Nephrotic/Nephritic Syndrome

AK. Soyibo
Department of Medicine
Review Class
 Learning Objectives
 Understand and define nephrotic and nephritic
syndromes.
 Describe the initial investigations and
management of nephrotic and nephritic
syndromes.
 Describe the complications of nephrotic and
nephritic syndromes.
 LN and PSGN as prototype
 Nephrotic Syndrome
 Triad of:
 MASSIVE Proteinuria >3g/24hours
 Or spot urine protein:creatinine ratio >300-350mg/mmol
 Hypoalbuminaema <25g/L
 Oedema

 And often:
 Hypercholesterolaemia/dyslipidaemia (total
cholesterol >10mmol/L)
 Nephritic Syndrome
 Clinical syndrome defined by:
 Haematuria/ red cell casts
 Hypertension (mild)
 Oliguria
 Uraemia
 Proteinuria (<3g/24 hours)
 Nephrotic Criteria:-
*Massive proteinuria:
qualitative proteinuria: 3+ or 4+,
quantitative proteinuria : more than 40 mg/m2/hr in children
(selective).

*Hypo-proteinemia :
total plasma proteins < 5.5g/dl and serum albumin : < 2.5g/dl.

*Hyperlipidemia:
serum cholesterol : > 5.7mmol/L

*Edema: pitting edema in different degree

 Pathophysiology

 Thin glomerular basement membrane with

pores that allow protein and blood into the
tubule.
 Nephritic Criteria
• -Hematuria: RBC in urine (gross hematuria)

• -Hypertension:
• ≥130/90 mmHg in school-age children
• ≥120/80 mmHg in preschool-age children
• ≥110/70 mmHg in infant and toddler’s children

• -Azotemia（renal insufficiency）:
Increased level of serum BUN 、Cr
• -Hypo-complementemia:
Decreased level of serum c3
 Classification:
• A-Primary Idiopathic NS (INS): majority
The cause is still unclear up to now. Recent 10
years ,increasing evidence has suggested that INS may
result from a primary disorder of T– cell function.
Accounting for 90% of NS in child. mainly discussed.

• B-Secondary NS:
NS resulted from systemic diseases, such as anaphylactoid
purpura , systemic lupus erythematosus, HBV infection.

• C-Congenital NS: rare

*1st 3monthe of life ,only treatment renal transplantation
 Secondary NS
• Drug,Toxic,Allegy: mercury, snake venom, vaccine, pellicillamine,
Heroin, gold, NSAID, captopril, probenecid, volatile hydrocarbons
• Infection: APSGN, HBV, HIV, shunt nephropathy, reflux nephropathy,
leprosy, syphilis, Schistosomiasis, hydatid disease

• Autoimmune or collagen-vascular diseases: SLE, Hashimoto’s

thyroiditis,, HSP, Vasculitis
• Metabolic disease: Diabetes mellitus

• Neoplasma: Hodgkin’s disease, carcinoma ( renal cell, lung,

neuroblastoma, breast, and etc)
• Genetic Disease: Alport syn, Sickle cell disease, Amyloidosis, Congenital
nephropathy
• Others: Chronic transplant rejection, congenital nephrosclerosis
 Idiopathic NS (INS):
• Minimal Change Pathology:-
Nephropathy (MCN): <80%
The glomeruli appear normal basically Under Light
microscopy, and Under Immunofluorescence
*under Electron microscopy – fusion of the foot
processes of the podocytes

• (2) Non—MCN： ＜20%

*Mesangial proliferative glomerulonephritis
(MsPGN): about 10%
*Focal segmental glomerulosclerosis (FSGS):
5%
*Membranous Nephropathy (MN) : 2%
*Membrane proliferative glomerulonephritis
• (MPGN) : 1%
– *Others： rare,Cresent glomerulonephritis
 Pathophysiology:

The Main Trigger Of primary Nephrotic Syndrome

and Fundamental and highly important change of
pathophysiology :-

Proteinuria

*Nephrotic syndrome is 15 times more common in

children than in adults
 Presentation
 New-onset oedema
 Initially periorbital or peripheral
 Later genitals, ascites, anasarca
 Frothy urine
 Generalised symptoms – lethargy, fatigue,
reduced appetite
 Causes of Nephrotic Syndrome
 Primary glomerulonephritis
 Minimal change disease (80% paeds cases)
 Focal segmental glomerulosclerosis (most
common cause in adults)
 Membranous glomerulonephritis
 Systemic Causes
 Secondary glomerulonephritis
 Diabetic nephropathy
 Sarcoidosis
 Autoimmune: SLE, Sjogrens
 Infection: Syphilis, hepatitis B, HIV
 Amyloidosis
 Multiple myeloma
 Vasculitis
 Cancer
 Drugs: gold, penicillamine, captopril, NSAIDs
 Complications
 Increased susceptibility to infection
 20% adult cases
 Due to reduced serum IgG, reduced complement
activity, reduced T cell function
 Thromboembolism
 40% adult cases
 Partly due to increased clotting factors and platelet
abnormalities
 Hyperlipidaemia
 due to hepatic lipoprotein synthesis to restore
osmotic pressure
 Signs and Symptoms
 Haematuria (E.g. cola coloured)
 Proteinuria
 Hypertension
 Oliguria
 Flank pain
 General systemic symptoms
 Post-infectious = 2-3 weeks after strep-
throat/URTI
 Pathogenesis of Proteinuria:-
• Increase glomerular permeability for proteins due to loss of
negative charged glycoprotein

