Glomerulonefritis Dan Sindroma Nefrotik

GLOMERULONEFRITIS

Linda Armelia

Definisi dan Etiologi

Brenner and Rector's The Kidney. 8th ed. 2008Harrison’s Principles of Internal Medicine. 17th ed. 2008

Anatomy & Histology

Junqueira, Basic Histology. 11th ed. 2007

Glomerular Capillary

Marieb EN. Human Anatomy & Physiology. 7th ed.Junqueira, Basic Histology. 11th ed. 2007

Glomerular Filtration Barrier• Barrier consists of

– Fenestrated endothelium– Glomerular basement

membrane– Podocyte slit diaphragm

• GBM – Discrete pores size

selectivity– Negatively charge

(heparan sulphate proteoglycan)

• Podocyte foot processes interdigitate slit diaphragm in between

The Renal System, 2001Primer on Kidney Disease, 5th ed, 2009

Oxford Textbook of Clinical Nephrology, 3rd Edition, 2005

Glomerular Filtration Barrier


Harrison’s Principle of Internal Medicine 16th ed

Primer : patologi terbatas hanya pada ginjal dan gambaran klinis sistemik merupakan konsekuensi langsung dari difungsi glomerular (mis : edema pulmoner, hipertensi, dan sindroma uremik)Sekunder : bagian dari kelainan multisistem

Akut : beberapa hari sampai beberapa minggu

Subakut/ rapidly progressive : beberapa minggu sampai beberapa bulanKronik : beberapa bulan sampai beberapa

tahunFokal : lesi < 50% glomeruliDifus : lesi > 50% glomeruli

Proliferatif : penambahan sel glomerulus yang dapat merupakan proliferasi dari sel glomerular asli atau hiperseluleritas akibat infiltrasi leukosit

Intrakapiler : endotel atau sel mesangial Ekstrakapiler : sel di ruang Bowman

:

Harrison’s Principle of Internal Medicine 16th ed

Crescent : kumpulan sel ekstrakapiler yang berproliferasi di ruang Bowman , berbentuk bulan sabit, terdiri dari epitel parietal ,infiltrasi makrofag, dan fibrin.

• Gagal ginjal progresif cepat rapidly progressive glomerulonephritis/ cerscentic glomerulonephritis

Membranous : didominasi dengan ekspansi deposit imun ke membrana basalis glomerulus (MBG)

Sklerosis : penambahan material nonfibrilar ekstraseluler homogen pada MBG dan matriks mesangial

Fibrosis : melibatkan deposisi kolagen tipe I dan III dan merupakan konsekuensi dari penyembuhan akibat inflamasi tubulointerstisial atau crescent

Patogenesis kerusakan glomerulus

• Otoimun• Genetik • Respon terhadap antigen asing • Pembentukan komplek imun • Identifikasi Antigen• Cell-mediated Immune Mechanisms• Mekanisme efektor: komplemen dan sel-sel

inflamasi

Comprehensive Clinical Nephrology, 2000

Patogenesis kerusakan glomerulus Otoimun


Self Reactive T and B cells are clonally deleted during fetal and neonatal life, but some survive

outside the thymusThese cells can be stimulated to generate response

to ‘self antigen’Infection altering host response to make them more immunogenic or by “molecular mimicry”

Certain bacteria act as “superantigen” can directly activate T-cell and cause monoclonal cell B

expansion

Patogenesis kerusakan glomerulus Genetik

• Respon terhadap antigen asing


Variations in HLA molecules and T-cell receptor are under strong genetic influence

Environmental events may have great importance, acting on genetic background in

inducing GN

Persistent antigenemia with circulating antigen-antibody complexes predispose to glomerular

injury classical example : chronic Hep B infection

Patogenesis kerusakan glomerulus• Pembentukan komplek imun

Identifikasi Antigen


In most cases of GN there is deposition of immune complex

Mechanisms of immune complex localization : “circulating immune complex” or “in situ

formation”

Regardless of the antigen origin, the spesific antigen involved remain largely unknown (except

anti-GBM, poststreptococcal GN)

