Glomerular disease includes
glomerulonephritis, i.e. inflammation of the
glomeruli and glomerulopathies when there
is no evidence of inflammation.
Glomerulonephritis is a subset of
Presence of glomerular disease as opposed to
tubulointersititial or vascular disease is suspected from
Haematuria (especially dysmorphic red cells)
Red cell casts
Lipiduria (glomerular permeability must be increased to
allow the filtration of large lipoproteins)
Proteinuria (may be in nephrotic range of >3.5 g/24hours)
Immune complex disease
Protease GBM degradation
O₂ free readicals cell damage
AA metabolites ↓ GFR
Complement- dependentComplement-leukocyte- mediated
Activation of the complement
pathway Recruitment of neutrophils
C₅- C₉ (MAC)
Epithelial cell detachment.
(+) epithelial & mesangial
cells to secrete damaging
Upregulates TGF receptors on
epithelial cells, excessive
synthesis of extracellular matrix
which leads to GBM
Named according to
Most common clinical presentations
acute nephritic syndrome
Most common cause is autoimmune
Autoimmune injury initiated by beta-hemolytic
aka acute proliferative glomerulonephritis
Presents as acute nephritic syndrome
increased urea & creatinine
low urine output
Antibodies produced by strep throat deposit in glomerulus
Most fully recover but about 10% evolve into rapidly
Unknown causes or secondary to
Some present as acute nephritic
syndrome & others as renal
Caused by deposition of An-Ab
All but a few progress to renal
Most common cause of
nephrotic syndrome in
About 10% proceed to
renal failure within 10
yrs, 25% recover
progress slowly with
proteinuria, HTN, loss
of renal function
Incidental discovery of occult proteinuria or
Usually presents as chronic renal failure or
Glomerulus has scar tissue
Dialysis & transplant
Diabetes most common cause
most common cause of renal failure
glycoproteins deposit in basement membrane
Acute glomerulonephritis is the
inflammation of the glomeruli which causes
the kidneys to malfunction
It is also called Acute Nephritis,
Glomerulonephritis and Post-Streptococcal
Predominantly affects children from ages 2
Incubation period is 2 to 3 weeks
Previously M-protein of the organism was
felt to be responsible for PSGN.
streptococcal cationic protease and its
zymogen precursor (NAPR) has been
identified as a glyceraldehyde-3-phosphate
dehydrogenase that functions as a
Diffuse proliferative GN (PGN)
proliferation of cells within the glomeruli, accompanied
by leukocyte filtrate
typical features of immune complex disease :
- granular deposits of IgG & complement on GBM
Implicated antigens seem to be endostreptosin and nephritis –
plasmin- binding ptn
Nausea and vomiting
High blood pressure
Pallor due to edema and/or anemia
Loss of muscle tissue
Enlargement of the liver
Hematuria: dark brown or smoky urine
Oliguria: urine output is < 400 ml/day
Edema: starts in the eye lids and face then
the lower and upper limbs then becomes
generalized; may be migratory
Hypertension: usually mild to moderate
Abrupt onset of:
glomerular haematuria (RBC
casts or dysmorphic RBC).
proteinuria (<2 g in 24 hrs).
oedema (periorbital, sacral).
transient renal impairment
Base line measurements:
- ↑ Urea
- ↑ Creatinine
a) Urine microscopy (red cell cast)
Hypertensive encephalopathy, heart failure and acute
pulmonary edema may occur in severe cases
Acute renal necrosis due to injury of capillary or capillary
Treat the underlying infections when acute GN is associated with chronic infections.
Antibiotics (eg, penicillin) are used to control local symptoms and to prevent
spread of infection to close contacts.
Antimicrobial therapy does not appear to prevent the development of GN,
except if given within the first 36 hours.
Loop diuretic therapy
Loop diuretics may be required in patients who are edematous and hypertensive
in order to remove excess fluid and to correct hypertension.
Relieves edema and controls volume, thereby helping to control volume-related
elevation in BP.
Vasodilator drugs (eg, nitroprusside, nifedipine, hydralazine, diazoxide) may be
used if severe hypertension or encephalopathy is present
Sodium and fluid restriction
Protein restriction for azotemic patients
Activity: Recommend bed rest until signs of glomerular inflammation and
circulatory congestion subside.
Post streptococcal GN
- Has a GOOD prognosis.
- Supportive measures until spontaneous recovery.
- Control HT.
- Fluid balance.
- Oliguric with fluid overload.
- GN complicating SLE or systemic vasculitides:
immunosuppression with prednisolone,
cyclophosphamide or azathioprine/MMF.
The condition is characterized by
irreversible and progressive glomerular and
-> ultimately leading to a reduction in the
glomerular filtration rate (GFR) and retention
of uremic toxins.
-> If disease progression is not halted with
therapy, the net result is chronic kidney
disease (CKD), end-stage renal disease
(ESRD), and cardiovascular disease
Nearly all forms of acute glomerulonephritis have a
tendency to progress to chronic glomerulonephritis.
The progression from acute glomerulonephritis to
chronic glomerulonephritis is variable.
Whereas complete recovery of renal function is the
rule for patients with poststreptococcal
glomerulonephritis, several other
glomerulonephritides, such as immunoglobulin A
(IgA) nephropathy, often have a relatively benign
course and many do not progress to ESRD.
Reduction in nephron mass from the initial injury
reduces the GFR.
This reduction leads to hypertrophy and
hyperfiltration of the remaining nephrons and to the
initiation of intraglomerular hypertension.
These changes occur in order to increase the GFR of
the remaining nephrons, thus minimizing the
functional consequences of nephron loss.
