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Approach to Rapidly Progressive Glomerulonephritis RPGN

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Clinical approach to Rapidly Progressive Renal failure and Rapidly Progressive Glomerulonephritis. Diagnosing crescentic Glomerulonephritis and Pauci immune vasculitis syndromes - churg strauss, wegeners and good pasture syndromes

Publicada em: Saúde e medicina

Approach to Rapidly Progressive Glomerulonephritis RPGN

  1. 1. 08.05.14 Clinical Approach to Rapid Progressive Glomerulonephritis Dr Garima Aggarwal - DM Nephrology - Amrita Institute of Medical Sciences, - Kochi, India
  2. 2. Rapidly Progressive Glomerulonephritis (RPGN) Refers to a clinical syndrome characterized by a Rapid loss of renal function, Oliguria or anuria, Features of glomerulonephritis dysmorphic erythrocyturia, erythrocyte cylindruria, glomerular proteinuria.
  3. 3. CRESCENTIC GN • RPGN – morphologically - extensive crescent formation. • The severity of the disease -degree of crescent formation. • nonspecific response to severe injury to the glomerular capillary wall . • Rents are induced in the glomerular capillary wall- movement of plasma products, including fibrinogen, into Bowman's space with subsequent • fibrin formation, • the influx of macrophages and T cells, • release of proinflammatory cytokines-IL-1 and TNF a
  4. 4. Normal Kidney Crescent Normal glomerulus
  5. 5. TYPES OF RPGN — Type 1: Anti-GBM antibody disease Type 2: Immune complex — • IgA nephropathy • postinfectious glomerulonephritis • lupus nephritis • cryoglobulinemia. Type 3: Pauci-immune ANCA-positive- Wegener’s, microscopic polyangiitis or Churg Straus ANCA-negative, pauci-immune RPGN Type 4: Double-antibody positive disease — Type 4 has features of both types 1 and 3. Idiopathic*
  6. 6. Rapid Progressive Renal Failure?
  7. 7. Types of Renal Failure (DURATION) Acute – HOURS TO DAYS ; <2 weeks ●An increase in serum creatinine of ≥0.3 mg/dL (≥26.5 micromol/L) within 48 hours; ●An increase in serum creatinine of ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days; or ●Urine volume <0.5 mL/kg per hour for more than six hours Chronic - WEEKS TO MONTHS ; >3months • Glomerular filtration rate (GFR) <60 mL/min per 1.73 m2 or • evidence of kidney damage - albuminuria or abnormal findings on renal imaging have been present for three months or more.
  8. 8. • The clinical diagnosis of these cases may be called Rapidly Progressive Renal Failure (RPRF), which may be defined as progressive renal impairment over a period of DAYS TO FEW WEEKS. • ~ 2weeks to 3 months • heterogeneous group of clinical syndromes • ‘Renal Emergency’ • may progress to irreversible end-stage renal disease (ESRD) needing life-long renal replacement therapy
  9. 9. RPRF TUBULO INTERSTITIAL GLOMERULAR VASCULAR ATIN ATN MYELOMA KIDNEY RPGN  Atheroembolic renovascular dis.  B/L Renal Vein thrombosis  TMA –  HUS/TTP  Mal. HTN  Sys. Sclerosis  APLA RARELY – Occult viscera sepsis, Sarcoidosis, Obstructive Nephropathy
  10. 10. Clinical Approach?
  11. 11. HISTORY RPRF vs CKD vs AKI History of hematuria, frothing of urine, HTN, Oliguria/Anuria, progressive renal failure SYSTEMIC FEATURES hemoptysis, longstanding asthma or petechiae is suggestive of vasculitis arthralgia, oral ulcers or photosensitivity indicates presence of lupus. Backache, fractures or bone pains - multiple myeloma. Recent Drug history, fluid loss, sepsis Long-standing history of DM/ HTN
  12. 12. PHYSICAL EXAMINATION Pallor – s/o CKD*, Normal/ High BP. - TMA and renal artery stenosis. Oral ulcer or butterfly rash is indicative of lupus Skin petechiae may indicate lupus or vasculitis Evidence of atheroembolic disease Upper Respiratory tract involvement – sinuses* RS – signs of asthma/alveolar hmghe CNS- peripheral neuropathy
  13. 13. ROUTINE INVESTIGATIONS CBC Leucocytosis – Sepsis, vasculitis, TE dis Eosinophilia – Churg Strauss TCP – HUS/TTP, TMA Peripheral smear – fragmented RBCs - TMA
  14. 14. URINE ANALYSIS Dysmorphic RBCS, active sediments, Rbc casts, Sub Nephrotic Proteinuria – Vasculitis, Lupus – RPGN Isomorphic RBCs , Eosinophiluria – AIN, TE dis Nephrotic Range proteinuria – causes other than RPGN
  15. 15. Hypercalcemia – Sarcoidosis, Myeloma Raised LDH – TMA Low complements – Lupus Nephritis, Cryoglobulinemia, PSGN(C4 normal) Raised ESR, CRP – Vasculitis, SLE HBsAg – MPGN , Vasculitis Hepatitis C – MPGN, Vasculitis Chest X ray – cavities/nodules – ANCA ass systemic vasculitis