• Degree of protineuria:-
• Mild less than 0.5g/m2/day
• Moderate 0.5 – 2g/m2/day
• Sever more than 2g/m2/day

• Type of proteinuria:-
• A-Selective proteinuria: where proteins of low molecular
weight .such as albumin, are excreted more readily than
protein of HMW
• B-Non selective :
• LMW+HMW are lost in urine
 pathogenesis of hypoalbuminemia

*Due to hyperproteinuria----- Loss of plasma

protein in urine mainly the albumin.

*Increased catabolism of protein during acute

phase.
 pathogenesis of hyperlipidemia:-
*Response to Hypoalbuminemia → reflex to liver --→
synthesis of generalize protein ( including
lipoprotein ) and lipid in the liver ,the lipoprotein
high molecular weight no loss in urine →
hyperlipidemia

*Diminished catabolism of lipoprotein

 pathogenesis of edema:-
• *Reduction plasma colloid osmotic pressure↓
secondary to hypoalbuminemia Edema and
hypovolemia

• *Intravascular volume↓ antidiuretic hormone

(ADH ) and aldosterone(ALD)  water and
sodium retention Edema

• *Intravascular volume↓ glomerular filtration

rate
• (GFR)↓ water and sodium retention 
Edema
How many pathological types
causes nephrotic syndrome?
 Investigations:-
• 1-Urine analysis:-
A-Proteinuria : 3-4 + SELECTIVE.

b-24 urine collection for protein

>40mg/m2/hr for children

c- volume: oliguria (during stage of edema formation)

d-Microscopically:-
microscopic hematuria 20%, large number of hyaline cast
 Investigations:-
• 2-Blood:
• A-serum protein: decrease >5.5gm/dL , Albumin levels are low (＜
2.5gm/dL).
• B-Serum cholesterol and triglycerides:
Cholesterol ＞5.7mmol/L (220mg/dl).

• C-- ESR↑＞100mm/hr during activity phase

• .
• 3.Serum complemen: Vary with clinical type.

• 4.Renal function

• .
 Kidney Biopsy:-
• Considered in:
• 1-Secondary N.S

• 2-Frequent relapsing N.S

• 3-Steroid resistant N.S

• 4- Hematuria

• 5-Hypertension

• 6- Low GFR
 Differential Diagnosis of NS:
• D.D of generalized edema:-

• 1-Protein –losing enteropathy

• 2-Hepatic Failure.

• 3-HF

• 4-Protein energy malnutrition

• 5-Acute and chronic GN

• 6-urticaria? Angio edema

 Complications of NS:-
1-Infections:Infections is a major complication in
children with NS. It frequently trigger relapses.

Nephrotic pt are liable to infection because :

A-loss of immunoglobins in urine.
B-the edema fluid act as a culture medium.
C-use immunosuppressive agents.
D- malnutrition

The common infection : URI, peritonitis, cellulitis and

UTI may be seen.

Organisms: encapsulated (Pneumococci,

H.influenzae), Gram negative (e.g E.coli
 Complication …
Vaccines in NS;-

polyvalent pneumococcal vaccine (if not previously

immunized) when the child is in remission and off daily
prednisone therapy.

Children with a negative varicella titer should be given varicella

vaccine.
 Complication…..
• 2-Hypercoagulability (Thrombosis).
• Hypercoagulability of the blood leading to venous or arterial
thrombosis:
• Hypercoagulability in Nephrotic syndrome caused by:
– 1-Higher concentration of I,II, V,VII,VIII,X and fibrinogen

– 2- Lower level of anticoagulant substance: antithrombin III

– 3-decrease fibrinolysis.

– 4-Higher blood viscosity

– 5- Increased platelet aggregation

– 6- Overaggressive diuresis
• 3-ARF: pre-renal and renal

• 4- cardiovascular disease :-Hyperlipidemia, may be a

risk factor for cardiovascular disease.

• 5-Hypovolemic shock

• 6-Others: growth retardation, malnutrition,

• adrenal cortical insufficiency
 Management of NS:
• General (non-specific )

• *Corticosteroid therapy
 General therapy:-
• Hospitalization:- for initial work-up and evaluation of
treatment.

• Activity: usually no restriction , except

• massive edema,heavy hypertension and infection.

