GN Worksheet Completed Full - WordPress.com€¦ · Demystifying+GNWorksheet++ + 3+ Download+@++...

Demystifying GN Worksheet 1 Download @ https://nerdc.org

Demystifying Glomerular Disease: A Worksheet Teaching Tool

Step 1: Review the Normal Glomerular Structure Step 2: Review the Complement Pathways

Step 3: Select and fill out a row. Draw the pattern of injury and discuss the glomerular disease. Disease Process

Histology (Light Microscopy, Immunofluorescence, Electron

Microscopy)

Clinical Presentation (physical signs & symptoms)

+ Pathophysiology

Treatment Prognosis

Minimal Change Disease

-‐Proteinuria and hypoalbuminemia leading to edema. -‐Diffuse effacement of podocyte -‐Normal Light microscopy

-‐Corticosteroids: Oral Prednisone 1mg/kg/day

-‐30 % Frequently relapse

Focal Segmental Glomerular Sclerosis (FSGS)

-‐Diverse clinic-‐pathologic syndromes -‐Primary and secondary causes are seen -‐Microhematuria and Proteinuria seen

-‐Primary FSGS: Treat with high dose Oral steroids; Second line if non-‐responsive. -‐Secondary FSGS: Treat underlying cause

-‐50% progress to ESRD in 10 yrs. -‐Tip variant with best outcome and Collapsing with worst. -‐40% with primary FSGS have recurrence in Allograft.

Lupus Nephritis

-‐Immune complex mediated -‐Hematuria and Proteinuria -‐Mesangial and Glomerular involvement -‐IF shows ‘full house’ -‐Class III and IV with sub endothelial deposits -‐ Class V has sub epithelial deposits

-‐Pulse dose steroids + Cyclophosphamide vs Steroids+ MMF. -‐Azathioprine in pregnancy -‐Rituximab for induction

-‐50% achieve remission in 1 year and 75% in 2 years. -‐8-‐15% progress to ESRD -‐Class IV with worst prognosis

I & II

III&IV

V


Membranous Nephropathy

-‐Proteinuria and resultant hypoalbuminemia -‐Thickening of the basement membrane without cell proliferation. -‐Primary MN: PLA2R -‐Secondary MN: Malignancy, Drugs, Hep B

-‐Again based on degree of proteinuria steroids+ cyclophosphamide vs MMF, Rituximab, Synthetic ACTH

-‐10% progress to ESRD -‐Relapse in 20-‐30% patients

Diabetic Nephropathy

-‐Leading cause of ESRD in US -‐Longstanding uncontrolled Diabetes is often noted -‐Albuminuria -‐Mesangial expansion is the highlight (Kimmelstein-‐wilsons nodule)

-‐ Diabetes control -‐ RAAS blockade

-‐Diabetic nephropathy increases overall mortality rate among diabetic patients

Ig A Nephropathy And IgA Vasculitis

-‐Isolated hematuria usually following a URI -‐Aberrantly galactosylated IgA1 molecules stimulate antibody production and the circulating complex deposits in the mesangium à mesangial proliferation. -‐IgA Vasculitis is with systemic manifestations and primarily in children (formerly Henoch Schonlein Purpura) -‐Diffuse mesangial IgA on IF is hallmark

-‐RAAS Blockade -‐Steroids if Proteinuria >1gm/day. -‐If rapidly progressive then PLEX+ Cyclophosphamide -‐IgA Vasculitis – supportive care

-‐Minimal proteinuria good prognosis. -‐Rapidly progressive often ESRD in 12 months

MPGN (Membrano-‐ Proliferative Glomerulo-‐Nephritis)

-‐Microhematuria and Proteinuria -‐Characterized by circulating immune complexes and constant antigenemia à mesangial proliferation and translocation à capillary walls with double contouring -‐Associated with HCV and cryoglobulinemia

-‐RAAS blockade -‐Cyclophosphamid or MMF + Steroids

-‐50% of patients with MPGN need RRT in 5 years

C3 GN and Dense Deposit Disease

-‐Associated with uncontrolled activation of the alternative complement pathway àC3 deposition with in the glomeruli and lead to capillary wall proliferation -‐Dense deposit disease -‐Resembles an MPGN pattern

-‐Eculizumab may be considered -‐May need PLEX + Cyclophosphamide or MMF + steroids

-‐50% recurrence in Renal allografts


ANCA Associated Vasculitis

-‐Pauci-‐immune lesion -‐Inflammation of the vesselsà necrosis of the tissue -‐Can lead to crescent formation and RPGN -‐MPA, GPA and EGPA -‐Systemic involvement

-‐Induction with Steroid + Cyclophosphamide vs Rituximab. -‐Needs maintenance with Cyclophosphamide or Azathioprine

-‐65-‐75% survival with treatment.

