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Acute Nephritic Syndromes
This document discusses acute nephritic syndrome, specifically acute post-streptococcal glomerulonephritis (PSGN). It notes that PSGN classically presents after a streptococcal throat or skin infection with hematuria, proteinuria, hypertension, and edema. Investigations may show elevated anti-streptococcal antibodies. On biopsy, there is diffuse mesangial proliferation with immune complex deposition. Management involves controlling symptoms while the infection resolves spontaneously in 6-8 weeks. Complications include hypertension, renal failure, and rarely chronic kidney disease.
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Acute Nephritic Syndromes
- 1. ACUTE NEPHRITIC SYNDROME C HA I R P E R S O N : D R M A H A B A L E S H WA R M AY YA S T U D E N T : D R R AV I K I R A N N H R M C I M
- 2. INTRODUCTION • Clinical presentationof nephritic syndrome includes • Acute nephritic syndrome, • Syndrome of rapidly progressive glomerulonephritis, • Syndrome of chronic glomerulonephritis
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- 4. INTRODUCTION Acute nephritic syndromesclassically present with the following: • Hematuria • Subnephrotic proteinuria (1- 2 g/24 h ) • Hypertension • Fluid retention • Red blood cell casts • Pyuria • Rise in serum creatinine • Reduction in GFR
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- 8. CAUSES ACCORDING TOAGE CHILDREN AND ADOLESCENTS • Post-streptococcal glomerulonephritis • MPGN • Cresentic GN • IgA nephropathy • Lupus Nephritis • Henoch-Schönlein purpura ADULTS • IgA Nephropathy • Rapidly progressive glomerulonephritis • SLE or lupus nephritis • ANCA associated • Membranoproliferative GN • Hepatitis B or C • Infective endocarditis • Abdominal abscesses • Viral diseases such as mononucleosis, measles, mumps
- 9. INFECTIOUS CAUSES OF ACUTENEPHRITIS • Infectious syndromes • Specific bacterial diseases • Mycobacterial, rickettsial, mycoplasmal, chlamydial, and spirochetal diseases • Fungal infections • Viruses • Parasitic infestations NON-INFECTIOUS CAUSES OF ACUTE NEPHRITIS • Immune mediated glomerulonephritis • Immune complex GN • IgAN,HSP,LN… • ANTI-GBM GN • GPS,Anti-GBM • ANCA associated GN • MP,WG,CSS Kanjanabuch, T. et al. Nat. Rev. Nephrol. 5, 259–269 (2009); doi:10.1038/nrneph.2009.44
- 10. SITE OF INJURYIN ACUTE NEPHRITIC SYNDROME
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- 12. CLINICAL APPROACH (POST-INFECTIOUS) On thebackground of Acute Nephritis features…. • 5 and 12 years(90%) and >40(10%) • boys > girls • Pharyngitis(1-3) • Impetigo(2-6) • may be severe enough to appear as RPGN • Constitutional symptoms - as many as 50% of cases IVDU Cardiac murmur Dental abscess. Osteomy elitis,dee p seated abscesse s Treated hydroce phalus PSGN Endocar ditis ShuntAbscess
- 13. IMMUNE MEDIATED GLOMERULONEPHRITIS IMMUNE COMPLEX GN ANTI-GBMGN ANCA ASSOCIATED GN
- 14. IMMUNE COMPLEX GN Onthe background of Acute Nephritis features…. • 20s and 30s • men > women • asymptoma tic microscopi c hematuria most often seen in adults • Recurrent synpharyng itic gross hematuria • No vasulitis • Asso with systemic diseases • <20 years of age(4-7) • Macroscopi c haematuria - time of infections • Purpuric rash, arthritis, abdominal pain (Systemic vasulitis) • Young women in 20 and 30s • Arthralgia, photosensiti ve skin rash, pleurisy, and pericarditis • 5 - 12 years • boys > girls • Acute Strept infection(1-6 weeks before presentation ) MPGN I MPGN II MPGN III IgA Nephropathy HSP Lupus Nephritis Acute PSGN MPGN
- 15. MPGN • 20s; women> men • Systemic symptoms - most common • Asso – HepC,Cryogloulin,ne oplasias • Teenage; women > men • Gaunt face due to partial Lypodystrop hy • 20s • women > men MPGN I MPGN II MPGN III • Middle age • Abnormal LFT(rarely cirrhosis), pupuric rash, neuropathy,p olyarthralgia, leg ulcers MPGN I with Hep C
