Nephrotic syndrome arises from numerous underlying factors and can be categorized based on whether the primary disease originates within the kidney or is a manifestation of a systemic condition.

Primary Causes

Minimal change disease (MCD): This is the most common cause of nephrotic syndrome in children. Its name reflects the normal appearance of nephrons under an optical microscope, with lesions only visible using an electron microscope. A pronounced proteinuria is a key symptom.

Focal segmental glomerulosclerosis (FSGS): This represents the most common cause of nephrotic syndrome in adults. It is characterized by the presence of tissue scarring within the glomeruli. The term “focal” indicates that some glomeruli are scarred while others are intact, and “segmental” means that only a portion of the affected glomerulus is damaged.

Membranous glomerulonephritis (MGN): This condition involves inflammation of the glomerular membrane, leading to increased leakage within the kidney. The exact reason for its development is often unclear, although an autoimmune mechanism is suspected.

Membranoproliferative glomerulonephritis (MPGN): This involves inflammation of the glomeruli along with the deposition of antibodies in their membranes, hindering the filtration process.

Rapidly progressive glomerulonephritis (RPGN): (Typically presents as a nephritic syndrome) In this condition, the glomeruli exhibit a characteristic crescent moon shape. Clinically, it is marked by a rapid decline in the glomerular filtration rate (GFR) by at least 50% over a short period, typically ranging from a few days to 3 months.

Secondary Causes

Diabetic nephropathy: This complication can occur in individuals with diabetes. Excess blood sugar accumulates in the kidneys, causing inflammation and impairing their normal function, which leads to protein leakage into the urine.

Systemic lupus erythematosus: This autoimmune disease can affect various organs, including the kidneys, due to the deposition of immune complexes characteristic of the disease. This can result in lupus nephritis.

Infections:

Syphilis: Kidney damage can occur during the secondary stage of this infection, approximately 2 to 8 weeks after onset.
Hepatitis B: Certain antigens present during Hepatitis B can accumulate in the kidneys and cause damage.
HIV: The virus’s antigens can cause an obstruction in the glomerular capillary lumen, disrupting normal kidney function.

Vasculitis: Inflammation of the blood vessels at the glomerular level can impede normal blood flow and damage the kidney.

Cancer: In conditions like myeloma, the invasion of the glomeruli by cancerous cells can disrupt their normal functioning.

Genetic disorders: Congenital nephrotic syndrome is a rare genetic disorder involving an alteration in the protein nephrin, a component of the glomerular filtration barrier.

Drugs (e.g., gold salts, penicillin, captopril): Gold salts can lead to varying degrees of protein loss in the urine due to metal accumulation. Penicillin can be nephrotoxic in patients with kidney failure, and captopril can exacerbate proteinuria.

 Diagnosis, Investigations, and Treatment of Nephrotic Syndrome

Diagnosis and Investigations

  Initial Assessment:
Obtain a thorough medical history, including any acute or chronic conditions, family history of kidney disease, and a review of systems to identify symptoms such as edema, fatigue, and foamy urine.
Perform a physical examination focusing on signs of fluid overload, such as edema and ascites, as well as other systemic findings.

  Laboratory Investigations:
Conduct urinalysis to detect the features of nephrotic syndrome: high levels of proteinuria.
Microscopic hematuria that may occasionally be present.
Biochemical tests to evaluate kidney function, including serum creatinine, blood urea nitrogen (BUN), electrolytes, albumin levels, and a lipid profile, as hyperlipidemia is often associated with nephrotic syndrome.
Perform a urine protein-to-creatinine ratio to quantify the degree of proteinuria.

Imaging Studies

• Ultrasound: Renal ultrasounds might reveal kidneys appearing brighter than normal (hyperechoic) with less clear distinction between the outer and inner layers (corticomedullary differentiation loss).

• Abdominal Ultrasound: If necessary, an ultrasound of the entire abdomen can be performed to check for complications like blood clots in veins (venous thrombosis) or to exclude other reasons for protein in the urine.

Immunological and Serological Testing

• Assess autoimmune markers, which includes:

  • Antinuclear Antibodies (ANA): To check for autoimmune diseases.

  • Anti-streptolysin O Titers (ASOT): To evaluate for past streptococcal infections.

  • Complement Components (e.g., C3): To assess the immune system’s complement pathway.

  • Cryoglobulins: To detect abnormal proteins that precipitate in cold temperatures.

  • Serum Electrophoresis: To look for monoclonal gammopathy, which can indicate certain blood disorders.

Kidney Biopsy

• A kidney biopsy is performed if initial tests are not conclusive or to pinpoint the precise cause of nephrotic syndrome.

• Microscopic examination of the kidney tissue (histological examination) can determine the specific type of glomerulonephritis or other kidney abnormalities causing the condition.

