Nephrotic Syndrome: Pathophysiology, Diagnosis, and Treatment Options

10 Questions

What is the primary cause of nephrotic syndrome?

Severe alteration of the glomerular filtration barrier

What is the cut-off value for serum albumin levels to diagnose nephrotic syndrome in children?

3.5 g/dL

Which of the following is NOT a common cause of nephrotic syndrome?

Hypertension

What is the initial treatment for nephrotic syndrome?

Daily oral prednisolone/prednisone

What percentage of steroid-resistant nephrotic syndrome cases have mutations in podocyte-associated genes?

10-30%

What is the unit of measurement for proteinuria in the diagnosis of nephrotic syndrome?

mg/m² per hour

Which of the following glomerular lesions is commonly associated with nephrotic syndrome in children?

Minimal change disease

What is the incidence of nephrotic syndrome in children per year?

1-3 per 100,000

What is the term for patients who do not achieve complete remission within 4-6 weeks of initial treatment?

Steroid-resistant nephrotic syndrome

What is the primary protein lost in the urine in nephrotic syndrome?

Albumin

Study Notes

Nephrotic Syndrome: Pathophysiology, Treatment Options, Complications, and Diagnostic Criteria

Nephrotic syndrome (NS) is a rare condition that affects approximately 1-3 per 100,000 children per year. It is characterized by severe proteinuria, hypoalbuminemia, and/or the presence of edema. The pathophysiology of NS involves a severe alteration in the glomerular filtration barrier, which allows large quantities of protein, mostly albumin, to freely pass in urine. The condition is diagnosed in children when proteinuria exceeds 40 mg/m² per hour, and serum albumin levels are below 3.5 g/dL.

Pathophysiology

The primary cause of NS is a severe alteration of the glomerular filtration barrier, leading to the loss of large quantities of proteins, mainly albumin, in urine. Various glomerular lesions are associated with NS, including minimal change disease in children, focal and segmental glomerulosclerosis in adults with African ancestry, and membranous glomerulopathy in Caucasian adults. Other causes include infections, extrarenal or systemic diseases, and drug-induced nephrotoxicity.

Treatment Options

The initial treatment for NS is a course of daily oral prednisolone/prednisone (PDN) for 4-6 weeks. Patients who do not achieve complete remission within this timeframe are considered to have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of SRNS cases, mutations in podocyte-associated genes can be detected. If a genetic cause is identified, specific therapies may be considered.

Complications

Nephrotic syndrome complications are driven by the magnitude of proteinuria or hypoalbuminemia or both. The most common clinical presentation of nephrotic patients is edema, which should be differentiated from generalized edema of heart failure and liver cirrhosis. Complications of NS include thromboembolic complications, acute kidney injury, and infections.

Diagnostic Criteria

The diagnosis of NS is based on laboratory data, specifically proteinuria over 3.5 g/day in adults or 40 mg/m² per hour in children, in association with a low serum albumin (<3.5 g/dL). A low serum albumin is also required for diagnosis.

Pediatric Considerations

In pediatric patients with SRNS, a kidney biopsy is recommended, except in cases of known infection. Genetic testing is also recommended, as mutations in podocyte-associated genes can be detected in 10-30% of SRNS cases. The treatment of steroid-resistant nephrotic syndrome is challenging due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation.