The lecture has been given on Nov. 7th, 11th, 2010 by Dr. Rasool.

1. Glomerulonephritis
Dr Rasol M Hasan

2. MINIMAL CHANGE NEPHROPATHY AND PRIMARY
FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)
• Patients with minimal change nephropathy and
a subgroup of patients with FSGS can be seen
as opposite ends of a spectrum of conditions
causing idiopathic nephrotic syndrome .
Minimal change disease occurs at all ages but
accounts for nephrotic syndrome in most
children and about one-quarter of adults.
Proteinuria usually remits on high-dose
corticosteroid therapy (1 mg/kg prednisolone
for 6 weeks), although some patients who
respond incompletely or relapse frequently
need maintenance corticosteroids, cytotoxic
therapy or other agents. Minimal change
disease does not progress to CRF; the main
problems are those of the nephrotic syndrome
and complications of treatment.

3. • FSGS is a histological description with
many causes. The primary FSGS group
that present with idiopathic nephrotic
syndrome and no other cause of renal
disease typically show little response to
corticosteroid treatment and often
progress to renal failure; the disease
frequently recurs after renal
transplantation, and sometimes
proteinuria recurs almost immediately.
However, a proportion of patients with
FSGS do respond to corticosteroids (a
good prognostic sign). As FSGS is a focal
process, abnormal glomeruli may not be
seen on renal biopsy if only a few are
sampled, leading to an initial diagnosis of
minimal change nephropathy.
Juxtamedullary glomeruli are more likely
to be affected in early disease.

4. Cont.
• In other patients with the
histological appearances of FSGS
but lesser proteinuria, focal
scarring reflects healing of previous
focal glomerular injury, such as
haemolytic uraemic syndrome,
cholesterol embolism or vasculitis.
In others, it seems to represent
particular types of nephropathy: for
example, those associated with
heroin misuse, HIV infection and
massive obesity. Associations with
numerous other forms of injury and
renal disorders are reported. There
is no specific treatment for most of

5. MEMBRANOUS NEPHROPATHY
• This is the most common cause of
nephrotic syndrome in adults. A
proportion of cases are associated with
known causes but most are idiopathic.
Of this group, approximately one-third
remit spontaneously, one-third remain in
a nephrotic state, and one-third show
progressive loss of renal function. Short-
term treatment with high doses of
corticosteroids and alkylating agents
(e.g. cyclophosphamide) may improve
both the nephrotic syndrome and the
long-term prognosis. However, because
of the toxicity of these regimens, most
nephrologists reserve such treatment for
those with severe nephrotic syndrome or
deteriorating renal function.

6. IgA NEPHRO AND HENOCH-SCHÖN PURPURA
• IgA nephropathy is the most commonly
recognised type of glomerulonephritis and can
present in many ways . Haematuria is almost
universal, proteinuria usual, and hypertension
very common. There may be severe proteinuria
and nephrotic syndrome, or in some cases
progressive loss of renal function. The disease
is a common cause of ESRF. A particular
hallmark in some individuals is acute
exacerbations, often with gross haematuria, in
association with minor respiratory infections.
This may be so acute as to resemble acute
post-infectious glomerulonephritis, with fluid
retention, hypertension and oliguria with dark
or red urine. Characteristically, the latency
from clinical infection to nephritis is short: a
few days or less. These episodes usually
subside spontaneously

7. IgA/ HSP
• In children, and occasionally in adults, a
systemic vasculitis occurring in response to
similar infections is called Henoch-Schönlein
purpura. A characteristic petechial rash
(cutaneous vasculitis, typically affecting
buttocks and lower legs) and abdominal pain
(gastrointestinal vasculitis) usually dominate the
clinical picture, with mild glomerulonephritis
being indicated by haematuria. When the disease
occurs in older children or adults, the
glomerulonephritis is usually more prominent.
Renal biopsy shows mesangial IgA deposition
and appearances indistinguishable from acute
IgA nephropathy. Occasionally, IgA nephropathy
progresses rapidly and crescent formation may
be seen. The response to immunosuppressive
therapy is usually poor. The management of less
acute disease is largely directed towards the
control of blood pressure in an attempt to
prevent or retard progressive renal disease.

8. GLOMERULONEPHRITIS ASSO WITH
INFECTION
• CAUSES OF GLOMERULONEPHRITIS
ASSOCIATED WITH LOW SERUM
COMPLEMENT
• Post-infection glomerulonephritis
• Subacute bacterial infection-
especially endocarditis
• SLE
• Cryoglobulinaemia
• Mesangiocapillary glomerulonephritis-
usually type II

9. • Bacterial infections, usually subacute (typically
subacute bacterial endocarditis), may cause a
variety of histological patterns of
glomerulonephritis, but usually with plentiful
immunoglobulin deposition and often with
evidence of complement consumption (low
serum C3. In the developed world, hospital-
acquired infections are now a common cause of
these syndromes. World-wide, glomerulonephritis
associated with malaria, hepatitis B, hepatitis C,
schistosomiasis, leishmaniasis and other chronic
infections is very common. The usual histological
patterns are membranous and mesangiocapillary
lesions, although many other types may be seen.
FSGS associated with HIV infection is prevalent
in black races. Proving a causative relationship
between renal disease and infection in individual
cases is extremely difficult. Acute and chronic
infections may also cause interstitial renal
disease .

10. Acute post-infectious glomerulonephritis
• This is most common following infection with certain
strains of streptococcus and therefore is often called post-
streptococcal nephritis, but it can occur following other
infections. It is much more common in children than adults
but is now rare in the developed world. The latency is
usually about 10 days after a throat infection or longer
after skin infection, suggesting an immune mechanism
rather than direct infection. An acute nephritis of varying
severity occurs. Sodium retention, hypertension and
oedema, are particularly pronounced. There is also
reduction of GFR, proteinuria, haematuria and reduced
urine volume. Characteristically, this gives the urine a red
or smoky appearance. There are low serum
concentrations of C3 and C4 and evidence of
streptococcal infection (perform antistrepto-lysin O (ASO)
titre, culture of throat swab, and other swab tests if skin
infection is suspected). Renal function begins to improve
spontaneously within 10-14 days, and management by
fluid and sodium restriction and use of diuretic and
hypotensive agents is usually adequate. Remarkably, the
renal lesion in almost all children and most adults seems
to resolve completely despite the severity of the
glomerular inflammation and proliferation seen

11. RAPIDLY PROGRESSIVE GLOMERULONEPTIS
• This describes an extreme
inflammatory nephritis which causes
rapid loss of renal function over days
to weeks. Renal biopsy shows
crescentic lesions often associated
with necrotising lesions within the
glomerulus (focal segmental
(necrotising) glomerulonephritis). It
is typically seen in Goodpasture's
disease, where there are specific
anti-GBM antibodies, and in small-
vessel vasculitides , but can also be
seen in SLE and occasionally IgA
and other nephropathies

12. INHERITED GLOMERULAR DISEASES
• Alport syndrome
• A number of uncommon diseases may affect the
glomerulus in childhood, but the most important one
affecting adults is Alport's syndrome. Most cases
arise from a mutation or deletion of the COL4A5 gene
on the X chromosome which encodes type IV
collagen, resulting in inheritance as an X-linked
recessive disorder. Mutations in COL4A3 or COL4A4
genes are less common and cause autosomal
recessive disease. The accumulation of abnormal
collagen results in a progressive degeneration of the
GBM. Affected patients progress from haematuria to
ESRF in their late teens or twenties. Female carriers
of COL4A5 mutations usually have haematuria but
rarely develop significant renal disease. Some other
basement membranes containing the same collagen
isoforms are similarly affected, notably in the
cochlea, so that Alport's syndrome is associated with
sensorineural deafness and ocular abnormalities. No
specific treatment has been devised to slow the
progress of this condition, but patients with Alport's
syndrome are good candidates for renal replacement
therapy as they are young and usually otherwise
healthy. Some of these patients develop an immune
response to the normal collagen antigens present in

13. THIN GBM DISEASE
• In 'thin GBM' disease there is glomerular
bleeding, usually only at the microscopic
or stick-test level, without associated
hypertension, proteinuria or reduction of
GFR. The glomeruli appear normal by
light microscopy, but on electron
microscopy the GBM is abnormally thin.
This autosomal dominant condition
accounts for a large proportion of
'benign familial haematuria' and has an
excellent prognosis. Some families may
be carriers of autosomal recessive
Alport's syndrome, but this does not

14. TUBULO-INTERSTITIAL DISEASES
• INTERSTITIAL NEPHRITIS A group of
inflammatory, inherited and other
diseases affect renal tubules and the
surrounding interstitium. The clinical
presentation is often renal failure,
but electrolyte abnormalities are
common, especially hyperkalaemia
and acidosis. Proteinuria (and
albuminuria) is rarely > 1 g/24 hrs but
low molecular weight proteinuria
(e.g. retinol-binding protein, β2-
microglobulin, lysozyme) with
haematuria and pyuria are common.

15. ACUTE INTERSTITIAL
NEPHRITIS (AIN)
• Acute inflammation within the tubulo-
interstitium is most commonly allergic,
particularly to drugs, but other causes
include toxins and a variety of systemic
diseases and infections . Renal biopsies
show intense inflammation, with
polymorphonuclear leucocytes and
lymphocytes surrounding tubules and
blood vessels and invading tubules
(tubulitis), and occasional eosinophils
(especially in drug-induced disease).

16. Cont.
• CAUSES OF ACUTE INTERSTITIAL
NEPHRITIS Allergic
• Penicillins
• NSAIDs
• Allopurinol
• Many other drugs

17. Cont.
• Immune
• Autoimmune nephritis ± uveitis
• Infections
• Acute bacterial pyelonephritis
• Leptospirosis
• Tuberculosis
• Hantavirus
• Toxic
• Myeloma light chains

18. Cont.
• Only a minority (perhaps 30%) of patients
with drug-induced AIN have a generalised
drug hypersensitivity reaction (e.g. fever,
rash, eosinophilia) and dipstick testing of
the urine is usually unimpressive. However,
leucocyturia is common, and eosinophils
are found in the urine in up to 70% of
patients. Deterioration of renal function in
drug-induced AIN may be dramatic and
resemble rapidly progressive
glomerulonephritis. Renal biopsy is usually
required to confirm the diagnosis. The
degree of chronic inflammation in a biopsy
is a useful predictor of the eventual
outcome for renal function. Many patients
are not oliguric despite moderately severe
ARF, and AIN should always be considered
in patients with non-oliguric ARF.

19. Cont.
• Management Some patients with
drug-induced AIN recover
following withdrawal of the drug
alone, but corticosteroids (e.g.
prednisolone 1 mg/kg/day)
accelerate recovery and may
prevent long-term scarring.
Dialysis is sometimes necessary,
but is usually only short-term.
Other specific causes should be
treated where possible

20. CHRONIC INTERSTITIAL NEPHRITIS
• Aetiology Chronic interstitial nephritis (CIN)
is caused by a heterogeneous group of
diseases, summarised in . However, it is
quite common for the condition to be
diagnosed late and for no aetiology to be
apparent. Toxic causes of CIN The
combination of interstitial nephritis and
tumours of the collecting system is seen in
Balkan nephropathy, so called because of
where cases are found, and has been
controversially attributed to ingestion of
fungal toxins, particularly ochratoxin A,
present in food made from stored grain. A
plant toxin, aristolochic acid, has been
blamed for a rapidly progressive syndrome
caused by mistaken identity of ingredients
in herbal preparations

21. Cont/CIN
• CAUSES OF CHRONIC INTERSTITIAL
NEPHRITIS Acute interstitial nephritis
• Any of the causes of AIN if persistent
•
• Glomerulonephritis
• Varying degrees of interstitial inflammation
occur in association with most types of
inflammatory glomerulonephritis
• Immune/inflammatory
• Sarcoidosis
• Sjögren's syndrome
• SLE, primary autoimmune
• Chronic transplant rejection

22. • Toxic
• Mushrooms
• Lead
• Chinese herbs
• Balkan nephropathy
• Drugs
• All drugs causing AIN
• Lithium toxicity
• Analgesic nephropathy
• Ciclosporin, tacrolimus
• Infection
• Consequence of severe pyelonephritis
• Congenital/developmental
• Vesico-ureteric reflux-is associated; causation not clear
• Renal dysplasias-often associated with reflux
• Inherited-now well recognised but mechanisms unclear
• Other-Wilson's disease, medullary sponge kidney, sickle-cell
nephropathy
• Metabolic and systemic diseases

23. Cont.
• Long-term ingestion (years to decades) of
analgesic drugs can cause renal papillary
necrosis and CIN. As the papillae are at the
end of the capillary distribution in the
kidney, they become ischaemic most easily
and may necrose in this condition, in sickle-
cell disease and occasionally in diabetes
and other conditions. Necrosed papillae
may cause ureteric obstruction and renal
colic. Papillary necrosis is difficult to
identify other than on IVU or retrograde
pyelography. In animals, lesions can be
induced with almost any NSAID; however,
there has been a dramatic fall in the
incidence of this disease following
withdrawal of phenacetin from compound
analgesics. If it is diagnosed, cessation of
analgesic intake may arrest progression