• Diet
Hypertension and edema: Low salt diet (<2gNa/ day) only
during period of edema or salt-free diet.
Severe edema: Restricting fluid intake
• Avoiding infection: very important.
• Diuresis: Hydrochlorothiazide (HCT) ：2mg/kg.d
• Antisterone ： 2～4mg/kg.d
• Dextran ： 10～15ml/kg , after 30～60m,
• followed by Furosemide (Lasix) at 2mg/kg .
 Induction
• Albumin + Lasix use
(20 % salt of
poor) albumin:-

• 1-Severe edema
• 2-Ascites
• 3-Pleural effusion
• 4-Genital edema
• 5-Low serum albumin
 Corticosteroid—prednisone therapy:-

Prednisone tablets at a dose of 60 mg/m2/day (maximum

daily dose, 80 mg divided into 2-3 doses) for at least 4
consecutive weeks.

After complete absence of proteinuria, prednisone dose

should be tapered to 40 mg/m2/day given every other
day as a single morning dose.

The alternate-day dose is then slowly tapered and

discontinued over the next 2-3 mo.
 Treatment of relapse in NS:
Many children with nephrotic syndrome will experience
at least 1 relapse (3-4+proteinuria plus edema).

daily divided-dose prednisone at the doses noted earlier

(where he has the relapse) until the child enters
remission (urine trace or negative for protein for 3
consecutive days).

The pred-nisone dose is then changed to alternate-day

dosing and tapered over 1-2 mo.
 According to response to prednisone
therapy:
*Remission: no edema, urine is protein free for 5 consecutive days.

* Relapse: edema, or first morning urine sample contains > 2 + protein

for 7 consecutive days.

*Frequent relapsing: > 2 relapses within 6 months (> 4/year).

*Steroid resistant: failure to achieve remission with prednisolone given

daily for 28 days.
 Side Effects With Long Term Use of
Steroids “Steroid toxicity
-Stunted growth • hyperglycemia
Cataracts
• myopathy
• peptic ulcer
- Pseudotumor cerebri
• poor healing of wound.
-Psycosis • Hirsutism
-Osteoporosis • Thromboembolism

- Cushingoid features

-Adrenal gland suppression

 Alternative agent:-
• When can be used:

• Steroid-dependent patients, frequent relapsers, and steroid-

resistant patients.

– Cyclophosphamide Pulse steroids

– Cyclosporin A

– Tacrolimus

– Microphenolate
Diet
Hypertension and edema:
Low salt diet (<2gNa/ day)
or salt-free diet.
Severe edema: Restricting
fluid intake.
 Increase proteins properly:
2g/(kg·day)
While undergoing the corti-
costeroid treatment: Give VitD
500~1000iu/day (or Rocaltrol)
and calcium.
Prevent infection
Diuretics
Not requires diuretics usually.
＊HCT 2~5mg/(kg · day)
＊Antisterone 3~5mg/(kg · day)
＊Triamterene
 pay attention:
Volume depletion
disorder of electrolyte
embolism.
 Apparent edema:
Give low molecular dextran
10~15ml/(kg·time);[+Dopamine
2~3ug/(kg·min) and/or Regitine
10mg +Lasix 1~2mg/kg].
 Corticosteroid therapy
Short-course therapy:
Prednisone 2mg/(kg·day) or
2
60mg/m /day (Max.60mg/day)
in 3 or 4 divided doses for 4wk
→maintenance treatment:
 Treatment of relapse and
recurrence
Extend the course of corti-
costeroid
Immunosuppressive agents
(Cytotoxic agents):
 ① CTX (Cytoxan)
2mg/(kg·day) for 8~12wk .
Total amount: 250mg/kg
Side effects: nausea, vomiting,
WBC↓, trichomadesis, hemo-
rrhagic cystitis and the damage
of sexual glands.
 CTX
2
0.5~0.75mg/m + NS/GS iv
drip (1hr), give liquid 2,000ml
/(m2.d) .
Every one mo for 6~8 times.
CB (Chlorambucil)
0.2mg/kg for 8wk .
Total amount : 10mg/kg
VCR & Levamisole
 Impulsive therapy
Methylprednisolone (MP)
15~30mg/kg(<1g/day+10%
GS 100~ 250ml, iv drip (within
1~2hr) , 3 times/one course. If
 CsA
5~7mg/kg, in 3 divided doses
for 3~6mo.
★expense and nephrotoxicity.
 Anticoagulants
Heparin
Persantin 5mg/(kg·day）for
6mo.
improve proteinuria
ACEI
Captopril, Enalapril and
Benazepril.
 Prognosis
Most cases of minimal
change disease eventually
remit permanently.
Lupus neprhitis
 Today’s objectives

