PATHOLOGY OF THE KIDNEY

Dody Novrial
Department of Pathology, JSU
Renal Diseases
Renal diseases are divided into 4
categories based on basic anatomic
compartment principally affected :
Glomeruli
Tubules
Interstitium
Blood vessels
Clinical Manifestation
Renal diseases clinically manifest
themselves within reasonably well-
defined syndromes :
Stages of renal diseases progression :
1. Diminished renal reserve (approximately
50% of normal GFR)
2. Renal insufficiency (20%-50% of normal
GFR)
3. Renal failure (<20% of normal GFR)
4. End-stage renal disease (<5% of normal
GFR

Congenital Anomalies
1. Renal agenesis
2. Hypoplasia
3. Ectopic kidneys
4. Horseshoe kidney

Most arise from developmental
defects rather than inherited genes
Horseshoe kidney
Cystic Diseases of the Kidney
Cystic Renal Dysplasia
Sporadic, non familial
May be uni or bilateral
Enlarged and
multicystic kidney
Histo: immature ducts
surrounded by undiff
mesenchyme, often
with focal cartilage
formation

Polycystic Kidney Disease
Autosomal dominant (adult)
Caused by mutation of PKD1 or PKD2
genes
Always bilateral
Can present from early childhood to as
late as 80 years of age
Enlarged kidney composed of cysts up to
3-4 cm in diameter
Associated with liver cysts, cerebral berry
aneurysms, mitral valve prolaps
Clinically : hypertension, chronic renal
failure, hematuria
Polycystic Kidney Disease
Autosomal recessive (childhood)
Rarely
Infants often succumb rapidly to
renal failure
Kidneys are enlarged by multiple,
cylindrically dilated collecting ducts
Associated with liver cysts and
congenital hepatic fibrosis

Cystic Diseases of Renal Medulla
Medullary Sponge Kidney
Multiple cystic dilatations in the
collecting ducts of the medulla
Usually presenting in adults
It can predispose to renal calculi
Cystic Diseases of Renal Medulla
Nephronophthisis-Medullary Cystic
Disease Complex
Progressive renal disorder
Onset in childhood
Small medullary cyst in corticomedullary
area associated with cortical tubular
atrophy and interstitial fibrosis
Variants : Sporadic (20%), Familial
juvenile nephronophthisis (50%), Renal-
retinal dysplasia (15%), adult-onset
medullary cystic disease (15%)

Cystic Diseases of Renal Medulla
Acquired (Dialysis-Associated)
Cystic Disease
End Stage kidney patients with
prolonged renal dialysis
Multiple cortical and medullary cysts
Often lined by atypical, hyperplastic
epithelium
Can undergo malignant
transformation renal cell ca

Cystic Diseases of Renal Medulla
Simple Cysts
Multiple or single cyst
1-5 cm, but can measured up to 10
cm
Commonly postmortem findings
without clinical significance
Composed of single layer of
cuboidal or flattened cuboidal
epithelium
GLOMERULAR DISEASES
Primary Glomerulopathies
Acute diffuse proliferative GN
- post streptococcal
- non post streptococcal
Rapidly progressive GN
Membranous glomerulopathy
Minimal change disease
Focal segmental glomerulosclerosis
Membranoproliferative GN
IgA nephropathy
Chronic GN
Systemic Diseases with Glomerular
Involvement
Systemic lupus erythematosus
Diabetes Mellitus
Amyloidosis
Goodpasture syndrome
Microscopic polyarteritis/polyangiitis
Wegener granulomatosis
Henoch-Schonlein purpura
Bacterial endocarditis
Hereditary Disorders
Alport syndrome
Thin basement membrane disease
Fabry disease
Pathogenesis of Glomerular Injury
Immune mechanism >>>
Non immune factors can initiate GN
or cause its progression
Immune Mechanism of
Glomerular Injury
Antibody mediated immune injury
In situ immune complex deposition
Fixed intrinsic tissue Ag :
- anti GBM nephritis
- Heymann antigen
- Mesangial antigen
Planted Ag :
- Exogenous (infectious agent, drug)
- Endogenous (DNA, nuclear prot, Ig,
immune complex)
Immune Mechanism of
Glomerular Injury
Circulating immune complex
deposition
- Endogenous (DNA, tumour Ag)
- Exogenous (Infectious products)
Cytotoxic Antibodies
Cell-mediated immune injury
Activation of alternative
complement pathway
The Glomerular Syndromes
Syndrome Clinical Features
Acute nephritic syndrome Hematuria, azotemia, variable
proteinuria, oliguria, edema and
hypertension
Rapidly progressive
glomerulonephritis
Acute nephritis, proteinuria, acute
renal failure
Nephrotic syndrome > 3.5 gm proteinuria,
hypoalbuminemia, hyperlipidemia,
lipiduria
Chronic renal failure Azotemia Uremia progressing for
years
Asymptomatic hematuria
or proteinuria
Glomerular hematuria,
subnephrotic proteinuria
Histologic Alteration
Hypercellularity
- Cellular proliferation of mesangial
and endothelial cells
- Leukocytic infiltration
- Formation of crescents
Basement membrane thickening
Hyalinization and sklerosis
Acute Glomerulonephritis
Poststreptococcal GN
Etiology : - hemolytic streptococci
types 12,4,1
Immune complex mediated
Clinically :
- Malaise, fever, nausea, oliguria,
hematuria after recovery from sore
throat
- Elevation of ASO
Morphology :
- enlarged and hypercellular glomeruli
Acute Glomerulonephritis
Nonstreptococcal GN
Etiology : other bacterial, viral or
parasitic infections
Immune complex mediated
Granular immunofluorescent and
subepithelial humps are present
Rapidly Progressive (Cressentic) GN
Rapid and progressive
loss of renal function
Morphology : the
presence of crescents
in most of the
glomeruli
Hematuria, red cell
cast, proteinuria,
hypertension, edema,
recurrent hemoptysis,
pulmonary
hemorrhage.
Rapidly Progressive (Cressentic) GN
Type I RPGN (Anti-GBM antibody)
Idiopathic
Goodpasture syndrome

