Renal Pathology

Normal Kidney

• From the standpoint of its diseases, the

kidney can be divided into:
• Blood vessels
• Glomeruli
• Tubules
• Interstitium
 • largely end-arteries
• occlusion of any branch usually results
in infarction
• all tubular capillary beds are derived from
the efferent arterioles
• Glomerular disease that interferes with
Blood vessels blood flow through the glomerular
capillaries has profound effects on the
tubules
• medulla does not have its own arterial
blood supply
• minor interference may result in
medullary necrosis from ischemia
Glomeruli
• visceral epithelium is incorporated into
and becomes an intrinsic part of the
capillary wall
• parietal epithelium, situated on
Bowman's capsule, lines the urinary
space
GLOMERULI

• glomerular filter:
1. Fenestrated endothelium
2. basement membrane
3. podocyte foot processes
Clinical
manifestations of
renal diseases
• Azotemia
• a biochemical abnormality that refers to an
elevation of the blood urea nitrogen (BUN)
and creatinine levels and is related largely to
a decreased glomerular filtration rate (GFR)
• Prerenal azotemia
• hypoperfusion of the kidneys that impairs
renal function in the absence of parenchymal
Definitions
damage
• Postrenal azotemia
• seen whenever urine flow is obstructed below
the level of the kidney
• Uremia
• a constellation of clinical signs and symptoms
and biochemical abnormalities associated definitions
with azotemia
 • Acute nephritic syndrome
• glomerular syndrome
Clinical • acute onset of usually grossly visible
hematuria, mild to moderate
syndromes proteinuria, and hypertension
• it is the classic presentation of acute
poststreptococcal glomerulonephritis
 • Nephrotic syndrome
• heavy proteinuria (more than 3.5 gm/day)
Clinical • hypoalbuminemia

syndromes • severe edema

• hyperlipidemia
• lipiduria
 • Asymptomatic hematuria and/or proteinuria
• usually a manifestation of subtle or mild glomerular
abnormalities

Clinical • Acute renal failure

• oliguria or anuria
syndromes • with recent onset of azotemia
• can result from glomerular, interstitial, or vascular
injury or acute tubular necrosis
• implies a rapid and frequently reversible
deterioration of renal function
 • Chronic renal failure
• prolonged symptoms and signs of uremia
• end result of all chronic renal parenchymal
diseases
Clinical • Renal tubular defects
• Polyuria
syndromes • Nocturia
• electrolyte disorders (e.g., metabolic acidosis)
• result of either diseases that directly affect
tubular structure or defects in specific tubular
functions
Clinical syndromes
• Urinary tract infection
• bacteruria and pyuria
• infection may be symptomatic or asymptomatic
• may affect the kidney (pyelonephritis) or the bladder (cystitis) only.
• Nephrolithiasis
• renal colic
• Hematuria
• recurrent stone formation
Congenital anomalies
 • Absence of renal development
• May be bilateral or unilateral
• Bilateral agenesis
• incompatible with life

Renal agenesis • usually encountered in stillborn infants

• Unilateral agenesis
• uncommon anomaly that is compatible with
normal life
• Associated with compensatory hypertrophy of the
remaining kidney
 • refers to failure of the kidneys to develop to a normal
size
Hypoplasia • Usually unilateral
• shows no scars and has a reduced number of renal
lobes and pyramids, usually six or fewer
 • lie either just above the pelvic brim or sometimes
ECTOPIC within the pelvis
• kinking or tortuosity of the ureters may cause some
KIDNEY obstruction to urinary flow, which predisposes to
bacterial infections
Horseshoe Kidneys
• Fusion of the upper or lower poles of the
kidneys produces a horseshoe-shaped
structure that is continuous across the midline
anterior to the great vessels
• 90%: fused at the lower pole
• 10%: fused at the upper pole
Cystic diseases of the kidney
Cystic renal dysplasia
• Sporadic, nonfamilial disorder
• kidney is usually enlarged, extremely irregular, and
multicystic
• characterized histologically by abnormal
structures:
• Cartilage
• undifferentiated mesenchyme
• immature collecting ductules
Renal Cystic Diseases
POLYCYSTIC
KIDNEY
DISEASE
•A and B, autosomal-dominant
adult polycystic kidney disease
viewed from the external
surface and bisected. The
kidney is markedly enlarged
with numerous dilated cysts. C,
autosomal-recessive childhood
polycystic kidney disease,
showing smaller cysts and
dilated channels at right angles
to the cortical surface
 medullary cystic disease
Cut section of kidney showing cysts at the corticomedullary junction and in the
medulla
Renal Cystic Diseases
Glomerular diseases
 • constitute some of the major problems in
nephrology
Glomerular • chronic glomerulonephritis is one of the
most common causes of chronic renal
Diseases failure in humans
• may be primary or secondary
Glomerular Syndromes
 • Diffuse: involving all glomeruli
• Global: involving the entire glomerulus
HISTOLOGIC • Focal: involving only a proportion of the
glomeruli;
ALTERATIONS • Segmental: affecting a part of each glomerulus
• Mesangial: affecting predominantly the
mesangial region
PATHOGENESI • Immune mechanisms predominate in
glomerular injury