• Overview of Lupus
– Types of lupus
– History
• Common manifestations
• SLE Nephritis
– WHO classification
– Biopsy Indications
– Biopsy Findings
– Treatment
• http://image.slidesharecdn.com/lupusnephrit
is2012-130323131311-phpapp01/95/slide-
2-638.jpg?cb=1364062454
Case Definition
Case Definition
 Differential Diagnosis
• hematuria
• proteinuria glomerulonephritis
• red blood cell casts
 DDx : Glomerulonephritic Dz
• SLE • Hepatitis B, C
• Minimal Change Dz • AIDS
• Membranous GN • Amyloidosis
• FSGS • HSP
• MPGN • Cryoglobulinemia
• RPGN • Vasculitides
• Ig A Nephropathy • Poststrept/ Poststaph
• Anti GBM Dz GN
• Goodpasture’s
• Wegener’s
 Red Blood Cell Casts
• red cell casts
– virtually diagnostic of
glomerulonephritis or
vasculitis
– only one needed
• absence does not exclude
diagnosis
 Types Of Lupus

• Systemic Lupus:
– most common and affects major organs
• Discoid Lupus:
– affects only the skin
– not fatal, but can cause severe scarring
• Drug-induced Lupus:
– is systemic Lupus caused by medications
– when the medicine is stopped, the disease goes
away
 What is Systemic Lupus Erythematous?

• autoimmune disorder
• multisystem microvascular inflammation
• defined by clinical picture and
generation of autoantibodies
– mostly against double stranded DNA
 SLE - Etiology
• The etiology of SLE remains unknown
• Yet, SLE is clearly multifactorial: EBV?
– Genetic factors
– Immunologic factors
– Hormonal factors
– Environmental factors

Genetic predisposition

Baseline immunological abnormalities

Infection Hormonal factors
Abnormal (control of) immune responses

SLE
 Pathogenesis of SLE
• autoantibodies
– mostly against double stranded DNA and the Smith
antigen
• Ab to Smith (Sm) antigen is very specific
for SLE
• 25% of patients
SLE Dermopathy
 Serological Tests to Aid Diagnosis of SLE

Test % positive in SLE

ANA 95%
Anti-nDNA 60%
Anti-nRNP 80%
Anti-Sm 20%
Anti-Ro 30%
Anti-La 10%
 Lupus Criteria

• American College of Rheumatology

– presence of 4 of 11 criteria can establish
SLE Dx
– 96% sensitive and specific
– updated 1995
American College of Rheumatology Criteria for
Diagnosis of SLE
• Serositis –pleuritis, • Blood Abnormalities –
pericarditis thrombocytopenia, lymphopenia,
• Oral ulcers - painless lymphopenia (x2),hemolytic
anemia
• Arthritis – 2 or more • Renal – casts, proteinuria,
peripheral joints hematuria
• Photosensitivity • ANA positive
• Immune Abnormalities – ANA, Anti
DS DNA, Smith Ag, false (+) syphilis
• Neurologic - seizures, psychosis
SOAP
BRAIN • Malar Rash- spares nasolabial folds
MD • Discoid Rash – scaling,scaring
 Autoantibodies: Early signs of lupus

Clinical criteria for systemic lupus erythematosus precede diagnosis and associated
autoantibodies are present before clinical symptoms
Arthritis & Rheumatism, Volume 56, Issue 7, July 2007, pp. 2344-235; Arbuckle NEJM 2005
 Lupus and the Kidney

• Lupus nephritis
– one of the most serious manifestations of
SLE
– typically arises within 5 years of diagnosis
• commonly within the first 6 to 36 months
• Renal failure rarely occurs before
American College of Rheumatology
classification criteria are met.
 Lupus and the Kidney
• total incidence of renal involvement
among patients with SLE exceeds 90 %
• abnormal urinalysis
– with or without an elevated Cr
– in approximately 50% at diagnosis time
– proteinuria present in 80%
– 40% have hematuria and/or pyuria
 Lupus and the Kidney

• ‘Silent’ lupus nephritis

– normal urinalysis
– no proteinuria
– normal serum creatinine levels
• However, renal biopsy reveals pathological
changes
 Lupus Nephritis
• Six types of renal involvement with
SLE
• Why do renal biopsy?
– to determine stage of disease
– histological evidence is present in most
SLE pts even if they do not have clinical
manifestations of renal disease
• Pattern of glomerular injury
– related to the site of formation of the
immune deposits
– is primarily due to anti DS DNA
 Indications for Renal Biopsy with SLE Patients

Proteinuria of >1g/day
conventionally 1-2g/day
Less proteinuria does not preclude biopsy if major serologic abnormalities,
especially hypocomplementemia
At the other extreme, the presence of full-blown nephrotic and nephritic syndromes

Progressive azotemia
Decreasing renal function in assocation with active urinary sediment

Ambiguity or inconsistency of data

Lupus nephritis of indeterminate duration, severity and potential responsiveness

Overlapping clinical features

Situations where clinical and laboratory data are compatible with different classes
of lupus nephritis, for which different approaches to management are warranted
Redirection of therapy
Partially treated or incompletely responsive lupus nephritis
Classification of Lupus Nephritis
ISN/WHO