The changes, however, are ultimately detrimental
because they lead to glomerulosclerosis and further
Segmental areas of
large glomeruli with mesangial
proliferation and ‘double’ BM. 2 histological
types: type I (subendothelial deposits) type II
thickened BM, IF +ve
for IgG & C3 and
Hypercellularity, mesangial proliferation,
inflammatory cell infiltrate, positive IF for IgG
and C3 and subepithelial deposits on EM.
Most common cause of GN in Asia but uncommon in Sth
America or Africa
15-40% of all biopsy proven GN
Male > Females
Most commonly asymptomatic with serendipitous finding of
haematuria and mild proteinuria
Another classic presentation is macroscopic haematuria in
conjunction with a viral infection
Renal function is usually normal but occasionally a patient
will present with acute renal failure due to acute tubular
necrosis secondary to the gross haematuria
Biopsy – mild to moderate mesangial cell proliferation, IgA
deposits in the mesangium on immunofluorescence, often
with C3 deposition also
By 20 years, 50% have end stage kidney
Worse prognosis if >1g/day proteinuria,
hypertension, increased creatinine of
glomerular fibrosis at biopsy, on presentation
Jugular venous distension (if severe volume overload is
Pulmonary rales (if pulmonary edema is present)
Pericardial friction rub in pericarditis
Tenderness in the epigastric region or blood in the stool
(possible indicators for uremic gastritis or enteropathy)
Decreased sensation and asterixis (indicators for advanced
Urinary protein excretion
Serum creatinine and urea nitrogen levels are elevated.
Impaired excretion of potassium, free water, and acid results
in hyperkalemia, hyponatremia, and low serum bicarbonate
Impaired vitamin D-3 production results in hypocalcemia,
hyperphosphatemia, and high levels of parathyroid
Low serum albumin levels may be present if uremia
interferes with nutrition or if the patient is nephrotic.
Obtain a renal ultrasonogram to determine renal
size, to assess for the presence of both kidneys,
and to exclude structural lesions that may be
responsible for azotemia.
Small kidneys often indicate an irreversible
The target pressure for patients with proteinuria greater
than 1 g/d is less than 125/75 mm Hg; for patients with
proteinuria less than 1 g/d, the target pressure is less than
130/80 mm Hg.
Angiotensin-converting enzyme inhibitors (ACEIs)
angiotensin II receptor blockers (ARBs)
combination therapy with ACEIs and ARBs.
calcium channel blockers,
central alpha-2 agonists (eg, clonidine),
direct vasodilators (eg, minoxidil, nitrates) may be used to achieve
the target pressure.
Renal osteodystrophy can be managed early by
replacing vitamin D and by administering phosphate
Seek and treat nonuremic causes of anemia, such as
iron deficiency, before instituting therapy with
Discuss options for renal replacement therapy (eg,
hemodialysis, peritoneal dialysis, renal
Treat hyperlipidemia (if present)
Expose patients to educational programs for early
rehabilitation from dialysis or transplantation.
Minimal change glomerulonephritis (MCGN)
Corticosteroids induce remission in >90% of
children and 80% of adults (slower response).
Indications for immunosuppression:
(cyclophosphamide, ciclosporin (=cylosporin)):
early/ frequent relapses; steroid SEs/dependence.
Prognosis: 1% progress to ESRF.
Focal segmental glomerulosclerosis
Poor response to corticosteroids (10–30%).
Cyclophosphamide or ciclosporin
(=cylosporin) may be used in steroid-resistant
Prognosis: 30–50% progress to ESRF.
Treatment: None is of proven benefit.
Prognosis: 50% develop ESRF.
If renal function deteriorates, consider
corticosteroids and chlorambucil.
Prognosis: Untreated, 15% complete
remission, 9% ESRF at 2–5yrs and 41% at
Mesangial proliferative GN
Antibiotics, diuretics, and
antihypertensives as necessary. Dialysis is
Aggressive control of blood pressure and
proteinuria with ACEI’s or AR2B’s
Corticosteroids +/- azathiprine – varied schools of
However if rapidly progressive GN with crescent
deposition treatment should be aggressive with
high dose steroids and cyclophosphamide
Consult the Nephrologist
Rapidly progressive glomerulonephritis
(RPGN) is a disease of the kidney that results
in a rapid decrease in the glomerular filtration
rate of at least 50% over a short period, from
a few days to 3 months.
Classic – haemoptysis after upper respiratory infection and
have nephritic urinary sediment
History of smoking or hydrocarbon exposure is common
CXR – pulmonary haemorrhage
Lab- iron deficiency anaemia and renal dysfunction,
circulating anti-GBM antibodies
Kidney biopsy crescentic GN with linear staining IgG and C3
along the glomerular basement membrane
More than 80% of patients with
pauci-immune RPGN were
subsequently found to have
cytoplasmic antibodies (ANCA),
and thus, this form of RPGN is now
termed ANCA-associated vasculitis.
RPGN is classified pathologically into 3
(1) anti-GBM antibody disease
(approximately 3% of cases),
(2) immune complex disease (45% of cases),
(3) pauci-immune disease (50% of cases).
Symptoms and signs of renal failure,
systemic symptoms (fever, malaise, myalgia,
The most important requirement in the diagnosis of antineutrophil
cytoplasmic antibodies (ANCA) ANCA-associated disease is a high index
of suspicion. Rapid diagnosis is essential for organ preservation.
Laboratory studies include the following:
Routine chemistry: The most common
abnormality is an increased serum
Urinalysis with microscopy:
Antinuclear antibody (ANA) titer: