2. OBJECTIVE
To know the embroyology and normal anatomy
of Kidney
Staging of CKD with CGA classification
Etiology and pathogenesis of CKD
Complication of CKD
3. Embryology of the kidney
Three Sets of Excretory Organs Formed in
Kidney Development:
Pronephric kidney
Mesonephric kidney
Metanephric kidney (definitive excretory
organ)
7. Definition
Chronic kidney disease is defined as the
presence of a diminished GFR that is
persistently less than 60 mL/minute/1.73 m2
for at least 3 months, from any cause, and/or
persistent albuminuria.
11. CKD Classification (KDIGO
2012)
Albuminuria and
proteinuria are
cornerstones in
classification of all stages
of CKD beside GFR.
CGA
Classification
• Cause
• GFR
• Albunimuria
13. Prevalance of CKD in
Nepal And India
Only one Nepalese study met eligibility criteria
for this systematic review. This moderated
quality study was conducted among ≥20 years
old adults residing in urban Dharan and
reported CKD prevalence as 10.6%. [Sharma
et al. 2013]
A study in Delhi; The prevalence of CKD in
adult population with mean age 42 + 13 years
was 0.785% or 7852/million. [Agrawal et al.
2005]
In India the projected number of deaths due to
chronic diseases will rise from 3.78 million in
1990 (40.4% of all deaths) to an expected 7.63
million in 2020 (66.7% of all deaths) [World
Health Organization: Preventing Chronic
Disease: A Vital Investment. Geneva, WHO,
2005].
14. ETIOPATHOGENESIS
The study of kidney diseases is facilitated by
dividing
them into those that affect the four basic
morphologic
components:
1. Glomeruli,
2. Tubules,
3. Interstitium, and
4. Blood vessels.
16. ETIOPATHOGENESIS:
GLOMERULAR DISEASES
Pathologic Responses of the Glomerulus
to Injury:
Hypecellularity
• Proliferation of
mesangial or
endothelial cells
• Infiltration of
leukocytes
• Formation of
cresents
Basement
membrane
thickening
• Deposition of
amorphous dense
material
• Increased
synthesis of
protein
component of the
BM.
Hyalinosis and
Sclerosis
• Hyalinosis
• Sclerosis
18. ETIOPATHOGENESIS:
GLOMERULAR DISEASES
Pathogenesis of Glomerular Injury
Diseases Caused by In Situ Formation of Immune
Complexes
Disease Caused by Antibodies Directed Against
Normal Components of the Glomerular Basement
Membrane
Glomerulonephritis Resulting from Deposition of
Circulating Immune Complexes
Mediation of Glomerular Injury Following Immune
Complex Formation
Cell-Mediated Immunity in Glomerulonephritis
Activation of Alternative Complement Pathway
Epithelial Cell Injury
19. ETIOPATHOGENESIS:
GLOMERULAR DISEASES
Glomerulonephritis Resulting from Deposition
of Circulating Immune Complexes
Site Example
1)
subepithelia
l
humps
acute glomerulonephritis
2)
epimembra
nous
deposits
membranous nephropathy
and Heymann nephritis
3)
subendothe
lial
deposits
lupus nephritis and
membranoproliferative
glomerulonephritis
23. Membranous Nephropathy
Approximate prevalence:
Children: 3%
Adult: 30%
Characterized by diffuse thickening of the
glomerular capillary wall due to the
accumulation of deposits containing Ig along
the subepithelialside of the basement
membrane.
Ig IF Microscopy shows granular
deposition of immune-complexes.
24. Minimal-Change Disease
Approximate prevalence:
Children: 75%
Adult: 8%
This relatively benign disorder is characterized
by diffuse effacement of foot processes of
visceral epithelial cells (podocytes), detectable
only by electron microscopy, in glomeruli that
appear virtually normal by light microscopy.
25. Focal Segmental
Glomeuloscelorosis (FSGS)
Approximate Prevalence:
Children: 10%
Adults: 35%
Most common cause of nephrotic syndome in
hispanics and blacks.
