Nephrotic&nephritic syn csbrp

NephroticNephrotic
andand
Nephritic SyndromeNephritic Syndrome
CSBR.Prasad, M.D.
CSBRP-May-2014CSBRP-May-2014 11

Some anatomySome anatomy

Some anatomySome anatomy
 Fenestrated endotheliumFenestrated endothelium
 Glomerular BMGlomerular BM
 Lamina rara externaLamina rara externa
 Lamina densaLamina densa
 Lamina rara internaLamina rara interna
 Type-IV collagen, laminin, proteoglycans,Type-IV collagen, laminin, proteoglycans,
fibronectin, enactin and other glycoproteinsfibronectin, enactin and other glycoproteins

Kidney diseasesKidney diseases
 With respect to clinical features,With respect to clinical features,
pathogenesis, treatment and prognosispathogenesis, treatment and prognosis
they are distinct, by the componentthey are distinct, by the component
affectedaffected
 Four basic componentsFour basic components::
1.1. GlomeruliGlomeruli
2.2. TubulesTubules
3.3. InterstitiumInterstitium
4.4. Blood vesselsBlood vessels

Kidney diseasesKidney diseases
 Four basic componentsFour basic components::
1.1. GlomeruliGlomeruli
2.2. TubulesTubules
3.3. InterstitiumInterstitium
4.4. Blood vesselsBlood vessels
 Because of their interdependence (anatomical &Because of their interdependence (anatomical &
functional), in the course of time more than onefunctional), 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 CSBRP-May-2014CSBRP-May-2014 66

Glomerular diseasesGlomerular diseases
 Glomerulonephritis:Glomerulonephritis: Presence of InflammationPresence of Inflammation
 Primary glomerular diseasePrimary glomerular disease
 Kidney is the only predominant organ involved inKidney is the only predominant organ involved in
disease processdisease process
 Secondary glomerular diseaseSecondary glomerular disease
 Systemic disease affecting the glomerulusSystemic disease affecting the glomerulus
 Glomerulopathy:Glomerulopathy: No inflammationNo inflammation

Glomerular diseasesGlomerular diseases

CLINICALCLINICAL
MANIFESTATIONSMANIFESTATIONS
 ACUTE NEPHRITIC SYNDROMEACUTE NEPHRITIC SYNDROME
 RAPIDLY PROGRESSIVERAPIDLY PROGRESSIVE
GLOMERULONEPHRITISGLOMERULONEPHRITIS
 NEPHROTIC SYNDROMENEPHROTIC SYNDROME
 CHRONIC RENAL FAILURECHRONIC RENAL FAILURE
 ASYMPTOMATIC HEMATURIA orASYMPTOMATIC HEMATURIA or
PROTEINURIAPROTEINURIA

PATHOLOGICPATHOLOGIC
MANIFESTATIONSMANIFESTATIONS
 CELLULAR PROLIFERATIONCELLULAR PROLIFERATION
 MesangialMesangial
 EndothelialEndothelial
 LEUKOCYTE INFILTRATIONLEUKOCYTE INFILTRATION
 CRESCENTS (RAPIDLY progressive)CRESCENTS (RAPIDLY progressive)
 BASEMENT MEMBRANE THICKENINGBASEMENT MEMBRANE THICKENING
 HYALINIZATIONHYALINIZATION
 SCLEROSISSCLEROSIS

PATHOGENESISPATHOGENESIS
 Antibodies againstAntibodies against GBMGBM
 Antibodies againstAntibodies against “planted” antigens“planted” antigens
 Trapping ofTrapping of Ag-Ab complexesAg-Ab complexes
 Antibodies againstAntibodies against glomerular cellsglomerular cells, e.g.,, e.g.,
mesangial cells, podocytes, etc.mesangial cells, podocytes, etc.
 Cell mediated immunity, i.e., sensitizedCell mediated immunity, i.e., sensitized T-T-
cellscells as in TBas 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 GLOMERULONEPHRITISGLOMERULONEPHRITIS
Some termsSome terms::
Diffuse / FocalDiffuse / Focal
Global / SegmentalGlobal / Segmental