Type II RPGN (Immune complex)
Idiopathic
Post infectious
SLE
Henoch-Schonlein purpura (IgA)

Type III RPGN (Pauci-Immune)
ANCA associated
Idiopathic
Wegener granulomatosis
Microscopic polyarteritis/polyangiitis
Nephrotic Syndrome
Primary glomerular lesions :
- Minimal change disease
- Membranous glomerulopathy
- Focal segmental glomerulosclerosis
Systemic causes :
- DM
- SLE
- Amyloidosis
Membranous glomerulopathy
The most common cause of NS
Immune complex mediated
Associated with drugs (penicilamine,
captopril, NSAID), malignant tumor, SLE,
infection, other autoimmune disorders
Morphology :
- diffuse thickening of glomerular capillary
wall without cells proliferation
- accumulation of electron dense
- Ig containing deposits along the
subepithelial side of the basement
membran
Minimal Change (Lipoid Nephrosis)
The most frequent cause of NS in
children
Associated with immunologic
disorders
Normal glomeruli by light
microscopy
Diffuse effacement of foot processes
of epithelial cells in glomeruli (by
electron microscopy
Focal Segmental Glomerulosclerosis
Focal sclerosis of
glomeruli
Only a portion of
the capillary tuft is
involved
10%-35%
idiopathic
HIV associated
nephropathy
Membranoproliferative GN
Characterized histologically by
- alterations in the basement membrane
- proliferation of glomerular cells
- leucocyte infiltration
Primary MPGN
- Type I and Type II
- Evidence of immune complexes
- Evidence of activation of both classical and
alternative complement pathway
Secondary MPGN
- Chronic immune complex disorders
- 1-antitrypsin deficiency
- Malignant diseases
- Hereditary deficiencies of complement
regulatory proteins



Ig A Nephropathy (Berger Disease)
Ig A deposits in mesangial regions
Frequent cause of recurrent
gross/microscopic hematuria
Alport Syndrome
Nephritis chronic renal failure
Nerve deafness
Various eye disorders (lens dislocation,
posterior cataracts, corneal dystrophy)
Chronic Glomerulonephritis
End stage glomerular disease
Some cases arise mysteriously
Thin cortex
Hyaline obliteration of glomeruli
Arterial and arteriolar sclerosis
Atrophy of associated tubules
Dialysis change
Uremic complication
Diseases Affecting
Tubules and Interstitium
Group of processes
Ischemic or toxic tubular injury
leading to acute tubular necrosis
(ATN) and acute renal failure
Inflammatory reaction
(tubulointerstitial nephritis)
Acute Tubular Necrosis
Destruction of tubular epithelial
cells
Diminution or loss of renal function
Causes :
- Ischemia
- Direct toxic injury to the tubules
- Acute tubulointerstitial nephritis
- DIC
- Urinary obstruction
Tubulointerstitial Nephritis
Involve predominantly the tubules and
interstitium
Acute TIN
Interstitial edema
Leukocytic infiltration of the interstitium and
tubules
Focal tubular necrosis
Chronic TIN
Infiltration of predominantly MN
Prominent interstitial fibrosis
Widespread tubular atrophy

