Nephrotic and Nephritic

Syndrome
January 22, 2008
Pamela J. Fall, M.D.
Section of Nephrology

Objectives

Define nephrotic syndrome and

glomerulonephritis
Identify clinical features of both
syndromes
Identify causes of each syndrome
Evaluation of glomerular disease
Management of glomerular diseases

Case

A 65 year old Caucasian man presents

with several months of lower extremity
edema.
PMH is unremarkable. No medications.
ROS is notable for fatigue and some
weight loss. Appetite remains good.
BP is 150/100 mm Hg, pulse 92,
periorbital plaques, edema and guaiac
+

Case

Lab: Cr 1.4 mg/dL, Hg 8 g/dL, MCV

70, cholesterol 450 mg/dL, albumin
2.0 g/dL UA with 4+ protein, no blood
and bland sediment.
24 hour urine 6 g protein
Ultrasound shows 11 cm kidneys
bilaterally with increased echogenicity

Case

The most likely cause of his nephrotic

syndrome is?

Hypertensive nephrosclerosis
Diabetic nephropathy
Focal segmental glomerulosclerosis
Membranous nephropathy
Membranoproliferative
glomerulonephritis

Nephrotic Syndrome

Proteinuria > 3.5 g/day/1.73 m2

Hypoalbuminemia < 3.5 g/dL
Edema
Hyperlipidemia
Lipiduria

Nephrotic Syndrome

Causes of primary idiopathic NS

Minimal change disease

Membranous nephropathy
Focal segmental glomerulosclerosis
Membranoproliferative
glomerulonephritis (overlap)

Nephrotic Syndrome

Causes of secondary NS

Minimal change disease

Membranous nephropathy
Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritis
Diabetic nephropathy (unique pathology)
Amyloid (unique pathology)
Light change deposition disease (unique
pathology)

Minimal Change Disease

Most cases primary/idiopathic

Secondary causes

Nonsteroidal anti-inflammatory agents

Malignancies (hematologic)

Focal Segmental
Glomerulosclerosis

Secondary causes

Healing of previous glomerular injury

Massive obesity
? OSA
Sickle cell anemia
HIV (other viruses)
Pamidronate
Heroin abuse

Membranous Nephropathy

Secondary causes

Malignancy, primarily solid tumors

Class V lupus nephritis
Rheumatoid arthritis
Hepatitis B and C
Drugs (penicillamine, gold, NSAIDs,
captopril)
Syphilis

Case

The most likely cause of his nephrotic

syndrome is?

Hypertensive nephrosclerosis
Diabetic nephropathy
Focal segmental glomerulosclerosis
Membranous nephropathy
Membranoproliferative
glomerulonephritis

Case

C.G. is a 33 year old white male who

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

Case

Exam: BP 140/95 mm Hg, pulse 78,

chest, abdomen, extremities are
normal. He has no rash or arthritis.
Lab: Cr 1.1 mg/dL, Hg 14 g/dl, UA
shows numerous RBCs, no casts. 24
hr urine protein is 1.5 g. Ultrasound
is normal.

Case

What is his diagnosis?

Lupus nephritis
IgA Nephropathy
Membranous nephropathy
Membranoproliferative
glomerulonephritis from hepatitis C
Nephrolithiasis

Glomerular Disease

Accounts for 51% of ESRD in the US

38% diabetic nephropathy

13% nondiabetic glomerular disease

Definition of glomerulonephritis

Intraglomerular inflammation
Cellular proliferation
Hematuria
Excludes nonproliferative disorders

Glomerulonephritis

Refers to that variety of kidney disease

in which proliferation and inflammation
of the glomerulus is secondary to an
immunologic mechanism.
Presentation of GN varies from
microscopic asymptomatic hematuria
or proteinuria to acute nephritis, to
rapidly progressive nephritis.

Nephritic Syndrome

Hematuria dysmorphic red blood

cells, red blood cell casts
Azotemia
Oliguria
Hypertension
Variable proteinuria (usually < 3
g/day)

Focal Proliferative
Glomerulonephritis

IgA nephropathy
Henoch-Schonlein purpura
Lupus nephritis (class II and III)
Heriditary nephritis (Alports)

Diffuse Proliferative
Glomerulonephritis

Poststreptococcal glomerulonephritis
Bacterial endocarditis
Lupus nephritis (Class IV)
Membranoproliferative
glomerulonephritis
Crescentic glomerulonephritis
Vasculitis

IgA Nephropathy

Common cause of glomerulonephritis

Mesangioproliferative
glomerulonephritis
Asians and Caucasians
Rare in African-Americans
Age 20-30
Males > Females
Pathogenesis altered regulation of IgA

IgA Nephropathy

Clinical presentation

50-60% episodic gross hematuria (synpharyngitic)

30-40% persistent microscopic hematuria
<5% acute glomerulonephritis
ESRD 20-40% at 5-25 years

Treatment no cure

N-3 fatty acids (fish oil)

Corticosteroids
ACE inhibitors/ARBs

Henoch-Schonlein Purpura

Systemic IgA nephropathy

Arthralgias
Purpura
Abdominal pain
Gastrointestinal bleeding
Hematuria

Poststreptococcal
Glomerulonephritis

Clinical presentation

Children 2-10 years

Uncommon over age 40 (< 10%)
Symptoms develop 7 days to 12 weeks after
the infection
Low complement levels (C3 and CH50)
Spontaneous recovery is the rule
Hematuria can persist 6 months
Proteinuria, mild can persist years

