nephrotic&nephritic syn csbrp
TRANSCRIPT
Nephrotic Nephrotic andand
Nephritic SyndromeNephritic SyndromeCSBR.Prasad, M.D.
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Some anatomySome anatomy
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Some anatomySome anatomy
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Fenestrated endotheliumFenestrated endothelium Glomerular BMGlomerular BM
Lamina rara externaLamina rara externa Lamina densaLamina densa Lamina rara internaLamina rara interna Type-IV collagen, laminin, Type-IV collagen, laminin,
proteoglycans, fibronectin, enactin and proteoglycans, fibronectin, enactin and other glycoproteinsother glycoproteins
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Kidney diseasesKidney diseases With respect to clinical features, With respect to clinical features,
pathogenesis, treatment and prognosis pathogenesis, treatment and prognosis they are distinct, by the component they are distinct, by the component affectedaffected
Four basic componentsFour basic components::1.1. GlomeruliGlomeruli2.2. TubulesTubules3.3. InterstitiumInterstitium4.4. Blood vesselsBlood vessels
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Kidney diseasesKidney diseases Four basic componentsFour basic components::
1.1. GlomeruliGlomeruli2.2. TubulesTubules3.3. InterstitiumInterstitium4.4. Blood vesselsBlood vessels
Because of their interdependence (anatomical & Because of their interdependence (anatomical & functional), in the course of time more than one functional), in the course of time more than one structure may be affectedstructure may be affected
NoteNote: whatever the origin, in chronic kidney : whatever the origin, in chronic kidney disease, all four components are destroyed–disease, all four components are destroyed–ESKDESKD
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Glomerular diseasesGlomerular diseases Glomerulonephritis: Glomerulonephritis: Presence of Presence of
InflammationInflammation Primary glomerular diseasePrimary glomerular disease
Kidney is the only predominant organ involved Kidney is the only predominant organ involved in disease processin disease process
Secondary glomerular diseaseSecondary glomerular disease Systemic disease affecting the glomerulusSystemic disease affecting the glomerulus
Glomerulopathy: Glomerulopathy: No inflammationNo inflammation
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Glomerular diseasesGlomerular diseases
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CLINICAL CLINICAL MANIFESTATIONSMANIFESTATIONS
ACUTE NEPHRITIC SYNDROMEACUTE NEPHRITIC SYNDROME RAPIDLY PROGRESSIVE RAPIDLY PROGRESSIVE
GLOMERULONEPHRITISGLOMERULONEPHRITIS NEPHROTIC SYNDROMENEPHROTIC SYNDROME CHRONIC RENAL FAILURECHRONIC RENAL FAILURE ASYMPTOMATIC HEMATURIA or ASYMPTOMATIC HEMATURIA or
PROTEINURIAPROTEINURIA
PATHOLOGIC PATHOLOGIC MANIFESTATIONSMANIFESTATIONS
