Pathology of Common

Glomerular Syndromes

Dr Purushotham Krishnappa

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Objectives

• Define the basic renal terminologies

• State the key clinical features of common

glomerular syndromes
• Nephrotic syndrome
• Nephritic syndrome
• Rapidly progressive glomerulonephritis
Basic terminology and concepts

Azotemia

Biochemical abnormality
Raised blood urea nitrogen and creatinine
Decreased GFR

The cause may be:

Renal
Extrarenal
Pre-renal: hypoperfusion
Post-renal: obstruction
Basic terminology and concepts

Uraemia

Azotaemia plus clinical signs and symptoms

Metabolic
Endocrine
Gastrointestinal – uraemic gastroenteritis
Peripheral nerves – peripheral neuropathy
Heart – uraemic fibrinous pericarditis.
Important terminology

•Proteinuria – protein in the urine

•Haematuria – blood in the urine
Clinical syndromes

• Clinical syndromes are convenient starting points to identify

and evaluate kidney diseases.

• Syndromes related to injury to the glomerular capillary wall

are quite specific for glomerular diseases.

• Clinical presentations of diseases of tubules, interstitium and

blood vessels are less specific.
They often present as non-specific acute or chronic renal
insufficiency.
Clinical syndromes

• Point to remember:
Some diseases may have more than 1 clinical presentation
with different syndromes or a mixture of syndromes, e.g. SLE

Therefore, clinical syndromes alone may not be sufficient.

A renal biopsy - based diagnosis may be required.
Clinical syndromes for glomerular diseases

1. Nephrotic syndrome
2. Acute nephritis
3. Asymptomatic haematuria
4. Asymptomatic proteinuria.
5. Rapidly progressive glomerulonephritis
6. Acute renal failure
7. Chronic renal failure
Nephrotic Syndrome

1. Heavy proteinuria (Nephrotic range is more than 3.5 gm /day)

2. Hypoalbuminaemia (less than 3 gm/dl)
3. Severe oedema- generalised
4. Hyperlipidemia

Classic example: minimal change disease

Causes of Nephrotic Syndrome
Primary Glomerular Disease
• Membranous glomerulopathy - Adults
• Minimal change disease - Children
• Focal segmental glomerulosclerosis
• Membranoproliferative glomerulonephritides
• Other proliferative glomerulonephritis (focal, "pure mesangial," IgA
nephropathy)
Systemic Diseases
• Diabetes mellitus
• Amyloidosis
• Systemic lupus erythematosus
• Drugs (nonsteroidal anti-inflammatory, penicillamine, "street heroin")
• Infections (malaria, syphilis, hepatitis B and C, acquired
immunodeficiency syndrome)
• Malignant disease (carcinoma, lymphoma)
• Miscellaneous (bee-sting allergy, hereditary nephritis)
Causes and conditions associated
with nephrotic syndrome
Frequency:
Children:
•Minimal change disease 88%
•Focal segmental glomerulosclerosis 5%
•Membranoproliferative glomerulonephritis 1%
Adults:
•Minimal change 15%
•Focal segmental glomerulosclerosis 35%
•Membranous glomerulopathy 33%
•Membranoproliferative glomerulonephritis 2%
Nephrotic syndrome

• Associated with a myriad of diseases.

• A few forms of glomerular diseases account of most of the cases of

nephrotic syndrome.
Hypoproteinemia

• Albumin
• Immunoglobulins
• Metal binding proteins
• Erythropoietin urinary loss
• Transferrin
• Complement deficiency
• Coagulation components
Hyperlipidemia
• Hypercholesterolemia
• Hypertriglyceridemia
• Low-density lipoproteins (LDL)
• Very low- density lipoproteins (VLDL)

• Increased hepatic synthesis of LDL, VLDL and

lipoprotein (a) in response to hypoalbuminemia

• Urinary loss of HDL

• Enzymatic changes with abnormal lipid biosythesis

and degradation
Edema

• Lower colloid osmotic pressure?