- 16. ANTI-GBM GN On thebackground of Acute Nephritis features…. Young men(late 20s) both sexes (50s and 70s) With lung haemorrhage GPS 20s:Young men; 50s and 60s:both sexes Without lung haemorrhage Anti-GBM GN
- 17. ANCA ASSOCIATED GN Withthe background of Acute Nephritis features…. • 50s/60s • men = women • Weight loss, malaise, LRT symptoms, arthritis, palpable purpura • no Asthma • 50s/60s • men = women • Weight loss, malaise, URT/LRT symptoms, arthritis, palpable purpura • no Asthma • 20-40 • Males>fema les • Asthma • Neuropthy Microscopic Polyangitis Wegeners Granulomatosis CSS
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- 19. DARK URINE DIPSTICK FOR HEMENEGATIVE DRUGS FOODDYES MELANIN POSITIVE GROSS HEMATURIA MICROSCOPIC HEMATURIA TRAUMA PRESENT TRAUMA ABSENT IMAGING OF ABDOME N AND PELVIS CYSTOS COPY PAINFUL PAINLESS URINE CALCIUM URINE CULTURE RENAL CALCULI U.CA FAMILIAL(Alp orts) HSP HB ELECTRO EUMORHIC RBCs DYSMORHI C RBCs U.CA R/O MEATAL STENOSIS FAMILY SCREENIN G(Thin GBM) W/U FOR GLOMER ULONEPH RITIS NO RBCs HB,MB
- 20. Photomicrograph of urine sedimentwith a red cell cast Phase contrast micrograph showing dysmorphic red cells in urine sediment Scanning electron micrograph showing dysmorphic red cells in urine sediment
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- 24. POST-INFECTIOUS GN • Anti streptolysin titre •anti-DNAse B • Throat swab or skin swab • 2D ECHO • TEE • USG • X-ray • VP shunt evidence PSGN Endocarditis ShuntAbscess OTHER SPECIFIC INVESTIGATIONS
- 25. IMMUNE COMPLEX GN Glomerularimmune complex localisatIon with granular capillary wall and/or mesangeal staining Raised serum IgA in 50% of cases, Leucocytocl astic vasulitis antinuclear antibody/ anti-ds DNA, anticardiolipi n antibody antistreptoly sin titre MPGN I MPGN II MPGN III IgA Nephropathy HSP Lupus Nephritis Acute PSGN MPGN OTHER SPECIFIC INVESTIGATIONS
- 26. MPGN Low C4 (classical path activation) LowC3 (alternative path activation), C3 nephritic factor Dense deposits Complement receptors defect MPGN I MPGN II MPGN III Low C4, +ve hepatitis C serology, hepatitis C RNA on PCR, serum cryoglobulins, +ve antinuclear antibody/ +ve Rh factor MPGN I with Hep C OTHER SPECIFIC INVESTIGATIONS
- 27. ANTI-GBM GN Circulating Anti-GBM antibodieswith linear GBM staining for IgG • With evidence of lung haemorrhage GPS • Without lung haemorrhage Anti-GBM GN OTHER SPECIFIC INVESTIGATIONS
- 28. ANCA ASSOCIATED GN CirculatingANCA with paucity of glomerular immunoglobulin staining P-ANCA(MPO) Vasculitis with no granuloma No cavities C-ANCA(RP3) Granulomas Cavitations P-ANCA(MPO) Eosinophilia Granuloma Microscopic Polyangitis Wegeners Granulomatosis CSS OTHER SPECIFIC INVESTIGATIONS
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- 30. ACUTE POST-STREPTOCOCCAL GLOMERULONEPHRITIS • AGNthat follows an infection with a nephritogenic strain of group A beta hemolytic streptococci. • The classic example of the acute nephritic syndrome. • Incidence of clinically detectable glomerulonephritis during an epidemic is up to 10% of children with pharyngitis and 25% of children with impetigo Nelson Textbook of Pediatrics, 7th Edition
- 31. STREPTOCOCCAL INFECTION OFTHE THROAT OR SKIN ( IMPETIGO)
- 32. EPIDEMIOLOGY • Globally -incidence has decreased in the past three decades. • Throat (serotype 12) - cold weather months. • Skin (serotype 49) - warm weather months. BUT • Most commonly – sporadic. • Despite that, epidemics and clusters of cases – in some poor or rural communities (© 2008 American Society of Nephrology) • Peak incidence - age 5-12 y/o, uncommon <3y/o. • Male : female ratio is 2 : 1. Nelson Textbook of Pediatrics, 7th Edition
