This document discusses glomerular disease and glomerulonephritis. It begins by defining glomerular disease and glomerulonephritis, noting that glomerulonephritis is a type of glomerular disease involving inflammation of the glomeruli. It then discusses the main clinical presentations of glomerular disease, including nephrotic syndrome, acute glomerulonephritis, and asymptomatic urinary abnormalities. The causes, symptoms, investigations, and management of various glomerular diseases are subsequently outlined. Throughout, examples are provided of specific diseases like post-streptococcal glomerulonephritis, membranous nephropathy, and crescentic glomerulone

1. PRESENTED BY
DR SHASHANK AGRAWAL
(MEDICINE)

2.  Glomerular disease includes
glomerulonephritis, i.e. inflammation of the
glomeruli and glomerulopathies when there
is no evidence of inflammation.
 Glomerulonephritis is a subset of
glomerulopathies

3.  Nephrotic syndrome.
 Acute glomerulonephritis (acute nephritic
syndrome).
 Rapidly progressive glomerulonephritis.
 Asymptomatic urinary abnormality
(haematuria, proteinuria or both).

4. Primary – confined to the kidney
Secondary – due to a systemic
disease

5. 5
 Proteinuria – asymptomatic
 Haematuria – asymptomatic
 Hypertension
 Nephrotic syndrome
 Nephritic syndrome
 Acute renal failure
 Rapidly progressive renal failure
 End stage renal failure

6. 6
 Presence of glomerular disease as opposed to
tubulointersititial or vascular disease is suspected from
history
 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)

8. Immune complex disease
 Neutrophils:
Protease GBM degradation
O₂ free readicals cell damage
AA metabolites ↓ GFR
Complement- dependentComplement-leukocyte- mediated
mechanism
 Activation of the complement
pathway Recruitment of neutrophils
and monocytes
C₅- C₉ (MAC)
Epithelial cell detachment.
 (+) epithelial & mesangial
cells to secrete damaging
chemical mediators.
Upregulates TGF receptors on
epithelial cells, excessive
synthesis of extracellular matrix
which leads to GBM
thickening

9.  Named according to
 etiology
 microscopic findings
 clinical syndrome
 Most common clinical presentations
 acute nephritic syndrome
 nephrotic syndrome
 Most common cause is autoimmune

10.  Autoimmune injury initiated by beta-hemolytic
streptococcus
 aka acute proliferative glomerulonephritis
 Presents as acute nephritic syndrome
 hematuria
 HT
 increased urea & creatinine
 low urine output
 edema
 Antibodies produced by strep throat deposit in glomerulus
 Most fully recover but about 10% evolve into rapidly
progressive glomerulonephritis

11.  Unknown causes or secondary to
poststreptococcal
glomerulonephritis
 Autoimmune
 aka crescentric
glomerulonephritis
 Some present as acute nephritic
syndrome & others as renal
failure
 Caused by deposition of An-Ab
complexes
 All but a few progress to renal
failure

12.  Autoimmune
 Most common cause of
nephrotic syndrome in
adults
 About 10% proceed to
renal failure within 10
yrs, 25% recover
completely, most
progress slowly with
proteinuria, HTN, loss
of renal function

13.  Incidental discovery of occult proteinuria or
HTN
 Usually presents as chronic renal failure or
occult proteinuria
 Glomerulus has scar tissue
 Dialysis & transplant

14.  Diabetes most common cause
 most common cause of renal failure
 glycoproteins deposit in basement membrane
 Vascular disease
 atherosclerosis
 HTN
 vascultitis

15. Heavy
proteinuria
Proteinuria &
haematuria
Predominant
haematuria
Minimal Change Lupus nephritis Acute post strep
Focal sclerosis
Membranous
Diabetes Mellitus
Amyloidosis
Membrano-
proliferative
Endocarditis
Henoch-Schonlein
purpura
Crescentic
(RPGN)
Haemolytic
uraemic syndrome

16.  Acute glomerulonephritis is the
inflammation of the glomeruli which causes
the kidneys to malfunction
 It is also called Acute Nephritis,
Glomerulonephritis and Post-Streptococcal
Glomerulonephritis
 Predominantly affects children from ages 2
to 12
 Incubation period is 2 to 3 weeks

17.  Infectious
 Streptococcal
 Nonstreptococcal postinfectious
glomerulonephritis
▪ Bacterial
▪ Viral
▪ Parasitic
 Noninfectious
 Multisystem systemic diseases
 Primary glomerular diseases

18. Previously M-protein of the organism was
felt to be responsible for PSGN.
Recently, nephritis-associated
streptococcal cationic protease and its
zymogen precursor (NAPR) has been
identified as a glyceraldehyde-3-phosphate
dehydrogenase that functions as a
plasmin(ogen) receptor.

19. Diffuse proliferative GN (PGN)
 proliferation of cells within the glomeruli, accompanied
by leukocyte filtrate
 typical features of immune complex disease :
- hypocomplimentemia
- granular deposits of IgG & complement on GBM
 Implicated antigens seem to be endostreptosin and nephritis –
plasmin- binding ptn

20.  Fever
 Headache
 Malaise
 Anorexia
 Nausea and vomiting
 High blood pressure
 Pallor due to edema and/or anemia
 Confusion
 Lethargy
 Loss of muscle tissue
 Enlargement of the liver

21.  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

22.  urinary (haematuria, proteinuria),
 nephritic (edemas, hypertension, gross
haematuria, proteinuria),
 nephrotic (edemas, proteinuria,
hypoproteinemia, hypercholesterolemia),
 mixed.