Additional Investigations

• Genetic Testing: Consider if hereditary causes of nephrotic syndrome are suspected, especially in children or when there’s a family history of kidney problems.

• Secondary Causes Assessment: Investigate potential underlying causes of nephrotic syndrome, including:

  • Tests for infections like hepatitis B and C, and HIV.

  • Diabetes management assessment (HbA1c test).

  • Evaluation for cancers if clinically indicated.

Treatment of Nephrotic Syndrome

Management Goals:

• Reduce swelling (edema).

• Correct low albumin levels in the blood (hypoalbuminemia).

• Lower elevated blood pressure.

• Decrease protein in the urine (proteinuria).

• Prevent complications like infections, blood clots (thrombosis), and malnutrition.

Medical Management:

1. Diuretics: Loop diuretics, such as furosemide, are primary medications for managing edema. Thiazide diuretics, like hydrochlorothiazide, can be added for enhanced effect if needed.

2. Albumin Infusions: Albumin infusions might be considered to raise blood albumin levels and reduce edema, but are often avoided due to high cost.

3. ACE Inhibitors or ARBs: Medications like lisinopril (ACE inhibitors) or losartan (ARBs) are used to manage blood pressure and reduce protein loss in urine.

4. Corticosteroids: Prednisone is a common corticosteroid used, typically starting at 1-2 mg/kg daily and gradually decreased. Lack of improvement after 4 weeks of prednisolone treatment may indicate the need for a kidney biopsy.

5. Immunosuppressants: Drugs like cyclophosphamide are used for patients who don’t respond adequately to corticosteroids.

6. Statins: Statins, for example atorvastatin, are prescribed to reduce high cholesterol levels.

7. Antiplatelet Agents: Antiplatelet medications, such as aspirin, may be used to prevent blood clot formation.

8. Nutritional Support: A diet high in protein is crucial to prevent malnutrition.

9. Vitamin D and Calcium: Supplements might be necessary to prevent low calcium levels (hypocalcemia).

10. Antibiotics: Used to treat any infections that arise.

11. Vaccinations: Vaccination against pneumococcal pneumonia and influenza is recommended for nephrotic syndrome patients.

Nursing Interventions for Nephrotic Syndrome:

Fluid Volume Excess:

• Elevate legs and feet to help fluid drain back towards the body’s core.

• Monitor for signs of fluid overload, such as edema, fluid in the abdomen (ascites), and fluid around the lungs (pleural effusions).

• Restrict fluid intake as directed by the doctor.

• Administer prescribed diuretics like furosemide (Lasix) to increase fluid excretion.

• Strictly track fluid intake and output and maintain accurate fluid balance records.

• Daily weight monitoring to assess fluid status changes.

Ineffective Breathing Pattern:

• Regularly assess respiratory status, including oxygen saturation, breathing rate, and breathing effort.

• Position the child in a semi-upright (semi-Fowler’s) position or supported over a table with pillows to aid lung expansion.

• Provide supplemental oxygen if prescribed to maintain adequate oxygen levels.

• Encourage slow, deep breaths and relaxation techniques to ease anxiety and improve breathing patterns.

• Administer bronchodilators if prescribed to open airways and reduce wheezing.

Risk for Infection:

• Monitor for infection signs, such as fever, chills, and elevated white blood cell count.

• Administer prescribed antibiotics to treat or prevent infections.

• Practice rigorous hand hygiene and maintain aseptic technique when caring for the child and performing procedures.

• Keep skin clean and dry to prevent skin infections.

• Monitor nutritional status and ensure a diet rich in protein and vitamins to support the immune system.

Altered Nutrition: Less Than Body Requirements:

• Provide small, frequent meals that are rich in protein and calories to meet increased nutritional needs.

• Offer a variety of foods to encourage eating and prevent food aversion.

• Consult a dietitian to create a tailored nutrition plan that meets individual needs and preferences.

• Supplement diet with nutritional supplements as prescribed to ensure sufficient intake of essential nutrients.

Dietary Management of Nephrotic Syndrome:

• Provide a balanced diet with sufficient protein (1.5-2 g/kg) and calories.

• Limit fat intake to less than 30% of total calories, especially avoiding saturated fats.

• Encourage a “no added salt” diet to minimize fluid retention.

• Discourage sugary drinks and snacks to prevent weight gain and fluid overload.

• Regularly monitor weight and adjust diet as needed to maintain a healthy weight.

Complications:

• Monitor for complications like ascites, pleural effusion, generalized edema, blood clotting issues, thrombosis, recurrent infections, kidney failure, growth delays, and calcium and vitamin D deficiency.

• Provide appropriate treatments and interventions for any complications that develop.

• Educate the child and family about potential complications and the importance of regular follow-up care.