1. Glomerular diseases involve inflammation or disorders of the glomerulus in the kidney. Common glomerular diseases include glomerulonephritis and glomerulopathy. 2. Proteinuria and hematuria are common signs of glomerular disease. Persistent proteinuria or hematuria should be investigated further. Causes can include infections, autoimmune diseases, genetic factors, metabolic disorders and other systemic illnesses. 3. Glomerular diseases are classified based on factors such as location of involvement in the glomerulus (focal vs diffuse) and whether the primary involvement is of the glomerulus or a secondary manifestation of another disease. Immune mechanisms underlie many primary and secondary glomerular

1. Glomerular Diseases
Natangwe Shimhanda
MBChB V

2. Glomerulus
• A tuft of capillaries situated within a
Bowman's capsule at the end of a renal tubule
in the vertebrate kidney that filters waste
products from the blood and thus initiates
urine formation.
• The basic filtration unit of the kidney.

3. Anatomy and Function

4. • Molecules <1.8nm are freely filtered e.g water,
sodium, insulin, glucose
• Molecules > 3.6nm are not filtered e.g
hemoglobin

5. Renal Corpuscle

6. 3 Layers of the Glomerulus

7. Ultrafiltration Barrier
• Capillary Endothelium with fenestration pores
filters everything except blood cells
• Basement membrane prevents filtration of
large proteins
• Podocytes make the outer layer, and they
have pedicels that allow only small molecules
to pass through.

8. Filtration forces
• Filtration Depends on the Starling forces
– Oncotic pressure exerted by the plasma proteins in the
glomerular capillaries and bowman’s capsule
– Hydrostatic pressure exerted by the fluid in the capillary
walls

10. Glomerular Filtration Rate
• Total amount of filtrate in all the renal
corpuscles in both kidneys per minute.
• Assesses kidney function
• Takes into account Net Filtration pressure
(NFP), the surface area available for filtration
and the permeability of the glomeruli

11. Creatinine Clearance
• Males
{(140-age)*wt*1.22}/Cr
• Females
{(140-age)*wt*1.22}/Cr
multiply the answer by 0.85
• Ranges M 97-137
F 88-128

12. GFR
• Normal GFR varies according to age, sex, and
body size, and declines with age.
• The formula eGFR = k × height (cm) ÷
creatinine (μmol/L) provides estimate of GFR.

13. Glomerular Diseases
• Glomerulonephritis is an inflammation of the
glomerulus, while glomerulopathy is a term for
disorders affecting this structure.
• Glomeruli may be injured by variety of factors
and in course of several systemic diseases.
• Most of the glomerular diseases are
immunologically mediated, whereas tubular and
interstitial disorders are frequently caused by
toxic or infectious agents.

14. Classification
• Focal (affecting only some of glomeruli) or
Diffuse (affecting most or all glomeruli)
• Segmental/Global
• Primary glomerular disease (glomeruli are the
predominant site of involvement) or
Secondary glomerular disease (includes
certain systemic and hereditary diseases
which secondarily involve the glomeruli)

15. • Immune mechanisms underlie most forms of primary
glomerulopathies and many of secondary glomerular disorders.
 Damage by immune complexes
 Damage by cytotoxic antibodies
 Cell-mediated immune injury (delayed type hypersensitivity )
 Damage by complement and proinflammatory mediators
PATHOGENESIS OF GLOMERULAR
INJURY

16. METABOLIC GLOMERULAR INJURY
Diabetic nephropathy, Fabry’s disease
HAEMODYNAMIC GLOMERULAR INJURY
Systemic hypertension
DEPOSITION DISEASES
Amyloidosis, cryoglobulinaemia.
INFECTIOUS DISEASES
HBV, HCV, HIV, E.coli-derived nephrotoxin
INHERITED GLOMERULAR DISEASES
Alports syndrome
NON IMMUNE MECHANISM OF CELLULAR
INJURY IN GLOMERULUS

18. 1. Proteinuria
• Transient proteinuria may occur during febrile
illnesses or after exercise and does not require
investigation.
• Persistent proteinuria is significant and should
be quantified by measuring the urine
protein/creatinine ratio in an early morning
sample (protein should not exceed 20
mg/mmol of creatinine).

19. Causes of proteinuria
• Orthostatic proteinuria
• Glomerular abnormalities
– Minimal change disease
– Glomerulonephritis
– Abnormal glomerular basement membrane (familial
nephritides)
• Increased glomerular filtration pressure
• Reduced renal mass
• Hypertension
• Tubular proteinuria.

20. (i) Nephrotic syndrome
A nonspecific disorder in which the kidneys are
damaged, causing them to leak large amounts
of protein from the blood into the urine.
Clinical state characterised by:
• Heavy proteinuria, 50mg/kg
• Hypoalubinaemia, 25gm/l
• Oedema
• Generalised hyperlipaedaemia

21. • Primary causes
– Minimal-change
nephropathy
– Focal glomerulosclerosis
– Membranous nephropathy
– Hereditary nephropathies
Nephrotic syndrome

22. • Secondary causes
– Diabetes mellitus
– Amyloidosis and paraproteinemias
– Post infectious-
– Group A beta haem strep and other bacteria eg.
Typhoid and syphilis
– Malaria
– Viral-chickenpox, HIV, Hep B, EBV
– Renal vein thrombosis
– Collagen vascular-SLE,
Nephrotic syndrome

23. Causes Cont’
• Hereditary nephritis- nail patella and Alport’s
• Sickle cell disease
• Malignancy: leukaemia, lymphoma, wilm’s
• Toxins: Bee stings, poison ivy, oak, snake
vernom
• Drugs: probrnicid, captopril, heroin, mercury,
gold, penicillamine etc

24. • Signs and symptoms
– Hypoalbuminemia
– Edema
– Hypercholesterolemia
– Hypoalbuminemia
– Tiredness
– Leukonychia
– Breathlessness
– fluid overload
– Dyslipidaemia
Nephrotic syndrome

25. • TREATMENT
–Supportive Treatment
• Monitoring and maintaining euvolemia
–Monitoring urine output, BP regularly
–Fluid restrict to 1L.
–Diuretics (IV furosemide).
Nephrotic syndrome

26. • TREATMENT
–Supportive Treatment
• Monitoring kidney function
–Do U&E daily and calculating GFR
–Treat hyperlipidemia to prevent further
atherosclerosis.
–Prevent and treat any complications
Nephrotic syndrome

27. • TREATMENT
–Specific Treatment
• Immunosuppression for the
glomerulonephritides
• Corticosteroid therapy: 60 mg/m2 per
day of prednisolone
Nephrotic syndrome

28. Treatment
• The steroid sensitive Nephrotic Syndrome resolves
spontaneously after a corticosteroid therapy course.
A renal biopsy must be done if unresponsive or
atypical features.
• Steroid-resistant nephrotic syndrome: Management
of the oedema is by diuretic therapy, salt restriction,
ACE inhibitors and sometimes NSAIDs which may
reduce proteinuria

29. (ii) Congenital nephrotic Syndrome
• Presents in utero, from birth up to 3/12
• Infantile: 4/12 up to 1 year of life.
Primary Causes
• Infantile microcytic disease
• Diffuse mesangial sclerosis (Drash)
• Minimal change lesion
• Focal Glomerulosclerosis

30. Secondary congenital and infantile:
• Infections: syphilis, Toxoplasmosis, CMV,
Rubella, Malaria
• Toxic: mercury
• SLE
• HUS
• Drug reaction
• Hepatoblastoma
• Syndromes: Nail patella, Lowe syndrome etc

31. Epidemiology:
• 2-7 children per 100,000 children/year
• 15 times more common in children than
adults
• Incidence higher in black children
• M:F=2:1

32. Pathophysiology:
• Protein: normal urine in children has 100mg
protein/24hrs (adults 150mg).
• Consists of albumin and Tamm-Horsfall
protein of tubular origin.
Increased protein loss is due to:
• Increased capillary permeability.
• Increased in size of pores of GBM

33. Pathophysiology continue:
• Selectivity: type of protein lost varies with the
underlying glomerular disease.
• Minimal change- highly selective, other
glomerular disease non selective.
• Hypoalbuminaemia: due to excessive urinary
loss of albumin.
• Oedema: cardinal feature of nephrotic due to
decreased plasma oncotic pressure

34. Clinical manifestations:
• Oedema usual and a predominant features
• Gastrointestinal disturbances e.g
• Dirrhoea (oedema of intestinal mucosa)
• hepatomegaly
• Abdominal pain- peritonitis, UTI
• Tachypnoea –pleural effusions, ascites, infection
• Poor appetite
• Psychological functional disturbances

35. Investigations:
• Proteinuria may be selective or non selective
• Urine Protein/creatinine ratio < 0,2 normal
• 0,1-0,5 minimal
• 0,2-2,0 moderate
• > 2,0 nephrotic
• FBC+ diff, ESR, u+e, Total protein, albumin,
cholesterol, INR, C3/C4, ASOT, Anti-DNASe B,
Hepatitis B, WR, HIV, ANA, CXR, TST, CMP

36. Complications:
• Renal failure: acute renal failure, HPT
• Infections: bacterial
• Thromboembolism: platelets, protein S&C def
• FTT and malnutrition
• Premature atherosclerosis from hyperlipemia
• Calcium and Vitamin D metabolism

37. 2. Hematuria
• Urine that is red in colour or tests positive for
haemoglobin on urine sticks should be examined
under the microscope to confirm haematuria
(>10 red blood cells per high-power field).
• Glomerular haematuria is suggested by brown
urine, the presence of deformed red cells (which
occurs as they pass through the basement
membrane) and casts, and is often accompanied
by proteinuria.

38. Causes of Hematuria
Non-glomerular
• Infection (bacterial, viral,
TB, schistosomiasis)
• Trauma to genitalia, urinary
tract or kidneys
• Stones
• Tumours
• Sickle cell disease
• Bleeding disorders
• Renal vein thrombosis
• Hypercalciuria.
Glomerular
• Acute glomerulonephritis
(usually with proteinuria)
• Chronic glomerulonephritis
(usually with proteinuria)
• IgA nephropathy
• Familial nephritis, e.g.
Alport syndrome
• Thin basement membrane
disease.

39. Acute nephritis
• Increased glomerular cellularity restricts
glomerular blood flow and therefore filtration
is decreased. This leads to:
– decreased urine output and volume overload
– hypertension, which may cause seizures
– oedema, characteristically around the eyes
– haematuria and proteinuria.

40. Causes
• Post-infectious (including streptococcus)
• Vasculitis (Henoch–Schönlein purpura or,
rarely, SLE, Wegener granulomatosis,
microscopic polyarteritis, polyarteritis nodosa)
• IgA nephropathy and mesangiocapillary
glomerulonephritis
• Anti-glomerular basement membrane disease
(Goodpasture syndrome) – very rare.

41. Management
• Management is by attention to both water and
electrolyte balance and the use of diuretics when
necessary.
• Rarely, there may be a rapid deterioration in renal
function (rapidly progressive glomerulonephritis).
• This may occur with any cause of acute nephritis, but is
uncommon when the cause is post-streptococcal.
• If left untreated, irreversible renal failure may occur
over weeks or months, so renal biopsy and subsequent
treatment with immunosuppression and plasma
exchange may be necessary.

42. Post-streptococcal and
post-infectious nephritis
• Usually follows a streptococcal sore throat or skin
infection and is diagnosed by evidence of a recent
streptococcal infection (culture of the organism,
raised ASO/ anti-DNAse B titres) and low
complement C3 levels that return to normal after
3–4 weeks.
• Streptococcal nephritis is a common condition in
developing countries, but has become
uncommon in developed countries.
• Longterm prognosis is good.

43. Treatment
• Phenoxymethylpenicillin 250mg/5ml P.O Q.I.D
5/7 or
• Azithromycin 10mg/kg P.O 3/7

44. Henoch–Schönlein purpura
• It usually occurs between the ages of 3 and 10 years, is
twice as common in boys, peaks during the winter
months and is often preceded by an upper
respiratoryinfection.
• Despite much research, the cause is unknown.
• It is postulated that genetic predisposition and antigen
exposure increase circulating IgA levels and disrupt IgG
synthesis.
• The IgA and IgG interact to produce complexes that
activate complement and are deposited in affected
organs, precipitating an inflammatory response with
vasculitis.

45. Henoch–Schönlein purpura
Henoch–Schönlein purpura is
the combination of some of
the following features:
• Characteristic skin rash
• Arthralgia
• Periarticular oedema
• Abdominal pain
• Glomerulonephritis.

46. Clinical Findings
• At presentation, affected children often have a
fever.
• The rash is the most obvious feature.
• It is symmetrically distributed over the buttocks,
the extensor surfaces of the arms and legs, and
the ankles.
• The trunk is spared unless lesions are induced by
trauma.
• The rash may initially be urticarial, rapidly
becoming maculopapular and purpuric.

47. Management
• if severe, can be treated with corticosteroids
• All children with renal involvement are
followed for a year to detect those with
persisting urinary abnormalities (5–10%), who
require long-term follow-up.
• This is necessary as hypertension and
declining renal function may develop after an
interval of several years.

48. IgA nephropathy
• This may present with episodes of
macroscopic haematuria, commonly in
association with upper respiratory tract
infections.
• Histological findings and management are as
for Henoch–Schönlein purpura, which may be
a variant of the same pathological process but
not restricted to the kidney.

49. Vasculitis
• The commonest vasculitis to involve the kidney is Henoch–Schönlein
purpura (see above).
• However, renal involvement may occur in rarer vasculitides such as
polyarteritis nodosa, microscopic polyarteritis and Wegener
granulomatosis.
• Characteristic symptoms are fever, malaise, weight loss, skin rash and
arthropathy with prominent involvement of the respiratory tract in
Wegener disease.
• ANCA (antineutrophil cytoplasm antibodies) are present and diagnostic in
these diseases.
• Renal arteriography, to demonstrate the presence of aneurysms, will
diagnose polyarteritis nodosa.
• Renal involvement may be severe and rapidly progressive.
• Treatment is with steroids, plasma exchange and intravenous
cyclophosphamide, which may need to be continued for many months.

50. Systemic lupus erythematosus (SLE)
• SLE is a disease that presents mainly in adolescent girls
and young women.
• It is much commoner in Asians and Afro-Caribbeans
than Caucasians. It is characterized by the presence of
multiple autoantibodies, including antibodies to
double-stranded DNA.
• The C3 and C4 components of complement may be
low, particularly during active phases of the disease.
• Haematuria and proteinuria are indications for renal
biopsy, as immunosuppression is always necessary and
its intensity will depend on the severity of renal
involvement.

51. Glomerulonephritis
• Also known as glomerular
nephritis (GN) or glomerular disease
• It is a disease of the kidney,
characterized by inflammation of the
glomeruli

52. • Acute Glomerulonephritis
–Cause
• infections such as strep throat
• Lupus erythematous
• Goodpasture's syndrome
• Wegener's disease
• polyarteritis nodosa
Glomerulonephritis

53. • Acute Glomerulonephritis
–Symptoms
• Puffy face in the morning
• hematuria (or brown urine)
• oliguria
Glomerulonephritis

54. • Chronic Glomerulonephritis
–Cause
• This condition may develop after survival
of the acute phase of rapidly progressive
glomerulonephritis
Glomerulonephritis

55. • Chronic Glomerulonephritis
–Signs and symptoms
• Proteinuria/hematuria
• High blood pressure
• oedema
• nocturia
• Very bubbly or foamy urine
Glomerulonephritis

56. • Diagnosis
–Urine test
–Blood test
–Throat swab
–Renal function tests
–Kidney biopsy
–Imaging tests
Glomerulonephritis

57. • Treatment
–Diet salts restrictions and adequate fluid
intake
–The following medications may also be
prescribed to treat possible underlying
causes:
• Bacterial infections - a targeted antibiotic
• Lupus or vasculitis - corticosteroids and
immunosuppressants
Glomerulonephritis

58. • Treatment
• IgA - possibly fish oil supplements.
• Goodpasture's syndrome -
plasmapheresis is a procedure designed
to reduce blood plasma levels without
depleting the body of its blood cells.
Antibodies are removed and donated
plasma replaces the depleted plasma
Glomerulonephritis

59. Investigations of Hematuria
All patients
• Urine microscopy (with phase contrast) and culture
• Protein and calcium excretion
• Kidney and urinary tract ultrasound
• Plasma urea, electrolytes, creatinine, calcium, phosphate, albumin
• Full blood count, platelets, clotting screen, sickle cell screen.
If suggestive of glomerular haematuria
• ESR, complement levels and anti-DNA antibodies
• Throat swab and antistreptolysin O/anti-DNAse B titres
• Hepatitis B and C screen
• Renal biopsy if indicated
• Test mother’s urine for blood (if Alport syndrome suspected)
• Hearing test (if Alport syndrome suspected).

60. Hemolytic Uraemic Syndrome
• Hemolytic-uremic syndrome (HUS) is a clinical
syndrome characterized by progressive renal failure
that is associated with microangiopathic (nonimmune,
Coombs-negative) hemolytic anemia and
thrombocytopenia.
• It predominantly, but not exclusively, affects children.
Most cases are preceded by an episode of infectious,
sometimes bloody, diarrhea acquired as a foodborne
illness or from a contaminated water supply caused by
E. coli O157:H7, other non-o157:H7 E. coli serotypes,
Shigella, and Campylobacter.

61. • The typical pathophysiology of HUS involves
the binding of Shiga-toxin to the
globotriaosylceramide (Gb3; also called
ceramide trihexoside which accumulates in
Fabry disease) receptor on the surface of the
glomerular endothelium.

62. Hereditary Glomerulopathies
• Predominant hematuria
– Alport’s syndrome
– Benign Familial hematuria
– Hemolytic Uraemic Syndrome

63. Alport’s syndrome
• Genetically heterogeneous disease arising
from mutations of the gene coding for type IV
collagen, a major constituent of the basement
membrane.
• Persistent hematuria often progressing
proteinuria, hypertension and renal failure.
• Often associated with high frequency sensori-
neural deafness and ocular defects

64. • Benign Familial hematuria is usually due to the
thin basement membrane. No associated
deafness and the condition is inherited as an
autosomal dominant.

65. References
• Lissauer T, Clayden G, 2012. Illustrated
Textbook Of Paediatrics. Fourth edition. ©
2012 Elsevier Ltd
• Wittenberg D.F. (2009), Coovadia’s Paediatrics
and Child Health. Oxford University Press
Southern Africa (pty) Ltd