Risk factors - most common in people with
AIDS, heroin and sickle cell disease. However,
most disease are idiopathic.
Glomerulus showing segmental sclerosis and hyaline insudation (
27. Membranoproliferative
Glomerulonephritis (MPGN)
Divided to two types based on immune deposit
type-
Subendothelial (type 1) - associated with
hepatitis B , hepatitis C. Type 1 has more
tramtracks association.
Within basement membrane (type 2) - pt have
C3 nephritic factor (autoantibody). This
antibody binds and stabilizes c3 convertase.
MPGN accounts for up to 10% of cases of
nephrotic
syndrome in children and young adults.
28.
29. Isolated Glomerular Abnormalities:
Approximate Prevalence:
Children: 2%
Adults: 17%
IgA Nephropathy
• Most common nephropathy worldwide
• IgA deposition seen in mesangium - gives granular IF
Hereditary Nephritis
Alport syndrome
37. Toxins and drugs can injure kidneys in at least
three ways:
(1)Trigger an interstitial immunologic reaction,
exemplified by the acute hypersensitivity nephritis
induced by drugs such as methicillin
(2)Cause acute tubular injury
(3)Cause subclinical but cumulative injury to
tubules that takes years to result in chronic renal
insufficiency.
42. Benign Hypertensive
Nephrosclerosis
Most common renal disease in hypertension.
Pathogenesis:
Hyaline arteriolosclerosis of
arterioles in the renal cortex.
Tubular atrophy, interstitial
fibrosis and glomerular
sclerosis.
43. Gross appearance of the cortical surface in benign
nephrosclerosis illustrating the fine, leathery granularity of the
surface.
44. Malignant Hypertensive
Nephrosclerosis
Sudden onset of accelerated hypertension
Vascular damage to arterioles and small
arteries.
Fibrinoid necrosis and necrotizing arteriolitis and
glomerulitis.
Pinpoint hemorrage on the cortical surface (flea-
bitten kidneys)
47. Congenital & Developmental
Anomalies
Agenesis of the Kidney
Hypoplasia
Horseshoe Kidneys
About 10% of people are born with significant
malformations
of the urinary system.
Renal dysplasias and hypoplasias
account for 20% of chronic kidney disease in
children.
57. Case Disscussion
A 64 y/o man, reports chronic low back pain after an injury 8 years
ago. The patient has since used a several OTC analgesics. He has
trace lower extremity edema.
Lab:
BUN: 32 mg/dl
S. Creatinine: 2.0 mg/dl
Renal USG: B/L shrunken and irregular kidneys with few papillary
calcifications.
Other history, physical examination and lab. values are unremarkable.
Which of the follwing is the most likely cause of this pt’s renal
dysfunction?
A. Chronic interstitial nephritis
B. Chronic pyelonephritis
C. Crystal Nephropathy
D. FSGS
Ans: A
58. A 55 y/o woman visited OPD with
C/O increased swelling around
her ankles and face that has
progressively worsened over
the last 1-2 months.
On examination: b/l pitting edema.
Normal cardiopulmonary
examination.
Lab: S. Creatinine= 2.0 mg/dl,
albumin= 2.8 g/dl
Urinalysis: 3+ proteinuria and no
hematuria & casts.
Kidney biopsy performed; light
microscopic findings is shown:
The most likely explanation is:
A. Hepatitis C infection
B. SLE
C. Diabetes Mellitus
D. HIV infection
Ans: C
59. Summary
Etiopathgenesis :
1. Progressive glomerular injury can be the result of either primary or secondary
glomerular injuries, of diseases that are either renal limited or systemic, and of
diseases that initially involve renal structures other than glomeruli.
2. Progressive glomerular injury is accompanied by chronic injuries to other renal
structures, typically manifest as tubulointerstitial fibrosis.
3. A set of progressive mechanisms, involving hyperfiltration and hypertrophy of the
remaining viable nephrons, that are a common consequence following long-term
reduction of renal mass, irrespective of underlying etiology.