CELLULAR PROLIFERATIONCELLULAR PROLIFERATION MesangialMesangial EndothelialEndothelial
LEUKOCYTE INFILTRATIONLEUKOCYTE INFILTRATION CRESCENTS (RAPIDLY progressive)CRESCENTS (RAPIDLY progressive) BASEMENT MEMBRANE THICKENINGBASEMENT MEMBRANE THICKENING HYALINIZATIONHYALINIZATION SCLEROSISSCLEROSIS
PATHOGENESISPATHOGENESIS Antibodies against Antibodies against GBMGBM Antibodies against Antibodies against “planted” antigens“planted” antigens Trapping of Trapping of Ag-Ab complexesAg-Ab complexes Antibodies against Antibodies against glomerular cellsglomerular cells, ,
e.g., mesangial cells, podocytes, etc.e.g., mesangial cells, podocytes, etc. Cell mediated immunity, i.e., sensitized Cell mediated immunity, i.e., sensitized
T-cellsT-cells as in TB as in TB
MEDIATORSMEDIATORS NEUTROPHILS, MONOCYTESNEUTROPHILS, MONOCYTES MACROPHAGES, T-CELLS, NK CELLSMACROPHAGES, T-CELLS, NK CELLS PLATELETSPLATELETS MESANGIAL CELLSMESANGIAL CELLS
SOLUBLESOLUBLE: CYTOKINES, CHEMOKINES, : CYTOKINES, CHEMOKINES, COAGULATION FACTORSCOAGULATION FACTORS
ACUTEACUTE GLOMERULONEPHRITISGLOMERULONEPHRITISSome termsSome terms::Diffuse / FocalDiffuse / FocalGlobal / SegmentalGlobal / Segmental
ACUTE ACUTE GLOMERULONEPHRITISGLOMERULONEPHRITIS
Hematuria, Azotemia, Oliguria, in children Hematuria, Azotemia, Oliguria, in children following a Strep infectionfollowing a Strep infection
POSTSTREPTOCOCCAL (old term)POSTSTREPTOCOCCAL (old term) HYPERCELLULAR GLOMERULIHYPERCELLULAR GLOMERULI INCREASED ENDOTHELIUM AND INCREASED ENDOTHELIUM AND
MESANGIUMMESANGIUM IgG, IgM, (not IgA), C3 along GMB FOCALLYIgG, IgM, (not IgA), C3 along GMB FOCALLY 95% full recovery95% full recovery
““RAPIDLY PROGRESSIVE” RAPIDLY PROGRESSIVE” GLOMERULONEPHRITISGLOMERULONEPHRITIS
Clinical definition, NOT a Clinical definition, NOT a specific pathologic onespecific pathologic one
““CRESCENTICCRESCENTIC”” Anti-GBM AbAnti-GBM Ab IMMUN CPLXIMMUN CPLX Anti-Neut. AbAnti-Neut. Ab
NEPHROTIC SYNDROMENEPHROTIC SYNDROMEMASSIVE PROTEINURIAMASSIVE PROTEINURIAHYPOALBUMINEMIAHYPOALBUMINEMIAEDEMAEDEMALIPIDEMIA/LIPIDURIALIPIDEMIA/LIPIDURIANUMEROUS CAUSES:NUMEROUS CAUSES:
MEMBRANOUS, MINIMAL CHANGE, FOCAL MEMBRANOUS, MINIMAL CHANGE, FOCAL SEGMTL.SEGMTL.
DIABETES, AMYLOID, SLE, DRUGSDIABETES, AMYLOID, SLE, DRUGS
MEMBRANOUS MEMBRANOUS GLOMERULONEPHRITISGLOMERULONEPHRITIS
Drugs, Tumors, SLE, InfectionsDrugs, Tumors, SLE, Infections Deposition of Ag-Ab complexesDeposition of Ag-Ab complexes Indolent, but >60% persistent proteinuriaIndolent, but >60% persistent proteinuria 15% go on to nephrotic syndrome15% go on to nephrotic syndrome
MINIMAL CHANGE GLOM.MINIMAL CHANGE GLOM.(LIPOID NEPHROSIS)(LIPOID NEPHROSIS)
MOST COMMON CAUSE of MOST COMMON CAUSE of NEPHROTIC SYNDROME in CHILDRENNEPHROTIC SYNDROME in CHILDREN
EFFACEMENT of FOOT PROCESSESEFFACEMENT of FOOT PROCESSES
FOCAL SEGMENTAL GLOMERULO-SCLEROSIS
Just like its nameJust like its name FocalFocal SegmentalSegmental Glomerulo-SCLEROSIS (NOT Glomerulo-SCLEROSIS (NOT
