This document provides an overview of kidney disease and glomerular diseases. It begins with the functions and anatomy of the kidney, focusing on the glomerulus and its role in filtration. It then discusses various glomerular diseases like nephrotic syndrome, nephritic syndrome, acute glomerulonephritis, and common causes like minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. Complications of nephrotic syndrome are also covered. The document provides detailed information on the pathology, clinical presentation, and treatment of different glomerular diseases.

1. Disease of Kidney
BY MERSHA .M
(MD)
1

2. OUTLINE Glomerular anatomy and physiology
 Pathology and classification of Glomerular
diseases
 Nephrotic syndrome
 Nephritic syndrome(AGN/RPGN)
 Urinary tract infection
 Acute kidney injury(AKI)
 Chronic kidney diseases (CKD) 2

3. MAJOR FUNCTIONS OF THE
KIDNEYS
 Regulation of fluid / electrolyte balance
 Regulation of blood pressure
 Regulation of red cell mass
 Regulation of calcium / phosphate
metabolism
3

4. KIDNEY COMPARTMENTS
 Glomerulus
 Filtration of plasma
 Tubulointerstitium
 Modification of glomerular filtrate
 Production Epo and Vit D3
 Vascular
 Maintain blood flow and monitor pressure
4

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
 Two human kidneys harbor nearly 1.8 million glomerular
capillary tufts 5

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. 6

7. 7

8. GLOMERULAR ANATOMY AND
PHYSIOLOGY
8

9. 9

10. 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

11. NORMAL GFR
 GFR is equal to the sum of the filtration
rates in all of the functioning nephrons
 Glomeruli filter approximately 180 liters
per day (125mL/min) of plasma
 Normal GFR ̃120ml/min/1.73m2
11

12. 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 time period: acute x subacute x chronic
- According renal biopsy: focal x segmental x diffuse
- According number of cells: non-proliferative x
proliferative 12

13. 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. 13

14. 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 etiologic 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
14

15. PATHOLOGY
 The glomerular changes can be usually seen by light microscopy.
 The identification of the various deposits in the glomeruli
requires the use of immunofluorescence
 Additional information can be gained by electron microscopy
 The prognosis of GN depends in large part on the distribution of
the pathological changes within the kidney and within the
glomerulus.
 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
15

16. 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

17. NEPHROTIC SYNDROME
17

18. 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

19. 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

20. 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

21. NEPHROTIC SYNDROME -EDEMA
 2 mechanisms have been proposed
 Decrease in plasma oncotic pressure.
 Primary renal sodium retention in
the collecting tubules
21

22. NEPHROTIC SYNDOME-
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) .
22

23. NEPHROTIC SYNDROME-
COMMON CAUSES
 Renal
 Minimal Change
 Membranous
 FSGS
 “Systemic”
 DM
 MM/Amyloidosis
 SLE
23

24. 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 pathologicalentity
defined by selective proteinuria
and hypoalbuminemiathat occurs
in the absence of
◦ cellular glomerular infiltrates
or
◦ immunoglobulin deposits
24

25. MCD
 Usually idiopathic
 Can be secondary
to systemic disease
or drugs
 Treatment of
idiopathic MCD
- steroids- MCD is
very responsive to
steroids
- Other
Immunosuppressiv
e - for steroid
resistant or
relapse.
25

26. FSGS – FOCAL SEGMENTAL
GLOMERULOSCLEROSIS
 Typically idiopathic,
 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.
26

27. 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
• Associated diseases
HIV , Obesity , Sickle cell anemia, malignancies ,
Chronic vesicoureteral reflux
– Serum albumin often near normal
Treatment
• 15% respond to steroids
• Other immunosuppression
Cyclosporine, cyclophosphamide
27

28. MEMBRANOUS NEPHROPATHY
 Heavy proteinuria with nephrotic syndrome is the usual presentation of
membranous nephropathy.
 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.
 Immunosupressive,idiopathic with poor prognostic indicator ; Male
Renal dysfunction.
Hypertesion
28

29. 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
 Anamia
 Vit D deficiency
29

30. 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.
30

31. 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 < 120/75
 Treatment of hypercholesterolemia
Target LDL < 2.0
 Calcium and vit D to reduce bone loss if steroid
therapy is prolonged
 Bactrim for PCP prophylaxis if steroids
 INH for TB prophylaxis if immunosuppressed
 Anticoagulant if high risk
 Treat underlying cause if secondary 31

32. 32

33. ACUTE NEPHRITIC
SYNDROME – AGN/RPGN
33

34. ACUTE NEPHRITIC
SYNDROME
 Syndrome
characterised in
typical cases by:
 haematuria
 oliguria
 oedema
 hypertension
 reduced GFR
34

35. AGN VS RPGN
 AGN is the clinical
correlate of diffuse
proliferative
glomerulonephritis.
• AGN presents with
sudden onset ( days)of
haematuria ,oliguria
,oedema and
hypertension
• AGN and RPGN are part
of a spectrum of
presentations of
immunologically mediated
proliferative
glomerulonephritis
35

36. 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. 36

37. AGN - CAUSES
 Post infectious GN- the most common being
post streptococcal AGN
 SLE
 Membranoproliferative GN (MPGN)
37

38. POSTSTREPTOCOCCAL
GLOMERULONEPHRITIS
 Is prototypical for acute endocapillary
 proliferative glomerulonephritis.
 In underdeveloped countries is epidemic
 Usually affects children between the ages of
2 and 14 years, but in
 Developed countries is more typical in the
elderly It is more common in males
 The familial or cohabitant incidence is as
high as 40%.
38

39. POST STREPTOCOCCAL…
 Skin and throat infections with particular
M types of streptococci (nephritogenic
strains) antedate glomerular disease;
 M types 47, 49, 55, 2, 60, and 57 are seen
following impetigo
 M types 1, 2, 4, 3, 25, 49, and 12 with
pharyngitis.
 Poststreptococcal glomerulonephritis due
to impetigo develops 2–6 weeks after skin
infection and 1–3 weeks after streptococcal
pharyngitis.
39

40. 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 40

41. INVESTIGATION
 Baseline measurements :
- ↑ Urea
- ↑ Creatinine
Urinalysis (MSU) :
a) Urine microscopy (red cell
cast)
b) proteinuria
41

42. Diagnostically useful tests :
 Culture (swab from throat or infected
skin)
 Serum anti-streptolysin-O titre
 Hepatitis B surface antigen
 Hepatitis C antibody
 anti DNA , ANCA
 ↓C3,4
 Renal biopsy
42

43. COMPLICATIONS OF THE
NEPHRITIC SYNDROME
 Hypertensive encephalopathy (seizures,
coma)
 Fluid oveload -pulmonary oedema
 Uraemia requiring dialysis
 Chronic glomerulonephritis and CKD
 HTN
43

44. MANAGEMENT & PROGNOSIS
Post streptococcal GN
- Has a GOOD prognosis .
-Supportive measures until spontaneous
recovery.
- Control HTN.
- Fluid balance.
-Oliguric with fluid overload.
-The prognosis in elderly patients is worse with
a high incidence of azotemia (up to 60%),
nephrotic-range proteinuria, and end-stage renal
disease.
- GN complicating SLE or systemic
vasculitides : immunosuppression with
44