Complications:
1.Anemia
2.Cardiovascular Disease
3.Mineral and bone disorder
4.Acidosis
5.Malnutrition
6. Final Progression to ESRD
60. Take home message
Chronic kidney disease
is a public health
problem
-outcomes include loss
of kidney function and
cardiovascular disease
CKD is an independent
risk factor for
cardiovascular mortality
which far outweighs the
risk of developing
ESRD.
Whatever the origin , all
forms of CKD ultimately
damage all four
components of the
kidney leading to
ESRD.
Progression of CKD to
ESRD is inevitable.
Thus, early diagnosis
and treatment can slow
down the progression
of CKD.
We can improve
outcomes
- Facilitate clinical
action plan based on
stages of severity.
-Doctor, patient, and
public education.
61. References:
(Robbins Pathology) Vinay Kumar, Abul K. Abbas, Jon C. Aster - Robbins
and Cotran Pathologic Basis of Disease-Saunders (2015)- 9th Edition
Practical Renal Pathology, A Diagnostic Approach (Pattern Recognition
Series)
Harrison's Principles of Internal Medicine 19th Edition
Wheater's Functional Histology A Text and Colour Atlas
Mescher - Junqueira's Basic Histology_ Text and Atlas 15th ed 2018
Sharma SK, Dhakal S, Thapa L, Ghimire A, Tamrakar R, Chaudhary S, et
al. Community-based screening for chronic kidney disease, hypertension
and diabetes in Dharan. JNMA J Nepal Med Assoc. 2013;52(189):205–212.
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Editor's Notes
Gastrulation: 3 layers
Mesederm: Paraxial, Intermediate and Lateral plate mesderm
Pronephric kidney: ). Signals from the surface ectoderm induce cells in the intermediate
mesoderm to differentiate into the nephric duct.
Although the pronephroi are rudimentary and never form functional
nephrons in the developing human embryo, the pronephric duct is
essential to the subsequent development of the kidney.
Mesonephric kidney: fourth week of development (or E8.5 to E9.5 in mice), the pronephric
kidney is replaced by the mesonephric kidney, which arises
from intermediate mesoderm surrounding the vertebral column in the
upper thoracic to midlumbar region
The
expanded medial end of the mesonephric tubule—which makes Bowman’s
capsule—is invaded by blood vessels that sprout from the dorsal
aorta.
duct. The renal corpuscle and its tubule form a mesonephric
excretory unit very similar to the nephron of the adult kidney.
The mesonephric duct is derived from intermediate mesoderm in
the thoracic region of the embryo early in the fourth week of gestation
and grows caudally until it reaches and fuses with the cloaca. The
region of fusion eventually becomes the trigone of the bladder.
Mesonephric units are functional between 6 and 10 weeks of gestation and produces small amounts of urine. After 10 wks its involutes. In male:
Mechanisms of Progression in Glomerular Diseases
Once any renal disease, glomerular or otherwise, destroys functioning nephrons and reduces the GFR to about 30% to 50% of normal, progression to end-stage renal failure proceeds at a steadyrate, independent of the original stimulus or activity of the underlying disease.
• refers to a group of heterogeneous
gfamilial renal diseases associated with mutations in collagen
enes that manifest primarily with glomerular
injury.
• Inherited defect of type IV collagen
• GBM becomes thin and splits
• Presents with isolated hematuria, sensory hearing loss and ocular disturba
• Most commonly seen in kids after mucosal infection (recall that IgA is dumped in mucosal layer)
•When infection goes away, hematuria decreases as well. New infection leads to new episode of hematuria. This can slowly lead to renal failure
Acute pyelonephritis. Cortical surface shows grayish white
areas of inflammation and abscess formation.
Acute pyelonephritis marked by an acute neutrophilic exudate
within tubules and interstitial inflammation.
Drug-induced acute tubulointerstitial nephritis. In allergic type tubulointerstitial nephritis the renal interstitium contains focally numerous eosinophils (A); however,
the interstitium may be expanded by a mononuclear inflammatory infiltrate containing primarily lymphocytes