S OF • Involves deposition of antigen-antibody

complexes
GLOMERULAR • Can be formed
• In situ with glomerular antigens
INJURY • Trapped circulating complex
MECHANISMS • once any renal disease destroys functioning
nephrons and reduces the GFR to about 30%
OF to 50% of normal, progression to end-stage
renal failure proceeds at a relatively constant
PROGRESSION rate
• Two major histologic characteristics of renal
IN damage:

GLOMERULAR • Glomerulosclerosis
• Tubulointerstitial inflammation and

DISEASES fibrosis
ACUTE
GLOMERULONEPHRI
TIS
• group of glomerular diseases
characterized
• anatomically by
inflammatory alterations in
the glomeruli ACUTE
• clinically by the syndrome of
acute nephritis GLOMERULONEPHR
• characteristic of acute
ITIS
proliferative glomerulonephritis
and is an important component
of crescentic glomerulonephritis
Acute Proliferative • Characterized by acute nephritic syndrome,
presenting 1 to 4 weeks after a pharyngeal
(Poststreptococcal, streptococcal infection of after a skin infection.
• An antibody-medicated disease, although the
Postinfectious) precise causal streptococcal antigen is
Glomerulonephriti unknown
• Biopsy specimens show diffuse GN with global
s hypercellularity
Acute Proliferative • Immunofluorescence shows a granular IgG, IgM, and
C3 deposition
(Poststreptococcal, • EM shows subepithelial humplike deposit, supporting
Postinfectious) the pathogenesis of immune complex deposition
Glomerulonephriti • Serum antistreptococcal antibody levels are elevated
s and serum complement C3 concentrations are
decreased
 • characterized clinically by rapid and progressive loss of
renal function associated with severe oliguria and (if
Rapidly progressive untreated) death from renal failure within weeks to
months
(crescentic) • all forms include hematuria with red cell casts in the
Glomerulonephritis urine, moderate proteinuria occasionally reaching the
nephrotic range, and variable hypertension and
edema
 Rapidly progressive (crescentic)
Glomerulonephritis
• classic histologic picture is
characterized by the presence of
crescents in most of the glomeruli
 • Clinical manifestation:

• Massive proteinuria
NEPHROTIC • Daily loss of 3.5gm or more of protein
• Hypoalbuminemia
SYNDROME • Plasma albumin levels less than
3gm/dL
• Generalized edema
• Hyperlipidimia and lipiduria
Table 20-8 -- Causes of Nephrotic Syndrome
Prevalence (%) *
Children Adults
Primary Glomerular Disease
Membranous glomerulopathy 5 30
Minimal change disease 65 10
Focal segmental glomerulosclerosis 10 35
Membranoproliferative glomerulonephritides 10 10
Other proliferative glomerulonephritis (focal, "pure mesangial,"
10 15
IgA nephropathy)
Systemic Diseases
Diabetes mellitus
Amyloidosis
Systemic lupus erythematosus
Drugs (nonsteroidal anti-inflammatory, penicillamine, "street heroin")
Infections (malaria, syphilis, hepatitis B and C, acquired immunodeficiency syndrome)
Malignant disease (carcinoma, lymphoma)
Miscellaneous (bee-sting allergy, hereditary nephritis)
MEMBRANOUS • most common cause of the nephrotic
GLOMERULOPAT syndrome in adults
• characterized by diffuse thickening of the
HY glomerular capillary wall and the
accumulation of electron-dense,
(MEMBRANOUS immunoglobulin-containing deposits along the
subepithelial side of the basement membrane.
NEPHROPATHY)
 MEMBRANOUS
GLOMERULOPAT • occurring in association with other systemic diseases
HY and a variety of identifiable etiologic agents is referred
(MEMBRANOUS to as secondary membranous glomerulopathy