Class Biopsy finding

I Minimal mesangial LN
II Mesangial LN
III Focal proliferative LN
IV Diffuse proliferative LN
V Membranous LN
VI Advanced glomerulosclerosis
 Normal Glomerulus
• light micrograph
• capillary lumens open
• glomerular capillary wall thickness
– similar to that of the tubular basement membranes
• mesangial cells and matrix are located in the
central or stalk regions of the tuft
 Mesangial Proliferative Lupus Nephritis: Class II

• segmental areas of
increased mesangial
matrix and cellularity
• light micrograph
 Focal Proliferative Nephritis (Class III) Subsets

• Divided by active and/or chronic lesions:

– Class III (A):
• active lesions
– Class III (A/C):
• active and chronic pathology
– Class III (C):
• chronic inactive lesions with scarring
• a.k.a. focal sclerosing lupus nephritis
 Focal Proliferative Nephritis (Class III)

• usually associated
with subendothelial
deposits
• areas of cellular
proliferation
• thickening of
glomerular capillary
– “wire loop”
 Diffuse Proliferative Nephritis
Class IV

• subendothelial deposits
• deposition of immunoglobulins and
complement
– results in thickening of the glomerular
capillary wall
• subsets
– segmental = < 50% of glomeruli
– diffuse = >50% of glomeruli
 Diffuse Proliferative Nephritis:
Class IV

• subendothelial
deposits
• thickening of
glomerular capillary
wall
 Membranous Nephritis

• Class five
• the one form of lupus nephritis that may present with
no other clinical or serologic manifestations of SLE
• typically presents with signs of nephrotic syndrome
• microscopic hematuria and hypertension also may be
seen
• Cr concentration is usually normal or only slightly
elevated
 Sclerosing Nephritis :Class VI

• sclerosis of more than 90% of glomeruli

• represents healing of previous
inflammatory injury
– as well as the advanced stage of
chronic class III, IV, or V lupus
nephritis
• immunosuppressive therapy is NOT
likely to be beneficial
Therapy for lupus patients with arthritis

• No internal organ involvement

• First line: NSAID’s
• Cyclooxygenase-2 specific inhibitor
– may induce thrombotic risk in patients with
antiphospholipid antibodies
• Low dose hydroxychloroquine
– 200mg twice a day
• Manifestations not often responsive to
glucocorticoids
– Thrombosis—includes strokes
– Glomerulonephritis
– Resistant thrombocytopenia or hemolytic anemia
Therapy for patients with lupus nephritis

• Previously untreated patients

• Active lupus nephritis or severe
manifestations
– decreased renal function and /or high-
grade proteinuria
• First line: high doses of corticosteroids
– about 1mg/kg/day
• Cytotoxic drugs or other
immunosuppressive drugs
The indications of cytotoxic drugs use in
the treatment of lupus nephritis

• Active and severe GN depsit high dose

steroids

• Responded to corticosteroids but require an

unacceptably high dose to maintain a
response.
• Side effects from corticosteroids
• Chronic damage on a renal biopsy
• diffuse (class IV) or severe focal (class
III) proliferative glomerulonephritis,
• severe or progressive membranous
lupus (class V)
• marked nephrotic syndrome
• rising serum creatinine
• membranous in association with class
III or class IV disease
– mixed disease
Use of Cytotoxic Drugs in SLE : Azathioprine

• requires 6–12 months to work well

• 1–3 mg/kg/day(initial dose)
• 1–2 mg/kg/day(maintenance dose)
• Advantage:probably reduces flares, reduces
renal
scarring, reduces glucocorticoid dose
requirement
• Side effects: Bone marrow suppression,
leukopenia, infection(herpes zoster),
infertility, malignancy, early menopause,
hepatic damage, nausea
• Advantage
– reduces flares, reduces renal
scarring, reduces glucocorticoid doses
• Side effects
– bone marrow suppression, leukopenia,
infection, malignancy, nausea,etc
 Use of Cytotoxic Drugs in SLE:
Cyclophosphamide

• requires 2–16 weeks to work well

• Initial dose:1-3 mg/kg/day orally or 8–20
mg/kg intravenously once a month
plus mesna
• Maintenance dose:0.5–2 mg/kg/day orally or 8–
20mg/kg intravenously every 4–12 wks
• Mesna
 Mycophenolate Mofetil
• mycophenoalte mofetil may be an
alternative to cyclophosphamide as
initial therapy
• particularly among patients who refuse
or cannot tolerate cyclophosphamide
• Biggest side effect is diarrhea, also
myelosuppression
• fewer side effects than
cyclophosphamide
 Rituximab
• interferes with the activation and
differentiation of B cells
• lysis mediated by:
– Complement
– Fc receptor-bearing cytotoxic cell
– Inducing apoptosis
• selective transient depletion of the CD20+
B-cell subpopulation
Other management principles in the treatment of lupus
patients