–itis)–itis) HIV, Heroine, Sickle Cell, HIV, Heroine, Sickle Cell,
ObesityObesity Most common cause of Most common cause of
ADULT nephrotic ADULT nephrotic syndromesyndrome
MEMBRANOPROLIFERATIVEMEMBRANOPROLIFERATIVEGLOMERULONEPHRITISGLOMERULONEPHRITIS
MPGN can be idiopathic or MPGN can be idiopathic or 22º to chronic immune º to chronic immune diseases Hep-C, alpha-1-diseases Hep-C, alpha-1-antitrypsin, HIV, antitrypsin, HIV, MalignanciesMalignancies
GBM alterations, subendo.GBM alterations, subendo. Leukocyte infiltrationsLeukocyte infiltrations Predominant MESANGIAL Predominant MESANGIAL
involvementinvolvement
IgA NEPHROPATHYIgA NEPHROPATHY(BERGER DISEASE)(BERGER DISEASE)
Mild hematuriaMild hematuria Mild proteinuriaMild proteinuria IgA deposits in mesangiumIgA deposits in mesangium
HEREDITARY HEMATURIA HEREDITARY HEMATURIA SYNDROMESSYNDROMES
ALPORT SYNDROMEALPORT SYNDROME Progressive Renal FailureProgressive Renal Failure Nerve DeafnessNerve Deafness VARIOUS eye disorderVARIOUS eye disorder DEFECTIVE COLLAGEN TYPE IVDEFECTIVE COLLAGEN TYPE IV
THIN GBMTHIN GBM (Glomerular Basement (Glomerular Basement Membrane) Disease, i.e., about HALF Membrane) Disease, i.e., about HALF as uniformly thin as it should beas uniformly thin as it should be
CHRONICCHRONICGLOMERULONEPHRITISGLOMERULONEPHRITIS
Can result from just about ANY Can result from just about ANY of the previously described of the previously described acute onesacute ones THIN CORTEXTHIN CORTEX HYALINIZED (fibrotic) HYALINIZED (fibrotic)
GLOMERULIGLOMERULI OFTEN SEEN IN DIALYSIS OFTEN SEEN IN DIALYSIS
PATIENTSPATIENTS
SECONDARYSECONDARYGLUMERULONEPHROPATHIESGLUMERULONEPHROPATHIES
SLESLE Henoch-Schonlein Purpura (IgA-NEPH)Henoch-Schonlein Purpura (IgA-NEPH) BACTERIAL ENDOCARDITISBACTERIAL ENDOCARDITIS DIABETESDIABETES ((Nodular Glomerulosclerosis or K-W Nodular Glomerulosclerosis or K-W
KidneyKidney)) AMYLOIDOSISAMYLOIDOSIS GOODPASTUREGOODPASTURE WEGENERWEGENER MYELOMAMYELOMA
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CaseCase A 65 year old man presents with several A 65 year old man presents with several
months of lower extremity edemamonths of lower extremity edema Past history is unremarkable. Not on Past history is unremarkable. Not on
any medicationany medication Recent symptoms: Fatigue and some Recent symptoms: Fatigue and some
weight loss. Appetite remains good.weight loss. Appetite remains good. BP is 150/100 mm Hg, pulse 92, BP is 150/100 mm Hg, pulse 92,
periorbital plaques, edema and guaiac +periorbital plaques, edema and guaiac +
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CaseCase Lab: Cr 1.4 mg/dL, Hg 8 g/dL, MCV Lab: Cr 1.4 mg/dL, Hg 8 g/dL, MCV
70, cholesterol 450 mg/dL, albumin 70, cholesterol 450 mg/dL, albumin 2.0 g/dL UA: 4+ protein, no blood and 2.0 g/dL UA: 4+ protein, no blood and bland sediment. bland sediment.