Patogenesis kerusakan glomerulus Cell-mediated Immune Mechanisms

• Mekanisme efektor: komplemen dan sel-sel inflamasi


Certain glomerular disease develop primarily through cell-mediated immunity

Cresentic nephritis direct role of T cells in mediating proteinuria and crescent formation MCD permeability defects results from a

T-cell products

Complement : C5b-9 (membrane attack complex), and C5a (chemotactic factor)

Infiltrating cells are neutrophils, Tcells, or monocytes/macrophage

Intrinsic glomerular cells (epithelial, mesangial, and endothelial) may be activated by the injury and behave like

inflammatory cells

Patologi GN Berbagai perubahan patologis yg terjadi :

Proliferasi sel intrinsik (endotel, mesangial, epitelial) Infiltrasi lekosit Penumpukan matriks mesangial Perubahan membran basalis glomerular Scarring

Glomerulonephritis

Harrison’s Principles of Internal Medicine. 17th ed. 2008

Patogenesis kerusakan glomerulus


Gambaran klinikAsymtomatic

Proteinuria 150mg-3g/dayHematuria > 2 red blood

cells/hpf in spun urine (usually dysmorphic)

Macroscopic HematuriaBrown/red painless

hematuria (no clots); typically coinsides with intercurrent infection

Asymptomatic hematuria + proteinuria between

attacks

Nephrotic syndromeProteinuria > 3,5 g/day

Hypoalbuminemia < 3,5g/dlEdema

HypercholesterolemiaLipiduria

Nephritic SyndromeOliguria

Hematuria : red cell castsProteinuria : usually < 3

g/dayEdema

HypertensionAbrupt onset, usually self

limiting

Rapidly Progressive Glomerulonephritis

Renal Failure over days/weeksProteinuria : usually < 3 g/day

Hematuria : red cell castsBlood pressure often normalMay have other features of

vasculitisChronic

GlomerulonephritisHypertension

Renal InsufficiencyProteinuria >3g/day

Shrunken smooth kidneyComprehensive Clinical Nephrology, 2000

Badr KF. Kidney Int 2005; 68: 1905–19.

Sindroma klinis penyakit glomerolus Hematuria asimtomatik dengan atau tanpa

proteinuria Sindroma Nefrotik Sindroma Nefritik RPGN Penyakit glomerular kronik

Glassock RJ. Clin Geriatr Med 2009; 25: 413–22.

Callaghan, Brenner. The Kidney At A Glance. 2000

Hematuria Eritrosit dismorfik atau silinder eritrosit pada

urinalisa lesi di glomerolus Hematuria > 2 eritrosit/LPB Gross hematuria

Glomerular Proteinuria > 3 gram / 24 jam Perubahan pada sifat “size selektif” GBM

molekul dgn BM > 70 kd ( protein ) ikut terfiltrasi

Perubahan pada sifat “charge selektif” GBM ultrafiltrasi molekul bermuatan negatif seperti albumin

Evaluation of Hematuria and/or Proteinuria

Harrison’s Principles of Internal Medicine. 17th ed. 2008

Nefrotik VS Nefritik

Proteinuria > 3.5 grm/1.73 m2/24 jam

Hipoalbuminemia Edema Hiperlipidemia Lipiduria

Hematuria Silinder eritrosit Proteinuria Insufisiensi renal Retensi garam

( hipertensi nefropati dan edema )

Sindroma Nefrotik Sindroma Nefritik

Current Diagnosis & Treatment: Nephrology & Hypertension. 2009

Differentiation Between Nephrotic and Nephritic Syndrome

Typical Featues Nephrotic NephriticOnset Insidous AbruptEdema ++++ ++Blood Pressure Normal RaisedJugular Venous Pressure

Normal/low Raised

Proteinuria ++++ ++Hematuria May/ may not occur +++Red-cell casts Absent PresentSerum Albumin Low Normal/Slightly

Reduced


Sindroma nefrotik• Primer nefropati membranosa, FSGS,

minimal changes, MPGN• Sekunder DM, SLE, amiloidosis, leukemia• Penyakit glomerolus mempengaruhi “charge

or size selectivity” dinding kapiler glomerolus peningkatan permeabilitas glomerolus proteinuria

• Komplikasi hiperlipidemia, trombosis, defisinsi vitamin D, hipokalsemia, infeksi, malnutri, anemia

Sindroma nefritik• Primer post infectious GN, Nefropati Ig-A,

nefritis lupus• Patogenesis Inflamasi di Glomerolus

a. Antibodi di sirkulasi b. Komplek imun di sirkulasi c. Antigen yang mengaktivasi komplemen

• Komplikasi edema, hipertensi, anemia, ESRD,

Nachman PJ, dkk. Brenner: Brenner and Rector's The Kidney. 8th ed.