NEPHROPATHY)
MEMBRANOUS
GLOMERULOPATHY
(MEMBRANOUS
NEPHROPATHY)
• By light microscopy, the
glomeruli either appear normal
in the early stages of the disease
or exhibit uniform, diffuse
thickening
of the glomerular capillary wall
MEMBRANOUS
GLOMERULOPATH
Y (MEMBRANOUS
NEPHROPATHY)
• By electron microscopy, the
thickening is seen to be caused
by irregular dense deposits
between the basement
membrane and the overlying
epithelial cells, the latter having
effaced foot processes
MINIMAL • relatively benign disorder is the most frequent
CHANGE cause of nephrotic syndrome in children
• characterized by diffuse effacement of foot
DISEASE processes of epithelial cells in glomeruli that
appear virtually normal by light microscopy
(LIPOID • Its most characteristic feature is its usually
dramatic response to corticosteroid therapy.
NEPHROSIS)
MINIMAL CHANGE
DISEASE (LIPOID
NEPHROSIS)

• glomeruli are normal by light

microscopy
• uniform and diffuse effacement
of foot processes
MINIMAL
CHANGE • it is only when effacement is associated with normal
glomeruli by light microscopy that the diagnosis of
minimal change disease can be made.
DISEASE • The visceral epithelial changes are completely

(LIPOID reversible after corticosteroid therapy, concomitant

with remission of the proteinuria.

NEPHROSIS)
MINIMAL
CHANGE • Despite massive proteinuria, renal function remains
good, and there is commonly no hypertension or
DISEASE hematuria.
• The proteinuria usually is highly selective, most of the
(LIPOID protein consisting of albumin.

NEPHROSIS
 • this lesion is characterized by sclerosis of some, but
FOCAL SEGMENTAL not all, glomeruli (thus, it is focal); and in the affected
glomeruli, only a portion of the capillary tuft is
GLOMERULOSCLERO involved (thus, it is segmental).
SIS • frequently accompanied clinically by the nephrotic
syndrome or heavy proteinuria.
 • The clinical signs differ from those of minimal change
disease in the following respects:
• (1) there is a higher incidence of hematuria,
reduced GFR, and hypertension;
• (2) proteinuria is more often nonselective;
FOCAL SEGMENTAL • (3) there is poor response to corticosteroid
GLOMERULOSCLERO therapy;
SIS • (4) there is progression to chronic
glomerulosclerosis, with at least 50% developing
end-stage renal disease within 10 years; and
• (5) immunofluorescence microscopy may show
nonspecific deposition ("trapping") of IgM and C3
in the sclerotic segment.
FOCAL SEGMENTAL
GLOMERULOSCLER
OSIS
• By light microscopy, the
segmental lesions may involve
only a minority of the glomeruli
and may be missed if the biopsy
specimen contains an insufficient
number of glomeruli

• By immunofluorescence
microscopy, IgM and C3 may be
present in the sclerotic areas
and/or in the mesangium.
 • characterized histologically by
alterations in the basement
MEMBRANOPROLIFERATI membrane, proliferation of
VE glomerular cells, and leukocyte
infiltration
GLOMERULONEPHRITIS • May present as nephrotic, or
combined nephrotic-nephritic
MEMBRANOPROLIFERATIV
E GLOMERULONEPHRITIS
GBM is thickened, often segmentally
Glomerular capillary wall often shows a “double-
contour” or “tram-track”appearance
 • Type I MPGN (the great majority of cases) is
characterized by the presence of subendothelial
electron-dense deposits. Mesangial and occasional
subepithelial deposits may also be present.
MEMBRANOPROLIFERATI
VE
GLOMERULONEPHRITIS • Type II MGN (dense-deposit disease) a relatively rare
entity, the lamina densa of the GBM is transformed
into an irregular, ribbon-like, extremely electron-
dense structure because of the deposition of dense
material of unknown composition in the GBM proper
IgA
• prominent IgA deposits in the mesangial regions
NEPHROPATH • Glomerulonephritis
Y (BERGER • Light microscopy showing mesangial proliferation and matrix increase
DISEASE)
HEREDITARY
SYNDROMES OF
ISOLATED
HEMATURIA
• Alport Syndrome
• accompanied by nerve deafness
and various eye disorders, including
lens dislocation, posterior
cataracts, and corneal dystrophy.

