Information
Editors
Nephrotic Syndrome
Essentials
- Suspect nephrotic syndrome as a rare cause of oedema. The most important symptom is oedema in the lower extremities and eyelids caused by accumulation of salt and fluid within the tissues.
- In addition to treatment directed at the primary disease, proteinuria, fat metabolism, hypertension (target blood pressure HASH(0x2fdd780) 120-130/80 mmHg) and oedema are treated.
Definition
- Nephrotic syndrome is caused by glomerular capillary wall damage. In nephrotic syndrome proteins are lost in the urine (in adults) > 3-3.5 g/day (urine albumin/creatinine ratio > 200 mg/mmol) and serum albumin concentration is decreased < 30 g/l.
- This will lead to decreased colloid osmotic pressure in the blood, accumulation of salt and water, and, usually, to oedema.
- The clinical picture also includes hyperlipidaemia, susceptibility to infections, and abnormal blood clotting predisposing the patient to thrombosis.
Signs and symptoms
- The main symptoms are oedema and weight gain due to fluid accumulation in the tissues as serum protein levels decrease and the capacity of the body to excrete sodium is impaired.
- Weight gain can exceed ten kilograms and can be gradual or sudden, depending on the disease.
- The oedema first appears in the ankles and, in the mornings, in the eyelids, but as the oedema increases it spreads to the whole body.
- Fluid accumulates according to gravity; in bedridden patients, the accumulation may be most visible on the back.
- In severe nephrosis, pleural fluid and ascites also accumulate.
- Symptoms usually emerge at the latest when the serum albumin concentration falls below 25 g/l due to excess proteinuria.
- The extent of oedema does not always correlate directly with the blood albumin concentration.
Diagnosis
- The diagnosis is based on the clinical picture and on the results of laboratory investigations.
- Swellings, urinary albumin +++ ( 24-h urinary protein excretion > 3 g, urine albumin/creatinine ratio > 200 mg/mmol), plasma albumin concentration low (< 30 g/l)
- Always also check plasma creatinine concentration (and eGFR; calculator Gfr Calculator) and possible haematuria (chemical screening of urine).
- Renal ultrasonography
- To establish the aetiology, a renal biopsy is often required. Therefore, the patient should be referred to hospital for investigations.
- Always consult specialized care. Refer as
- urgent if the symptoms are severe or have developed within a few days
- non-urgent if the symptoms have developed within weeks.
- Treatment of the underlying disease
- Reduction of proteinuria
- In chronic proteinuric diseases, SGLT2 inhibitors are also recommended if GFR > 25 ml/min (note: not in patients with type 1 diabetes).
- Optimal treatment of hypertension
- Target HASH(0x2fdd780) 120-130/80 mmHg
- Drug therapy consists of an angiotensin-receptor blockers (ARB) or an ACE inhibitor, and additionally, as necessary, a diuretic, a calcium-channel blocker or other antihypertensive drug.
- Reduction of oedema
- Restricted salt intake (aim < 2 g of sodium, equivalent to < 5 g of sodium chloride / day)
- Fluid restriction
- A diuretic
- Furosemide 20-80 mg two to four times daily orally. In severe oedema, treatment may be instigated with intravenous administration (the corresponding dose is 10-40 mg). Beware of hypovolaemia.
- The dose of furosemide is increased according to response.
- A thiazide diuretic enhances the effect of furosemide. The dose of hydrochlorothiazide is 25-50 mg/day (higher in renal failure). In severe renal failure, metolazone can also be used.
- Avoid excessive weight loss; 0.5-1 kg/day is appropriate.
- An infusion of intravenous albumine and furosemide has been used in oedema resistant to other therapy, but its use remains controversial.
- In treatment-resistant situations, mechanical removal of excess fluid with ultrafiltration therapy may sometimes be required.
Complications
- Hypercoagulability; risk of venous thrombosis of the lower limbs, pulmonary embolism and renal vein thrombosis.
- Aspirin should be given routinely.
- During the stay on a hospital ward prophylactic low molecular weight heparin should be used, especially if the patient has prominent swellings. Sometimes it is still worth continuing treatment at home if the nephrosis is severe.
- Prophylactic oral anticoagulation is usually not administered but it should be considered if the nephrotic syndrome is severe (serum albumin concentration < 20 g/l, 24-h urinary protein excretion > 10 g) and bleeding risk is not considered too high.
- Most experience is with warfarin. Research evidence on the use of direct oral anticoagulants (DOACs: dabigatran, rivaroxaban, apixaban and edoxaban) for thromboprophylaxis in patients with nephrosis is still scarce.
- Anticoagulant therapy should always be instigated in patients with a history of deep venous thrombosis or pulmonary embolism and continued whilst the patient remains nephrotic.
- Susceptibility to infections. The loss of IgG, for example, in the urine predisposes the patient to infections.
- Gradual muscle wasting as a consequence of hypoproteinaemia
- The diet should include high quality protein, approximately 0.8-1 g/kg/day.
- Energy intake should exceed 35 kcal/kg/day.
- Atherosclerotic changes as a consequence of hyperlipidaemia
- Altered calcium metabolism
- Severe nephrotic syndrome may be associated with acute kidney injury (AKI) Acute Kidney Injury.
- Binding of drugs may be altered.
- With most drugs, it is not necessary to change the dosage.
- Warfarin dosage, for example, may have to be changed.
References