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  Nephrotic syndrome Nephritic syndrome

Dx >3500mg proteinuria (or protein:Cr) in <3500mg proteinuria in 24h
24h

Pathophys Low levels of albumin and anti- Inflammation of glomerulus

thrombinIII (--|factor 2, 10)

Sx Edema, hyperlipidemia (liver tries to Periorbital edema, hypertension

compensate for decreased oncotic
pressure)

Systemic etiologies Diabetes, amyloidosis  

General tx statins, anticoagulants, loop diuretic  

Urinalysis "Maltese cross" pattern, oval fat bodies RBC casts/dysmorphic erythrocytes
 
 Nephrotic syndrome
o Focal segmental glomerulosclerosis/FSGS
 Path: <50% of glomeruli affected + only small segment affected
 RF: African American, IV drug user, HIV (w/ bad prognosis "collapsing" FSGS),
obesity, NPHS1/2 mutation
 Dx: renal biopsy, "podocyte foot process effacement"
 Tx: steroids, cyclophosphamide
 C/b chronic renal failure (50% of FSGS pts)
 *Tip lesion form has good prognosis
o Membranous nephropathy/glomerulonephropathy
 MCC nephrotic syndrome in adults
 RF: White, Ab-phospholipaseA2, solid malignancies, HepB/HepC, malaria, lupus
 Vs. minimal change disease RF: heme malignancies
 Path: Ab complement region activates complement cascade --> "everything
goes haywire"
 Sx: renal vein thromboses (d/t anti-thrombinIII deficiency --> sudden onset flank
pain + fevers)
 Dx: biopsy, "subepithelial spike and dome"
 Tx: cyclophosphamide +/- steroids
 Also treat underlying disease i.e. HepB (|-- emtricitabine, lamivudine,
tenofovir "HepBELT")
o Minimal change disease
 RF: kiddos, also found less commonly in adults, URI, heme malignancy
 Dx: "podocyte foot process effacement"
 --> loss of negative charges @ foot processes --> albumin leaks through
 Tx: steroids
 Good response, rarely progress to renal failure
o Diabetic nephropathy
  Dx: clinical, microalbuminuria
 Ppx: @ time of DM diagnosis --> measure albumin:Cr ratio
 If not done at time of diagnosis, start 5y after dx is made
 Tx: ACEi/ARB, glucose + BP control
 Nephritic syndrome
o Goodpasture's syndrome/anti-GBM disease
 Path: Ab-alpha 3 chain of Type4 collagen = T2HS
 Sx: hematuria, hemoptysis
 Dx: linear pattern of Ig deposition
 Tx: plasmapheresis, steroids
o Pauci-immune: Wegeners/GPA, microscopic polyangiitis, Churg-Strauss/EGPA
 Sx: rapidly progressive glomerulonephritis = normal renal function --> failure
over days-weeks
 Wegener's: hematuria, hemoptysis, sinusitis/mastoiditis, otitis media,
eustachian tube dysf(x)
 Path: c-ANCA (Ab-proteinase3)
 Microscopic polyangiitis: >60Y, fever, hematuria, p-ANCA (Ab-
myeloperoxidase)
 Churg-Strauss/EGPA: asthma/allergies, tons of eosinophils, hematuria,
p-ANCA
 Dx: crescent-shaped = monocytes leak through GBM into Bowman's space and
proliferate
 Complement levels are normal
 Tx: steroids, cyclophosphamide, rituximab
o IgA nephropathy/synpharyngitic nephropathy
 RF: recent URI
 Pathophys: Ab against glycosylated-IgA (from N-acetylgalactosamine on bugs)
--> deposits in mesangium of kidneys --> inflammation
 Systemic manifestation = HSP (purpura x abdominal pain x hematuria)
 Sx: hematuria
 Dx: biopsy, complement levels are normal
 Tx: supportive
o Lupus nephritis
 Sx: malar rash, anti-Sm Ab, anti-dsDNA, low complement levels ("full-house
pattern")
 Subtypes
 Diffuse proliferative glomerulonephritis
o Post-infectious glomerulonephritis/PSGN
 RF: URI, Strep infection (nephritogenic strains)
 --> abx for Strep throat do not decrease chance of PSGN
 Pathophys: Ab against GAS cross react with antigens in glomerulus -->
complement "destroys everything in its wake"
 Sx: 1-6wks post-URI, hematuria, low complement
 Dx: anti-DNAseB, anti-streptolysinO, anti-hyaluronidase, "granular pattern"
 C/b: chronic renal failure (kids 1% vs adults 40%)
o Membranoproliferative glomerulonephritis (MPGN)
 RF: lupus, HepB/C
  Dx: low C3, "subendothelial tram tracks"
 Subtype: dense-deposit disease ("ribbon-shaped" deposits around basement
membrane of glomerulus, C3 nephritic factor = C3 convertase --> low C3)
o Alport syndrome
 Sx: "can't pee, can't see, can't hear a bee" = cataracts/dislocation of lens,
nephritic syndrome, sensorineural hearing loss
 Path: X-linked dominant mutation in alpha2* chain of Type4 collagen/COL4A5
 *A comes before G[oodpasture] in the alphabet!
 (same inheritance as Fragile X syndrome)
 
Disease Light microscopy findings

Minimal change disease Podocyte effacement

FSGS Podocyte effacement

PSGN Subepithelial humps, granular

Membranous nephropathy Subepithelial spike and dome

Membranoproliferative glomerulonephritis subendothelial tram tracks

Lupus nephritis wire-loop appearance

Goodpasture's syndrome/anti-GBM disease Linear pattern of IgG deposition

IgA nephropathy Mesangial proliferation, IgA deposits

 
 
Complement levels Disease

Low PSGN, lupus, membranoproliferative (C3)

Normal IgA nephropathy, pauci-immune entities

High