Edema
Diagnosis

• Diagnosis:
Nephrotic Syndrome?
Primary or secondary?
Complications?
Differential diagnosis

Primary Secondary
Children Minimal change Allergic purpura
disease
Teenage Mesangial FSGS
proliferative nephritis

Middle age Mesangial capillary Lupus

nephritis

Old age Membranous Amyloid

nephropathy Myeloma
Complications

• Acute renal failure( ARF)

• Blood clots
• High blood cholesterol and elevated blood triglycerides
• Acute kidney injury
• Chronic kidney disease
• Infections.
Treatment

Support care
• Rest in bed; limitation of protein intake(0.8-1.0g/kg/d); limitation of
salt intake (<3g/d)

• Diuretic therapy

• Diminishing proteinuria: ACEI and ARB

Treatment

• Minimal changes: sensitive to steroids; single drug; reuse when

relapse; combined with cytotoxic drugs when resistant or dependent
on steroids
• Membranous GN: combine steroid with cytotoxic drugs or
cyclosporin; avoid using drugs when Scr>354umol/L; for the patients
with risks for progressing, otherwise, investigate 6 months
(antihypertensive).
• FSGS: sensitive to steroids in 30-50% of patients; slow response to
therapy; steroids therapy (onset) for 3-4 months; if not response until
6 month (resistant), then try cyclosporine.
• Mesangial proliferative GN: no evidence show that adults will
response to steroids; aspirin
Acute Nephritis

• Acute onset
• Gross hematuria
• Hypertension
• Mild to moderate proteinuria

Classic example: acute post-streptococcal glomerulonephritis

Asymptomatic hematuria or proteinuria

• Haematuria

• Subnephrotic proteinuria
Rapidly Progressive Glomerulonephritis

Characterised by:

• Acute nephritis

• Proteinuria

• Acute renal failure

Classic example: Crescentic glomerulonephritis

Normal Glomerulus – PAS staining
basement membrane
Histologic Alteration of glomerulus

1. Hypercellularity (proliferative)

2. Basement membrane thickening

3. Hyalinisation or sclerosis of
glomerulus
 Histologic Alteration of glomerulus -
1
Hypercellularity
(proliferative)
Increase in number of cells
in glomerular tuft.
Due to:
• Cellular proliferation of
mesangial or endothelial cells
(endocapillary)
• Leukocyte infiltration
• Crescent formation
(extracapillary)
 Histologic Alteration of glomerulus -
2
Basement membrane
thickening

• Thickening of capillary wall by light

microscopy

• On electron microscopy -deposition of

amorphous material often immune
complexes on endothelial/epithelial
side of basement membrane e.g.
membranous glomerulopathy

OR
• Thickening of basement membrane
proper e.g diabetic glomerulosclerosis
Histologic Alteration of glomerulus-
3
Hyalinisation or
sclerosis of
glomerulus
• Amorphous substance – plasma proteins
• Collagen
• Capillary lumina obliterated
• End result of various glomerular damage
Glomerular Pathology Terminology

• Diffuse - all glomeruli affected

• Global - the whole glomerulus affected

• Focal – only a portion of glomeruli affected

• Segmental – only a part (segment) of each glomerulus affected

• Mesangial – mesangium affected.

Summary of Glomerular Syndromes
Acute nephritic syndrome Hematuria, azotemia, variable
proteinuria, oliguria, edema, and
hypertension

Rapidly progressive Acute nephritis, proteinuria, and

glomerulonephritis acute renal failure

Nephrotic syndrome >3.5 gm proteinuria,

hypoalbuminemia, hyperlipidemia,
lipiduria
Chronic renal failure Azotemia Õ uremia progressing for
years

Asymptomatic hematuria or Glomerular hematuria; subnephrotic

proteinuria proteinuria
CASE 1

• A child abruptly develops malaise, fever, nausea, oliguria, and

hematuria (smoky or cola-colored urine) 1 to 2 weeks after recovery
from a sore throat.
• There is periorbital edema, and mild to moderate hypertension.
• Urine analysis showed - red cell casts and mild proteinuria (< than 1
gm/day),
• Important laboratory findings include elevations of antistreptococcal
antibody titers.
References:

• Charles E. Alpers and Anthony Chang. Robbins and

Cotran Pathologic Basis of Disease. 9th Edition. The
Kidney. Chapter 20, 897-957.
• Sinha A, Bagga A. Indian J Pediatr. Nephrotic
syndrome. 2012 Aug;79(8):1045-55.
• Khanna R. Clinical presentation & management of
glomerular diseases: hematuria, nephritic &
nephrotic syndrome. Mo Med. 2011 Jan-
Feb;108(1):33-6.
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