24. Cont.
• Clinical and biochemical features Most
patients present in adult life with CRF,
hypertension and small kidneys. CRF is
often moderate (urea < 25 mmol/l or 150
mg/dl) but, because of tubular dysfunction,
electrolyte abnormalities are typically
more severe (e.g. hyperkalaemia,
acidosis). Urinalysis abnormalities are
non-specific. A minority of patients
present with hypotension, polyuria and
features of sodium and water depletion
(e.g. low blood pressure and jugular
venous pressure)-salt-losing nephropathy.
Impairment of urine-concentrating ability
and sodium conservation places patients
with CIN at risk of superimposed ARF with
even moderate salt and water depletion
during an acute illness. Hyperkalaemia
may be disproportionate in CIN or in
diabetic nephropathy because of

25. Glomerulonephritis / Glomerulosclerosis
• Glomerulonephritis - An
inflammatory condition that
affects predominantly the
glomeruli.
• Causes
•IgA nephropathy
• Streptococcus bacteria
•Autoimmune
• Glomerulosclerosis - scarring of
the glomeruli

26. GN/GS
Signs and Symptoms
• Blood or protein in urine
• Frothy urine (signifying protein in
urine)
• Dark or pink-coloured urine
• Leg swelling
• Systemic disease like diabetes or
autoimmune disease will have
systemic manifestations, e.g.
weight loss, arthritis, or skin rash

27. GN/GS
Treatment
Specific
• Suppression of inflammation
may be achieved by certain
medications (eg steroids).
General
• Medications to decrease
excretion of urinary protein
• Control of blood pressure
• Dietary modifications

28. Glomerulus – Anato / Histo

29. Nephr I / O tic ????
• NephrOtic
(PrOtein)
• 3 Systemic
Diseases
• Diabetes
• SLE
• Amyloidosis
• 1 “membrane”
• Membranous
GN
• 2 others
• Minimal Change
• NephrItic (RBC +/-
casts)
• 3 Autoimmune
• Poststrep GN
(Type III)
• IgA Nephropathy
(Type III)
• Goospasture’s
(Type II)
• 1 “membrane”
• Membranoproliferati
ve
• 2 others
• Crescentic
• Alport’s (collagen IV

30. Hypersensitivity Essentials of GN
• Type I – IgE cross-linking on
presensitizes mast cells 
inflammatory mediators released
• Type II – Antibodies directed
against specific “enemies.”
Damage cells via complement
mediated “MAC” Inflammatory
response NOT necessarily present
• Type III – Immune complex
deposits (eg SLE)  activates
complement  C5a chemotactic to
neutrophils  damage
• Type IV – T-cell mediated

31. NephrOtic
• Membranous (#1)– Type III HS
• Immune deposits IN the GBM
• Assoc w/ hepatitis B antigenemia,
autoimmune diseases, thyroiditis,
malignancies, pharm (gold, penicillamine,
captopril, NSAIDs).
• Minimal Change Disease (#1 Kids)
• “lipoid nephrosis (why???)”
• Tx w/ steroids
• Focal Segmental Glomerulosclerosis
• Presents w/ acute onset; Glomerular
“scarring”
• Mutliple etiology: Podocyte injury, Nephron
loss, Renal vasodilatation (diabetic
nephropathy, sickle cell, obesity, Von
Gierke’s, Pregnancy, Obesity, Healing of

32. NephrOtic – Systemic Disease
• Diabetes – (1) GBM thickening,
(2) KW Nodules, (3) DIFFUSE
glomerular sclerosis
• SLE (Type III) –
SubENDOthelial deposits
• Amyloidosis
“apple green”

33. NephrItic – Autoimmune
• Poststrep GN (#1 acute) – type III
(“small” – subepithelial “humps”) –
follows sore throat or cellulitis
•Peripheral & periorbital edema
(autoimmune)
• IgA – post-infectious – type III
•Mild, self-limiting, assoc w/
Henoch-Sch
• Goodpastures – type II
•Men in mid 20’s

34. NephrItic – Other 3
• Membranoproliferative –
MESANGIAL CELLS proliferate.
Assoc w/ Hep C, SLE, a1-
antitrypsin.
• Crescentic GN – Fibrin deposition
in Bowman’s. Assoc w/ post-strep
& membranous GN.
• Alport’s – Hereditary, type IV
collagen defect, CN VIII defective

35. Membranoproliferative
“tram-tracking”

36. Linear – Type II
Goodpasture’s
(anti-GBM)
Capillary BM of glomerulus & alveolar walls

37. Granular – Type III
IgA
Nephropathy
(mesangial
deposits)
Post-Strep GN
(Subepithelial)
Membranous GN
(deposits are in
the GBM)
SLE GN
(Subendothelial)
Colon CA (anti-
CEA deposits)