- 33. Clinical course • Spontaneousimprovement typically begins within 1 wk • Resolution of edema in 5-10 days • Hypertension in 3-4 wk • Proteinuria -- normalize by 4-6 wk • Acute phase resolves within 6-8 wk • Urinalysis may be abnormal (persistent microscopic hematuria) upto a year
- 34. ANTIBODIES TO STREPTOCOCCAL ANTIGEN(S) •Anti-streptolysin O titer (ASOT) >333 TOD Units • COMMONLY elevated after a pharyngeal infection but • RARELY increases after streptococcal skin infections • Anti deoxyribonuclease (DNase) B antibodies • best single antibody titer to document cutaneous streptococcal infection • Anti-hyaluronidase antibodies • Anti-streptokinase antibodies
- 35. INDICATIONS FOR RENALBIOPSY • Severe acute renal failure requiring dialysis. • Features suggesting non post-infectious AGN as the cause of acute nephritis. • Absence of the latent period between streptococcal infection and acute glomerulonephritis • Normal complement levels initially in early course • Persistence of low C3 beyond 6-8 wks • Delayed resolution • Oliguria > 2 weeks • Azotaemia > 3 weeks • Gross haematuria > 3 weeks • Persistent proteinuria > 6 months
- 36. LIGHT MICROSCOPE (NOT SPECIFICFOR POST STREPTOCOCCAL NEPHRITIS) • Glomeruli - enlarged,hypercel lular. • Diffuse mesangial cell proliferation • Increase in mesangial matrix. • PMNs - common in glomeruli • Crescents and interstitial inflammation
- 37. PSGN.. Immunofluorescence microscopy • Lumpy-bumpy depositsof immunoglobulin • Complement • Glomerular basement membrane (GBM) • Mesangium Electron microscopy • Electron-dense deposits, or "humps," on the epithelial side of the GBM
- 40. MANAGEMENT • Treatment issupportive • control of hypertension, edema, and dialysis as needed. • Strict monitoring – I/O/weight/BP • Penicillin V for 10 days to eliminate β - haemolytic streptococcal infection (give erythromycin if penicillin is contraindicated) patients • Cohabitants(if culture positive for GAS) • NOTE: Antibiotic therapy does not affect natural history of glomerulonephritis
- 41. MANAGEMENT… • Diet –no added salt to diet,Protein restriction is unnecessary • No role for immunosuppressive therapy(even in the setting of crescents) FOLLOW UP: • Recheck serum complement at 6-8 wks. • Check BP, renal function test and urinalysis every 1-3 month for 1 yr then yearly
- 42. COMPLICATIONS • Hypertensive encephalopathyusually presenting with seizures • Pulmonary oedema (acute left ventricular failure) • Acute renal failure
- 43. POOR PROGNOSIS INDICATED IN…(PSGN) •History of childhood PSGN • Older age. • History of massive proteinuria. • History of Alcoholism or drug abuse. • Underlying disease such as Diabetes, Cardiovascular and liver disease. • Persistent abnormal renal function. • History of dialysis at presentation. • Biopsy feature(including crescent)
- 44. OUTCOME • Short termoutcome: Excellent, mortality <0.5%. • RPGN – 4.6% • Long term outcome: 1.8% (1-3%) of children develop chronic kidney disease • Complete resolution within 3–6 weeks • Complete recovery • >95% of children • 60% of adult.
- 45. VARIANTS OF PIGN •Staphylococcus associated GN. • Associated with ventrilovascular shunt, IE . • Some resemble IgA nephropathy. • HBV associated GN. • HIV associated GN such as HIVAN • Other infection associated GN
- 46. GN ASSOCIATED WITHIE • Incidence range from 22-78%. • Highest among IV drug abusers • Particularly in patients who: • Remain untreated for an extended period of time • Have negative blood cultures • Have right-sided endocarditis (IVDU) • Grossly, subcapsular hemorrhages with a "flea-bitten" appearance • Most typical finding is focal and segmental proliferative GN. • Primary treatment is eradication of the infection with 4–6 weeks of antibiotics • Prognosis is good.