• diffuse glomerular basement

membrane thinning.

• basket-weave appearance
• most common presenting sign is:
• gross or microscopic hematuria,
• frequently accompanied by erythrocyte casts.
• Proteinuria may occur, and rarely, the
nephrotic syndrome develops. Alport
• Symptoms appear at ages 5 to 20 years, and Syndrome
the onset of overt renal failure is between
ages 20 and 50 years in men. The auditory
defects may be subtle, requiring sensitive
testing.
• This is a fairly common entity manifested clinically
by familial asymptomatic hematuria—usually Thin Basement
uncovered on routine urinalysis—and
morphologically by diffuse thinning of the GBM to
Membrane Disease
between 150 and 250 nm (compared with 300 to (Benign Familial
400 nm in normal adult individuals).
Hematuria)
 CHRONIC • is best considered a pool of end-stage glomerular
GLOMERULONEPHRITI disease fed by a number of streams of specific types of
S glomerulonephritis.
GLOMERULAR
LESIONS • Systemic Lupus Erythematosus
• recurrent microscopic or gross hematuria, acute
ASSOCIATED nephritis, the nephrotic syndrome, chronic renal
failure, and hypertension
WITH SYSTEMIC • “wire loop lesions”
DISEASES
 • purpuric skin lesions characteristically involving
the extensor surfaces of arms and legs as well as
buttocks; abdominal manifestations including
Henoch- pain, vomiting, and intestinal bleeding;
nonmigratory arthralgia; and renal abnormalities.
Schönlein The renal manifestations occur in one-third of
patients and include gross or microscopic
Purpura hematuria, proteinuria, and nephrotic syndrome.
• Whatever the histologic lesions, the prominent
feature by fluorescence microscopy is the
deposition of IgA, sometimes with IgG and C3, in
the mesangial region.
 • Bacterial Endocarditis
• Hematuria and proteinuria of various degrees
characterize this entity clinically, but an acute
GLOMERULAR nephritic presentation is not uncommon, and
even RPGN may occur in rare instances.
LESIONS • Diabetic Glomerulosclerosis
ASSOCIATED • The morphologic changes in the glomeruli include
WITH SYSTEMIC • (1) capillary basement membrane thickening,
DISEASES • (2) diffuse mesangial sclerosis, and
• (3) nodular glomerulosclerosis.
Disease affecting Tubules and Interstitium
• Acute tubular Necrosis
• Tubulointerstitial Nephritis
• Pyelonephritis and Urinary Tract Infection
Acute Tubular Necrosis
• Characterized morphologically by destruction of tubular epithelial
cells and clinically by acute dimunition or loss of renal function
• Most common cause of acute renal failure
• Causes
• Ischemia
• Direct toxic injury
• Acute tubulointerstitial nephritis
• DIC
• Urinary obstruction by tumors, prostatic hypertrophy, or blood clots
Ischemic ATN
• Focal tubular epithelial
necrosis with large skip areas
in between
ATN
• Necrotic tubular
cells
• Sloughed of into the
lumen
Toxic Type
• Most obvious in PCT
• Mercuric chlorite: large
acidophilic inclusion
• CCl4: accumulation of
neutral lipid
• Ethylene glycol:
balooning and hydropic
or vacuolar degeneration
ATN – Clinical Course
• Initiation phase
• Dominated by the inciting event
• Slight decline in urine output with increase BUN
• Maintenance phase
• Sustained decrease in urine output between 40-400 mL/day with salt and water
overload, rising BUN conc, hyperkalemia, metabolic acidosis
• Recovery phase
• Steady increase in urine volume (up to 3L/day)
• Tubules are still damaged  loss of H2O, Na, K
• Eventually with improved concentrating ability
• BUN and creatinine levels return to normal
• Causes of Tubulointerstitial Nephritis
• Infections
• Acute bacterial pyelonephritis
• Chronic pyelonephritis (including reflux nephropathy)
• Other infections (e.g., viruses, parasites)

• Toxins
• Drugs
• Acute hypersensitivity interstitial nephritis
• Analgesic nephropathy
• Heavy metals
• Lead, cadmium

• Metabolic Diseases
• Urate nephropathy
• Nephrocalcinosis (hypercalcemic nephropathy)
• Hypokalemic nephropathy Oxalate nephropathy