Clinical Manifestations of Glomerular Diseases and Representative Disease that Cause ThemAsymptomatic

ProteinuriaFSGS

Mesangioproliferative GNNephrotic Syndrome

Minimal Change GNMembranous GN

Idiopathic (pimary)Secondary (lupus)

FSGSMesangioproliferative GN

Membranoproliferative (Type I & II)

Fibrillary GNDiabetic Glomerulosclerosis

AmyloidosisLight Chain Deposition

Disease

Asymptomatic Microscopic Hematuria

Thin Basement membrane nephropathy

IgA NephropathyMesangioproliferative GN

Alport’s syndrome

Recurrent Gross HematuriaThin Basement membrane

nephropathyIgA Nephropathy

Alport’s syndrome

Acute NephritisAcute postinfectious GN

Poststreptococcal GNPoststaphylococcal GN

Type I & II Membranoproliferative GN,

Fibrillary GN,Focal or Diffuse Proliferative

GNIgA NephropathyLupus Nephritis

Primer on Kidney Disease, 5th ed, 2009

Clinical Manifestations of Glomerular Diseases and Representative Disease that Cause Them

Rapidly Progressive GNCresentic GNAnti GBM GN

Immune Complex GNANCA GN

Pulmonary-Renal Vasculitic Syndrome

Goodpasture’s (anti GBM) syndrome

Immune complex vasculitisLupus

ANCA VasculitisMicroscopic Polyangitis

Wegener’s granulomatosisChurg-strauss Syndrome

Chronic Kidney DiseaseChronic sclerosing GN


Minimal Change Disease (MCD)

= nil (Nothing-In-Light microscopy lesion) disease• Penyebab terbanyak penyebab sindroma nefrotik

pada anak , pada orang dewasa 10-15%.• Biopsi ginjal (penting pad dewasa)

– Normal/minimal changes pada mikroskop cahaya– Negative immunofluorescent microscopy– Podocyte foot process effacement pada mikroskop

elektron• Mayoritas idiopathic , tetapi bisa juga timbul

sekunder.

Waldman M, et al. Clin J Am Soc Nephrol 2007; 2:445-53. Saha TC, Singh H. Minimal Change Disease: A Review. 2006 Southern Medical Association

Minimal Change Disease

Abnormal T-cell

Function and

immune mediated defects

Inhibits sulfate

incorporation to GBM

Vasc Endothelial

Growth Factor

Diminished negative charge

Increased permeability to

protein

Toxic Epithelial Cell Injury

Foot process fusion and epithelial

detachmentPrimer on Kidney Disease, 5th ed, 2009Comprehensive Clinical Nephrology, 2000

Minimal Change Disease (MCD)Neoplasma Limfoma, leukemia, timoma, renal cell

carcinoma, colon carcinoma , pancreatic carcinoma

Obat-obatan NSAIDs, trimethadion, paramethadione, lithium, interferon, methimazole, tamoksifen

Infeksi Sifilis, HIV , mikoplasma, skistosomiasisAtopi Pollen, susu sapi, debu rumah, sengatan

lebahSuperimposed dengan penyakit ginjal lainnya

IgA nefropati, SLE, DM tipe 1, Polisitik kidney, HIV associated nefropati

Lainnya Sklerosing cholangitism sclerosing mesentricm GBS, MG, renal artery stenosis, partial lipodistropi

