Uraemic Cardiomyopathy

Uraemic cardiomyopathy is myocardial disease caused by chronic kidney disease (CKD) and its treatment. It is marked by left ventricular hypertrophy, interstitial fibrosis, and diastolic then systolic dysfunction.

Left ventricular hypertrophy is present in about 30 to 50% of patients with moderate CKD and in up to 70% at the start of dialysis. Heart failure affects roughly 20 to 40% of dialysis patients.

Cardiovascular disease causes about 40 to 50% of deaths on dialysis, and sudden death accounts for about a quarter of all deaths. Events cluster after the long interdialytic interval.

Contributors are hypertension, volume overload, anaemia, arteriovenous access, vascular calcification and coronary disease. The diagnosis needs other causes of cardiomyopathy to be excluded.

Pathophysiology. Pressure load (hypertension, arterial stiffness) and volume load (sodium retention, anaemia, arteriovenous fistula) drive concentric and eccentric hypertrophy.

Non-haemodynamic factors add to it: raised FGF23, hyperphosphataemia, secondary hyperparathyroidism, uraemic toxins, inflammation, oxidative stress, and activation of the renin angiotensin and sympathetic systems.

Capillary rarefaction and fibrosis reduce flow reserve. Haemodialysis with intradialytic hypotension causes repeated myocardial stunning.

• Dyspnoea, orthopnoea, oedema, fatigue, cramps and intradialytic hypotension. Many patients are asymptomatic early.
• Hypertension, raised venous pressure, third heart sound and pulmonary congestion that responds to ultrafiltration.
• Atrial fibrillation, ventricular ectopy and sudden death, especially after the long interdialytic interval.
• Uraemic pericarditis: pleuritic pain, friction rub and pericardial effusion in under dialysed patients.
• Features of the kidney disease: pallor, pruritus, uraemic frost, access fistula with a thrill.

Red flags.

• Pulmonary oedema not responding to ultrafiltration
• Recurrent intradialytic hypotension
• Potassium over 6.0 mmol/L or ECG changes of hyperkalaemia
• Pericardial effusion with falling blood pressure (tamponade)
• Syncope or ventricular arrhythmia
• Ejection fraction under 40%
• High flow arteriovenous access with new heart failure

• Echocardiography on the day after dialysis at dry weight, because chamber size and filling pressures depend on volume status. Record left ventricular mass index (over 115 g/m2 in men, over 95 g/m2 in women), relative wall thickness, ejection fraction, E/e' ratio, left atrial volume index, pericardial effusion and valve calcification.
• Natriuretic peptide and troponin are chronically raised in CKD. Compare each result with the patient's own dry weight baseline, and give weight to a rising trend.
• ECG and ambulatory ECG for arrhythmia, conduction disease and hyperkalaemia.
• Cardiac MRI. Avoid gadolinium agents at eGFR under 30 mL/min/1.73 m2 unless a macrocyclic agent is chosen after specialist review. Native T1 mapping needs no contrast.
• Coronary assessment by stress imaging or angiography when symptoms or risk factors are present. Stress test accuracy is reduced in CKD.
• Laboratory: haemoglobin, ferritin, transferrin saturation, calcium, phosphate, parathyroid hormone, bicarbonate, potassium, albumin, urea, creatinine. Bioimpedance for volume status where available.

Differential diagnosis.

• Ischaemic cardiomyopathy and hypertensive heart disease
• Cardiac amyloidosis (dialysis related and transthyretin)
• Fabry disease
• Uraemic pericarditis and pericardial tamponade
• High output failure from arteriovenous access or anaemia
• Calcific aortic stenosis and mitral annular calcification
• Iron overload cardiomyopathy
• Pure volume overload without myocardial disease

Volume and blood pressure.

• Reach dry weight by ultrafiltration. Extend dialysis time or add sessions for recurrent overload. Keep the ultrafiltration rate under 13 mL/kg/h, because higher rates raise mortality.
• Sodium under 2 g daily and fluid restriction by urine output. Avoid dialysate sodium loading.
• Pre-dialysis blood pressure under 140/90 mm Hg, and avoid intradialytic hypotension (cool dialysate, withhold antihypertensives before dialysis).
• Ramipril 2.5 mg orally once daily, increased every 2 to 4 weeks to 10 mg once daily (maximum 10 mg daily, and 5 mg daily at creatinine clearance under 30 mL/min). Give after dialysis. Check potassium and creatinine 1 to 2 weeks after each change. Contraindicated in pregnancy and bilateral renal artery stenosis.
• Amlodipine 5 mg orally once daily, increased to 10 mg (maximum 10 mg daily; start 2.5 mg in older adults and liver impairment).