• Physical Factors
• Chronic urinary tract obstruction
• Radiation nephropathy

• Neoplasms
• Multiple myeloma (cast nephropathy)

• Immunologic Reactions
• Transplant rejection
• Sjögren syndrome
• Sarcoidosis

• Vascular Diseases
• Miscellaneous
Pyelonephritis and UTI
• Gram negative bacilli (85% of cases)
• Most common: E. Coli
• Followed by Proteus, Klebsiella, Enterobaccter
• Mostly derived from patient’s own fecal flora
 • Nearly all diseases of the kidney involve the
renal blood vessels secondarily.
Diseases of
• Hypertension is intimately linked with the
Blood Vessels kidney, because kidney disease can be both
the cause and consequence of increased blood
pressure.
 • renal pathology associated with sclerosis of renal arterioles and
small arteriesresulting to focal ischemia of parenchyma supplied by
vessels with thickened walls and consequent narrowed lumens.

• increasing age, more in blacks than whites, preceding or in the

absence of hypertension

• Hypertension and diabetes mellitus increase the incidence and

BENIGN severity of the lesions

NEPHROSCLEROS Pathogenesis.

IS Two processes participate in inducing the arterial lesions:

Medial and intimal thickening, as a response to hemodynamic

changes, aging, genetic defects, or some combination of these

Hyaline deposition in arterioles, caused partly by extravasation of

plasma proteins through injured endothelium and partly by
increased deposition of basement membrane matrix
• In gross appearance, the kidneys are either
normal in size or moderately reduced, with
average weights between 110 and 130 gm.
The cortical surfaces have a fine, even
granularity that resembles grain leather. The
loss of mass is due mainly to cortical scarring
and shrinking.

• On histologic examination, there is narrowing

of the lumens of arterioles and small arteries,
caused by thickening and hyalinization of the
walls (hyaline arteriolosclerosis)
 • moderate reductions in renal plasma flow but the GFR
is normal or only slightly reduced
• mild proteinuria

Clinical • 3 groups of hypertensives with increased risk of

developing renal failure:

Features • Blacks
• Severe blood pressure elevations
• With a second underlying disease, especially
diabetes
 • Malignant nephrosclerosis is the form of renal disease associated
with the malignant or accelerated phase of hypertension.

MALIGNANT • often is superimposed on pre-existing essential benign hypertension,

HYPERTENSION secondary forms of hypertension, or an underlying chronic renal
disease, particularly glomerulonephritis or reflux nephropathy
AND
ACCELERATED • frequent cause of death from uremia in patients with scleroderma.
NEPHROSCLEROS
IS • occurring in 1% to 5% of all patients with elevated blood pressure

• younger individuals, men and in blacks

 • Initial insult appears to be some form of vascular damage to the kidneys from
long-standing benign hypertension, with eventual injury to the arteriolar
walls, or the initiating injury may spring de novo from arteritis or a
coagulopathy or some injury causing acute exacerbation of the hypertension.

• result is increased permeability of the small vessels to fibrinogen and other

plasma proteins, endothelial injury, focal death of cells of the vascular wall,
and platelet deposition

Pathogenesis • leads to the appearance of fibrinoid necrosis of arterioles and small arteries,
swelling of the vascular intima, and intravascular thrombosis.

• Mitogenic factors from platelets (e.g., platelet-derived growth factor [PDGF]),

plasma, and other cells cause hyperplasia of intimal smooth muscle of vessels,
resulting in the hyperplastic arteriolosclerosis that is typical of malignant
hypertension and further narrowing of the lumens
• kidneys become markedly ischemic

• patients with malignant hypertension have markedly

elevated levels of plasma renin

• sets up a self-perpetuating cycle in which angiotensin

II causes intrarenal vasoconstriction, and the attendant
renal ischemia perpetuates renin secretion

• Aldosterone levels are also elevated, and salt retention

undoubtedly contributes to the elevation of blood
pressure

• malignant arteriosclerosis - consequences of the

markedly elevated blood pressure on the blood vessels
throughout the body
• malignant nephrosclerosis - renal disorder
• Small, pinpoint petechial hemorrhages may appear on the cortical
surface from rupture of arterioles or glomerular capillaries
• "flea-bitten" appearance.
• Two histologic alterations characterize blood vessels in malignant
hypertension:
• Fibrinoid necrosis of arterioles
• onion-skinning also called hyperplastic arteriolitis
 • diastolic pressures greater than 130 mm Hg
• papilledema retinopathy
Clinical • Encephalopathy

