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Approach to Rapidly Progressive Glomerulonephritis RPGN
- 1. 08.05.14 Clinical Approach to Rapid Progressive Glomerulonephritis Dr Garima Aggarwal - DM Nephrology - Amrita Institute of Medical Sciences, - Kochi, India
- 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. 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
- 5. Normal Kidney Crescent Normal glomerulus
- 6. 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*
- 7. Rapid Progressive RenalFailure?
- 8. Types of RenalFailure (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.
- 9. • The clinicaldiagnosis 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
- 10. 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
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- 13. HISTORY RPRF vsCKD 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
- 14. 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
- 15. ROUTINE INVESTIGATIONS CBC Leucocytosis – Sepsis, vasculitis, TE dis Eosinophilia – Churg Strauss TCP – HUS/TTP, TMA Peripheral smear – fragmented RBCs - TMA
- 16. URINE ANALYSIS DysmorphicRBCS, active sediments, Rbc casts, Sub Nephrotic Proteinuria – Vasculitis, Lupus – RPGN Isomorphic RBCs , Eosinophiluria – AIN, TE dis Nephrotic Range proteinuria – causes other than RPGN
- 17. 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
- 18. 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
- 19. Rapid progressive renalfailure 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
- 20. 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
- 21. IMMUNOFLUORESCENCE RPGN IRPGN 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
- 22. linear staining forIgG - diffuse binding of anti- GBM Ab Granular staining on IF in PSGN Scanty Background staining of puaci immune
- 23. ELECTRON MICROSCOPY •RPGN I and III – absence of electron dense immune complex deposits • RPGN II – Multiple electron dense deposits
- 24. Anti GBM DiseaseEM – 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
- 25. RPGN Clinical/serology/Bx LinearIF, 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
- 26. RPGN Clinical/serology/Bx GranularIF, 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
- 27. RPGN Clinical/serology/Bx NoIF, 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
- 28. 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.
- 29. 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.
- 30. •Patchy parenchymal consolidationsare present, which usually are •bilateral, symmetric perihilar, and bibasilar. •The apices and costophrenic angles usually are spared
- 31. 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.
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- 35. Microscopic polyangitis Wegener’s Granulom-atosis Churg Strauss Kidney +++ ++ + Skin ++ ++ +++ Lungs ++ +++ ++ Neurological + ++ +++ URT + +++ +
- 36. 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 %
- 37. C-ANCA on ethanolfixed 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
- 38.
Editor's Notes
- #4 patients with circumferential crescents, > 80%glomeruli -advanced renal failure- may not respond well to therapy crescents <50 percent of the glomeruli, noncircumferential, follow a more indolent course or in rare cases even undergo a remission.
- #7 — an immune complex (type 2) disease that does not fit into any of the identifiable categories; and a pauci-immune (type 3) disease that is ANCA-negative.
- #10 There are also a number of renal diseases that do not fit easily under these current definitions. These patients are neither Acute Kidney Injury (previously called acute renal failure) nor Chronic Kidney Disease (previously called chronic renal failure).
- #13 ANTI GBM- 2 peaks- 1st peak 2nd and 3rd decade – 2nd peak sixth and seventh; IC GN – majority of cgn IN CHILDREN; Disease of elderly
- #14 Detailed and appropriate history taking is essential both to make the initial diagnosis of
- #15 But maybe seen in vasculitis syndromes, SLE, TMA
- #18 Hepatitis B – PAN, mpgn/ MN?IgA, Hepatitis C – Mixed Cryoglobulinemia
- #20 Diagnosis, prognosis, chronicity, guide treatment
- #21 Anti GBM – lesions are in similar temporal evolution as opposed to ANCA