GLOMERULONEPHRITIS

SUHARDI, D.A.
Division of Nephrology
Department of Internal Medicine,
School of Medicine, Gadjah Mada University/
Sardjitos Hospital
 Glomerulonephritis
Glomerulonephritis and glomerulopathy
are usually used interchangeably to
denote: glomerular injury
Glomerulonephritis injury with:
Evidence of inflammation such as
Leukocyte infiltration
Deposition antibody, and
Activation of complement
Immunologic glomerular injury
Classification of Glomerulonephritis

Primary: when pathology is

Confined to the kidney and
Systemic features are direct
consequence of glomerular dysfunction
Pulmonary edema, periphery edema
Hypertension and

The uremic syndrome

The term Primary Idiopathic

 Primary Glomerulonephritis
Minimal Change Disease/N L Disease
/Lipoid Nephrosis
Focal and Segmental Glomerulosclerosis
Membranous Glomerulopathy
Membrano Proliferative Glomerulonephritis
Mesangial Proliferative Glomerulonephritis
Classification of Glomerulonephritis

Secondary:
Partof multi system disorder
Systemic Lupus Erythematosus
Systemic features are direct
consequence of glomerular dysfunction
The five mayor clinical
presentations of glomerulopathy
Acute nephritic syndrome
Rapidly progressive glomerulonephritis
(RPGN)
Nephrotic syndrome
Asymptomatic abnormalities of the urinary
sediment (hematuria, proteinuria)
Chronic glomerulonephritis
 Acute Glomerulonephritis
Acute glomerular inflammation
Characterized by:

Sudden onset (days-weeks) of acute renal failure

with oliguria (<400 ml urine/day)
Renal blood flow and GFR fall as obstruction of
glomerular capillary lumen by infiltrating
inflammatory cells and proliferating resident
glomerular cells
Injury to the glomerular capillary wall
urinalysis:
Red blood cell casts
Dysmorphic red blood cells
Hematuria macroscopic
Leucocytes
Subnephrotic proteinuria (<3,5 g/day)
 Acute Glomerulonephritis
Acute glomerular inflammation
Characterized by:

Classic pathologic of Nephritis syndrome is

proliferative GN
Initially infiltration of the glomerulo tuft by:
Neutrophils
Monocytes
Subsequently: proliferation of resident
endothelial and mesangial cells (endocapillary
proliferation)
 Acute Glomerulonephritis
Acute glomerular inflammation
Characterized by:

Severe form: nephritic syndrome with acute

inflammation of most glomeruli acute diffuse
proliferative gloerulonephritis such as:
Rapid progresses glomerulonephritis =
Crescentic GN

Less vigoreous: < 50% of glomeruli may be

involved, focal proliferative glomerulonephritis
Milder form of nephritic injury:
Confined to mesangium cellular proliferation:
mesangio proliferative glomerulo nephritis
Treatment of Acute Glomerulonephritis
Antibiotic if needed
Corticosteroid with or without cytotoxic
agent
Symptomatic agent:
Hypertension
Proteinuria
Hyperlipidemia
Thrombotic
 Asymptomatic Abnormalities of The
Urinary Sediment
In the initially phase is not associated
with:
Edema
Hypertension
Insufficiency renal
Hematuria and or Proteinuria
Glomerular hematuria
Red blood cell casts
Dysmorphic red blood cells
Proteinuria less than 2 g/24 h
 Asymptomatic Abnormalities of The
Urinary Sediment
Prognosis of this disease:
IgA Nephropathy (Bergers disease): As many
as 20-50% of patients develop to ESRD within
20 years
Persistent isolated proteinuria:
After 20 years: 20-40% developing renal
insufficiency
Treatment of asymptomatic abnormalities
of the urinary sediment
Some authorithies advocate: a trial high dose
glucocorticoid with or without cytotoxic agent
 Chronic Glomerulonephritis
This syndrome is characterized by:
Persistent proteinuria and or hematuria and renal
insufficiency that progresses slowly over years (15-40
years)
Elevated:
Blood urea nitrogen
Creatinine
Unexplained anemia
Following discovery: bilateral small kidney (imaging
abdominal)
Tubulo interstitial inflammation and scarring a poor
prognosis
Following:
Hypertension
Edema
Anemia
Uremic syndrome
Acidosis metabolic
Treatment of Chronic Glomerulonephritis

A trial high dose glucocorticoid with or

without cytotoxic agent
Lowering systemic and glomerular
hypertension:
ACE inhibitor
AIIRB
Controlling extra cellular fluid volume:
diuretics
Controlling anemia:
Erythropoietin
Supplement iron i.v./oral
ESRD Dialysis
 Nephrotic Syndrome
is a clinical complex characterized by:
Proteinuria of > 3.5 g/per 1.73 m2/ per
24 h
Hypoalbuminemia
Edema
Hyperlipidemia
Lipiduria and
Hypercoagulability
 Correlation between Site of Glomerular Injury
and Clinicopathologic Presentation

