Focal segmental GN

► Most common progressive renal disease in children

► 20 – 25 % in adults► Primary & secondary ► Acute NS presentation.

►Secondary have slowly progressing non nephrotic range proteinuria & renal insufficiency.

►Diffuse foot processes fusion in primary type. focal & limited to sclerotic area in the secondary type.

►Recurrence in 20 – 40 % RXT

Etiological classification

► Primary idiopathic FSGS.► Familial ► Secondary to hereditary

nephropathies► HIV associated nephropathy ► Heroin associated nephropathy► Secondary FSGS

Tip lesion in FSGS

The lesion is towards the proximal tubules pole of the glomerulus with foamy cells in the injured area.

Tip lesion

Secondary FSGS

► Secondary to reduced renal mass

* oligomeganephronia** reflux nephropathy *** renal dysplaia

► Secondary to glomerular adaptation * Diabetic.N** morbid obesity *** sickle cell disease**** pre-eclampsia

► Circulating factor implicated in the pathogenesis 30 – 50 KD

► Glomerular hypertrophy ( Fego et al)

Familial

► Genetic mutation in memb proteins► Podocin , actinin4, CD2 assosciated

protein ,NPHS2 & wilm`s tumor gene.► Steroid resistance ► No recurrence after RXT

Secondary FSGS

► Reduced No or increased stress on nephrons lead to compensatory intraglomerular HTN & hypertrophy in the rest of glomeruli.

► Glom cell proliferation,macrophage, extra cellular matrix components.

► Transforming growth factor TGFb► >50% nephron mass loss is required

Pathology

► Area of solidification in the perihilar region in continuity with the vascular pole

► Collapse & wrinkling of the CW with obliteration of capillary lumens.

► Adjacent podocytes are prominent ► Oesinophylic material with in the

Capillary loop ( hyalinosis lesion)► Foam cells

Sub endothelial hyaline material deposits

Variants ► FSGS other wise unclassified► Cellular type:

More sever & have poor prognosis► Collapsing type :

HIV Parvovirus infection Alendronate.

► Tip lesion :The segmental lesions occur exclusively at the tubular part, suggesting better response to steroids .

Collapsed capillary loops

Crowded cells in the remaining open loops

Widened Bowman’s capsule space

Capillary loops

Intra-endothelial tubuloreticular structure pathgnomonic of HIV infection FSGS

FSGS and proteinuria

Prognosis is rather poor in FSGS in relation to proteinuria presentation

Treatment

► Spontaneous remission is rare.► Prognosis is poor if :

1- not treated2- S.Cr>1.3mg/dl3- histological abnormalities outside the glomeruli4- interstitial fibrosis at presentation

Corticosteroids

► I mg/kg/day for 2 – 3 /12 then taper & continue for 5 – 9 month.

►Other therapies : Calcineurin inhibitor :

** 39% of children & 21% of adults could enter complete remission within 3/12 using cyclosporine.** normal RF,diffuse GS or interstitial F & at adose < 5mg/kg/day

Stop if level of Cr increased by more than 30% for 1/12

Alkylating agents

1. Cyclophosphamide 2 mg/kg/day Or Chlorambucil 0.1 – 0.2 mg/kg/dayfor 2 – 3 month usually with steroids lead to reestablishment of remission in steroids dependent Pt >70%

Purine synth. Inhibitors

► There is insufficient information supporting their beneficial effects.

► Aphoresis - immunoadsorption Found to be effective ► Pefloxacin 200 – 400 twice a day for 4 – 8 /52► Immunomodulator ► Vit E 200 IU twice a day for 3/12