24 hour urine: 6 g protein24 hour urine: 6 g protein Ultrasound shows 11 cm kidneys Ultrasound shows 11 cm kidneys
bilaterally with increased echogenicitybilaterally with increased echogenicity
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CaseCase The most likely cause of his The most likely cause of his
nephrotic syndrome is?nephrotic syndrome is? Hypertensive nephrosclerosisHypertensive nephrosclerosis Diabetic nephropathyDiabetic nephropathy Focal segmental glomerulosclerosisFocal segmental glomerulosclerosis Membranous nephropathyMembranous nephropathy Membranoproliferative Membranoproliferative
glomerulonephritisglomerulonephritisCSBRP-May-2014CSBRP-May-2014 3333
Nephrotic SyndromeNephrotic Syndrome Proteinuria > 3.5 g/day/1.73 mProteinuria > 3.5 g/day/1.73 m22 Hypoalbuminemia < 3.5 g/dLHypoalbuminemia < 3.5 g/dL EdemaEdema HyperlipidemiaHyperlipidemia Lipiduria Lipiduria
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Nephrotic SyndromeNephrotic Syndrome Causes of primary idiopathic NSCauses of primary idiopathic NS
Minimal change diseaseMinimal change disease Membranous nephropathyMembranous nephropathy Focal segmental glomerulosclerosisFocal segmental glomerulosclerosis Membranoproliferative Membranoproliferative
glomerulonephritis (overlap)glomerulonephritis (overlap)
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Nephrotic SyndromeNephrotic Syndrome Causes of secondary NSCauses of secondary NS
Minimal change diseaseMinimal change disease Membranous nephropathyMembranous nephropathy Focal segmental glomerulosclerosisFocal segmental glomerulosclerosis Membranoproliferative glomerulonephritisMembranoproliferative glomerulonephritis Diabetic nephropathy (unique pathology)Diabetic nephropathy (unique pathology) Amyloid (unique pathology)Amyloid (unique pathology) Light change deposition disease (unique Light change deposition disease (unique
pathology)pathology)
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Minimal Change DiseaseMinimal Change Disease Most cases primary/idiopathicMost cases primary/idiopathic Secondary causesSecondary causes
Nonsteroidal anti-inflammatory agentsNonsteroidal anti-inflammatory agents Malignancies (hematologic)Malignancies (hematologic)
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Focal Segmental Focal Segmental GlomerulosclerosisGlomerulosclerosis
Secondary causesSecondary causes Healing of previous glomerular injuryHealing of previous glomerular injury Massive obesityMassive obesity ? OSA? OSA Sickle cell anemia Sickle cell anemia HIV (other viruses)HIV (other viruses) Pamidronate Pamidronate Heroin abuseHeroin abuse
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Membranous NephropathyMembranous Nephropathy Secondary causesSecondary causes
Malignancy, primarily solid tumorsMalignancy, primarily solid tumors Class V lupus nephritisClass V lupus nephritis Rheumatoid arthritisRheumatoid arthritis Hepatitis B and CHepatitis B and C Drugs (penicillamine, gold, NSAID’s, Drugs (penicillamine, gold, NSAID’s,
captopril)captopril) Syphilis Syphilis
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CaseCase The most likely cause of his The most likely cause of his
nephrotic syndrome is?nephrotic syndrome is? Hypertensive nephrosclerosisHypertensive nephrosclerosis Diabetic nephropathyDiabetic nephropathy Focal segmental glomerulosclerosisFocal segmental glomerulosclerosis Membranous nephropathyMembranous nephropathy Membranoproliferative Membranoproliferative
glomerulonephritisglomerulonephritisCSBRP-May-2014CSBRP-May-2014 4141
CaseCase A 33 year old male presents with A 33 year old male presents with
right flank pain and gross hematuria right flank pain and gross hematuria Past history: 3-4 episodes of Past history: 3-4 episodes of
hematuria per year, 6 hematuria per year, 6 hospitalizations for pain control, hospitalizations for pain control, multiple evaluations with no multiple evaluations with no diagnosisdiagnosis
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CaseCase Exam: BP 140/95 mm Hg, pulse 78, Exam: BP 140/95 mm Hg, pulse 78,
chest, abdomen, extremities are chest, abdomen, extremities are normal. He has no rash or arthritisnormal. He has no rash or arthritis
Lab: Cr 1.1 mg/dL, Hg 14 g/dl, UA Lab: Cr 1.1 mg/dL, Hg 14 g/dl, UA shows numerous RBC’s, no casts. 24 shows numerous RBC’s, no casts. 24 hr urine protein is 1.5 g. Ultrasound hr urine protein is 1.5 g. Ultrasound is normalis normal
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CaseCase What is his diagnosis?What is his diagnosis?