Target of Injury Physiologic Role Response to Injury Representative

Glomerular Disease

Endothelial cell Maintains glomerular Vasoconstriction Acute renal failure

perfusion Leukocyte infiltration Focal or diffuse
Prevents leukocyte Intravascular proliferative GN
adhesion microthrombi Thrombotic
Prevents platelet microangiopathies
aggregation and
clotting
Mesangial cell Controls glomerular Proliferation/increased Mesangioproliferative
filtration surface area matrix GN/Glomerulosclerosis

Basement Prevents filtration of Proteinuria Membranous

membrane plasma proteins nephropathy

Visceral epithelial Prevents filtration of Proteinuria Minimal change

cell plasma proteins disease and FSGS

Parietal epithelial Maintains Bowmans Crescent formation Crescentic GN

cell space
GN: Glomerulonephritis; FSGS: focal segmental glomerulosclerosis
 The Cause of Nephrotic Syndrome
Minimal change disease (MCD)
Focal and segmental glomerulosclerosis
(FSGS)
Membranous glomerulopathy
Membrano proliferative glomerulonephritis
Diabetic nephropathy
Amyloidosis
 Nephrotic Syndrome in Adult

About 30% cause by:

DM
Amyloidosis
SLE
The remaining cause by primary renal disorder:
Minimal Change Disease
Focal Segmental Glomerulosclerosis
Membranous Nephropathy
Renal biopsy is a valuable tool in adults NS for
establishing:
A definitive diagnosis
Guiding therapy, and
Estimating prognosis
 Minimal Change Disease (MCD)

Clinical & Laboratory:

Nephrotic syndrome
Massive proteinuria 3 20 g/day
Hematuria (-)
Severe hipoalbuminemia
Hypercholesterolemia
Normotension
 Pathology Anatomy of MCD

Light Microscope (LM):

Normal
Proliferative mesangial - minimal
Immunofluorescent (IF):
Deposit immune (-)
Electron Microscope (EM):
Diffusion epithelial cell foot processes
 Minimal Change Disease (MCD)

Diagnosis: requires biopsy

Suggested approach for initial treatment
Adult: metylprednisolone
1 mg/kg/day 6 weeks than
1.6 mg/kg/48 h 4 weeks
Reduce: 0.2 0.4 mg/kg/48 h every month
Contraindication to prednisolone:
Cyclophosphamid 2 mg/kg/day or chlorambucil 0.15
mg/kg/day for 8-12 weeks
REMISSIONS: complete, partial, relapse,
resistant, side effect of drug
Response Treatment of MCD

The result is excellent.

 Focal Segmental Glomerulosclerosis
(FSGS)

Clinical & Laboratory:

Nephrotic syndrome
Nephritic syndrome
Microscopic hematuria (+)
Hypertension (+)
Decrease of kidney function (+)
Requires biopsy to determine diagnosis of
FSGS
LM:
Focal segmental glomerulosclerosis
Yuxta medullary glomeruli
Superficial cortex
IF:
IgM, C3 sclerotic lesions
EM:
Epithelial foot process like MCD
 Response Treatment
(Corticosteroid; Cyclophosphamid; Cyclosporine)

Complete remissions
Partial remissions
Relapse
Dependent
Resistant
Side effect of drugs

Disappointing
After 5-10 years ESRD
 Membranous Nephropathy (MN)

Clinical & Laboratory:

Almost find out in adult nephrotic syndrome (NS)
The illustration of NS is clear
More often thrombosis
Hypertension (+)
Massive proteinuria > 10 g/day
Progress to ESRD after 3-10 years
Requires biopsy to determine diagnosis of MN
LM:
Capillary cells thickening
Symptom of inflammation without cell proliferative
Spike, dome
IF:
IgG + C3
EM:
Discontinue pattern of dense deposit base membrane
 Response Treatment of MN
Steroid
Cyclophosphamid/chlorambucil
Cyclosporine:
Complete remissions
Partial remissions
Relapse
Dependent
Resistant
Side effect of drugs

Unsatisfying
After 3-10 years 50% progress to ESRD
Membrano Proliferative Glomerulonephritis
(MPGN)

Synonym: Mesangio capillary glomerulonephritis

Nephrotic syndrome:
7% in adults
4% in children
Clinical:
MPGN Type I: nephrotic syndrome
MPGN type II: nephritic syndrome
nephrotic syndrome
Diagnosis: requires biopsy
 Response Treatment of MPGN
Steroid
Cyclophosphamid/chlorambucil
Cyclosporine:
Complete remissions
Partial remissions
Relapse
Dependent
Resistant
Side effect of drugs

Unsatisfying
There is no effective treatment for the disease
The benefit of treatment are not clear
After 10 years 50% MPGN ESRD
 The Treatment of NS
Specific treatment of the underlying
causative disease
General measure to control proteinuria:
Immunosuppressive therapy
Non specific measure:
A II RA
ACE Inhibitor
General measure to control nephrotic
complications:
Edema
Hyperlipidemia
Thromboembolism
Malnutrition
Vit. D deficiency
 Conclusion

Prognosis of nephrotic syndrome or

glomerulonephritis in adults are not excellent
Requires biopsy to determine the diagnosis,
therapy and prognosis
Sustain remissions proteinuria therapy is
needed to obtain better result