Nephrotic syndrome (NS) is a clinical syndrome defined by massive proteinuria responsible for hypoalbuminemia, with resulting hyperlipidemia, oedema, and various complications. The aetiology, evaluation and management of nephrotic syndrome are elucidated in this article.

---

Nephrotic syndrome (NS)

The nephrotic syndrome could affect adults and children of both genders and any race. Nephrotic-range proteinuria is defined as the urinary loss of 3 grams or more of proteins per 24 hours. The first indication of nephrotic syndrome in children is the swelling of the face which then progresses to the entire body. Adults may present with dependent oedema.

---

Aetiology

Common primary causes of nephrotic syndrome are intrinsic kidney diseases, such as membranous nephropathy, minimal-change nephropathy, and focal glomerulosclerosis.

Secondary causes of nephrotic syndrome include the following:

1. Diabetes mellitus
2. Immune

• SLE
• ANCA vasculitis
• Goodpasture syndrome
• Membranoproliferative glomerulonephritis

3. Infection: Human Immunodeficiency Virus (HIV), hepatitis B virus, hepatitis C, cytomegalovirus, amyloidosis, and paraproteinemias.

---

Evaluation

A. History taking

1. The first sign of nephrotic syndrome in the pediatric population is usually swelling on the face. This is followed by oedema of the entire body. Adult patients can present with dependent oedema.
2. Frothy urine may be a presenting symptom.
3. Tiredness and lack of appetite are common features.
4. A thrombotic consequence, such as deep venous thrombosis (DVT) of the calf veins or a pulmonary embolus, could be the first indication of nephrotic syndrome.
5. Additional features in a patient's history are related to the cause of the nephrotic syndrome. For instance, a recent commencement of NSAIDs suggests such drugs as the cause. Similarly, a more than 10-year history of diabetes mellitus with symptomatic neuropathy suggests diabetic nephropathy.

B. Physical examination

1. Oedema is the most prominent feature of nephrotic syndrome, and in the beginning, it develops around the eyes and legs. Over time, the oedema becomes generalised and leads to increasing weight and the development of ascites or pleural effusions.
2. Hematuria and hypertension may be present less frequently, although these are more prominently seen in nephritic syndrome.
3. Additional features on examination vary according to the cause of the nephrotic syndrome. Also, it depends on whether or not renal function impairment is present. For instance, in the case of longstanding diabetes mellitus, the patient could have diabetic retinopathy, which is closely associated with diabetic nephropathy. If the kidney function is impaired, the patient may have anaemia, hypertension, or both.

C. Laboratory tests

Urine tests: Nephrotic-range proteinuria will be apparent by Urine protein creatinine ratio of more than 3 grams.

Blood tests

1. The serum albumin level is classically low in nephrotic syndrome. Serum albumin often is less than the normal range of 3.5 to 4.5 g/dL.
2. Creatinine concentrations vary by degree of renal impairment. Total cholesterol and triglyceride levels are typically increased.
3. Serum PLA2R Antibody is used to detect primary membranous nephropathy.
4. Serologic studies: The role of testing for secondary causes of nephrotic syndrome is controversial (because yield may be low). Tests are best done as indicated by clinical context. Consider serum HbA1c, ANA, Hepatitis B and C serologic tests, serum or urine protein electrophoresis, HIV antibody test, and complement levels.

Ultrasonography: Individuals with a single kidney may be prone to developing focal glomerulosclerosis; having only one kidney is also a relative contraindication to kidney biopsy. Ultrasonography also demonstrates renal echogenicity. Increased renal echogenicity is consistent with intrarenal fibrosis.

Renal biopsy: This is indicated for the following:

• Congenital nephrotic syndrome
• Children older than eight years at the onset
• Steroid resistance, frequent relapses or steroid dependency
• Significant nephritic manifestations

---

Management

Specific treatment of nephrotic syndrome is dependent on its cause. Therefore, management varies between adult and pediatric populations.

Specific treatment in children

Corticosteroids are mainly used for children with idiopathic nephrotic syndrome. Alternative immunosuppressive agents are often necessary for children with frequently relapsing or steroid-dependent nephrotic syndrome. Examples of these drugs include cyclophosphamide, mycophenolate mofetil (MMF), calcineurin inhibitors, and levamisole.

Specific treatment in adults

Treatment varies by aetiology, as follows:

1. Minimal change nephropathy in adults usually responds to prednisone.
2. In lupus nephritis, prednisone combined with cyclophosphamide or mycophenolate mofetil induces remission.
3. Secondary amyloidosis with nephrotic syndrome will improve with the anti-inflammatory management of the primary disease.

Acute nephrotic syndrome in childhood

Hospitalisation is not usually necessary with close outpatient follow-up care and good parental and patient education. Hospitalisation becomes helpful if any of the following are present:

• Generalised oedema severe enough to result in respiratory distress
• Tense scrotal or labial oedema
• Complications such as bacterial peritonitis, pneumonia, sepsis, or thromboembolism

Diuretics are usually needed. Furosemide (1 mg/kg/day) and spironolactone (2 mg/kg/day) help when fluid retention is severe enough, provided there are no signs of kidney failure or volume contraction.

Acute nephrotic syndrome in adults

The principles of treatment in adults with acute nephrotic syndrome are not different from those for children. Diuretics, such as furosemide, spironolactone, and even metolazone, may be needed. Diuretic use may lead to volume depletion, which should be assessed by monitoring symptoms, weight, pulse, and blood pressure.

Anticoagulation has been suggested to prevent thromboembolic complications, but its role in primary prevention is not proven. Hypolipidemic agents could be used.

In patients with secondary nephrotic syndrome, such as that secondary to diabetic nephropathy, some medications are widely used to reduce proteinuria, such ACEi/ARB. By reducing proteinuria, these drugs will lead to reduced intraglomerular pressure causing a reduction in systemic blood pressure.

Diet and activity

The diet in patients with nephrotic syndrome is aimed to provide sufficient caloric and protein (1 g/kg/d) intake. Supplemental dietary proteins are of no proven value. A low-salt diet helps limit fluid retention and oedema.

Long-term monitoring

The patient's oedema and proteinuria define the adjustment of diuretics and angiotensin antagonists. Follow-up in the nephrotic syndrome also involves immunisations and monitoring for steroid toxicity.

---

Complications

The complications involved are as follows:

• Infection
• Hypocalcemia and bone abnormalities
• Hyperlipidemia and atherosclerosis
• Hypercoagulability
• Hypovolemia
• Acute Kidney Injury (AKI)

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Bhavin Mandowara is a practising nephrologist at Zydus Hospital, Ahmedabad.