Course • cardiovascular abnormalities

• renal failure
• early symptoms are related to increased intracranial
pressure

• "Hypertensive crises“ characterized by episodes of

loss of consciousness or even convulsions

• onset of rapidly mounting blood pressure, marked

proteinuria and microscopic or sometimes
macroscopic hematuria but no significant alteration in
renal function

• 75% of patients will survive 5 years, and 50% survive

with pre-crisis renal function.
 • Unilateral renal artery stenosis is a relatively
uncommon cause of hypertension
RENAL ARTERY • 2% to 5% of cases
• potentially curable form of hypertension
STENOSIS • surgical treatment is successful in 70% to 80
 • constriction of one renal artery results in hypertension
and that the magnitude of the effect is roughly
proportional to the amount of constriction

Pathogenesis • A large proportion of patients with renovascular

hypertension have elevated plasma or renal vein renin
levels
• almost all show a reduction of blood pressure when
given competitive antagonists of angiotensin II
 TYPES:
1. atheromatous plaque at the origin of the renal artery - the
most common cause of renal artery stenosis (70% of cases)
men, with advancing age and diabetes mellitus. The plaque
is usually concentrically placed, and superimposed
thrombosis often occurs

Morphology 2. fibromuscular dysplasia of the renal artery characterized by

fibrous or fibromuscular thickening and may involve the
intima, the media, or the adventitia of the artery
subclassified into intimal, medial, and adventitial
hyperplasia, the medial type being by far the most common
women and tend to occur in younger age
single well-defined constriction or a series of
narrowings, usually in the middle or distal portion of the renal
artery
Clinical Course
• resemble those presenting with essential
hypertension
• bruit can be heard on auscultation of the
kidneys
• arteriography is required to localize the
stenotic lesion
 • group of disorders with overlapping clinical
manifestations that are characterized morphologically
by thrombosis in capillaries and arterioles throughout
the and clinically by microangiopathic hemolytic
anemia, thrombocytopenia, and, in certain conditions,
THROMBOTIC renal failure
MICROANGIOPATHI
ES • The renal failure is associated with platelet or platelet-
fibrin thrombi in the interlobular renal arteries,
arterioles, and glomeruli together with necrosis and
thickening of the vessel walls.
Classification
1. Classic childhood HUS, most frequently associated with
bloody diarrhea caused by intestinal infection by
verocytotoxin-releasing bacteria
2. Adult HUS, associated with
a. Infection
b. Antiphospholipid antibodies
c. Complications of pregnancy and contraceptives
d. Vascular renal diseases such as scleroderma and
hypertension
e. Chemotherapeutic and immunosuppressive drugs
f. Radiation
3. Familial HUS
4. Idiopathic TTP
 • two processes dominate the pathogenetic sequence
of events
• endothelial injury and activation, with subsequent
intravascular thrombosis
• platelet aggregation
Pathogenesis
Both cause vascular obstruction
and vasoconstriction and thus precipitate distal
ischemia
 • verocytotoxin-producing E. coli (e.g., type O157:H7
• ingestion of infected ground meat (as in hamburgers)

Classic • sudden onset, usually after a gastrointestinal or

(Childhood) influenza-like prodromal episode, of bleeding

manifestations (especially hematemesis and melena),
severe oliguria, hematuria, a microangiopathic
Hemolytic- hemolytic anemia, and (in some patients) prominent
neurologic changes
Uremic
Syndrome • Hypertension is present in about half the patients
• If the renal failure is managed properly with dialysis,
most patients recover in a matter of weeks
 1. In association with infection, such as typhoid fever, E. coli septicemia, viral
infections, and shigellosis (postinfectious HUS). Endotoxin, or Shiga toxin
(from Shigella species)

2. antiphospholipid syndrome, either primary or secondary to SLE (lupus

anticoagulant). Changes in the kidney tend to be more chronic, and healing of
the thrombotic changes in glomeruli can result in changes mimicking
Adult membranoproliferative glomerulonephritis by light microscopy but without
evidence of immune complex deposition.

Hemolytic- 3. postpartum renal failure - as complications of pregnancy (placental

hemorrhage) or the postpartum period. Occurs after an uneventful pregnancy,
Uremic 1 day to several months after delivery, and is characterized by
microangiopathic hemolytic anemia, oliguria, anuria, and initially mild
hypertension. The condition has a grave prognosis, although recovery can

Syndrome occur in milder cases.