Anti-‐GBM Disease

-‐Auto antibodies against non-‐collagenous domain of Type 4 Collagen -‐May present with diffuse alveolar hemorrhage resulting in hemoptysis (Pulm-‐Renal Syndrome) -‐Hematuria and Proteinuria

-‐PLEX + Cyclophosphamide and Steroids

-‐if in RPGN state then progression to ESRD is rapid -‐Rarely recurs once treated

Thrombotic Micro-‐Angiopathy (TMA)

-‐Anemia and Thrombocytopenia -‐Schiztocytes on peripheral smear -‐TTP vs secondary causes (most common Hypertensive emergency)

-‐PLEX -‐Treat the underlying cause

-‐Often will require RRT

Cryo-‐globulinemic Glomerulo-‐nephritis

-‐Microhematuria and Nephrotic Proteinuria -‐Association is HCV -‐Can be rapidly progressing -‐May need PLEX if crescentic -‐MPGN pattern often seen

-‐Rituximab vs Cyclophosphamide -‐Anti retroviral therapy

-‐Risk of rapid progression with heavy proteinuria -‐High recurrence rates in Allografts

Immuno-‐tactoid And Fibrillary Glomerulo-‐Nephritis

-‐Very rare -‐Associated with Cryo GN/ HCV and plasma cell dyscrasias -‐Fibrils are (18-‐22 nm) in fibrillary GN -‐Deposits in Immunotactoid are >30 nm

-‐No standardized therapy

-‐Progress to ESRD

Amyloid, Light Chain, & Heavy Chain Deposition Disease

-‐Proteinuria and reduced Renal function -‐Immunoglobulin light chain deposition -‐Bence Johns protein -‐Serum electrophoresis -‐Fibrils 7-‐10 mm -‐Mesangial Nodules and positive congo red stain

-‐Drugs targeting Multiple myeloma or reducing monoclonal plasma cell proliferation like Bortezomib, Thalidomide

-‐Prognosis depends on the control over myeloma


Fabry’s Disease

-‐X-‐linked lysosomal storage disorder -‐Systemic symptoms: rash, neuropathy, and cardiovascular disease -‐Deficiency of α-‐Galactosidase A -‐deposition of glycosphingolipids -‐Diagnosis by urinary globotriaosylceramide, biopsy, or enzyme activity

-‐ IV recombinant human α-‐Galactosidase or chaperone therapy

-‐Poor. 3 year survival once on RRT begins -‐CV disease is primary cause of death

C1Q Nephropathy

-‐Nephrotic range proteinuria, hematuria and renal insufficiency are common -‐C1q deposits on IF -‐No evidence of SLE

-‐Treatment depending on underlying histology

-‐If seen in combination with FSGS higher risk for ESRD

Alport’s Disease

-‐Microscopic Hematuria -‐X linked disease most common -‐Abnormal Type 4 Collagen along with ears and eyes involvement -‐Interstitial and tubular foam cells -‐Thickened GBM

-‐Supportive care -‐Males progress to ESRD -‐25% of females progress to ESRD

IRGN (Infection-‐Related GN)

-‐Similar in presentation on Post infectious GN -‐Ongoing active infection is commonly noted -‐Active sediments in the urine along with Proteinuria. -‐Hypocomplementemia is a key feature

-‐Supportive therapy and treating the underlying infection. -‐Rarely Steroids may be useful.

-‐Up to 50% patients will require interim RRT.

Thin Basement Membrane Disease

-‐Microscopic hematuria -‐Autosomal dominant -‐Thinning of the basement membrane -‐Benign course

-‐No therapy needed -‐Excellent prognosis

Icebreaker

Whoa, congratulations! We have learned a lot of glomerular disease today… so, which GN best exemplifies you? And why? Perhaps Fibrillary GN due to your curly hair or C1Q because you are mysterious!

GN Worksheet Completed Full - WordPress.com€¦ · Demystifying+GNWorksheet++ + 3+ Download+@++...

Documents

Transcript of GN Worksheet Completed Full - WordPress.com€¦ · Demystifying+GNWorksheet++ + 3+ Download+@++...