Lupus nephritisLupus nephritis IgA NephropathyIgA Nephropathy Membranous nephropathyMembranous nephropathy Membranoproliferative Membranoproliferative
glomerulonephritis from hepatitis Cglomerulonephritis from hepatitis C NephrolithiasisNephrolithiasis
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Glomerular DiseaseGlomerular Disease Accounts for 51% of ESRD in the USAccounts for 51% of ESRD in the US
38% diabetic nephropathy38% diabetic nephropathy 13% nondiabetic glomerular disease13% nondiabetic glomerular disease
Definition of glomerulonephritisDefinition of glomerulonephritis Intraglomerular inflammationIntraglomerular inflammation Cellular proliferationCellular proliferation HematuriaHematuria Excludes nonproliferative disorders Excludes nonproliferative disorders
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GlomerulonephritisGlomerulonephritis Refers to that variety of kidney disease in Refers to that variety of kidney disease in
which proliferation and inflammation of which proliferation and inflammation of the glomerulus is secondary to an the glomerulus is secondary to an immunologic mechanismimmunologic mechanism
Presentation of GN varies fromPresentation of GN varies from:: Microscopic asymptomatic hematuria or Microscopic asymptomatic hematuria or
proteinuria proteinuria Acute nephritisAcute nephritis Rapidly progressive nephritisRapidly progressive nephritis
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Nephritic SyndromeNephritic Syndrome Hematuria – dysmorphic red blood Hematuria – dysmorphic red blood
cells, red blood cell castscells, red blood cell casts AzotemiaAzotemia OliguriaOliguria HypertensionHypertension Variable proteinuria (usually < 3 Variable proteinuria (usually < 3
g/day)g/day)CSBRP-May-2014CSBRP-May-2014 5151
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Focal Proliferative Focal Proliferative GlomerulonephritisGlomerulonephritis
IgA nephropathyIgA nephropathy Henoch-Schonlein purpuraHenoch-Schonlein purpura Lupus nephritis (class II and III)Lupus nephritis (class II and III) Heriditary nephritis (Alport’s)Heriditary nephritis (Alport’s)
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Diffuse Proliferative Diffuse Proliferative GlomerulonephritisGlomerulonephritis
Poststreptococcal glomerulonephritisPoststreptococcal glomerulonephritis Bacterial endocarditisBacterial endocarditis Lupus nephritis (Class IV)Lupus nephritis (Class IV) Membranoproliferative Membranoproliferative
glomerulonephritisglomerulonephritis Crescentic glomerulonephritisCrescentic glomerulonephritis VasculitisVasculitis
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IgA NephropathyIgA Nephropathy Common cause of glomerulonephritisCommon cause of glomerulonephritis Mesangioproliferative Mesangioproliferative
glomerulonephritisglomerulonephritis Asians and CaucasiansAsians and Caucasians Rare in African-Americans Rare in African-Americans Age 20-30Age 20-30 Males > FemalesMales > Females Pathogenesis – altered regulation of IgAPathogenesis – altered regulation of IgA
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IgA NephropathyIgA Nephropathy Clinical presentationClinical presentation
50-60% episodic gross hematuria (synpharyngitic) 50-60% episodic gross hematuria (synpharyngitic) 30-40% persistent microscopic hematuria30-40% persistent microscopic hematuria <5% acute glomerulonephritis<5% acute glomerulonephritis ESRD 20-40% at 5-25 yearsESRD 20-40% at 5-25 years