Glasssock RJ . Secondary minimal change disease. Nephrol Dial Transplant 2003

Biopsi histopatologi

UNC kidney center

Mikroskop cahaya glomerolus yang tampak normal GBM tipis, tanpa adanya hiperselularitas

dan expansi matriks mesangial

Electron microscope foot process effacement

UNC kidney center

Tatalaksana MCD• Terapi non-immunosupresif:

– Diuretik– ACE inhibitor/ARB– Statin

• Terapi immunosupresif :Prednisone (drug of choice)– Pada dewasa prednison 1 mg/kgBB/hari selama

8–16 minggu kemudian di–tappering off secara perlahan selama 6 bulan

Nakayama M, et al. Am J Kidney Dis 2002; 39:503Saha TC, Singh H. Minimal Change Disease: A Review. 2006 Southern Medical Association

.

Minimal Change Disease : Treatment

MCNS Patients

Children and AdultsSecond-line TherapyCyclophosphamide

Mycophenolate mofetilCyclosporine/

tacrolimus

AdultsSecond-line

TherapyCyclophosphamide

Mycophenolate mofetil

Cyclosporine/tacrolimus

Frequent relapsesSteroid

dependencySteroid

toxicity (30%

Frequent relapses

No steroid toxicity (30%)

Infrequent Relapses

(30%)

No Further Relapses

(10%)


Respons terapi Remisi komplit ekskresi protein urin < 300/hari

atau 3 hari berturut-turut dgn menggunakan dipstik, didapatkan prroteinuria (-).

Remisi parsial didapatkan penurunan kadar ≥50% (ekskresi protein urin antara 300-3500 mg/hari).

Relaps ekskresi urin> 3500 mg/hari setelah sebelumnya tercapai remisi komplit atau parsial.

Waldman M, et al. Clin J Am Soc Nephrol 2007; 2:445-53.

Steroid resisten dan Relaps Cyclophosphamide 2 mg/kg/hari Chlorambucil 0.15 mg/ kg/hari Cyclosporine 5 mg/kg/hari 6 - 12 months

ditappering 25% tiap 2 bulan MMF dan azatriophine steroid resisten Diagnosisnya mungkin bukan MCD tetapi

Focal Segmental Glomerulosclerosis (FSGS)

12 minggu

Beck LH, et al. Prim Care Clin Office Pract 2008; 35: 265–96.

Focal Segmental Glomerulosclerosis (FSGS)

Penyebab utama kejadian sindroma nefrotik pada dewasa berisiko tinggi terjadi ESRD ( 50% ) dalam 5-10 thn

FSGS primer dan sekunder Manifestasi asimtomatik proteinuria VS

sindroma nefrotik Hematuria, HT, azotemia 15-30% pasien Gold standar histopatologi biopsi

Chun MJ . Focal segmental glomerulosklersosis in neprotic adults: presentation, prognosis and respon theraphy.J am Soc nephrol 2004

Klasifikasi FSGS

Brenner and Rector's The Kidney. 8th ed. 2008

Terapi• Steroid prednisone 1 mg/kg BB/ hari ( max

60-80 mg/hari selama 6-8 bulan • Terapi adjuvant - Diet dan diuretik- ACE-I dan ARB- Kontrol lipid statin - Vitamin E- Plasmaferesis

Respon terapi • Respons komplit prednison dilanjutkan

sampai 1–2 minggu tappering off dalam 2–3 bulan.

• Respons parsial tappering off dalam 6–9 bulan.

• Steroid–dependent dan steroid–resistant a) Siklosporin dan prednison dosis rendahb) Siklofosfamidc) Mycophenolate mofetil

Beck LH, dkk. Prim Care Clin Office Pract 2008; 35: 265–96.