• Avoid possible disease triggers-sulfa

antibiotics, sun, high estrogen-containing
birth control pills,alfalfa sprouts
• Prevent atherosclerosis
• Prevent osteoporosis
• Prevent infection
• Prevent progression of renal disease
• Prevent clots in patients with
antiphospholipid antibodies
 Scope
• Introduction
• PSGN
– Epidemiology, Pathogenesis, Morphological features
– Children: Clinical features, Treatment, Prognosis,
Future, Prevention
• Infection-associated GN (Adults)
• Conclusions
 Introduction
• Infectious agents are the most common
inciting antigens associated with immune
complex mediated glomerulonephritis (GN)
– Post-streptococcal GN (PSGN) is the most
common form of GN in children
• Occurs following a skin or pharyngeal infection
with Group A betahemolytic streptococci
 Introduction (Contd)

• Post-infectious GN has also been associated

with other
– Bacterial
– Viral
– Parasitic
– Rickettsial
– Fungal infections
 PSGN: Epidemiology
• PSGN is one of the oldest recognized renal
diseases
– In the past three decades, significant changes have
occurred in its epidemiology
• Now rare in industrialized nations, but in the
underprivileged world, the burden of PSGN
ranges between
– 9.5 and 28.5 new cases/100,000 individuals/year

J Am Soc Nephrol 2008;19: 1855–64.

 PSGN: Epidemiology (Contd)

• PSGN
– Practically disappeared in central Europe,
• Where it is now more frequent in the elderly,
• Especially in association with debilitating conditions
such as
– Alcoholism or intravenous drug use

J Am Soc Nephrol 2008;19: 1855–64.

 PSGN: Epidemiology (Contd)

• In India, postinfectious GN represent 73%

of the acute glomerulonephridities affecting
the elderly, which
– May or may not represent a shift in age
predominance such as has been referred to
previously for Central Europe

J Am Soc Nephrol 2008;19: 1855–64.

 PSGN: Epidemiology (Contd)

• The proportion of cases of acute renal failure that

correspond to acute postinfectious GN of
demonstrated or assumed poststreptococcal
etiology is
– 13% in New Delhi
– 27% in Bombay
– 19.2% in Lucknow
– 17.4% in Chandrigarth
– 9.3% in Varanasi

J Am Soc Nephrol 2008;19: 1855–64.

PSGN: Epidemiology (Contd)

J Am Soc Nephrol 2008;19: 1855–64.

 PSGN: Epidemiology (Contd)

The annual incidence of PSGN is 9.5 to 28.5 new cases per

100,000 population of all ages in underdeveloped countries

J Am Soc Nephrol 2008;19: 1855–64.

 PSGN: Pathogenesis
• The precise nature of the antigens involved
in the formation of the nephritogenic
immune complexes is unknown
– Streptococcal antigenic substances have been
inconsistently detected in glomeruli and
circulating immune complexes have been
detected in some patients
 PSGN: Pathogenesis (Contd)

• Since streptococcal antigens do not always cause

disease, other mechanisms may be involved,
including
– Alterations in IgG or glomerular components making
them immunogenic
• Antigens derived from infectious agents may bind
to glomerular structures and induce development
of in situ immune complexes
 PSGN: Morphologic Features
• The glomeruli in post-infectious GN show
– Diffuse mesangial proliferation and
endocapillary proliferation accompanied by
– Infiltration of neutrophils and mononuclear
inflammatory cells
– Crescents may also be present
PSGN: Morphologic Features (Contd)

• Immunofluorescence microscopy
– Granular deposits of C3 and IgG along the
• Capillary loops and in the
• Mesangium
– The capillary loop deposits become less
frequent after a few weeks, but the mesangial
deposits persist for a longer period
PSGN: Morphologic Features (Contd)

• Immunofluorescence microscopy (Contd)

– Ultrastructurally large subepithelial deposits are

present which are usually scattered along the
basement membrane
• Mesangial deposits are also present
 PSGN: Children (Clinical features)

• PSGN is primarily a disease of children, 6

to 7 years of age
– The onset is usually abrupt, with a latent period
of 7 to 21 days between infection and the
development of nephritis
– During epidemic, the clinical attack rate is 10-
12%, but subclinical disease occurs four times
more frequently than overt disease
 PSGN: Children (Clinical features)
(Contd)

• Asymptomatic contacts may have hematuria

• Common initial clinical manifestations of
PSGN are:
– Hematuria (Micro or macroscopic)
– Edema
– Hypertension
– Oliguria
PSGN: Children (Clinical features) (Contd)

Clinical manifestations—typical course, atypical features

Pediatr Nephrol Epub 23 July 2010

 PSGN: Children (Clinical features)
(Contd)

• The acute clinical episode of PSGN is

– Usually self-limited and complement levels
return to normal within 6 weeks
– In most patients hematuria disappears by 6
months but
– Proteinuria may persist for two years in a 1/3rd
of patients

