Internal Medicine Nephrology

Nephrotic Syndome

Nephrotic Syndrome Kidney
Renal ultrasonography in a patient with nephrotic syndrome.

Introduction – Nephrotic Syndrome

The definition of Nephrotic Syndrome is the combination of:

  • Prominent proteinuria
  • Hypoalbuminemia
  • Edema
  • Hyperlipidemia

Loss of >3.5 g protein per day is expressed as pronounced proteinuria.

Causes – Nephrotic Syndrome

Nephrotic syndrome is a clinical condition with a variety of kidney and systemic diseases as a possible cause. Some of these conditions are genetic and debut at an early age. Common to the causes is that the glomerular barrier is affected and becomes more permeable to proteins with proteinuria as a result. It is mainly albumin that is lost and there is also increased renal catabolism of albumin in nephrotic syndrome.

For the past ten years, research has provided us with molecular explanations for the genetic diseases in the form of defective proteins in glomerular cells, mainly in podocytes. However, most adult nephrotic syndromes do not appear to be genetic, but, here our knowledge is more rudimentary with regard to molecular mechanisms.

Examples of underlying diseases/conditions in nephrotic syndrome:

  • Renal: glomerulonephritis
  • Systemic diseases : Diabetes, SLE , amyloidosis , hepatitis B and hepatitis C, HIV, malignancy
  • Medicines : NSAIDs, bisphosphonates
  • Toxic substances : Heavy metals

Clinical Findings

  • Proteinuria – large amounts of protein in the urine makes it foamy during micturition.
  • Hypoalbuminemia – The lower the S-albumin, the more severe the nephrotic syndrome. There may be a risk of toxic effects of certain protein binding drugs.
  • Edema – In nephrotic syndrome, there is both water and sodium retention. The nephrotic edema is of a hypostatic nature and differs from other edematous conditions as they usually debut as eyelid edema. Patients usually tolerate a significantly greater amount of retained fluid than in cardiac edema. The degree of edema can vary significantly, from slight swelling of the face and around the ankles to pronounced edema with pleural fluid and ascites. The latter usually occurs when the fluid retention amounts to 20 liters or more.
  • Hyperlipidemia – both hypercholesterolemia and hypertriglyceridemia are common and are related to the nephrotic syndrome’s severity.
  • Thromboembolic disease – All patients with nephrotic syndrome have an increased risk of thromboembolic disease, especially if S-albumin <25 g/L. This may manifest as renal vein thrombosis, deep vein thrombosis and pulmonary embolism, however, arterial thrombosis may also occur.
  • Infections – Patients with nephrotic syndrome have an increased susceptibility to infection. The cause is not entirely clear, but the following factors contribute to the problem:
    – increased losses of opsonins
    – lowered IgG levels
    – dysfunction of the complement system
    – frequent malnutrition
    – vitamin D deficiency
    – treatment with immunosuppressive agents

Diagnostics – Nephrotic Syndrome

Initial diagnostics for suspected nephrotic syndrome:

  • Urinalysis, albumin (alternatively protein or albumin/creatinine ratio)
  • S-albumin, S-creatinine, S-urea
  • S-cholesterol, S-triglycerides
  • Serological antibodies (ANA, anti-DNA, ANCA, anti-MPO)

Contact is made without delay, preferably by telephone, with the kidney medical clinic for further treatment and investigation aimed at diagnosing underlying disease and its severity.

The investigation includes:

  • Kidney Biopsy
  • Ultrasound examination of the kidneys
  • Renal Function Measurement

Treatment – Nephrotic Syndrome

Symptomatic Treatment

Aims to correct the systemic complications of nephrotic syndrome.

  • Proteinuria – ACE inhibitor or ARB in combination with sodium restriction
  • Edema – Loop diuretics and sodium restriction, possibly metolazone, ultrafiltration in severe cases
  • Hyperlipidemia – Statins
  • Thromboembolic Risk – Low Molecular Heparin (LMWH) or Warfarin
  • Infection – Aggressive treatment in bacterial infections, possibly pneumococcal vaccination

Specific treatment

Intends to treat underlying disease or to cause the nephrotic syndrome to go into remission. Then all the complications such as proteinuria, hypoalbuminemia and edema usually resolve.

Prognosis – Nephrotic Syndrome

The prognosis depends entirely on the underlying disease. Among children and adolescents, the most common condition is minimal change disease that usually responds well to steroids and the patient usually regains normal renal function. Among older people, membranous glomerulonephritis dominates, with one-third of cases progressing to dialysis-requiring renal failure. For about a third of affected patients, the prognosis is favorable and they regain good function within a few months to years. There is great potential for the development of more specific therapy as the drugs used today are nonspecific and have substantial side effects.


Patients are monitored by specialist health care units, usually by nephrologists.

Further Reading