Nephrotic And Nephritic Syndrome 2008

““Nephrotic and Nephritic Nephrotic and Nephritic Syndrome”Syndrome”

January 22, 2008January 22, 2008

Pamela J. Fall, M.D.Pamela J. Fall, M.D.

Section of NephrologySection of Nephrology

ObjectivesObjectives

Define nephrotic syndrome and Define nephrotic syndrome and glomerulonephritisglomerulonephritis

Identify clinical features of both Identify clinical features of both syndromessyndromes

Identify causes of each syndromeIdentify causes of each syndrome Evaluation of glomerular diseaseEvaluation of glomerular disease Management of glomerular diseasesManagement of glomerular diseases

CaseCase

A 65 year old Caucasian man presents A 65 year old Caucasian man presents with several months of lower extremity with several months of lower extremity edema.edema.

PMH is unremarkable. No medications.PMH is unremarkable. No medications. ROS is notable for fatigue and some ROS is notable for 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 with 4+ protein, no blood 2.0 g/dL UA with 4+ protein, no blood and bland sediment. and 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 bilaterally with increased echogenicityechogenicity

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

glomerulonephritisglomerulonephritis

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


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)


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

glomerulonephritisglomerulonephritis

CaseCase

C.G. is a 33 year old white male who C.G. is a 33 year old white male who presents with right flank pain and presents with right flank pain and gross hematuria. gross hematuria.

PMH: 3-4 episodes of hematuria per PMH: 3-4 episodes of hematuria per year, 6 hospitalizations for pain year, 6 hospitalizations for pain control, multiple evaluations with no control, multiple evaluations with no diagnosis.diagnosis.

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 arthritis.normal. 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 normal.is 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 Refers to that variety of kidney disease in which proliferation and inflammation in which proliferation and inflammation of the glomerulus is secondary to an of the glomerulus is secondary to an immunologic mechanism.immunologic mechanism.

Presentation of GN varies from Presentation of GN varies from microscopic asymptomatic hematuria microscopic asymptomatic hematuria or proteinuria to acute nephritis, to or proteinuria to acute nephritis, to rapidly progressive nephritis.rapidly 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)

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

T.G. is a 47 year old white man who presents T.G. is a 47 year old white man who presents with 3 weeks of malaise, anorexia, weight with 3 weeks of malaise, anorexia, weight loss, cough and dark urine.loss, cough and dark urine.

PMH: mild asthma, nonsmokerPMH: 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? 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 60-70% present with pulmonary

hemorrhagehemorrhage 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 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


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 black female presents with 24 year old black 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

PMH: unremarkablePMH: 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 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 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 cellularity and immune depositsdeposits

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 Idiopathic rapidly progressive

glomerulonephritisglomerulonephritis 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.

Health & Medicine

Nephrotic And Nephritic Syndrome 2008