Pediatr Nephrol Epub 23 July 2010

 PSGN: Children (Treatment)
• Early antimicrobial therapy in affected individuals
and family members may prevent the spread of
streptococcal infections

• Treatment of established infection does not

prevent the development of PSGN, but may lessen
its severity
 PSGN: Children (Treatment) (Contd)

• Treatment remains largely supportive and

• Usually addresses the most urgent problem of
hypertension
• No modern studies are available to guide the first
choice of antihypertensive agent
– However, salt restriction and loop diuretics are the first-
line treatment for fluid overload and hypertension;
thereafter, hypertensive therapy is often transitioned to
vasodilators

Pediatr Nephrol Epub 23 July 2010

 PSGN: Children (Treatment) (Contd)

• Although successful treatment with ACE

inhibition has been reported,
– ACE inhibitors are generally not used during the acute
phase due to the potential for decrease in GFR and
hyperkalemia
• In those individuals with hypertensive
emergencies,
– Continuous infusion of anti-hypertensive medication is
the preferred initial approach

Pediatr Nephrol Epub 23 July 2010

 PSGN: Children (Prognosis)
• The prognosis for complete recovery is
excellent in children,
– Even in patients with the nephrotic syndrome or
crescentic disease at presentation

Pediatr Nephrol Epub 23 July 2010

 PSGN: Children (Prognosis) (Contd)

• Generally accepted that epidemic cases of PSAGN

carry a better prognosis than sporadic cases, with
some asserting that healing occurs in all cases
– This may be secondary to sporadic cases often
presenting in a hospital setting, while
– The increased index of suspicion inherent in epidemics
leads to the presentation of a greater number of mild
cases

Pediatr Nephrol Epub 23 July 2010

 PSGN: Children (Future)
• The availability of a vaccine for group A
streptococci is highly desirable and
anticipated,
– Both in terms of preventing invasive disease
and nonsuppurative complications
• Current thrust of group A streptococcal
vaccine research has been to target M
proteins

Pediatr Nephrol Epub 23 July 2010

 PSGN: Children (Future) (Contd)

• Unfortunately, no M proteins from nephritogenic

streptococci were included in the vaccine
• In addition, because the most common M protein
types differ geographically, this vaccine may be of
limited efficacy in the developing world, which
would presumably continue to bear the majority of
the world burden of PSGN and ARF

Pediatr Nephrol Epub 23 July 2010

 PSGN: Children (Prevention)
• Thus, prevention of PSAGN in the developing
world continues to be based upon public health
measures such as
– Improved hygiene and better housing conditions
• The elimination of epidemic pyoderma, as
occurred in the southern United States over the
past 25 years, offers the best hope for control

Pediatr Nephrol Epub 23 July 2010

 Infection-associated GN (Adults)
• Infection-associated GN is rare in adults
– Incidence is progressively declining in
developed countries
• The pattern of the disease has changed over
recent decades
– Not only Streptococcus but also other bacterial,
viral, and parasitic agents have been implicated
in the pathogenesis of GN

Int Urol Nephrol 2010; 42:477–85.

Infection-associated GN (Adults) (Contd)

• In developed countries, GN associated with

nonstreptococcal infections is assuming greater
importance
– This is thought to be secondary to a decline in the
incidence of group A streptococcal infections in
children and a relative increase in the incidence of GN
associated with other infections in adults
• Furthermore, an increasing number of adult cases has been
observed in alcoholics, patients with diabetes, and intravenous
drug abusers

Int Urol Nephrol 2010; 42:477–85

Infection-associated GN (Adults) (Contd)

• Atypical clinical presentation often issues complex

diagnostic challenges and highlights the important
diagnostic role of renal biopsy

• The more extensive use of renal biopsy has

demonstrated the presence of atypical histological
features of the disease

Int Urol Nephrol 2010; 42:477–85.

Infection-associated GN (Adults) (Contd)

• Classically, acute postinfectious GN occurs after

streptococcal pharyngitis or skin infection
• More recently, other sites of infection and more
diverse organisms have been linked to adult
infection- associated GN
– Studies have demonstrated that Staphylococcus was
responsible for an increasing number of cases
– MRSA accounted for the majority of cases

Int Urol Nephrol 2010; 42:477–85.

Infection-associated GN (Adults) (Contd)

• Common sites
– Upper respiratory tract
– Skin
– Lung
– Heart/endocarditis and
– Teeth

Int Urol Nephrol 2010; 42:477–85.

Infection-associated GN (Adults) (Contd)

• In studies,
– 7–16% of patients had no clinical evidence of infection
preceding the renal disease, and
– In 24–59% of patients the offending microorganism
could not be identified
• These data suggests
– Infection-associated GN should be included in the
differential diagnosis of nephritic/nephrotic syndrome
in adults even in the absence of a history of infection

Int Urol Nephrol 2010; 42:477–85.