Treatment – no cureTreatment – no cure N-3 fatty acids (fish oil)N-3 fatty acids (fish oil) Corticosteroids Corticosteroids ACE inhibitors/ARB’sACE inhibitors/ARB’s
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Henoch-SchHenoch-Schoonlein Purpuranlein Purpura ““Systemic” IgA nephropathySystemic” IgA nephropathy
ArthralgiasArthralgias PurpuraPurpura Abdominal painAbdominal pain Gastrointestinal bleedingGastrointestinal bleeding Hematuria Hematuria
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Poststreptococcal Poststreptococcal GlomerulonephritisGlomerulonephritis
Clinical presentationClinical presentation Children 2-10 yearsChildren 2-10 years Uncommon over age 40 (< 10%)Uncommon over age 40 (< 10%) Symptoms develop 7 days to 12 weeks after Symptoms develop 7 days to 12 weeks after
the infectionthe infection Low complement levels (CLow complement levels (C33 and CH50) and CH50) Spontaneous recovery is the ruleSpontaneous recovery is the rule Hematuria can persist 6 monthsHematuria can persist 6 months Proteinuria, mild can persist yearsProteinuria, mild can persist years
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Poststreptococcal Poststreptococcal GlomerulonephritisGlomerulonephritis
PathogenesisPathogenesis Nephritogenic strains of streptococciNephritogenic strains of streptococci Planted antigenPlanted antigen
Nephritis associated plasmin receptor (GAPDH)Nephritis associated plasmin receptor (GAPDH) Zymogen (cationic protein-subepithelial deposits)Zymogen (cationic protein-subepithelial deposits)
Host immune response (ab/ag)Host immune response (ab/ag) Alternative pathway of complement activationAlternative pathway of complement activation IgG and CIgG and C33 found in glomeruli found in glomeruli
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CaseCase A 47 year old man presented with 3 weeks A 47 year old man presented with 3 weeks
of malaise, anorexia, weight loss, cough of malaise, anorexia, weight loss, cough and dark urineand dark urine
Past history: mild asthma, nonsmokerPast history: mild asthma, nonsmoker Exam: BP 145/70, lungs with diffuse Exam: BP 145/70, lungs with diffuse
rhonchi, heart, abdomen normal, no rash, rhonchi, heart, abdomen normal, no rash, 2+ edema2+ edema
Lab: Cr 6.3 mg/dL, UA 3+ blood and Lab: Cr 6.3 mg/dL, UA 3+ blood and protein, dysmorphic rbc’sprotein, dysmorphic rbc’s
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CaseCase What is his diagnosis?What is his diagnosis?
Lupus nephritisLupus nephritis IgA nephropathyIgA nephropathy Poststreptococcal glomerulonephritisPoststreptococcal glomerulonephritis Anti-GBM diseaseAnti-GBM disease Focal segmental glomerulosclerosisFocal segmental glomerulosclerosis
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Rapidly Progressive Rapidly Progressive GlomerulonephritisGlomerulonephritis
Clinical syndromeClinical syndrome Glomerulonephritis (nephritic syndrome)Glomerulonephritis (nephritic syndrome) Rapid decline in renal functionRapid decline in renal function Rare – 2-4% of all glomerulonephritisRare – 2-4% of all glomerulonephritis Pathologic hallmark – crescentsPathologic hallmark – crescents Classified based on presence or absence Classified based on presence or absence
of immune complexesof immune complexes
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Rapidly Progressive Rapidly Progressive GlomerulonephritisGlomerulonephritis
Immune complex mediated:Immune complex mediated: Henoch-Schonlein purpuraHenoch-Schonlein purpura Cryoglobulinemia (often associated with Cryoglobulinemia (often associated with