Membranous Nephropathy (MN) Istilah MN perubahan histologi

Penebalan membran basal glomerular Frekuensi lebih sering terjadi pada laki-laki,

dewasa dekade 4-5 Penyebab tersering sindrom nefrotik pada

pasien non-diabetes Primer VS sekunder ( SLE, hepatitis B,

hepatitis C, NSAID, penisilamin, kanker kolon)

Ponticelli C. Jnephrol 2007; 20: 268–87. Clin J Am Soc Nephrol 3: 905-919, 2008

Mikroskop cahaya pada MNPenebalan difuse pada Glomerular Basement Membrane pada seluruh glomerolus

Clin J Am Soc Nephrol 3: 905-919, 2008

Immunofluoresence pada MNDiffuse granular pattern dari Ig-G di sepanjang membran basal glomerular

Clin J Am Soc Nephrol 3: 905-919, 2008

Miroskop elektron pada MNElectron dense deposits are present in the subepithelial space across the glomerular basement membrane and under the epithelial cells

Mikroskop Cahaya dengan pewarnaan perak pada MN

•Spike appearance

•Menggambarkan membran basal yang tumbuh di antara subephitelial immune deposits

UpToDate 18.2, 2010

Klasifikasi MN• Stage I:

Subepithelial dense deposits (arrow)

• Stage II:Projections of basement membrane

• Stage III: Deposits surrounded by basement membrane

• Stage IV:Thickened basement membrane


Manifestasi Klinis MN Sindrom nefrotik (80%) Proteinuria asimptomatik Hematuria mikroskopik (50%) Tekanan darah dan GFR normal pada

70% pasien

Ponticelli C. Jnephrol 2007; 20: 268–87.

Algoritma tatalaksana pada MN

Cattran D. J Am Soc Nephrol 2005; 16: 1188–94.

Membranous Nephropathy : Treatment

Mild Proteinuria (<4g/day)

Normal GFR

Maintain BP

below 130/80ACEI

Monitor

Moderate Proteinuri

a (4-8 g/day) Normal

GFR

Maintain BP below 130/80

ACEIMonitor

progress for 6 mo

Persistent (>4g/day)

Cytotoxic + steroids or

Cyclosporine

Heavy Proteinuria

(>8g/day) with or without

diminished GFR

Maintain BP below 130/80

ACEI, consider low protein diet

Monitor progress for < 6 mo (may initiate therapy early if renal function deteriorates

Persistent (> 8g/day) with or

without diminished GFR

Cyclosporine or cytotoxic +steroidsPrimer on Kidney Disease, 5th ed, 2009

Membranoproliferative GN (MPGN)

Terbagi atas 3 tipe MPGN tipe I, II, III Dicirikan adanya difus proliferasi sel

mesangial dan penebalan dinding kapiler glomerolus

Primer >>> , sekunder ( monoclonal immunoglobulin, SLE, chronic thrombotic microangiopathies, infeksi kronik hepatitis C)

Alchi B, Jayne D. Pediatr Nephrol (2010) 25:1409–1418

Klasifikasi MPGN 3 types on MPGN:

Type I: discrete immune deposits in the mesangium and subendothelial space

Type II: continuous, dense ribbon-like deposits along the basement membranes

Type III: immune complex disease, similar to type I. However, subepithelial deposits are prominent in type III


MPGN tipe I Subendotelial, dan mesangial dense deposit MPGN bentuk terbanyak Aktivasi komplemen jalur klasik Secondary to a chronic or subacute infectious process:

Hepatitis C virus (HCV) Slowly progressive course to ESRD in 40-50% of cases Long-term treatment with high-dose alternate-day

prednisone 120 mg of prednisone every other day For 12 to 16 weeks tappering

Alchi B, Jayne D. Pediatr Nephrol (2010) 25:1409–1418 Beck LH, et al. Prim Care Clin Office Pract 2008; 35: 265–96

MPGN Tipe II Intra membranous dense deposit Berhubungan dengan C3 nephritic factor

aktivasi jalur alternatif Sindrom nefrotik Prognosis buruk sebagian besar

pasien mengalami ESRD setelah 7 tahun Jarang remisi spontan

Beck LH, et al. Prim Care Clin Office Pract 2008; 35: 265–96. Alchi B, Jayne D. Pediatr Nephrol (2010) 25:1409–1418Gerald BA et all. J Am Soc Nephrol 2005 :16: 1392–1404

MPGN tipe III Deposit di subendotel, mesangial dan

subepitelial Alternative pathway ( C5 convertase)

Gambaran klinis Sindroma nefrotik(40–70%) Sindroma nefritik (20–30%) proteinuria asimtomatik dan hematuria

