic fluid overload to improve symptoms and prevent hospital admissions 6

For Heart Failure with Reduced Ejection Fraction (HFrEF)

• Initiate β-blockers, which improve outcomes in HFrEF across all CKD stages, including dialysis patients 6
• Start SGLT2 inhibitors, which substantially reduce cardiovascular complications and have been shown to improve mortality and hospitalization in HFrEF patients with CKD stages 3 and 4 (eGFR >20 mL/min/1.73 m²) 6, 3
• Consider angiotensin receptor neprilysin inhibitors in patients with eGFR as low as 20 mL/min/1.73 m² 6
• Avoid hesitation with renin-angiotensin-aldosterone axis inhibitors in mild-to-moderate CKD despite concerns about hyperkalemia and worsening kidney function—the benefits are proven 6
• Cardiac resynchronization therapy reduces death and hospitalizations in heart failure patients with CKD stage 3 6

For Anemia

• Initiate iron supplementation when serum ferritin <100 mcg/L or transferrin saturation <20%, as the majority of CKD patients require supplemental iron during ESA therapy 5
• Intravenous iron improved symptoms in heart failure patients with CKD stage 3, and high-dose iron reduced heart failure hospitalizations by 44% in dialysis patients 6
• Consider erythropoiesis-stimulating agents (ESAs) only when hemoglobin <10 g/dL in dialysis patients, using the lowest dose to reduce transfusion need 5
• For non-dialysis CKD patients, initiate ESAs only when hemoglobin <10 g/dL AND the rate of decline indicates likely transfusion need 5
• Target hemoglobin should NOT exceed 11 g/dL, as higher targets increase risks of death, serious cardiovascular reactions, and stroke 5
• Start with 50-100 Units/kg three times weekly IV or subcutaneously for adult CKD patients 5

For Refractory Dyspnea Despite Optimal Management

• Consider low-dose oral morphine (10 mg per day as modified release once daily or 2.5 mg immediate release four times daily) for chronic breathlessness, though data in heart failure are conflicting 4
• 63% of patients with chronic breathlessness from various causes (including heart failure) experience clinically important improvement with morphine 4
• In CKD stages 4 and 5 (GFR <30 mL/min), avoid morphine or use with extreme caution due to accumulation of active metabolites with renal excretion 4
• Consider switching to alternative opioids without renally excreted active metabolites in severe renal impairment 4
• Avoid benzodiazepines as first-line therapy due to association with increased all-cause mortality and falls; reserve as second- or third-line for acute episodes when anxiety significantly aggravates distress 4

Cardiovascular Risk Reduction Strategy

• Estimate 10-year cardiovascular risk using a validated risk tool 4
• Choose statin-based regimens to maximize absolute LDL cholesterol reduction 4
• Consider a plant-based Mediterranean-style diet in addition to lipid-modifying therapy 4
• For secondary prevention in established ischemic cardiovascular disease, use oral low-dose aspirin 4

Monitoring and Referral

• Monitor hemoglobin weekly after initiating or adjusting ESA therapy until stable, then monthly 5
• Avoid frequent ESA dose adjustments; do not increase dose more frequently than once every 4 weeks 5
• Refer to combined cardiology-nephrology clinics if available, as multidisciplinary approaches improve management of HFrEF with CKD 6
• Refer to nephrology if eGFR <30 mL/min/1.73 m², persistent electrolyte abnormalities, or rapid decline in kidney function 7