Tubulointerstitial Nephritis
Causes of TIN :
Infection
Toxins
Metabolic diseases
Physical factors
Neoplasms
Immunologic reactions
Vascular diseases
Idiopathic
Pyelonephritis and UTI
Renal disorder affecting the tubules,
interstitium and renal pelvis
Acute : UTI
Chronic : UTI, vesicoureteral reflux,
obstruction
E. Colli, Proteus, Klebsiella, etc
Hematogenous or ascending
infection
Acute Pyelonephritis
Acute suppurative inflammation of
the kidney caused
Morphology :
Patchy interstitial suppurative
inflammation
Intratubular aggregates of neutrophils
Tubular necrosis
Complication
Papillary necrosis
Pyonephrosis
Perinephric abcess
Pyelonephritic scar



Chronic Pyelonephritis
Chronic tubulointerstitial inflammation
and renal scarring associated with
pathologic involvement of the calyces and
pelvis
Morphology
Gross : irregularly scarred, asymmetric if
bilateral
Atrophy and or hypertrophy or dilatation of
tubules
Coloid casts (thyroidization)
Chronic interstitial inflammation
Fibrosis in the cortex or medulla
Diseases of Blood Vessels
Benign Nephrosclerosis
Renal pathology associated with
sclerosis of renal arterioles and
small arteries
Morphology
Medial and intimal thickening
Hyaline deposition in arterioles (hyaline
arteriosclerosis)
Malignant Hypertension and
Accelerated Nephrosclerosis
Associated with the malignant or
accelerated phase of hypertension
Relatively uncommon
Pathogenesis is unclear
Morphology
Gross : flea-bitten appearance
Fibrinoid necrosis of arterioles
Interlobular arteries/arteriole ntimal
thickening (onion-skinning)

Renal Artery Stenosis
Occlusion by an atheromatous
plaque (70%)
Fibromuscular dysplasia
Intimal
Medial
Adventitial
Thrombotic Microangiopathies
Thrombosis in capillaries
Clinically :
Microangiopathic hemolytic anemia
Thrombocytopenia
Renal failure
Categories :
Classic childhood hemolytic-uremic syndrome
(HUS)
Adult HUS
Familial HUS
Idiopathic TromboticTrombocytophenic Purpura
(TTP)

Types of Hypertension Related
Renal Diseases
Primary or essential hypertension
Secondary hypertension
Acute GN
Chronic renal disease
Renal artery stenosis
Renal vasculitis
Renin-producing tumors
Obstructive Uropathy
and Urolithiasis
Obstructive Uropathy
Increases susceptibility to infection and stone
formation
Leads to permanent renal
atrophy/hydronephrosi/obstructive uropathy
Causes
Congenital anomalies
Urinary canaliculi
BPH
Tumors
Inflammation
Sloughed papillae or blood clots
Normal pregnancy
Uterine prolaps and cystocele
Functional disorders
Urolithiasis
Various types of renal stones
Calcium oxalate and phosphate (70%)
Magnesium ammonium phosphate
(struvite) (15-20%)
Uric acid (5-10%)
Cystine
Others or Unknown
Urolithiasis
Morphology
Unilateral in about 80% of patients
Usually in renal calyces, pelvis and
bladder
Progressive accretion of salts
Staghorn stones
Tumors of the Kidney
Benign Tumors
Rarely cause clinical problems
except oncocytoma
Consist of :
Renal papillary adenoma
Renal fibroma
Angiomyolipoma
Oncocytoma
Malignant Tumor
Most common type
Renal Cell Carcinoma
Wilms tumor
Urothelial Ca of renal pelvis
Renal Cell Carcinoma
1-3% of all visceral cancer
85% of renal ca in adults
Age : older individual (60-70)
M:F = 3:1
Arise from tubular epithelium
Risk factors
Tobacco
Obesity
Hypertension
Estrogen therapy
Exposure to asbestos, petroleum products,
heavy metal
Renal Cell Carcinoma
The major types of tumor :
Clear cell ca
Papillary ca
Chromophobe renal ca
Collecting duct (Bellini duct) ca
Urothelial Ca of Renal Pelvis
5% - 10 % of primary renal tumors
Originate from urothelium of renal
pelvis
Almost never palpable clincally
Histo : exact counterpart of those
found in the urinary bladder
Wilms Tumor
The most common primary renal
tumor of childhood
5-10% bilateral
Associated with WAGR Syndrome
Aniridia
Genital anomalies
Mental retardation
Wilms Tumor
Morphology
Gross : large, solitary, well
circumscribed mass. On cut section,
the tumor is soft, homogenous, tan to
gray with occasional foci of
hemorraghe, cyst form, necrosis
Histo : The classic triphasic
combination of blastemal, stromal and
epithelial cell types.
Referrences
Robbins and Cotran. Pathologic basis of
disease. 7
th
ed. Elsevier. 2005.
Rosai and Ackermans. Surgical
pathology.9
Th
ed. Mosby. 2004.
Rubin's Pathology : Clinicopathologic
Foundations of Medicine, 5th Edition.
Lippincott Williams & Wilkins.2008.
www.pathconsult.com
www.webpath.com
www.pathblog.net
THANK YOU