Heart failure with reduced ejection fraction.

• Carvedilol 3.125 mg orally twice daily, doubled every 2 weeks to the target 25 mg twice daily (50 mg twice daily if over 85 kg), maximum 100 mg daily. It is not removed by dialysis. Reduce in liver impairment. Contraindicated in decompensated heart failure, asthma, severe bradycardia and high grade atrioventricular block without a pacemaker.
• Sacubitril/valsartan 24/26 mg orally twice daily at eGFR under 30 mL/min/1.73 m2, only under specialist care because data on dialysis are limited.
• Spironolactone is avoided at eGFR under 30 mL/min/1.73 m2 and used on dialysis only under specialist care with potassium monitoring. Dapagliflozin is not started on dialysis.
• Furosemide 40 mg orally once daily in the morning, increased to 80 to 120 mg daily as needed (higher doses in renal impairment under specialist care) while urine output remains. Monitor sodium, potassium and creatinine.

Anaemia and iron.

• Epoetin alfa 50 to 100 units/kg intravenously or subcutaneously three times weekly, adjusted by 25% every 4 weeks, to a haemoglobin of 100 to 110 g/L. Do not exceed 115 g/L. Reduce the dose when haemoglobin rises by over 20 g/L in 4 weeks. Monitor blood pressure. Contraindicated in uncontrolled hypertension and pure red cell aplasia. Correct iron deficiency and look for inflammation, hyperparathyroidism and under dialysis when response is poor.
• Iron sucrose 100 mg intravenously at each of 10 consecutive dialysis sessions (1 g in total) when transferrin saturation is 30% or less and ferritin is 500 microgram/L or less. Withhold during active infection.

Mineral and bone disorder. Control phosphate by diet and binders chosen with nephrology, with calcium free binders preferred when vascular calcification is present, and avoid calcium and vitamin D excess. Cinacalcet 30 mg orally once daily, titrated every 2 to 4 weeks to a maximum of 180 mg daily, with calcium checked within 1 week, for secondary hyperparathyroidism. It does not reduce cardiovascular events. Contraindicated in hypocalcaemia.

Hyperkalaemia with ECG changes. Calcium gluconate 10% 30 mL intravenously over 10 minutes with continuous ECG monitoring, repeated once after 10 minutes if changes persist. Soluble insulin 10 units (5 units in severe renal impairment or low body weight) with glucose 25 g intravenously over 15 minutes, and glucose checks hourly for 6 hours. Salbutamol 10 to 20 mg nebulised over 10 minutes. Urgent dialysis for refractory or severe cases.

Atrial fibrillation. Warfarin to an INR of 2.0 to 3.0 is the established option on dialysis. Apixaban 2.5 mg orally twice daily is used in some practice by specialist decision, and benefit is unproven. The usual apixaban dose rules do not apply at creatinine clearance under 15 mL/min.

Uraemic pericarditis. Intensive daily dialysis, preferably heparin free. Avoid anti-inflammatory drugs. Pericardiocentesis or a surgical window for tamponade or persistent large effusion.

Lipids. Atorvastatin 20 mg orally once daily needs no renal adjustment. It is not started on dialysis and is continued if already taken.

Definitive. Renal transplantation regresses hypertrophy and improves survival.

Special groups. Sudden death risk rises with low dialysate potassium (under 2 mmol/L), so keep dialysate potassium at 3 mmol/L or more. In sub-Saharan Africa, late presentation, limited dialysis access and HIV-associated nephropathy increase the burden, so prioritise blood pressure, volume and anaemia control.

Monitoring. Dry weight and pre-dialysis blood pressure each session. Haemoglobin monthly, ferritin and transferrin saturation every 3 months, and potassium, calcium, phosphate each month. Echocardiography at diagnosis, then every 1 to 2 years or with symptoms.

Referral and escalation. Refer to nephrology and cardiology jointly. Urgent for pulmonary oedema, tamponade, hyperkalaemia with ECG change, syncope or ventricular arrhythmia.