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MINIMAL CHANGE DISEASE (MCD)

-sometimes known as nil lesion

-causes nephrotic syndrome

7090% in childhood 1015% in adults.

-usually presents as a primary renal disease

-But can be associated with several other conditions:

Hodgkin's disease Allergies use of nonsteroidal anti-inflammatory agents;

significant interstitial nephritis often

accompanies cases associated with

nonsteroidal use.

DIAGNOSTICS:

-MCD on renal biopsy : light microscopy -shows no obvious glomerular lesion immunofluorescent microscopy- negative for deposits, occasionally shows small amounts of IgM in the

mesangium

-Electron microscopy, however, consistently demonstrates an effacement

of the foot process supporting the epithelial podocytes with weakening of

slit-pore membranes.

- pathophysiology of this lesion is uncertain.

-circulating cytokine, perhaps related to a T cell response that

alters capillary charge and podocyte integrity. The evidence for cytokine-

related immune injury is circumstantial and is suggested by the presence of

preceding allergies, altered cell-mediated immunity during viral infections,

and the high frequency of remissions with steroids.

CLINICAL PRESENTATION:

-presents clinically with the abrupt onset of edema and nephrotic

syndrome accompanied by acellular urinary sediment.

-Average urine protein excretion reported in 24 hours is 10 grams with

severe hypoalbuminemia.

-Less common clinical features:

hypertension (30% in children, 50% in adults),

microscopic hematuria (20% in children, 33% in adults), atopy or allergic symptoms (40% in children, 30% in adults), decreased renal function ( biopsied.o Primary responders -> w/ complete remission (complete remission after 8 weeks of steroid

therapy

- 8085% of adults ->complete remission only after 2024 weeks.

-Patients with steroid resistance may have FSGS on repeat biopsy.

-Some hypothesize that if the first renal biopsy does not have a

sample of deeper corticomedullary glomeruli, then the correct early

diagnosis of FSGS may be missed.

-Relapses occur in 7075% of children after the first remission

early relapse predicts multiple subsequent relapses

The frequency of relapses decreases after puberty

rapid tapering of steroids( all groups)->increased risk of relapse.

Relapses:

-less common in adults

-more resistant to subsequent therapy.

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TREATMENT:

-Prednisone -> first-line therapy( daily or on alternate days)

-Other immunosuppressive drugs

> saved for frequent relapsers, steroid-dependent, or steroid-

resistant patients>e.g: cyclophosphamide, chlorambucil, and mycophenolate

mofetil.

*Cyclosporine >can induce remission

>when withdrawn, relapse is common

- The long-term prognosis in adults is less favorable when acute renal

failure or steroid resistance occurs.

FOCAL SEGMENTAL GLOMERULOSCLEROSIS(FSGS)

>refers to a pattern of renal injury characterized by segmental glomerular

scars that involve some but not all glomeruli;

CLINICAL FINDINGS:

-largely manifest as proteinuria

-ADULTS represent up to 1/3 of cases of nephrotic syndrome

-AFRICAN AMERICANS -1/2 of cases

-seen more commonly.

-can present with

*hematuria *hypertension

*any level of proteinuria or renal insufficiency.

-associated with poor outcome: (50% of patients reaching renal failure in

68 years)

*Nephrotic-range proteinuria

*African-American race

* renal insufficiency

-rarely remits spontaneously, but treatment-induced remission of

proteinuria significantly improves prognosis

-pathogenesis >probably multifactorial.

- Possible mechanisms:

a T cellmediated circulating permeability factor TGF-mediated cellular proliferation and matrix synthesis podocyte abnormalities associated with genetic

mutations.

-The pathologic changes >are most prominent in glomeruli located at the

corticomedullary junction (focal & segmental scarring) so if the renalbiopsy specimen is from superficial tissue, the lesions can be missed, which

sometimes leads to a misdiagnosis of MCD.

In addition to focal and segmental scarring, other variants have

been described, including cellular lesions with endocapillary

hypercellularity and heavy proteinuria; collapsing glomerulopathy with

segmental or global glomerular collapse and a rapid decline in renal

function; a hilar stalk lesion or the glomerular tip lesion, which may have

a better prognosis.

TREATMENT:

*primary FSGS-inhibitors of the renin-angiotensin system.

*Proteinuria remits in only 2045% of patients receiving a course of

steroids over 69 months. *use of cyclosporine in steroid-responsive

patients helps ensure remissions.

Cessation of Cylclosporine therapy- Relapse

Cyclosporine use -can lead to a deterioration of renal function due

to its nephrotoxic effects.

*FSGS recurs in 2540% of patients given allografts at end-stage disease,

leading to graft loss in half of those cases.

* secondary FSGS

-treating the underlying cause

-controlling proteinuria.

- steroids or other immunosuppressive agents->no role

Ref:

Harrisons Principle of Internal Medicine, 18th

ed.

By: Onofre W. Tayocnog

Med-2B