(20–30%) gross hematuria (10–20%). Lab kadar C3 dan C4 yang rendah, C3

nephritic factor (+)

Alchi B, Jayne D. Pediatr Nephrol (2010) 25:1409–1418Gerald BA et all. J Am Soc Nephrol 2005 :16: 1392–1404

Alchi B, Jayne D. Pediatr Nephrol (2010) 25:1409–1418Lenvin A. Management of membarnoproliferative glomerulonephritis:Evidence based recommendation. Kidney international 1999 ; 55(70)

Algoritme Tatalaksana MPGN

Immunoglobulin A Nephropathy (IgAN) = Berger’s Diseases th 1968 oleh Dr Berge Berger’s

disease Prevalensi tersering pada ras Asian dan

Kaukasian Penyebab utama primary GN Klinis gross hematuria disertai infeksi

saluran nafas bagian atas Lab eritrosit dismorfik dan silinder

eritrosit pada urinalisa, proteinuria (+)Beck LH, et al. Prim Care Clin Office Pract 2008; 35: 265–96 Donadio JV, Grande JP. IgA Nephropathy. N Eng J Med 2001;347(10): 738-48.

Patogenesis Immunoglobulin A Nephropathy

Donadio JV, Grande JP. IgA Nephropathy. N Eng J Med 2001;347(10): 738-48

Histopatologi

Mikroskop cahaya:Peningkatan matrik

mesangial dan selularita

Mikroskop elektron:

Deposit IgA di daerah mesangial

Immunofluoresence:

Deposit Ig-ADi mesangial

Tumlin JA, et al. Clin J Am Soc Nephrol 2004; 2: 1054–61.

Tatalaksana

Proteinuria ringan < 500 mg/hari, fungsi ginjal normal, tekanan darah normal observasi, monitor tiap 6 bulan.

Fungsi ginjal normal, proteinuria 500-1000 mg/hari, tekanan darah meningkat ACE-Inhibitor/ARB

Glukokortikoid: Sindrom nefrotik episode akut Progresif aktif

Prognosis: stable disease atau progresif lambat

Alexopoulos, E. Kidney Int 2004; 65:341Donadio JV, Grande JP. IgA Nephropathy. N Eng J Med 2001;347(10): 738-48

Poststreptococcal GN (PSGN) Etiologi Streptococcus ( grup A dan C),

Staphylococcus aureus , Staphylococcus epidermidis, Salmonella typhi dan parathyphi, Treponema pallidum, Brucella abortus

GN terjadi 2-3 minggu setelah faringitis atau infeksi kulit

Peningkatan titer Anti-streptolysin O (ASO) Hypocomplementemia CH50 dan C3

berkurang, C4 normal


Poststreptococcal GN (PSGN) Klinis Nefritik sindrom hematuria

gross / mikroskopik, hipertensi, edema, oligouria 2 minggu

4% massive proteinuria masif, azotemia progresif dan cresentic glomerulonefritis

Tatalaksana Sindrom nefritik self limiting terapi

simtomatik (edema dan hipertensi) meliputi kontrol tekanan darah (ACEI/ ARB) dan diet rendah garam

Infeksi streptococcal 1.2 juta unit benzathine penisiline dosis tunggal atau 4x250 mg eritromisin oral selama 7-10 hari


Rapidly Progressive GN (RPGN) Sindroma klinis ditandai onset yang tiba tiba

dari hematuria, proteinuria dan anemia yang berkembang secara cepat menjadi gagal ginjal dalam hitungan minggu atau bulan

3 tipe kelainan berdasarkan imunofluorosen: Tipe I : Anti–GBM antibodies Tipe II : Immune complex glomerulonephritis Tipe III : Pauci–immune glomerulonephritis ( ANCA

associated crecentic GN) paling sering (>50%).

Jennette JC.Rapidly progresive crescentic glomerulonephritis. Kidney International, Vol. 63 (2003), pp. 1164–1177

Tampilan RPGN

Penurunan fungsi ginjal yang sangat cepat ( penurunan GFR>50% dalam 3 bulan)

Ukuran ginjal normal atau membesar Sindroma nefritik ( proteinuria, eritrosit

dismorfik, silinder eritrosit) Ditemukan glomerular cresent pada

pemeriksaaan imunoflurosense Tidak pernah remisi spontas


Tipe I (Anti–GBM antibodies) Antibodi anti-GBM yang patogen terhadap domain

NCI dari rantai α-3 kolagen tipe IV yang mrpk komponen dari membran basalis glomerolus dan alveolus

Klinis: edema, hipertensi, uremia , oligouria, hematuria, hemoptisis dan sesak

Lab: hematuria, proteinuria, anti GBM antibodi, peningkatan ureum dan kreatinin,

Bila disertai dengan perdarahan pulmoner Goodpasture Syndrome

Biopsi nekrosis segmental, kebocoran darah masuk ke bowman’s space dan terbentuknya cresent

Lupus Nephritis Lupus nephritis involved deposition of

preformed immune complexes, initially in the mesangial interstices with eventual spillover into subendothelial space, which initiates progressive stages of inflammation as well as mesangial and endocapillary proliferative disease

Circulating nuclear remnants from excessive apoptotic breakdown bound to capillary glomerular sites binding to autoantibodies


Lupus Nephritis


Lupus Nephritis : Classification, ISN 2004Designation DescriptionClass I : Minimal Mesangial LGN Near-normal glomeruli dy LM; mesangial deposits are

present by IF and/or EMClass II : Mesangial Proliferative GN Mesangial Hypercellularity and matrix expansion, with

mesangial deposits by IF and EMClass III : Focal LGN < 50% of glomeruli display active or inactive

segmental (<50% of the tuft) or global (>50% of the tuft) endocapillary proliferation or sclerosis; predominantly mesangial and subendothelial deposits are present on IF and EM

Class IV : Diffuse LGN

Class IV-S : Segmental diffuse LGN Class IV-G : Global diffuse LGN

>50% of glomeruli have endocapillary or extracapillary glomerulonephritis; predominantly mesangial and subendothelial deposits are present on IF and EM; two subsets are defined>50% of affected glomeruli have segmental lessions

>50% of affected glomeruli have global lessionsClass V : Membranous LGN Capillary loop thickening in association with

predominantly subepithelial deposits by IF and EMClass VI : Advanced Sclerosis >90% of glomeruli are obsolescent, with substatial

activity in remaining glomeruli


Lupus nephritis

Lupus Nephritis : Treatment Remission criteria :

a reduction in proteinuria below 0.5 g/24 h or urine protein to creatinine ratio below 0.5 g/g absence of glomerular hematuria or red cell casts, and Normalization or at least stabilization of GFR.

Flare : isolated increase in proteinuria, typically at least doubling and

above 1 g/24 h, as a proteinuric flare; or appearance of glomerular hematuria or red cell casts with

proteinuria, with or without hypertension and a decline in GFR, as a nephritic flare

In general, patients assigned to ISN class I and class II need no therapy directed at the kidney

active proliferative LN into an induction phase and a maintenance phase


Lupus Nephritis : Treatment






Overt SN No hipertention No hematuria Normal renal function Normal complex imun

MCD

Nephrotic syndrome Hipotensi Associated with myeloma Hamotura (-) Renal function insuficiensi

Amyloidosis

Nephrotic syndrome Non selection

proteinuria Microhematuria Hypertension GFR ↓ Complement normal

FSGS

Heavy proteinuria Microhematuria Hypertension

(normal) Slowly GFR ↓ Tromboemboli

MGN

NS-Nephritic Hypertension Minimal or rapidly decreases of renal

function Low complement Hematuria

MPGN

Hematuria after URI Reccent of

proteinuria/microhematuria

Proteinuria (minimal to moderate neprotic range)

Hipotension Normal complement IgA

nephropathy

Acute onset of edema

Non nephrotic proteinuria

Hypertension GFR low Low complement Acute post

streptococal GN

Nephrotic rane Oliguria Rapid progressive loss of renal function Lack system respon (Anti GM

nonAb/coplement) Anti GBM

Steroid responsiveness MCD FSGS IgM Mesangial proliperatif

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Glomerulonefritis Dan Sindroma Nefrotik