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Sari Aaltonen

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 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.

Aetiology

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.

Treatment Lipid Lowering Therapies in Renal Disease, ACE Inhibitors and Angiotensin Receptor Blockers for Progression of Non-Diabetic Renal Disease, ACE Inhibitors and Angiotensin II Receptor Blockers for Diabetics with Microalbuminuria, Immunosuppressive Treatment or Alkylating Agents for Idiopathic Membranous Nephropathy, Antiproteinuric and Renoprotective Effects of ACE Inhibitors and Angiotensin II Receptor Blockers, Interventions for Minimal Change Disease in Adults with Nephrotic Syndrome

  • 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 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.

Related Keywords

ATC Code:

B01AB04

B01AB05

B01AB10

C03CA01

C10AA01

C10AA02

C10AA03

C10AA04

C10AA05

C10AA07

B01AC06

C09CA01

C09CA02

C09CA03

C09CA04

C09CA06

C09CA07

C09CA08

H02AB01

H02AB02

H02AB04

H02AB06

H02AB07

H02AB08

H02AB09

H02AB13

H02BX01

C03AA03

C03BA08

C03BA11

J07AL01

J07AL02

J07AL52

L04AD01

C09AA01

C09AA02

C09AA03

C09AA04

C09AA05

C09AA06

C09AA15

L01XC02

A12CA01

Primary/Secondary Keywords