PATHOLOGY OF THE KIDNEY

Dody NovrialDepartment 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 agenesis2. Hypoplasia3. Ectopic kidneys4. 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 DiseaseAutosomal 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 injuryIn situ immune complex depositionFixed intrinsic tissue Ag : - anti GBM nephritis- Heymann antigen- Mesangial antigenPlanted 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 FeaturesAcute 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 : α-β 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) GNType 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- α1-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. 7th ed. Elsevier. 2005.

Rosai and Ackerman’s. Surgical pathology.9Th ed. Mosby. 2004.

Rubin's Pathology : Clinicopathologic Foundations of Medicine, 5th Edition. Lippincott Williams & Wilkins.2008.

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