ACUTEACUTE
 Hematuria, Azotemia, Oliguria, in childrenHematuria, Azotemia, Oliguria, in children
following a Strep infectionfollowing a Strep infection
 POSTSTREPTOCOCCAL (old term)POSTSTREPTOCOCCAL (old term)
 HYPERCELLULAR GLOMERULIHYPERCELLULAR GLOMERULI
 INCREASED ENDOTHELIUM ANDINCREASED ENDOTHELIUM AND
MESANGIUMMESANGIUM
 IgG, IgM, (not IgA), C3 along GMBIgG, IgM, (not IgA), C3 along GMB
FOCALLYFOCALLY
 95% full recovery95% full recovery

““RAPIDLY PROGRESSIVE”RAPIDLY PROGRESSIVE”
 Clinical definition, NOT aClinical definition, NOT a
specific pathologic onespecific pathologic one
““CRESCENTICCRESCENTIC””
 Anti-GBM AbAnti-GBM Ab
 IMMUN CPLXIMMUN CPLX
 Anti-Neut. AbAnti-Neut. Ab

NEPHROTIC SYNDROMENEPHROTIC SYNDROME
 MASSIVE PROTEINURIAMASSIVE PROTEINURIA
 HYPOALBUMINEMIAHYPOALBUMINEMIA
 EDEMAEDEMA
 LIPIDEMIA/LIPIDURIALIPIDEMIA/LIPIDURIA
 NUMEROUS CAUSES:NUMEROUS CAUSES:
 MEMBRANOUS, MINIMAL CHANGE, FOCALMEMBRANOUS, MINIMAL CHANGE, FOCAL
SEGMTL.SEGMTL.
 DIABETES, AMYLOID, SLE, DRUGSDIABETES, AMYLOID, SLE, DRUGS

MEMBRANOUSMEMBRANOUS
 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 NEPHROTICMOST COMMON CAUSE of NEPHROTIC
SYNDROME in CHILDRENSYNDROME in CHILDREN
 EFFACEMENT of FOOT PROCESSESEFFACEMENT of FOOT PROCESSES

FOCAL SEGMENTAL
GLOMERULO-SCLEROSIS
 Just like its nameJust like its name
 FocalFocal
 SegmentalSegmental
 Glomerulo-SCLEROSIS (NOTGlomerulo-SCLEROSIS (NOT
–itis)–itis)
 HIV, Heroine, Sickle Cell,HIV, Heroine, Sickle Cell,
ObesityObesity
 Most common cause ofMost common cause of
ADULT nephrotic syndromeADULT nephrotic syndrome

MEMBRANOPROLIFERATIVEMEMBRANOPROLIFERATIVE
 MPGN can be idiopathic orMPGN can be idiopathic or
22º to chronic immuneº 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 MESANGIALPredominant MESANGIAL
involvementinvolvement

IgA NEPHROPATHYIgA NEPHROPATHY
(BERGER DISEASE)(BERGER DISEASE)
 Mild hematuriaMild hematuria
 Mild proteinuriaMild proteinuria
 IgA deposits in mesangiumIgA deposits in mesangium

HEREDITARY HEMATURIAHEREDITARY 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 asMembrane) Disease, i.e., about HALF as
uniformly thin as it should beuniformly thin as it should be

CHRONICCHRONIC
 Can result from just about ANY ofCan result from just about ANY of
the previously described acutethe previously described acute
onesones
 THIN CORTEXTHIN CORTEX
 HYALINIZED (fibrotic) GLOMERULIHYALINIZED (fibrotic) GLOMERULI
 OFTEN SEEN IN DIALYSISOFTEN SEEN IN DIALYSIS
PATIENTSPATIENTS

SECONDARYSECONDARY
GLUMERULONEPHROPATHIESGLUMERULONEPHROPATHIES
 SLESLE
 Henoch-Schonlein Purpura (IgA-NEPH)Henoch-Schonlein Purpura (IgA-NEPH)
 BACTERIAL ENDOCARDITISBACTERIAL ENDOCARDITIS
 DIABETESDIABETES ((Nodular Glomerulosclerosis or K-WNodular Glomerulosclerosis or K-W
KidneyKidney))
 AMYLOIDOSISAMYLOIDOSIS
 GOODPASTUREGOODPASTURE
 WEGENERWEGENER
 MYELOMAMYELOMA