hepatitis C)hepatitis C) Lupus nephritisLupus nephritis Acute postinfectious glomerulonephritisAcute postinfectious glomerulonephritis Bacterial endocarditisBacterial endocarditis
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Rapidly Progressive Rapidly Progressive GlomerulonephritisGlomerulonephritis
Direct antibody attack mediatedDirect antibody attack mediated Anti-GBM disease/Goodpasture’s Anti-GBM disease/Goodpasture’s
syndromesyndrome Pauci-immune (ANCA associated)Pauci-immune (ANCA associated)
Wegener’s granulomatosisWegener’s granulomatosis Microscopic polyarteritisMicroscopic polyarteritis
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Anti-GBM DiseaseAnti-GBM Disease Clinical presentation:Clinical presentation:
Bimodal age distribution (3Bimodal age distribution (3rdrd and 6 and 6thth decades)decades)
60-70% present with pulmonary hemorrhage60-70% present with pulmonary hemorrhage Systemic symptoms - malaise, fatigue, Systemic symptoms - malaise, fatigue,
anorexia, weight loss, arthralgias, myalgiasanorexia, weight loss, arthralgias, myalgias CaucasiansCaucasians Rare in African-AmericansRare in African-Americans
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Anti-GBM DiseaseAnti-GBM Disease PathogenesisPathogenesis
Antibodies develop against Antibodies develop against 3 chain 3 chain type IV collagen in GBMtype IV collagen in GBM
Linear deposition of IgG along GBMLinear deposition of IgG along GBM Antibodies detected by ELISAAntibodies detected by ELISA ANCA found in ~30% of patientsANCA found in ~30% of patients
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Anti-GBM DiseaseAnti-GBM Disease Outcome poor without therapyOutcome poor without therapy TreatmentTreatment
Corticosteroids alone insufficientCorticosteroids alone insufficient CyclophosphamideCyclophosphamide Plasma exchange with albumin 14 daysPlasma exchange with albumin 14 days
Renal recovery rare if patients Renal recovery rare if patients present needing dialysispresent needing dialysis
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CaseCase 24 year old female presents with 24 year old female presents with
hypertension and edema. Two weeks hypertension and edema. Two weeks prior she developed a cough, chest prior she developed a cough, chest pain, nasal congestion and pain in her pain, nasal congestion and pain in her right ear and received a course of right ear and received a course of amoxicillin. One week prior she noted amoxicillin. One week prior she noted a rash on her face and chest and a rash on her face and chest and complained of some pain in her hands. complained of some pain in her hands.
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CaseCase Past history: unremarkablePast history: unremarkable Exam: BP 180/126 mm Hg. She has Exam: BP 180/126 mm Hg. She has
periorbital edema, normal periorbital edema, normal oropharynx. Heart, lungs and oropharynx. Heart, lungs and abdomen are normal. She has lower abdomen are normal. She has lower extremity edema and an extremity edema and an erythematous maculopapular rash erythematous maculopapular rash over her chest.over her chest.
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CaseCase Lab:Lab:
Cr 1.6 mg/dLCr 1.6 mg/dL UA 3+ blood, 4+ protein, > 50 UA 3+ blood, 4+ protein, > 50
RBC’s/HPF, many dysmorphicRBC’s/HPF, many dysmorphic WBC 3.0, Hg 10, platelets 120WBC 3.0, Hg 10, platelets 120 Complements – CComplements – C33 low, C low, C44 low low
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CaseCase What is your diagnosis?What is your diagnosis?
