Nephritic Syndrome

Done by: Ahmad Al-Masri

• It’s an Inflammatory process that involves glomeruli (damage involving the basement membrane ,capillary endothelium , and mesangium) (while in nephrOtic syndrome the main structure to be damaged is Podocyte)

• Due to the glomeruli damage:

• filtration barrier is weakened and enables passage of proteins ,erythrocytes

• ↓GFR Oliguria & ↑BUN/Cr ratio

• ↑Hydrostatic pressure Hypertension & Edema

Classic presentation: • Dark urine (RBCs)

• Proteinuria (<3.5g/day)

• Swelling/edema

• Fatigue (uremia)

• Hypertension

Causes

• Could be classified Primary ( idiopathic) v.s. Secondary

• Or classified as Immune mediated v.s. Pauci-immune

Rapid progressive glomerulonephritis (RPGN)

• is an acute GN resulting from the secondary sequelae of inflammatory (crescenteric) GN, of which there are many causes.

Crescenteric apperance

Negative IF Granular IF Linear IF

Post-infectious GN

• GN secondary to bacterial infection most commonly the nephritogenic strains of streptococcus (group A beta hemolytic streptococci).

• Immune complexes deposit in subendothelial space.

• Common in children (can also occur in adults) • Classic case: • Child presented 2-3 weeks following strep throat

infection or 6 weeks post impetigo with Nephritic syndrome findings

Post-infectious GN • If we take a Bx. we will see

• Under light microscope: Enlarged, hypercellular glomeruli

• Under immunofluorescence: Granular apperance (IgG, IgM, C3)

• Under Electron microscopy: Subepithelial “humps’’

Post-infectious GN

• Good prognosis in children (95% recover completely)

• Adults have worse prognosis (About 60% recover)

• No specific therapy (supportive with management of high blood pressure and fluid overload , spontaneous resolution is expected )

IgA Nephropathy Berger’s Disease

• Most common form glomerulonephritis in adults worldwide.

• Most common cause of repeated episodes of hematuria (nephritic).

• Typically cause hematuria 2 days post URTI or Diarrheal illness.

• Over time leads to ESRD and HD (50% patients)

• Affect mainly Males ,especially Asian or white population.

IgA Nephropathy Berger’s Disease

• IgA Immune complexes deposit in mesangium. • Bx. under immunofluorescence: Granular apperance (IgA)

• Classic case: • Recurrent episodes hematuria since childhood, follow URI or

diarrheal illness, Slowly worsening renal function (BUN/Cr) over time, Possible progression to ESRD and HD (20yrs+)

• Don’t confuse with other glomerular disorders 1) Post-strep GN: weeks after infection 2) IgA GN: days after infection 3) Minimal change: nephrotic syndrome after URI

IgA Nephropathy Berger’s Disease

• Patients who have IgA nephropathy with a low risk of progressive disease should be treated with ACE-I to maintain a goal 24 hour urine protein excretion of less than 1 g /24 hours , and a blood pressure of less than 130 / 80 .

• Immunosuppressive therapy must be considered for: 1- patients with persistent proteinuria ( more than 1g/24 h) , 2-progressive kidney dysfunction, 3-or histological findings indicative of RPGN ( like crescents ) This includes pulse corticosteroids and cyclophosphamide followed by azathioprine with ACE-I . • Few studies shows that Fish Oil have role in delay some of the

late complications of IgA nephropathy

Henoch-Schonlein Purpura

• IgA nephropathy + extra-renal involvement

• Skin: palpable purpura on buttocks/legs

• GI: abdominal pain, melena

• Joint pains

• Most common childhood systemic vasculitis

• Diffuse IgA deposition

• Tissue biopsy: demonstrates IgA

Lupus Nephritis

• They are subdivided into 6 types, here in nephrtic syndrome we are concern with

type lll (Focal Proliferative lupus nephritis) & type IV (Diffuse Proliferative lupus nephritis). • Focal: less than 50% glomeruli affected

• Diffuse: More than 50% glomeruli affected

• Anti-dsDNA Subendothelial deposits

Lupus Nephritis • If we take a Bx. we will see

• Under light microscope: capillary loops thickened

• “Wire looping”

• Under immunofluorescence: Granular apperance

• “Full house” immunofluorescence (IgG, IgA, IgM, C3, C1q)

Lupus Nephritis

• Usually we take Bx. To know the severity to decide the prepare treatment.

• Steroids alone or with Cyclophosphamide?

Membranoproliferative glomerulonephritis

• Also called mesangiocapillary GN.

• Immune complex formation secondary to chronic antigen stimulation.

• Common causes are : 1. Chronic indolent infections including hepatitis C, syphilis ,

mastoiditis …etc. .

2. Autoimmune such as Sjogren , lupus …etc.

3. Essential cryoglobulinemia ( types I and II )

4. Malignancies such as carcinomas , sarcomas , lymphomas and leukemias .

immune-complex and/or complement protein deposition in the mesangium and sub endothelium of the capillaries this results in proliferation of the mesangial and remodeling of the capillary wall

• We usually treat them with:

1. Corticosteroids

2. Immunosuppressive agents

3. Antiplatelets

• More than 50 % progress to advanced CKD .

Anti-GBM antibodies disease Goodpasture’s Syndrome

• IgG antibodies develop against the GBM (alpha-3 chain to type IV collagen ) , deposited in a linear patter.

• Classic case: • Young adult, Male present with Hemoptysis &

Hematuria • Treatment usually is Plasmapheresis using albumin

replacement for 1-2 weeks ,followed by corticosteroids and cyclophosphamide for 3-6 months , Maintenance with azathioprine for 1-2 years

Vasculities syndrome

• Most patients ANCA positive (c-ANCA or p-ANCA)

• All vasculities are associated with Fever + weight loss.

• Churg-Strauss syndrome (p-ANCA): they present with Eosinophilia, history of resistant asthma.

• Wegener's Granulomatosis (c-ANCA): they present with upper respiratory findings (sinusitis/otitis)

• All can lead to pauci-immune nephritis

Alport Syndrome Hereditary Nephritis

• Genetic Mutations in alpha-3, alpha-4, or alpha-5 chains of type IV collagen.

• Chains found in basement membranes kidney, eye, ear

• Inherited: X-linked

• Classic triad:

• Hematuria, Hearing loss, eye abnormalities

• Look for child with triad and family history

Thank You