Minimal Change Disease Flashcards
Minimal Change Disease
Background
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
Minimal Change Disease
Pathology
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.
Minimal Change Disease
Pathology
IF: no immunoglobulin or complement deposition
EM: podocyte foot process effacement (>75%)
Minimal Change Disease
Clinical Manifestation
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.
Minimal Change Disease
Clinical Manifestation
Nephrotic syndrome
Microscopic hematuria is seen in 20% to 25% in children, but more commonly in adults.
Minimal Change Disease
Clinical Manifestation
AKI at presentation: common and often improve with diuresis, treatment of anasarca. Renal vein thrombosis should also be considered.
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):
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.
Minimal Change Disease
Pathogenesis
B-cell dysfunction:
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.
Minimal Change Disease
Pathogenesis
B-cell dysfunction:
Glomerular permeability factor possible, likely TH2-derived cytokines, e.g., interleukin IL-13. IL-13 induces CD80 expression, which can induce podocyte fusion and proteinuria. Notably, IL-13 is associated with allergic states, conditions associated with MCD.
Minimal Change Disease
Pathogenesis
B-cell dysfunction:
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
Minimal Change Disease
Clinical Conditions Associated with MCD
Malignancies: lymphomas, Hodgkins, non-Hodgkins leukemia, rarely solid organ tumors
Allergy, atopy, insect/bee stings, pollens, house dust
Immunizations
Minimal Change Disease
Clinical Conditions Associated with MCD
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)
Minimal Change Disease
Management of MCD (KDIGO 2012)
Initial episode:
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.
Minimal Change Disease
Management of MCD (KDIGO 2012)
Initial episode:
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
Minimal Change Disease
Management of MCD (KDIGO 2012)
Initial episode:
For patients with infrequent relapses, restart glucocorticoids as mentioned earlier.