23.  Abrupt onset of:
glomerular haematuria (RBC
casts or dysmorphic RBC).
non-nephrotic range
proteinuria (<2 g in 24 hrs).
oedema (periorbital, sacral).
hypertension.
transient renal impairment
(oliguria, uraemia).

24. Base line measurements:
- ↑ Urea
- ↑ Creatinine
Urinalysis (MSU):
a) Urine microscopy (red cell cast)
b) proteinuria
COMPLICATION
Hypertensive encephalopathy, heart failure and acute
pulmonary edema may occur in severe cases
Acute renal necrosis due to injury of capillary or capillary
thrombosis

25. Treat the underlying infections when acute GN is associated with chronic infections.
 Antimicrobial therapy
 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
 Diet:
 Sodium and fluid restriction
 Protein restriction for azotemic patients
 Activity: Recommend bed rest until signs of glomerular inflammation and
circulatory congestion subside.

26. 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.

27. The condition is characterized by
irreversible and progressive glomerular and
tubulointerstitial fibrosis.
-> 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

28. 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.

29. 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
nephron loss.

30. fusion of podocytes
on electron microscopy

31. Segmental areas of
glomerular sclerosis,
hyalinization of
glomerular capillaries

32. large glomeruli with mesangial
proliferation and ‘double’ BM. 2 histological
types: type I (subendothelial deposits) type II
(intramembranous deposits)

33. thickened BM, IF +ve
for IgG & C3 and
subepithelial deposits
on EM

34. Hypercellularity, mesangial proliferation,
inflammatory cell infiltrate, positive IF for IgG
and C3 and subepithelial deposits on EM.

35.  Most common cause of GN in Asia but uncommon in Sth
America or Africa
 15-40% of all biopsy proven GN
 Male > Females
 2nd
-3rd
decade
 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

36.  Slowly progressive
 By 20 years, 50% have end stage kidney
disease
 Worse prognosis if >1g/day proteinuria,
hypertension, increased creatinine of
glomerular fibrosis at biopsy, on presentation

37.  Uremia-specific findings
 Edemas
 Hypertension
 Jugular venous distension (if severe volume overload is
present)
 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
uremia)

38.  Latent (changes in urine)
 Hypertensive (increased blood pressure)
 Hematuric
 Nephrotic (edemas, proteinuria,
hypoproteinemia, hypercholesterolemia),
 Mixed

39.  Urinalysis
 Urinary protein excretion
 Serum chemistry
 Serum creatinine and urea nitrogen levels are elevated.
 Impaired excretion of potassium, free water, and acid results
in hyperkalemia, hyponatremia, and low serum bicarbonate
levels, respectively.
 Impaired vitamin D-3 production results in hypocalcemia,
hyperphosphatemia, and high levels of parathyroid
hormone.
 Low serum albumin levels may be present if uremia
interferes with nutrition or if the patient is nephrotic.

40.  Renal ultrasonogram
 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
process.
 Kidney biopsy

41.  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.
 Diuretics
 Beta-blockers,
 calcium channel blockers,
 central alpha-2 agonists (eg, clonidine),
 alpha-1 antagonists
 direct vasodilators (eg, minoxidil, nitrates) may be used to achieve
the target pressure.

42.  Renal osteodystrophy can be managed early by
replacing vitamin D and by administering phosphate
binders.
 Seek and treat nonuremic causes of anemia, such as
iron deficiency, before instituting therapy with
erythropoietin.
 Discuss options for renal replacement therapy (eg,
hemodialysis, peritoneal dialysis, renal
transplantation).
 Treat hyperlipidemia (if present)
 Expose patients to educational programs for early
rehabilitation from dialysis or transplantation.

43. 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.

44. Focal segmental glomerulosclerosis
Poor response to corticosteroids (10–30%).
Cyclophosphamide or ciclosporin
(=cylosporin) may be used in steroid-resistant
cases.
Prognosis: 30–50% progress to ESRF.

45. Mesangiocapillary GN
Treatment: None is of proven benefit.
Prognosis: 50% develop ESRF.

46. Membranous nephropathy
If renal function deteriorates, consider
corticosteroids and chlorambucil.
Prognosis: Untreated, 15% complete
remission, 9% ESRF at 2–5yrs and 41% at
15yrs.

47. Mesangial proliferative GN
Antibiotics, diuretics, and
antihypertensives as necessary. Dialysis is
rarely required.
Prognosis: Good.

48.  Management
 Aggressive control of blood pressure and
proteinuria with ACEI’s or AR2B’s
 Corticosteroids +/- azathiprine – varied schools of
thought
 However if rapidly progressive GN with crescent
deposition treatment should be aggressive with
high dose steroids and cyclophosphamide
 Consult the Nephrologist

49. 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.

50. 50
 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

51. More than 80% of patients with
pauci-immune RPGN were
subsequently found to have
circulating antineutrophil
cytoplasmic antibodies (ANCA),
and thus, this form of RPGN is now
termed ANCA-associated vasculitis.

52. RPGN is classified pathologically into 3
categories:
 (1) anti-GBM antibody disease
(approximately 3% of cases),
 (2) immune complex disease (45% of cases),
 (3) pauci-immune disease (50% of cases).

53.  Symptoms and signs of renal failure,
 pain,
 haematuria,
 systemic symptoms (fever, malaise, myalgia,
weight loss).

54.  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
creatinine level.
 Urinalysis with microscopy:
 Antinuclear antibody (ANA) titer:
 ANCA .

55. High-dose corticosteroids;
cyclophosphamide ± plasma exchange/ renal
transplantation. Prognosis: Poor if initial
serum creatinine >600µmol/L.

56. THANK YOU