Glomerular diseases involve the glomeruli of the kidney and can lead to proteinuria and/or hematuria. They are classified based on clinical presentation, pathology, and renal biopsy findings. The most common presentations are nephrotic syndrome and nephritic syndrome. Nephrotic syndrome is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Nephritic syndrome presents with hematuria, hypertension, and reduced kidney function. Common causes include minimal change disease, membranous nephropathy, and focal segmental glomerulosclerosis.

1. GLOMERULAR DISEASES
Henok J ( MD)

2. Glomerular Diseases
 Glomerular anatomy and physiology
 Pathology and classification of Glomerular diseases
 Clinical presentation
 Investigation of Glomerular diseases
 Nephrotic syndrome
 Nephritic syndrome(AGN/RPGN)
 Asymptomatic proteinuria and hematuria

3. Kidney compartments
 Glomerulus
◦ Filtration of plasma
 Tubulointerstitium
◦ Modification of glomerular filtrate
◦ Production Epo and Vit D3
 Vascular
◦ Maintain blood flow and monitor pressure

5. Anatomy
 The blood flow to the kidneys averages 20 % the cardiac
output.
Per weight ..... 4X higher than the liver & skeletal muscle
...... 8x higher than the coronary blood flow
 Blood enters the kidney through the renal arteries and passes
serial branches to enter the glomeruli via the afferent
arterioles.
 The portion of the plasma not filtered across the glomeruli
leaves via the efferent arterioles.
 The glomerulus is a tuft of capillaries (specialized
microvasculature) that is interposed b/n the afferent & efferent
arterioles

6. Anatomy
 Each glomerulus is enclosed within an epithelial cell capsule =
Bowman's capsule(BC)
 The BC is continuous with the epithelial cells that surround the
glomerular capillaries & with the cells of the proximal tubule.
 The glomerular capillary wall consists of three layers:
1. Fenestrated endothelial cell
2. Glomerular basement membrane (GBM)
3. Epithelial cell
• The epithelial cells are attached to the GBM by discrete foot
processes.
• The pores b/n the foot processes (slit pores) are closed by a thin
membrane called the slit diaphragm.

7. Glomerular Architecture

8. Glomerular Anatomy
 Glomerular apparatus
◦ Endothelium
◦ Basement membrane
◦ Podocytes

9. Function
 Filtration of small solutes (such as Na and urea) and water,
while restricting the passage of larger molecules (larger
proteins).
 The free filtration of small solutes like Na, K and urea, allows
the kidney to maintain the steady state by excreting the load.
 Restricted filtration of larger proteins prevents problems like
negative nitrogen balance, hypoalbuminemia, & infection due to
the loss IgG.
 Filtration is effected by size and charge selectivity of GBM.
Smaller and Cationic molecules are filtered better.
 The glomerular cells also have synthetic(Production of GBM),
phagocytic(Mesangial cell), and endocrine(NO, endothelin)
functions.

10. Glomerular diseases
 Heterogeneous group of inflammatory and /or non
inflammatory insults to the filtering unit of the kidney.
 The hallmark of glomerular diseases is an alteration in
glomerular permeablity and selectivity resulting in proteinuria
and /or hematuria.
 Classification
- Clinical: primary x secondary
- According to time period: acute x subacute x chronic
- According to renal biopsy: focal x segmental x diffuse
- According number of cells: non-proliferative x proliferative

11. Pathology of Glomerular diseases (Glomerulonephritis)
 The majority of GN cases involve immune mechanisms, most
often humoral immune responses.
 In some cases immune complexes are formed in situ within the
glomeruli. In other forms of preformed circulating immune
complexes are trapped.
 Non-immune injury-
- Numerous Pathologies renal or extrarenal in origin, can lead to
glomerulosclerosis .
-The remaining glomeruli are subjected to increased
intraglomerular pressure, which produces glomerular injury .
This process is called hyperfiltration injury.
 There are also some inherited glomerular diseases.

12. Pathology
 The glomerulus will react in a limited number of ways with a
variable degree of severity.
 One pattern can have multiple etiological causes and one
etiology can have different pathologic pattern, so all biopsies
must be evaluated with clinical correlation.
- pathological changes most often encountered are as follows:
1.Increase in the number of cells (Proliferation), affecting either:
▪ mesangial cells, with or without endothelial cells
▪ epithelial cells, leading to the formation of cellular
crescents
obliterating the Bowman's space.
2. Necrosis of one or more segments of the glomerulus
3. GBM thickening
4 . Sclerosis of one segment or of entire glomerulus
5. Trapping of immunoglobulins or complement proteins

13. Pathology
 The following vocabulary is used to characterize the distribution of
the lesions:
* diffuse: most glomeruli are affected
* focal: only a proportion ( less than half) of the glomeruli
are affected
* global: the entire glomerulus is affected
* segmental: part of an individual glomerulus is affected

14. Clinical presentation
 Patients with glomerular diseases usually present with
one of following
 Nephrotic syndrome
 Nephritic syndrome
 Asymptomatic proteinuria
 Asymptomatic Hematuria
 Proteinuric CKD
• The commonest presentations are the nephrotic and nephritic
syndromes.
 Note that these represent two broad categories of clinical
presentation and are not specific glomerulopathies by
themselves.
• Nephritic and nephrotic syndromes are not mutually
exclusive (There is a nephrotic-nephritic
presentation)

16. Nephrotic syndrome

17. Nephrotic syndrome
 Definition
-A clinical syndrome characterized by renal and extra renal
features the most important of which are
 proteinuria of >3.5 grams per1.73m2 per 24 h (in practice >3.0 -
3.5 grams /24 h) or spot urine protein:creatinine ratio of >300-350
mg/mmol- this is the central problem
 Hypoalbuminemia,
 Edema,
 Hyperlipidemia
 Lipiduria and
 Hypercoagulability

18. Nephrotic syndrome-proteinuria
 Proteinuria — There are three basic types of proteinuria;
glomerular; tubular; and overflow.
 It is glomerular proteinuria that is responsible for protein loss in
the nephrotic syndrome.
 Albumin is the principal urinary protein lost
 Other plasma proteins including clotting inhibitors, transferrin,
and hormone carrying proteins such as vitamin D-binding
protein may be lost as well.

19. Nephrotic syndrome- Hypoalbuminemia
 Serum albumin falls as a consequence of the proteinuria
 Hepatic albumin synthesis increases in response to the
albumin loss.
 The normal liver has a synthetic capacity to increase the total
albumin pool by approximately 25 grams per day.
 It remains unclear why the liver of most patients with
nephrotic syndrome is unable to increase albumin synthesis
sufficiently to normalize the plasma albumin concentration.
 Renal catabolism of filtered protein is leading to
underestimation of the protein loss from the body is a
speculated mechanism.

20. Nephrotic syndrome -edema
 Two mechanisms have been proposed
Decrease in plasma oncotic pressure.
Primary renal sodium retention in the collecting tubules

21. Nephrotic syndrome- Hyperlipidemia and
lipiduria
 The two most common lipid abnormalities in the nephrotic
syndrome are hypercholesterolemia and hypertriglyceridemia.
 Decreased plasma oncotic pressure appears to stimulate hepatic
lipoprotein synthesis resulting in hypercholesterolemia.
 Impaired metabolism is primarily responsible for nephrotic
hypertriglyceridemia.
 Lipiduria is usually present in the nephrotic syndrome.
 Urinary lipid may be present in the sediment, entrapped in casts,
enclosed by the plasma membrane of degenerative epithelial
cells(oval fat bodies) .
 Under polarized light oval fat bodies have the appearance of a
Maltese cross

22. Nephrotic syndrome-lipiduria

23. Nephrotic syndrome -complications
 Protein malnutrition — A loss in lean body mass often occurs
in patients with marked proteinuria, although it may be masked
by concurrently increasing edema.
 Decreased circulatory volume —
- severe hypoalbuminemia causes fluid movement from the
intravasular space into the interstitium
- over diuresis
 Acute Kidney injury — several factors including
hypovolemia, interstitial edema, ischemic tubular injury play a
role

24. Nephrotic syndrome -complications
 Thromboembolism — Patients with the nephrotic syndrome
have an increased incidence of arterial and venous
thromboemboli, particularly deep vein and renal vein thrombosis
.
- A variety of hemostatic abnormalities have been described,
 decreased levels of antithrombin and plasminogen (due to urinary
losses),
 increased platelet activation,
 hyperfibrinogenemia,
 inhibition of plasminogen activation
-Renal vein thrombosis is found disproportionately in patients with
membranous nephropathy,
 Infection— Patients with the nephrotic syndrome are
susceptible to infections.
- Low levels of immunoglobulin G may play a role.

25. Nephrotic syndrome -complications
 Vitamin D deficiency.
 A decrease in thyroxine-binding globulins can cause marked
changes in various thyroid function tests, although patients
are clinically euthyroid.
 Anemia - perhaps due to the urinary loss or impaired
synthesis of erythropoietin and loss of transfferin.

26. Nephrotic Syndrome- Common causes
 Renal
◦ Minimal Change
◦ Membranous
◦ FSGS
 “Systemic”
◦ DM
◦ MM/Amyloidosis
◦ SLE

27. MCD- Minimal change disease/Nil disease/lipoid
nephrosis
 Most common cause of the
nephrotic syndrome in children
 ~10-15% of nephrotic syndrome in
adults, third most common after
MN and FSGS
◦ More common in Hispanics,
Asians, Arabs and Caucasians
 clinical and pathological entity
defined by selective proteinuria
and hypoalbuminemia that occurs
in the absence of
◦ cellular glomerular infiltrates or
◦ immunoglobulin deposits

28. MCD
 Usually idiopathic
 Can be secondary to
systemic disease or
drugs
 Treatment of
idiopathic MCD
- steroids- MCD is very
responsive to
steroids
- Other
Immunosuppressive -
for steroid resistant
or relapse.

29. FSGS – Focal segmental glomerulosclerosis
 Typically idiopathic,
Associated diseases
HIV , Obesity , Sickle cell anemia,
malignancies,
Chronic vesicoureteral reflux.
 This disease entity has a name based on the
nature of its histologic changes: focal and
segmental
 No inflammatory cells are present in the
glomeruli
 sclerosis of the glomeruli are more pronounced
at the cortico-medullary junction.
 Most common cause of idiopathic nephrotic
syndrome in African Americans
 Clinically, patients present with the nephrotic
syndrome, hematuria, hypertension and
decreased renal function.

30. FSGS
• 50% of patients develop end-stage renal failure 10 years after the
onset of the disease.
• Proteinuria and FSGS is a final common pathway
after many different forms of renal injury– secondary FSGS
To differentiate primary from secondary FSGS:
– foot processes in all glomeruli are abnormal in
primary FSGS
– Foot processes only abnormal in visibly
affected glomeruli in secondary FSGS
– Serum albumin often near normal
Treatment
• 15% respond to steroids
• Other immunosuppression
Cyclosporine, cyclophosphamide

31. Membranous nephropathy
 Heavy proteinuria with nephrotic syndrome is the usual
presentation of membranous nephropathy.

32. Cont.
 A common cause of the nephrotic syndrome in adults.
 Pathological changes are characterized by thickening of the capillary wall. No
glomerular hypercellularity or inflammatory changes .
 Few red blood cells are found in urine, no hypertension at the early stage. Renal
function is normal initially and progresses very slowly.
 10% of adults are in end-stage renal failure 10 yrs after the onset.
.
 Membranous nephropathy is occasionally caused by an infection (e.g. Hepatitis B),
autoimmune disease (e.g. SLE), or an underlying malignancy.
TREATMENT
 Immunosupressive,
- idiopathic with poor prognostic indicator ; Male
Renal dysfunction.
Hypertesion

33. Membranous nephropathy

34. TREATMENT
 Specific therapy : underlying causes
-
Immunosuppressive,idiopathic
- Treating infectious causes
Syphilis
Hep B
Hep C,HIV etc
- avoid offending agent
 Non Immunologic – universal rx for all
Nephrotic syndrome

35. Non immunologic Therapy for all
Nephrotic syndrome
 Treat underlying cause
 Salt restrict
◦ <2g sodium per day
 Diuretics
◦  doses loop as reduced delivery to tubule
◦ Combine with thiazide
 Renin-angiotensin blockade
 Treatment of hypertension esp. ACEI, ARB ,Target < 140/90
 Treatment of hypercholesterolemia
Target LDL < 2.0
 Calcium and vit D to reduce bone loss if steroid
therapy is prolonged
 Bactrim for PCP prophyllaxis if steroids
 INH for TB prophylaxis if immunosuppressed
 ?Anticoagulant if high risk?

37. Acute nephritic syndrome –
AGN/RPGN

39. Acute Nephritic Syndrome
Syndrome
characterised in
typical cases by:
 haematuria
 oliguria
 oedema
 hypertension
 reduced GFR
 proteinuria

40. AGN VS RPGN
 AGN is the clinical correlate
of diffuse proliferative
glomerulonephritis.
• AGN presents with sudden
onset ( days)of haematuria
,oliguria ,oedema and
hypertension
• Causes - Post infectious(
commonest PSGN),
SLE,MPGN,cryoglobul.GN
• AGN and RPGN are part of a
spectrum of presentations of
immunologically mediated
proliferative
glomerulonephritis

41. AGN Vs RPGN
 RPGN is characterized by
rapidly progressive
deterioration in renal
function associated with
oliguria.
 Decline in GFR occurs over
weeks.
 RPGN is the clinical
correlate of crescentic
glomerulonephritis
 Many crescents are seen on
biopsy.

43. Linear Deposits
Granular
Deposits

44. Clinical Features of the Acute Nephritic
Syndrome (AGN/RPGN)
 haematuria is usually macroscopic with pink or brown urine
(like coca cola)
 oliguria may be overlooked or absent in milder cases
 oedema is usually mild and is often just peri-orbital- weight
gain may be detected
 hypertension common and associated with raised urea and
creatinine
 proteinuria is variable but usually less than in the nephrotic
syndrome

45. Investigation
 Basline measurements :
↑ Urea
↑ Creatinine
Urinalysis :
a) Urine microscopy (red cell cast)
b) proteinuria

46. Diagnostically useful tests :
 Culture (swab from throat or infected skin)
 Serum ASO titre, Anti DNAase
 Hepatitis B surface antigen
 Hepatitis C antibody
 HIV screen -- HIVIC
 Anti DNA , ANA– SLE
 ANCAs --- Small vessel vasculitidis
 ↓C3,4 – lupus, post infectious,MPGN
 Cryoglobulins & RF -- Cryoglobulinemia
 Anti—GBM Abs -- GBM disease
 Renal biopsy

47. Complications of the Nephritic
Syndrome
 Hypertensive encephalopathy (seizures, coma)
 Fluid oveload -pulmonary oedema
 Uraemia requiring dialysis
 Chronic glomerulonephritis and CKI
 HTN

48. Management & Prognosis
Post streptococcal GN
- Has a GOOD prognosis .
- Supportive measures until spontaneous recovery.
- Control HTN.
- Fluid balance.
-Oliguric with fluid overload--- dialysis
GN complicating SLE or systemic vasculitides :
immunosuppression with prednisolone,
cyclophosphamide or azathioprine/ MMF.