Poststreptococcal glomerulonephritisPoststreptococcal glomerulonephritis IgA nephropathyIgA nephropathy Lupus nephritisLupus nephritis Membranous nephropathyMembranous nephropathy Wegener’s granulomatosisWegener’s granulomatosis
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Systemic Lupus Systemic Lupus ErythematosisErythematosis
Complex multisystem autoimmune Complex multisystem autoimmune diseasedisease
11 criteria – 4 present for diagnosis11 criteria – 4 present for diagnosis Kidney is most common organ involved Kidney is most common organ involved
(50-75%)(50-75%) Females > MalesFemales > Males African-Americans have higher rates of African-Americans have higher rates of
lupus nephritis and worse renal survivallupus nephritis and worse renal survivalCSBRP-May-2014CSBRP-May-2014 8282
Lupus NephritisLupus Nephritis Clinical spectrumClinical spectrum
Mild urinary abnormalitiesMild urinary abnormalities Acute and chronic kidney failureAcute and chronic kidney failure Usually develops within 3 yearsUsually develops within 3 years
Pathogenesis of renal involvementPathogenesis of renal involvement Histone-DNA complex – planted antigenHistone-DNA complex – planted antigen Anti-dsDNA antibodies eluted from nephritic Anti-dsDNA antibodies eluted from nephritic
kidneys kidneys WHO recognizes 6 classesWHO recognizes 6 classes
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Classification of Lupus Classification of Lupus NephritisNephritis
Class IClass I “normal”“normal” Class IIClass II variable mesangial hyper-variable mesangial hyper-
cellularity and immune depositscellularity and immune deposits Class IIIClass III focal proliferative focal proliferative
glomerulonephritisglomerulonephritis Class IVClass IV diffuse proliferative diffuse proliferative
glomerulonephritisglomerulonephritis Class VClass V membranous nephropathymembranous nephropathy Class VIClass VI chronic glomerulosclerosischronic glomerulosclerosis
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Lupus NephritisLupus Nephritis 10-20% mesangial or focal proliferative10-20% mesangial or focal proliferative 40-60% diffuse proliferative40-60% diffuse proliferative 10-20% membranous nephropathy10-20% membranous nephropathy TreatmentTreatment
CorticosteroidsCorticosteroids AzathioprineAzathioprine CyclophosphamideCyclophosphamide Mycophenolate Mycophenolate
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Evaluation of Evaluation of GlomerulonephritisGlomerulonephritis
History and examHistory and exam Urinalysis – blood, protein and Urinalysis – blood, protein and
dysmorphic rbc’s +/- rbc castsdysmorphic rbc’s +/- rbc casts Complements Complements Additional serology as dictated by Additional serology as dictated by
presentationpresentation
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Laboratory Tests - Laboratory Tests - ComplementsComplements
Low serum complement levelLow serum complement level Systemic diseasesSystemic diseases
SLE (75-90%)SLE (75-90%) Subacute bacterial endocarditis (90%)Subacute bacterial endocarditis (90%) Cryoglobulinemia (85%)Cryoglobulinemia (85%)
Renal diseasesRenal diseases Acute poststreptococcal glomerulonephritis Acute poststreptococcal glomerulonephritis
(90%)(90%) Membranoproliferative glomerulonephritis (90%)Membranoproliferative glomerulonephritis (90%)
CSBRP-May-2014CSBRP-May-2014 8989
Laboratory Tests - Laboratory Tests - ComplementsComplements
Normal serum complement levelNormal serum complement level Systemic diseasesSystemic diseases
VasculitisVasculitis Henoch-Schonlein purpuraHenoch-Schonlein purpura
Renal diseasesRenal diseases IgA nephropathyIgA nephropathy Idiopathic rapidly progressive glomerulonephritisIdiopathic rapidly progressive glomerulonephritis
Anti-GBM diseaseAnti-GBM disease IC diseaseIC disease
CSBRP-May-2014CSBRP-May-2014 9090
SummarySummary Glomerular disease is an important Glomerular disease is an important
cause of CKD and ESRD.cause of CKD and ESRD. Patients can present with a variety of Patients can present with a variety of
clinical syndromes.clinical syndromes. A good history, exam and certain lab A good history, exam and certain lab
tests in conjunction with renal biopsy tests in conjunction with renal biopsy can often lead to a diagnosis.can often lead to a diagnosis.
CSBRP-May-2014CSBRP-May-2014 9191