- 47. SHUNT NEPHRITIS RELATEDGN • Immune mediated complex GN. • Complication of chronic infection via ventriculovascular shunts, common in treatment of hydrocephalus. • In contrast to vascular shunt, VP shunt rarely developed GN. • Typical type I MPGN (deposit - mesangial and subendothelial). • Typical organisms are Staphylococcus spp
- 48. HCV INFECTION RELATEDGN • HCV frequently causes extrahepatic manifestation. • Kidney involvement… • Most common associated with type II cryoglobulinemia.(1) • Type I MPGN (Cryoglobulin deposits). • Best long term prognostic indicator is HCV with SVR. • RNA clearance from serum at least 6 month. • Paucity of controlled study in HCV associated GN. • Rituximab plus Peg-interferon a2b and Ribavarin show good response in stabilized kidney function in cryoglobulinemic vasculitis(2) (1) Chapter 9; Infection-related GN. Kidney International Supplements (2012) 2, 200–208 (2) Saadoun D, Resche-Rigon M, Sene D et al. Rituximab combined with Peg-interferon-ribavirin in refractory HCV -cryoglobulinaemia vasculitis. Ann Rheum Dis 2008; 67: 1431–1436.
- 49. HBV INFECTION RELATEDGN • Pattern of kidney involvement included. • MN is the most common form, especially in children. • Other such as MPGN, FSGS and IgAN. • Exclude other cause of GN first. • Prognosis… • – In children high spontaneous remission. • – In adult usually progressive, especially with abnormal LFT and nephrotic syndrome, >50% progressing to ESRD. • Treat HBV infection(Ente,Lami,Teno,Adefovir) • Currently no data about efficacy of treatment in HBV- related GN.
- 50. HIV RELATED GN •Variety spectrum of kidney disease. • HIVAN is the most common cause of CKD in HIV-1. • APOL1 gene related. • Typical collapsing FSGS on pathology. • HAART is beneficial in both preservation and improvement in kidney function. • Not effective in other GN associated with HIV infection. • ACE-I may benefit in HIV with nephrotic syndrome
- 51. SCHISTOSOMAL NEPHROPATHY • S.Mansoniand S.japonicum, blood fluke. • Incidence is not well defined. • Young adult males. • Commonly seen eosinophiluria (65%) and hypergammaglobilinemia (30%). • Aware co-infection with salmonella,Especially in Hepatosplenic involvement. • Once established GN, currently no effective therapy. • None of immunosuppresant recommended. • Prevent by Praziquantel or Oxamiquine
- 52. FILARIAL NEPHROPATHY • Loaloa, Onchocerca volvulus, W. bancrofti and B. Malayi. • Immune mediated from worm antigens. • Urinary abnormalities have been reported 11-25%. • Nephrotic syndrome 3-5%, concomitant with polyarthritis and chorioretinitis. Especially in lymphatic filariasis. • Can induce diffuse GN and MPGN, MPGN, MND or Sclerosing GN. • Treat by Ivermectin or Diethylcarbamazine.
- 53. MALARIAL NEPHROPATHY • P.Falciparum. •May resulted in AKI or proliferative GN. • P.Malariae. • Variety of kidney disease especially MN or MPGN. • Currently no RCT for evidence base treatment. • Suggestion only appropriate anti-Malarial agent
- 54. IgA NEPHROPATHY (IgAN) • Berger'sdisease/Synpharyngitic glomerulonephritis • MC type of GN worldwide • Male preponderance • Peak incidence in the 2nd and 3rd decades • Recurrent painless gross hematuria. • Preceded by (usually 1-3 days ) infections(URTI,GE). • Defined by the presence of diffuse mesangial IgA deposits often associated with mesangial hypercellularity.
- 55. IgA NEPHROPATHY • Depositsof IgA are also found in the glomerular mesangium in a variety of systemic diseases, including: • Chronic liver disease • Crohn's disease • Gastrointestinal adenocarcinoma • Idiopathic interstitial pneumonia • Dermatitis herpetiformis • Mycosis fungoides • Leprosy • Ankylosing spondylitis
- 56. • IgA -polymeric forms • Only IgA1 forms the nephritogenic deposits • A genetic or acquired abnormality of immune regulation leading to increased IgA synthesis in response to respiratory or gastrointestinal exposure to environmental agents • HTN & renal insufficiency --- uncommon • 30% to 40% have only microscopic hematuria, with or without proteinuria • 5% to 10% develop a typical acute nephritic syndrome
- 57. PATHOGENESIS- SECONDARY IGA NEPHROPATHY •IgA nephropathy occurs with increased frequency • gluten enteropathy (celiac disease), in whom intestinal mucosal defects are well defined • liver disease, in which there is defective hepatobiliary clearance of IgA complexes (secondary IgA nephropathy). • Alternatively, there is evidence for qualitative alterations in the IgA1 molecule itself