CaseCase
 A 65 year old man presents with severalA 65 year old man presents with several
months of lower extremity edemamonths of lower extremity edema
 Past history is unremarkable. Not on anyPast history is unremarkable. Not on any
medicationmedication
 Recent symptoms: Fatigue and someRecent 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 +

CaseCase
 Lab: Cr 1.4 mg/dL, Hg 8 g/dL, MCV 70,Lab: Cr 1.4 mg/dL, Hg 8 g/dL, MCV 70,
cholesterol 450 mg/dL, albumin 2.0 g/dLcholesterol 450 mg/dL, albumin 2.0 g/dL
UA: 4+ protein, no blood and blandUA: 4+ protein, no blood and bland
sediment.sediment.
 24 hour urine: 6 g protein24 hour urine: 6 g protein
 Ultrasound shows 11 cm kidneysUltrasound shows 11 cm kidneys
bilaterally with increased echogenicitybilaterally with increased echogenicity

CaseCase
 The most likely cause of his nephroticThe most likely cause of his nephrotic
syndrome is?syndrome is?
 Hypertensive nephrosclerosisHypertensive nephrosclerosis
 Diabetic nephropathyDiabetic nephropathy
 Focal segmental glomerulosclerosisFocal segmental glomerulosclerosis
 Membranous nephropathyMembranous nephropathy
 Membranoproliferative glomerulonephritisMembranoproliferative glomerulonephritis

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
 LipiduriaLipiduria

 Causes of primary idiopathic NSCauses of primary idiopathic NS
 Minimal change diseaseMinimal change disease
(overlap)(overlap)

 Causes of secondary NSCauses of secondary NS
 Minimal change diseaseMinimal change disease
 Diabetic nephropathy (unique pathology)Diabetic nephropathy (unique pathology)
 Amyloid (unique pathology)Amyloid (unique pathology)
 Light change deposition disease (uniqueLight change deposition disease (unique
pathology)pathology)

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)

Focal SegmentalFocal Segmental
GlomerulosclerosisGlomerulosclerosis
 Healing of previous glomerular injuryHealing of previous glomerular injury
 Massive obesityMassive obesity
 ? OSA? OSA
 Sickle cell anemiaSickle cell anemia
 HIV (other viruses)HIV (other viruses)
 PamidronatePamidronate
 Heroin abuseHeroin abuse

Membranous NephropathyMembranous Nephropathy
 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, captopril)Drugs (penicillamine, gold, NSAID’s, captopril)
 SyphilisSyphilis

CaseCase
 The most likely cause of his nephroticThe most likely cause of his nephrotic
syndrome is?syndrome is?
 Hypertensive nephrosclerosisHypertensive nephrosclerosis
 Diabetic nephropathyDiabetic nephropathy

CaseCase
 A 33 year old male presents with rightA 33 year old male presents with right
flank pain and gross hematuriaflank pain and gross hematuria
 Past history: 3-4 episodes of hematuriaPast history: 3-4 episodes of hematuria
per year, 6 hospitalizations for painper year, 6 hospitalizations for pain
control, multiple evaluations with nocontrol, multiple evaluations with no
diagnosisdiagnosis

CaseCase
 Exam: BP 140/95 mm Hg, pulse 78,Exam: BP 140/95 mm Hg, pulse 78,
chest, abdomen, extremities are normal.chest, abdomen, extremities are normal.
He has no rash or arthritisHe has no rash or arthritis
 Lab: Cr 1.1 mg/dL, Hg 14 g/dl, UA showsLab: Cr 1.1 mg/dL, Hg 14 g/dl, UA shows
numerous RBC’s, no casts. 24 hr urinenumerous RBC’s, no casts. 24 hr urine
protein is 1.5 g. Ultrasound is normalprotein is 1.5 g. Ultrasound is normal

CaseCase
 What is his diagnosis?What is his diagnosis?
 Lupus nephritisLupus nephritis
 IgA NephropathyIgA Nephropathy
from hepatitis Cfrom hepatitis C
 NephrolithiasisNephrolithiasis

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 disordersExcludes nonproliferative disorders

