nephrotic&nephritic syn csbrp

Nephrotic Nephrotic andand

Nephritic SyndromeNephritic SyndromeCSBR.Prasad, M.D.

CSBRP-May-2014CSBRP-May-2014 11

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, Type-IV collagen, laminin,

proteoglycans, fibronectin, enactin and proteoglycans, fibronectin, enactin and other glycoproteinsother glycoproteins

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

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

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

Glomerular diseasesGlomerular diseases

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

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 +

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

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

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)

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)

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 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

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

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

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

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

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

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

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

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)

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

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

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

Henoch-SchHenoch-Schoonlein Purpuranlein Purpura ““Systemic” IgA nephropathySystemic” IgA nephropathy

ArthralgiasArthralgias PurpuraPurpura Abdominal painAbdominal pain Gastrointestinal bleedingGastrointestinal bleeding Hematuria Hematuria

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

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

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

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

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

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

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

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

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

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

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.

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.

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

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

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

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

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

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

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%)

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

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.

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