Minimal change disease Flashcards
What is the most common cause of nephrotic syndrome in children?
Minimal change disease (MCD).
What is the pathophysiology of minimal change disease (MCD)?
MCD is a nephrotic syndrome caused by cytokine and T-cell mediated injury to podocytes, leading to increased glomerular permeability to albumin. This results in massive proteinuria, hypoalbuminemia, and edema. The primary mechanism is idiopathic (most commonly) or from an infection and the most common secondary cause is from lymphoma.
What are the classic clinical features of minimal change disease?
1) Nephrotic syndrome: Periorbital and gravity dependant peripheral edema (pretibial), proteinuria, hypoalbuminemia, and hyperlipidemia.
2) Often triggered by an infection or allergic reaction.
3) Most common cause of nephrotic syndrome in children.
How does nephrotic syndrome lead to hyperlipidemia?
Hypoalbuminemia causes increased hepatic lipoprotein production, leading to elevated cholesterol and triglycerides.
How is minimal change disease diagnosed?
Clinical diagnosis in children (no biopsy needed unless atypical features present). If biopsy is performed, it shows diffuse effacement of foot processes on electron microscopy. minimal change disease
What is the characteristic histologic finding in minimal change disease?
Diffuse effacement of podocyte foot processes on electron microscopy.
What findings on urinalysis and serum studies are characteristic of minimal change disease?
1) Urinalysis: >+2 proteinuria, no hematuria, no casts.
2) Serum: Low albumin (<3.0 g/dL), hyperlipidemia, normal complement levels.
How is minimal change disease managed in young children?
- In young children, diagnosis of MCD is usually clinical, and management is empiric immunosuppressive therapy with corticosteroids to counter T-cell dysregulation and cytokine-mediated damage. The mainstay of treatment for minimal change disease (MCD) is an empiric course of corticosteroids (eg, prednisone), usually for at least 2-3 months. Over 90% of patients will achieve remission with therapy, defined as resolution of proteinuria, whereas only 5% of patients achieve spontaneous resolution without therapy.
- Albumin can transiently increase oncotic pressure in patients with nephrotic syndrome, but this therapy is not recommended for patients with localized or mild edema due to complications of vascular volume overload (eg, hypertension). Moreover, it does not correct the underlying pathology of hypoalbuminemia, which is increased glomerular permeability.
- Albumin with diuretic therapy can be considered in patients with massive edema (eg, anasarca, pleural effusions).
- Statins may be used in children with prolonged dyslipidemia, however, they are generally not called for in patients with hyperlipidemia is due to nephrotic syndrome. Rather, treatment involves addressing the underlying renal pathology, which typically improves the high cholesterol.
What is the prognosis of minimal change disease?
Excellent prognosis, as most children achieve remission with corticosteroids. However, frequent relapses are common. The initial course of corticosteroids is very effective in achieving initial remission, the vast majority of patients with minimal change disease will have at least one relapse, and some children will relapse frequently (several times in a year). Therefore, once initial remission is achieved, monitoring for proteinuria is required for early identification of relapse. Children under age 5 are at her risk, and infections are a common trigger. Relapses typically remain steroid responsive; most children eventually have a progressive decrease in the number of relapses with age and often achieve permanent remission. Renal outcome is excellent with maintenance of normal renal function into adulthood. Patients with presumed minimal change disease who do not achieve remission of proteinuria with the initial course of steroids require a kidney biopsy due to an increased likelihood of an alternative pathology (eg, focal segmental glomerulosclerosis).
When is a kidney biopsy indicated in minimal change disease?
If atypical features are present, such as hematuria, hypertension, or poor response to steroids.
Do patients with minimal change disease progress to chronic kidney disease?
No. minimal change disease does not cause glomerulosclerosis or chronic kidney disease unless steroid-resistant.
What is the first-line treatment for minimal change disease?
Empiric corticosteroid therapy (prednisone) for 2-3 months to induce remission.
What are the most common side effects of prolonged corticosteroid therapy?
1) Metabolic: Hyperglycemia, weight gain, adrenal suppression, Hypertension
2) Skeletal: Osteoporosis, impaired growth in children.
3) Immune: Increased infection risk.
4) Ophthalmologic: Cataracts (requiring ophthalmologic exams).
Although most adverse effects are at least partially reversible, cataract formation is not. Therefore, children on chronic steroid therapy warrant frequent ophthalmologic examinations for early detection of cataracts. Prevention and screening of other adverse effects may include frequent blood pressure checks, linear growth measurements, and vitamin D and calcium supplementation.
Which long-term monitoring is required for children on corticosteroids for minimal change disease?
Frequent ophthalmologic examinations to detect cataracts.
What are the options for patients with significant adverse effects from prolonged corticosteroid therapy?
Options for management of patients with MCD and significant steroid toxicity include switching to a steroid-sparing agent (eg, cyclosporine) or decreasing frequency of steroid administration (eg, alternate days).