GlomerulonephritisGlomerulonephritis
 Refers to that variety of kidney disease inRefers to that variety of kidney disease in
which proliferation and inflammation of thewhich proliferation and inflammation of the
glomerulus is secondary to anglomerulus is secondary to an
immunologic mechanismimmunologic mechanism
 Presentation of GN varies fromPresentation of GN varies from::
 Microscopic asymptomatic hematuria orMicroscopic asymptomatic hematuria or
proteinuriaproteinuria
 Acute nephritisAcute nephritis
 Rapidly progressive nephritisRapidly progressive nephritis

Nephritic SyndromeNephritic Syndrome
 Hematuria – dysmorphic red blood cells,Hematuria – dysmorphic red blood cells,
red blood cell castsred blood cell casts
 AzotemiaAzotemia
 OliguriaOliguria
 HypertensionHypertension
 Variable proteinuria (usually < 3 g/day)Variable proteinuria (usually < 3 g/day)

Focal Proliferative GlomerulonephritisFocal Proliferative Glomerulonephritis
 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)

Diffuse Proliferative GlomerulonephritisDiffuse Proliferative Glomerulonephritis
 Poststreptococcal glomerulonephritisPoststreptococcal glomerulonephritis
 Bacterial endocarditisBacterial endocarditis
 Lupus nephritis (Class IV)Lupus nephritis (Class IV)
 Crescentic glomerulonephritisCrescentic glomerulonephritis
 VasculitisVasculitis

IgA NephropathyIgA Nephropathy
 Common cause of glomerulonephritisCommon cause of glomerulonephritis
 Mesangioproliferative glomerulonephritisMesangioproliferative glomerulonephritis
 Asians and CaucasiansAsians and Caucasians
 Rare in African-AmericansRare in African-Americans
 Age 20-30Age 20-30
 Males > FemalesMales > Females
 Pathogenesis – altered regulation of IgAPathogenesis – altered regulation of IgA

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)
 CorticosteroidsCorticosteroids
 ACE inhibitors/ARB’sACE inhibitors/ARB’s

Henoch-SchHenoch-Schoonlein Purpuranlein Purpura
 ““Systemic” IgA nephropathySystemic” IgA nephropathy
 ArthralgiasArthralgias
 PurpuraPurpura
 Abdominal painAbdominal pain
 Gastrointestinal bleedingGastrointestinal bleeding
 HematuriaHematuria

Poststreptococcal GlomerulonephritisPoststreptococcal Glomerulonephritis
 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 theSymptoms develop 7 days to 12 weeks after the
infectioninfection
 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

Poststreptococcal GlomerulonephritisPoststreptococcal Glomerulonephritis
 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 glomerulifound in glomeruli

CaseCase
 A 47 year old man presented with 3 weeks ofA 47 year old man presented with 3 weeks of
malaise, anorexia, weight loss, cough and darkmalaise, anorexia, weight loss, cough and dark
urineurine
 Past history: mild asthma, nonsmokerPast history: mild asthma, nonsmoker
 Exam: BP 145/70, lungs with diffuse rhonchi,Exam: BP 145/70, lungs with diffuse rhonchi,
heart, abdomen normal, no rash, 2+ edemaheart, abdomen normal, no rash, 2+ edema
 Lab: Cr 6.3 mg/dL, UA 3+ blood and protein,Lab: Cr 6.3 mg/dL, UA 3+ blood and protein,
dysmorphic rbc’sdysmorphic rbc’s

CaseCase
 What is his diagnosis?What is his diagnosis?
 Anti-GBM diseaseAnti-GBM disease

Rapidly Progressive GlomerulonephritisRapidly Progressive Glomerulonephritis
 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 ofClassified based on presence or absence of
immune complexesimmune complexes

 Immune complex mediated:Immune complex mediated:
 Cryoglobulinemia (often associated withCryoglobulinemia (often associated with
hepatitis C)hepatitis C)
 Acute postinfectious glomerulonephritisAcute postinfectious glomerulonephritis
 Bacterial endocarditisBacterial endocarditis

 Direct antibody attack mediatedDirect antibody attack mediated
 Anti-GBM disease/Goodpasture’s syndromeAnti-GBM disease/Goodpasture’s syndrome
 Pauci-immune (ANCA associated)Pauci-immune (ANCA associated)
 Wegener’s granulomatosisWegener’s granulomatosis
 Microscopic polyarteritisMicroscopic polyarteritis