4. Associated with vascular renal diseases, such as systemic sclerosis and

malignant hypertension.

5. In patients treated with chemotherapeutic and immunosuppressive drugs,

such as mitomycin, cyclosporine, bleomycin, cisplatin, and radiation.
 • recurrent thromboses
• higher mortality rate (about 50%)
• inherited deficiency of the complement regulatory
Familial HUS protein Factor H
• normally breaks down the alternative pathway C3
convertase and protects cells from damage by
uncontrolled complement activation
 • manifested by fever, neurologic symptoms, hemolytic
anemia, thrombocytopenic purpura, and the presence
of thrombi in glomerular capillaries and afferent
arterioles
• women, and most patients are younger than 40 years
• central nervous system involvement is the dominant
Idiopathic TTP feature
• The thrombi are composed of platelets and fibrin and
are found in arterioles of many organs throughout the
body
• exchange transfusions and corticosteroid therapy have
reduced mortality to less than 50%
Urinary Tract • obstruction increases susceptibility to infection and to
Obstruction stone formation, and unrelieved obstruction almost
always leads to permanent renal atrophy -
(Obstructive hydronephrosis or obstructive uropathy

Uropathy)
 1. Congenital anomalies: posterior urethral valves and urethral
strictures, meatal stenosis, bladder neck obstruction; ureteropelvic
junction narrowing or obstruction; severe vesicoureteral reflux
2. Urinary calculi
3. Benign prostatic hypertrophy
4. Tumors: carcinoma of the prostate, bladder tumors, contiguous
malignant disease (retroperitoneal lymphoma), carcinoma of the
Common cervix or uterus
5. Inflammation: prostatitis, ureteritis, urethritis, retroperitoneal
Causes: fibrosis
6. Sloughed papillae or blood clots
7. Normal pregnancy
8. Uterine prolapse and cystocele
9. Functional disorders: neurogenic (spinal cord damage or diabetic
nephropathy) and other functional abnormalities of the ureter or
bladder (often termed dysfunctional obstruction)
 • dilation of the renal pelvis and calyces associated with
progressive atrophy of the kidney due to obstruction
to the outflow of urine

Hydronephrosis • Only later does the GFR begin to diminish

• Obstruction also triggers an interstitial inflammatory

reaction, leading eventually to interstitial fibrosis
 • sudden and complete - reduction of glomerular filtration
usually leads to mild dilation of the pelvis and calyces but
sometimes to atrophy of the renal parenchyma

• subtotal or intermittent - glomerular filtration is not

suppressed, and progressive dilation ensues

• the kidney may have slight to massive

Morphology
• chronic cases, cortical tubular atrophy with marked
diffuse interstitial fibrosis. Progressive blunting of the
apices of the pyramids occurs, and these eventually
become cupped and kidney may become transformed
into a thin-walled cystic structure having a diameter of up
to 15 to 20 cm with striking parenchymal atrophy, total
obliteration of the pyramids, and thinning of the cortex
 • Acute obstruction - pain attributed to distention of the collecting
system or renal capsule. Most of the early symptoms are produced
by the underlying cause of the hydronephrosis. Thus, calculi lodged
in the ureters may give rise to renal colic, and prostatic
enlargements may give rise to bladder symptoms

• Unilateral, complete, or partial hydronephrosis may remain silent

for long periods, since the unaffected kidney can maintain adequate
renal function. Ultrasonography is a useful noninvasive technique in
the diagnosis of obstructive uropathy.

Clinical Course • In bilateral partial obstruction, the earliest manifestation is inability

to concentrate the urine, reflected by polyuria and nocturia.
Hypertension is common in such patients

• Complete bilateral obstruction results in oliguria or anuria and is

incompatible with long survival unless the obstruction is relieved.
Curiously, after relief of complete urinary tract obstruction,
postobstructive diuresis occurs. This can often be massive, with the
kidney excreting large amounts of urine that is rich in sodium
chloride.
 • most arise in the kidney
• Men are affected

Urolithiasis • age at onset is between 20 and 30 years

• Familial and hereditary
(Renal Calculi, • inborn errors of metabolism, such as gout,
cystinuria, and primary hyperoxaluria
Stones) • characterized by excessive production and
excretion of stone-forming substances
 • There are four main types of calculi
• (1) calcium oxalate or calcium oxalate mixed
with calcium phosphate - most stones (about
70%)
• (2) triple stones or struvite stones - 15%,
composed of magnesium ammonium phosphate
• (3) 5% to 10% are uric acid stones
Cause and • (4) 1% to 2% are made up of cystine