Poststreptococcal
Glomerulonephritis

Pathogenesis

Nephritogenic strains of streptococci

Planted antigen
Nephritis associated plasmin receptor (GAPDH)
Zymogen (cationic protein-subepithelial deposits)

Host immune response (ab/ag)

Alternative pathway of complement activation
IgG and C3 found in glomeruli

Case

T.G. is a 47 year old white man who presents

with 3 weeks of malaise, anorexia, weight
loss, cough and dark urine.
PMH: mild asthma, nonsmoker
Exam: BP 145/70, lungs with diffuse rhonchi,
heart, abdomen normal, no rash, 2+ edema
Lab: Cr 6.3 mg/dL, UA 3+ blood and protein,
dysmorphic rbcs

Case

What is his diagnosis?

Lupus nephritis
IgA nephropathy
Poststreptococcal glomerulonephritis
Anti-GBM disease
Focal segmental glomerulosclerosis

Rapidly Progressive
Glomerulonephritis

Clinical syndrome

Glomerulonephritis (nephritic syndrome)

Rapid decline in renal function
Rare 2-4% of all glomerulonephritis
Pathologic hallmark crescents
Classified based on presence or absence
of immune complexes

Rapidly Progressive
Glomerulonephritis

Immune complex mediated:

Henoch-Schonlein purpura
Cryoglobulinemia (often associated with
hepatitis C)
Lupus nephritis
Acute postinfectious glomerulonephritis
Bacterial endocarditis

Rapidly Progressive
Glomerulonephritis

Direct antibody attack mediated

Anti-GBM disease/Goodpastures
syndrome

Pauci-immune (ANCA associated)

Wegeners granulomatosis
Microscopic polyarteritis

Anti-GBM Disease

Clinical presentation:

Bimodal age distribution (3rd and 6th

decades)
60-70% present with pulmonary hemorrhage
Systemic symptoms - malaise, fatigue,
anorexia, weight loss, arthralgias, myalgias
Caucasians
Rare in African-Americans

Anti-GBM Disease

Pathogenesis

Antibodies develop against 3 chain

type IV collagen in GBM
Linear deposition of IgG along GBM
Antibodies detected by ELISA
ANCA found in ~30% of patients

Anti-GBM Disease

Outcome poor without therapy

Treatment

Corticosteroids alone insufficient

Cyclophosphamide
Plasma exchange with albumin 14 days

Renal recovery rare if patients

present needing dialysis

Case

24 year old black female presents with

hypertension and edema. Two weeks
prior she developed a cough, chest
pain, nasal congestion and pain in her
right ear and received a course of
amoxicillin. One week prior she noted a
rash on her face and chest and
complained of some pain in her hands.

Case

PMH: unremarkable
Exam: BP 180/126 mm Hg. She has
periorbital edema, normal
oropharynx. Heart, lungs and
abdomen are normal. She has lower
extremity edema and an
erythematous maculopapular rash
over her chest.

Case

Lab:
Cr 1.6 mg/dL
UA 3+ blood, 4+ protein, > 50
RBCs/HPF, many dysmorphic
WBC 3.0, Hg 10, platelets 120
Complements C3 low, C4 low

Case

What is your diagnosis?

Poststreptococcal glomerulonephritis
IgA nephropathy
Lupus nephritis
Membranous nephropathy
Wegeners granulomatosis

Systemic Lupus
Erythematosis

Complex multisystem autoimmune

disease
11 criteria 4 present for diagnosis
Kidney is most common organ involved
(50-75%)
Females > Males
African-Americans have higher rates of
lupus nephritis and worse renal survival

Lupus Nephritis

Clinical spectrum

Pathogenesis of renal involvement

Mild urinary abnormalities

Acute and chronic kidney failure
Usually develops within 3 years
Histone-DNA complex planted antigen
Anti-dsDNA antibodies eluted from nephritic
kidneys

WHO recognizes 6 classes

Classification of Lupus
Nephritis

Class I normal
Class II variable mesangial hypercellularity and immune deposits
Class III focal proliferative
glomerulonephritis
Class IV diffuse proliferative
glomerulonephritis
Class V membranous nephropathy
Class VI chronic glomerulosclerosis

Lupus Nephritis

10-20% mesangial or focal proliferative

40-60% diffuse proliferative
10-20% membranous nephropathy
Treatment

Corticosteroids
Azathioprine
Cyclophosphamide
Mycophenolate

Evaluation of
Glomerulonephritis

History and exam

Urinalysis blood, protein and
dysmorphic rbcs +/- rbc casts
Complements
Additional serology as dictated by
presentation

Laboratory Tests Complements

Low serum complement level

Systemic diseases
SLE (75-90%)
Subacute bacterial endocarditis (90%)
Cryoglobulinemia (85%)

Renal diseases
Acute poststreptococcal glomerulonephritis
(90%)
Membranoproliferative glomerulonephritis (90%)

Laboratory Tests Complements

Normal serum complement level

Systemic diseases
Vasculitis
Henoch-Schonlein purpura

Renal diseases
IgA nephropathy
Idiopathic rapidly progressive glomerulonephritis

Anti-GBM disease
IC disease

Summary

Glomerular disease is an important

cause of CKD and ESRD.
Patients can present with a variety of
clinical syndromes.
A good history, exam and certain lab
tests in conjunction with renal biopsy
can often lead to a diagnosis.