Anti-GBM DiseaseAnti-GBM Disease
 Clinical presentation:Clinical presentation:
 Bimodal age distribution (3Bimodal age distribution (3rdrd
and 6and 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

 PathogenesisPathogenesis
 Antibodies develop againstAntibodies develop against αα3 chain type IV3 chain type IV
collagen in GBMcollagen 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

 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 presentRenal recovery rare if patients present
needing dialysisneeding dialysis

CaseCase
 24 year old female presents with24 year old female presents with
hypertension and edema. Two weekshypertension and edema. Two weeks
prior she developed a cough, chest pain,prior she developed a cough, chest pain,
nasal congestion and pain in her right earnasal congestion and pain in her right ear
and received a course of amoxicillin. Oneand received a course of amoxicillin. One
week prior she noted a rash on her faceweek prior she noted a rash on her face
and chest and complained of some pain inand chest and complained of some pain in
her hands.her hands.

CaseCase
 Past history: unremarkablePast history: unremarkable
 Exam: BP 180/126 mm Hg. She hasExam: BP 180/126 mm Hg. She has
periorbital edema, normal oropharynx.periorbital edema, normal oropharynx.
Heart, lungs and abdomen are normal.Heart, lungs and abdomen are normal.
She has lower extremity edema and anShe has lower extremity edema and an
erythematous maculopapular rash overerythematous maculopapular rash over
her chest.her chest.

CaseCase
 Lab:Lab:
 Cr 1.6 mg/dLCr 1.6 mg/dL
 UA 3+ blood, 4+ protein, > 50UA 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, Clow, C44 lowlow

CaseCase
 What is your diagnosis?What is your diagnosis?
 Wegener’s granulomatosisWegener’s granulomatosis

Systemic Lupus ErythematosisSystemic Lupus Erythematosis
 Complex multisystem autoimmuneComplex multisystem autoimmune
diseasedisease
 11 criteria – 4 present for diagnosis11 criteria – 4 present for diagnosis
 Kidney is most common organ involvedKidney is most common organ involved
(50-75%)(50-75%)
 Females > MalesFemales > Males
 African-Americans have higher rates ofAfrican-Americans have higher rates of
lupus nephritis and worse renal survivallupus nephritis and worse renal survival

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 kidneysAnti-dsDNA antibodies eluted from nephritic kidneys
 WHO recognizes 6 classesWHO recognizes 6 classes

Classification of Lupus NephritisClassification of Lupus Nephritis
 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 proliferativefocal proliferative
glomerulonephritisglomerulonephritis
 Class IVClass IV diffuse proliferativediffuse proliferative
glomerulonephritisglomerulonephritis
 Class VClass V membranous nephropathymembranous nephropathy
 Class VIClass VI chronic glomerulosclerosischronic glomerulosclerosis

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
 MycophenolateMycophenolate

Evaluation ofEvaluation of
GlomerulonephritisGlomerulonephritis
 History and examHistory and exam
 Urinalysis – blood, protein and dysmorphicUrinalysis – blood, protein and dysmorphic
rbc’s +/- rbc castsrbc’s +/- rbc casts
 ComplementsComplements
 Additional serology as dictated byAdditional serology as dictated by
presentationpresentation

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 (90%)Acute poststreptococcal glomerulonephritis (90%)
 Membranoproliferative glomerulonephritis (90%)Membranoproliferative glomerulonephritis (90%)

Laboratory Tests -Laboratory Tests -
ComplementsComplements
 Normal serum complement levelNormal serum complement level
 Systemic diseasesSystemic diseases
 VasculitisVasculitis
 Renal diseasesRenal diseases
 Idiopathic rapidly progressive glomerulonephritisIdiopathic rapidly progressive glomerulonephritis
 Anti-GBM diseaseAnti-GBM disease
 IC diseaseIC disease

SummarySummary
 Glomerular disease is an important causeGlomerular disease is an important cause
of CKD and ESRD.of CKD and ESRD.
 Patients can present with a variety ofPatients can present with a variety of
clinical syndromes.clinical syndromes.
 A good history, exam and certain lab testsA good history, exam and certain lab tests
in conjunction with renal biopsy can oftenin conjunction with renal biopsy can often
lead to a diagnosis.lead to a diagnosis.

Nephrotic&nephritic syn csbrp

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