Minimal Change Disease

Question 1

Minimal Change Disease

Background

Answer 1

Most common cause of nephrotic syndrome in children (70% to 90% of nephrotic syndrome in children < 10 years of age); 50% in older children; 10% to 15% of primary nephrotic syndrome in adults

Question 2

Minimal Change Disease

Pathology

Answer 2

LM: normal glomeruli

Tubules may have acute injury and luminal proteinaceous material due to heavy proteinuria.

Other glomerulonephropathies that may present with minor changes on LM include: IgM nephropathy, C1q nephropathy, minimal mesangial LN.

Question 3

Minimal Change Disease

Pathology

Answer 3

IF: no immunoglobulin or complement deposition

EM: podocyte foot process effacement (>75%)

Question 4

Minimal Change Disease

Clinical Manifestation

Answer 4

NOTE: classic presentation of MCD is sudden onset of edema (i.e., days to weeks) as opposed to slowly progressive edema seen with MGN and most forms of FSGS, except tip variant.

Nephrotic syndrome

Microscopic hematuria is seen in 20% to 25% in children, but more commonly in adults.

AKI at presentation: common and often improve with diuresis, treatment of anasarca. Renal vein thrombosis should also be considered.

Question 5

Minimal Change Disease

Pathogenesis

T-cell dysfunction (likely immature and relatively undifferentiated T cells (CD34+) rather than mature T cells (CD34−) have been implicated in the pathogenesis of MCD):

Answer 5

MCD improves with measles (known to modulate cell-mediated immunity).

MCD seen more commonly in patients with Hodgkin disease

Atopic individuals are at higher risk for MCD.

Question 6

Minimal Change Disease

Pathogenesis

B-cell dysfunction:

Answer 6

Rituximab (chimeric monoclonal antibody that depletes the B-20 cells) may improve steroid sensitive disease, suggesting a possible role for a glomerular permeability factor produced by B or T cells through pathways regulated or stimulated by B cells.

Question 7

Minimal Change Disease

Pathogenesis

B-cell dysfunction:

Answer 7

Alterations in GBM, loss of negative charges induced by circulating factor

Defect/alterations of key proteins in slit diaphragm, e.g., mutation of NPHS2 (nephrin) gene

Drug-induced direct injury to podocytes

Question 8

Minimal Change Disease

Clinical Conditions Associated with MCD

Answer 8

Malignancies: lymphomas, Hodgkins, non-Hodgkins leukemia, rarely solid organ tumors

Allergy, atopy, insect/bee stings, pollens, house dust

Immunizations

Question 9

Minimal Change Disease

Clinical Conditions Associated with MCD

Answer 9

Drugs: NSAIDS and selective COX-2 inhibitors (long-term use), pamidronate, alendronate (both bisphosphonates are also associated with FSGS), lithium, D-penicillamine, tiopronin, γ-interferon, sulfasalazine and 5-aminosalicylic acid derivatives, antimicrobials (rifampin, PCN derivatives)

Question 10

Minimal Change Disease

Management of MCD (KDIGO 2012)

Initial episode:

Answer 10

Prednisone or prednisolone at 1 mg/kg/d (maximum 80 mg/d) or alternate day dose of 2 mg/kg (maximum 120 mg) for ≥4 to 16 weeks as dictated by remission. NOTE: Daily and alternating steroid dosing are equivalent in terms of complications and achieving remission.

Question 11

Minimal Change Disease

Management of MCD (KDIGO 2012)

Initial episode:

Answer 11

Once remission occurs, slowly taper to off for up to 6 months.

For glucocorticoid relative contraindications or intolerance (e.g., uncontrolled diabetes, psychiatric conditions, severe osteoporosis), consider PO CYC or CNIs

Question 12

Minimal Change Disease

Management of MCD (KDIGO 2012)

Initial episode:

Answer 12

For patients with infrequent relapses, restart glucocorticoids as mentioned earlier.

Question 13

Minimal Change Disease

Management of MCD (KDIGO 2012)

Initial episode:

Answer 13

Frequent relapsing (i.e., ≥2 within 6 months or ≥4 within 12 months) or steroid dependent (two relapses on steroid taper or within 1 month of ending therapy) MCD:

Oral CYC 2 to 2.5 mg/kg/d for 8 weeks is suggested.

Question 14

Minimal Change Disease

Management of MCD (KDIGO 2012)

Initial episode:

Answer 14

CNI: cyclosporine 3 to 5 mg/kg/d or TAC 0.05 to 0.1 mg/kg/d in divided doses for 1 to 2 years for those who relapse despite CYC or those who wish to preserve fertility

Question 15

Minimal Change Disease

Management of MCD (KDIGO 2012)

Initial episode:

Answer 15

MMF 500 to 1,000 mg twice daily for 1 to 2 years for those who are intolerant to corticosteroids, CYC, and CNIs.

Question 16

Minimal Change Disease

Management of MCD (KDIGO 2012)

Supportive therapy:

Answer 16

Statins not be used to treat hyperlipidemia as risk of coronary artery disease is not increased with MCD. Benefit of statin’s anti-inflammatory property has not been proven.

Question 17

Minimal Change Disease

Management of MCD (KDIGO 2012)

Supportive therapy:

Answer 17

ACEI or ARBs use is not suggested in normotensive individuals with MCD for the sole purpose of lowering proteinuria.

Question 18

Minimal Change Disease

Management of MCD (KDIGO 2012)

Supportive therapy:

Answer 18

NOTE

In case of steroid resistant or frequent relapsing MCD, consider erroneous diagnosis due to poor tissue sampling. Rebiopsy to evaluate for FSGS should be considered.

Question 19

Minimal Change Disease

Management of MCD (KDIGO 2012)

Supportive therapy:

Answer 19

There are limited data that patients with steroid dependent/frequent relapse MCD may benefit from rituximab.