- 59. IgAN • IgA nephropathyis typically an isolated renal disease, similar IgA deposits are present in a systemic disorder of children, Henoch-Schönlein purpura which has many overlapping features with IgA nephropathy. • In addition, secondary IgA nephropathy occurs in patients with liver and intestinal diseases
- 60. IgAN..CLINICAL COURSE • Thehematuria typically lasts for several days and then subsides, only to return every few months. The subsequent course is highly variable • Many patients maintain normal renal function for decades. • Slow progression to chronic renal failure occurs in 15% to 40% of cases over a period of 20 years • Recurrence of IgA deposits in transplanted kidneys is frequent
- 61. IgAN… CLINICAL COURSE •Clues to an increased risk of progression(loss of renal function) • Onset in old age • Heavy proteinuria • Hypertension • Extent of glomerulosclerosis on biopsy • Absence of episodes of macroscopic hematuria, • male
- 62. IgA NEPHROPATHY • Angiotensin-convertingenzyme (ACE) inhibitors in patients with proteinuria or declining renal function. • When presenting as RPGN, patients typically receive: • Steroids • Cytotoxic agents • Plasmapheresis
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- 64. INTRODUCTION • MPGN- nota diagnosis per se • Rather a histopathologic pattern of injury • See for potential underlying causes of injury • Clinical classification • Idiopathic or primary • Secondary • Primary MPGN – based on ultrastructural appearance and location of electron-dense deposits • Type I • Type II • Type III
- 65. • DDD wasrenamed MPGN2 in 1975 • Now considered inappropriate to refer to DDD as MPGN2 • Pathological pattern of MPGN is absent in the majority of cases of DDD.
- 67. SUMMARY OF CLINICALAND LABORATORY FEATURES OF C3 GLOMERULOPATHIES
- 68. MANAGEMENT • Predictors ofoutcome • Renal dysfunction – Sr Cr, GFR • Proteinuria • DDD- older age at diagnosis - an independent predictor of ESRD • C3GN may have a more benign course than patients with DDD
- 69. TREATMENT • Targeted therapieshave not proven to be universally beneficial – • Heterogeneity of the C3 glomerulopathies • Control of alternative complement pathway activity • Replacement of factor H - viable option • Pts with genetic defects of inhibitory proteins of the alternative complement pathway - replacement of factors
- 70. TREATMENT… • Replacement • Plasmaexchange • Pharmaceteucal preparation (not available at present) • Replacement not successful in certain pts • Mutant C3 convertase that is resistant to factor H Control • Pts with an acquired antibody to an inhibitory protein of the alternative pathway • Immunosuppressive therapy • Corticosteroids • mycophenolate mofetil • rituximab • Eculizumab • Humanized monoclonal antibody to C5 • Prevents the generation of the MAC
- 71. C3 GN VSDDD • C3GN have a slightly better prognosis than do pts with DDD • DDD – progression to ESRD • 25% after 5 years • 50% after 10 years from diagnosis • French cohort - C3 glomerulopathy • ¼th of adult pts with C3GN progressed to ESRD over 10 years of f/u • American cohort - C3GN • No significant decline in renal function over a mean follow-up of 26 months
- 72. REFERENCES • Harrisons Principlesof Internal Medicine – 19th Edition • Brenner and Rector – The Kidney – 9th Edition • Comprehensive Clinical Nephrology - John Feehally, Richard J. Johnson, Jürgen Floege – 5th edition • Nelson Textbook of Pediatrics, 7th Edition • Acute glomerulonephritis ; C S Vinen, D B G Oliveira: Postgrad Med J 2003;79:206–213 • An update on acute postinfectious glomerulonephritis worldwide Talerngsak Kanjanabuch, Wipawee Kittikowit and Somchai Eiam-Ong - Nat. Rev. Nephrol. 5, 259–269 (2009); doi:10.1038/nrneph.2009.44 • INCIDENCE OF ACUTE POST STREPTOCOCCAL GLOMERULONEPHRITIS IN CHILDREN doi:10.1136/archdischild-2012-302724.1205
- 73. REFERENCES • The KoreanSociety of Nephrology - New Classification of MPGN/Kidney Res Clin Pract 33 (2014)171–173 http://dx.doi.org/10.1016/j.krcp.2014.10.005 • WG Couser and RJ Johnson: The etiology of glomerulonephritis: roles of infection and autoimmunity - Kidney International (2014) 86, 905–914; doi:10.1038/ki.2014.49 • Chapter 9; Infection-related GN. Kidney International Supplements (2012) 2, 200–208 • Saadoun D, Resche-Rigon M, Sene D et al. Rituximab combined with Peg-interferon-ribavirin in refractory HCV -cryoglobulinaemia vasculitis. Ann Rheum Dis 2008; 67: 1431–1436
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