Pathogenesis • the most important determinant is an increased

urinary concentration of the stones' constituents,
such that it exceeds their solubility in urine
(supersaturation)
• A low urine volume in some metabolically normal
patients may also favor supersaturation.
 • unilateral in about 80%
• within the renal calyces and pelves and in the bladder
• in the renal pelvis, they tend to remain small, having an
average diameter of 2 to 3 mm with smooth contours

Morphology or may take the form of an irregular, jagged mass of

spicules
• progressive accretion of salts leads to the development
of branching structures known as staghorn stones,
which create a cast of the pelvic and calyceal system
 • smaller stones are most hazardous, because they may
pass into the ureters, producing pain referred to as
colic (one of the most intense forms of pain) as well as
ureteral obstruction

• larger stones cannot enter the ureters and are more

Clinical likely to remain silent within the renal pelvis

Course • larger stones first manifest themselves by hematuria

• predispose to superimposed infection, both by their

obstructive nature and by the trauma they produce
 • Both benign and malignant tumors occur in the kidney
• With the exception of oncocytoma, the benign tumors
rarely cause clinical problems
Tumors of the • renal cell carcinoma - the most common of these
malignant tumors
Kidney • Wilms tumor – 2nd most common is found in children
• urothelial tumors of the calyces and pelves – 3rd MC
 • Small, discrete adenomas arising from the renal
tubular epithelium

Renal • 7% to 22% at autopsy

Papillary • Morphology

Adenoma • small tumors, usually less than 5 mm in

• composed of complex, branching, papillomatous
structures with numerous complex fronds
• the current view is to consider and treat all
adenomas, regardless of size, as early
cancers until an unequivocal marker of
benignity is discovered
 • small foci of gray-white firm
tissue
Renal Fibroma or • less than 1 cm in diameter

Hamartoma • found within the pyramids of the

kidneys
(Renomedullary • fibroblast-like cells and
collagenous tissue
Interstitial Cell • the cells have features of renal
interstitial cells
Tumor) • no malignant propensities.
• benign tumor consisting of
vessels, smooth muscle, and fat
• present in 25% to 50% of
patients with tuberous sclerosis
• a disease characterized by
lesions of the cerebral
Angiomyolipoma
cortex that produce epilepsy
and mental retardation as
well as a variety of skin
abnormalities
• epithelial tumor composed of
large, eosinophilic cells having
small, round, benign-appearing
nuclei that have large nucleoli
• from the intercalated cells of
collecting ducts
• 5% to 15% of surgically resected
renal neoplasms
• the eosinophilic cells have
numerous mitochondria Oncocytoma
• the tumors are tan or mahogany
brown, relatively homogeneous,
and usually well encapsulated
• may achieve a large size (up to 12
cm in diameter)
• familial cases these tumors are
multicentric rather than solitary.
 • about 1% to 3% of all visceral cancers
Renal Cell • 85% of renal cancers in adults

Carcinoma • older individuals, usually in the sixth and

seventh decades of life, showing a male
(Adenocarcinoma preponderance in the ratio of 2 to 3:1
• gross yellow color
of the Kidney) • arise from tubular epithelium and are
therefore renal adenocarcinomas.
Renal cell carcinoma. A, Clear cell
type, B, Papillary type. Note the
papillae and foamy macrophages
in the stalk. C, Chromophobe type.
 • Association with chromosome 3 deletion, von hippel
lindau syndrome

Renal Cell • Papillary variant of RCC highest variant on chronic

kidney disease patients on dialysis

Carcinoma • Chromophobe variant may arise from oncocytoma

• Tobacco is the most significant risk factor
• obesity (particularly in women)
• Hypertension
• unopposed estrogen therapy
• exposure to asbestos, petroleum products, and
heavy metals
Epidemiology
• increased incidence in patients with chronic renal
failure and acquired cystic disease and in tuberous
sclerosis.
• sporadic
Urothelial Carcinomas
of the Renal Pelvis
• Approximately 5% to 10% of primary renal tumors
originate from the urothelium of the renal pelvis
• These tumors span the range from apparently
benign papillomas to invasive urothelial (transitional
cell) carcinomas