  16. 16. SEROLOGICAL TESTS ANA, APLA – Lupus Nephritis, APLA ANCA – Pauci Immune GN Anti GBM – Goodpasture’s Syndrome/Anti GBM dis ASLO, Anti DNAse- PSGN Cryoglobulins- Cryoglobulinemia Anti Scl70 – Systemic sclerosis
  17. 17. Rapid progressive renal failure Systemic features – Pulmonary renal/ rashes/ peripheral neuropathy/ flu like syndrome Hematuria, sub nephrotic proteinuria, active urinary sediment Low complements ANCA/ ANA/ Anti GBM/ ASLO – positive Renal Biopsy
  18. 18. Renal Biopsy findings LIGHT MICROSCOPY • Hallmark lesions – Crescents • Cellular, fibro cellular, fibrous • Lesions usually in various stages of activity/ resolution • Necrotising inflammation-10% • Fibrinoid necrosis, peri glomerular granulomas • (RPGN III) Anti-GBM glomerulonephritis with a large cellular crescent forming a cap over the glomerular tuft
  19. 19. IMMUNOFLUORESCENCE RPGN I RPGN II RPGNIII (Anti GBM) (IC mediated) (pauci immune) Linear staining Granular mild or absent IgG and C3 glomerular glomerular tuft staining staining Diff Igs +/or complements
  20. 20. linear staining for IgG - diffuse binding of anti- GBM Ab Granular staining on IF in PSGN Scanty Background staining of puaci immune
  21. 21. ELECTRON MICROSCOPY • RPGN I and III – absence of electron dense immune complex deposits • RPGN II – Multiple electron dense deposits
  22. 22. Anti GBM Disease EM – Absence of electron dense IC deposits with distinct breaks in the GBM – triggering crescent formation MPGN showing several electron dense IC deposits subepithelial and sub endothelial
  23. 23. RPGN Clinical/serology/Bx Linear IF, IgG Anti GBM +ve Granular IF, immune complex Anti dsDNA, ANA/ Low C3-C4/ IgA/ ASLO, etc +ve No IF, ANCA +ve Lung Hmrhge YES Goodpasture syndrome NO Anti GBM GN
  24. 24. RPGN Clinical/serology/Bx Granular IF, immune complex Anti dsDNA, ANA/ Low C3-C4/ IgA/ ASLO, etc +ve No IF, ANCA +ve IgA Acute MPGN Others Staph/strep infection Mesangio DD Sub others No Systemic Cap. Epithelial Vasc. Vasculitis IgA HSP PSGN MPGN I MPGN II MN SLE, etc
  25. 25. RPGN Clinical/serology/Bx No IF, ANCA +ve Sytemic vasculitis No Systemic features ANCA GN Vasculitis with Granulomas Eosinophilia No asthma or No asthma Granulomas granulomas Asthma Microscopic Wegeners Churg-Strauss Polyangitis Garnulomatosis Granulomatosis
  26. 26. RPGN Type I: Anti GBM Disease • Cells accumulate in Bowman’s space, form crescents. • Peptides within the noncollagenous portion of the α3-chain of collagen type IV. • What triggers the formation of these antibodies is unclear in most patients. • There is linear deposition of antibodies and complement components along the GBM.
  27. 27. RPGN Type I: Goodpasture’s Syndrome • The anti-GBM antibodies cross-react with pulmonary alveolar basement membranes to produce the clinical picture of pulmonary hemorrhage associated with renal failure.
  28. 28. •Patchy parenchymal consolidations are present, which usually are •bilateral, symmetric perihilar, and bibasilar. •The apices and costophrenic angles usually are spared
  29. 29. Pauci immune vasculitis • A group of small vessel vasculitis related to ANCA. • Can be renal limited/systemic. • Systemic –microscopic polyangitis,Wegener’s granulomatosis,Churg Strauss syndrome. • Wegener’s-Granulomatous inflammation + necrotizing vasculitis. • Churg Strauss-Eosinophil-rich and granulonatous inflammation + necrotizing vasculitis. • Microscopic polyangitis-necrotizing vasculitis.
  30. 30. Wegener’s Granulomatosis
  31. 31. Microscopic Polyangitis
  32. 32. Churg- strauss Syndrome
  33. 33. Microscopic polyangitis Wegener’s Granulom-atosis Churg Strauss Kidney +++ ++ + Skin ++ ++ +++ Lungs ++ +++ ++ Neurological + ++ +++ URT + +++ +
  34. 34. cANCA pANCA Negative W.G 70 % 25 % 5% Mic.polyan gitis 40% 50 % 10 % Churg Str. 10 % 60 % 30 % Pauci immune GN 20 % 70 % 10 %
  35. 35. C-ANCA on ethanol fixed slide C-ANCA is identified as a positive result when there is intense positive granular staining of the cytoplasm that extends to the border of the human granulocyte substrate displaying a 1+ or greater fluorescence and there is absence of nuclear staining P-ANCA on ethanol fixed slide P-ANCA exhibits intense positive perinuclear staining of the multi-lobed nucleus with a poorly defined cell border. A 1+ or greater fluorescence is considered a positive result
  36. 36. THANK YOU..