Infection-associated GN (Adults) (Contd)

• There is a broad spectrum of glomerular

histological findings
– The classic glomerular pattern is diffuse endocapillary
proliferative GN
– Focal mesangial proliferative pattern is also noted in
some cases

Int Urol Nephrol 2010; 42:477–85.

Infection-associated GN (Adults) (Contd)

• 2 histological patterns of GN associated

with staphylococcal infection
– Diffuse endocapillary and exudative pattern,
resembling classic PSGN in patients with S.
aureus infection
– Pattern identical to membranoproliferative GN
in patients with Staphylococcus epidermidis
infection secondary to ventriculovascular
shunts

Int Urol Nephrol 2010; 42:477–85.

Infection-associated GN (Adults) (Contd)

• In recent years,a third form of

Staphylococcus- associated GN
– Mesangial proliferation with IgA-dominant or
codominant deposits has been increasingly
recognized, which generally occurs in patients
with infections caused by MRSA

Int Urol Nephrol 2010; 42:477–85.

 Postinfectious GN (PIGN):
Histology classification
• Acute diffuse endocapillary or proliferative GN
– Group A streptococcus
– Streptococcus viridans
– Staphylococcus aureus
– Diplococcus pneumoniae
– Brucella melitensis
– Salmonella typhi
– Yersinia enterocolitica
– Mycobacterium leprae
– Plasmodium falciparum

Nephrol Dial Transplant 2001;16(Suppl 6):68–70

 Postinfectious GN (PIGN):
Histology classification (Contd)
• Acute diffuse endocapillary or proliferative GN
(contd)
– Meninococcus
– Mycoplasma
– Klebsiella
– Measles
– Mumps
– Varicella
– Vaccina
– Variola
– Cat scrats etc
Nephrol Dial Transplant 2001;16(Suppl 6):68–70
 Postinfectious GN (PIGN):
Histology classification (Contd)
• Less commonly,
• Diffuse cresentic GN
– Streptococcus
– Staphylococcus
– Legionella
– Varicella
– Treponema pallidum
• Focal cresentic GN
– Streptococcus A

Nephrol Dial Transplant 2001;16(Suppl 6):68–70

 Postinfectious GN (PIGN):
Histology classification (Contd)
• Rarely,
• Mesangiocapillary GN
– Streptococcus viridans
– Hepatitis C virus
• Diffuse/focal mesangial proliferative GN
– Diplococcus
– Salmonella
– Hepatitis B virus
– Influenza virus
– Adenovirus

Nephrol Dial Transplant 2001;16(Suppl 6):68–70

 Postinfectious GN (PIGN):
Histology classification (Contd)
• Rarely,
• Focal segmental, necrotizing and sclerosing GN
– Bacterial endocarditis
• Membranous GN
– Syphilis
– Hepatitis B virus
– Filaria
– Schistosoma
– Mycobacterium
– Plasmodium falciparum
• Focal proliferative (Mycoplasma)
• Mesangiolytic GN (ECHO)
• HUS (Epstein-Barr virus, handavirus)

Nephrol Dial Transplant 2001;16(Suppl 6):68–70

 Infection-associated GN (Adults)

• The prognosis of has not been well defined

– But general agreement that the prognosis is less
favorable than that of PSGN in children
• Complete remission
– Before the 1990s: 60–80% of adults
– Recent studies found:only 26–56% of adults

Int Urol Nephrol 2010; 42:477–85.

Infection-associated GN (Adults) (Contd)

• Thus, prognosis of infection-associated GN

is worsening in adults
– This is probably because typical PSGN has
become rarer and the number of patients with
severe underlying diseases is progressively
increasing

Int Urol Nephrol 2010; 42:477–85.

Infection-associated GN (Adults) (Contd)

• The prognosis in adults is less favourable,

– Especially when accompanied by initial severe
impairment in renal function, persistent
proteinuria and the nephrotic syndrome
– The development of crescents is more common
in adults
 Conclusions
• PSGN
– One of the oldest recognized renal disease
– Occurs mostly in children
– Still a huge burden for underdeveloped
countries like India
– Treatment remains largely supportive
– Hypertension control with salt restriction and
diuretics followed by vasodilators
 Conclusions (Contd)

• PSGN in children (Contd)

– Prognosis for recovery is excellent

– Vaccines are being developed in developed
world
– For developing countries
• Preventive measures like better hygiene and
improved housing conditions are recommended
 Conclusions (Contd)

• Infection-associated GN in adults
– Undergoing change in pattern in recent decades
– Nonstreptococcal infections like
Staphyloccocus, MRSA are being detected
– More common in alcoholics, diabetics, and
intravenous drug abusers
 Conclusions (Contd)

• Infection-associated GN.. (Contd)

– Associated with poor prognosis

– Complete remission rates ranging 26-56%
– Should be included in the differential diagnosis
of nephritic/nephrotic syndrome in adults even
in the absence of a history of infection (as 24–
59% patients organism may not be identified)
• THE END….

THANK YOU….