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Dr. dr.H. Delyuzar, M.Ked(PA),SpPA(K)

Departemen Patologi Anatomi

Fakultas Kedokteran
Universitas Sumatera Utara
Depending on the affected segment, non-tumor nephropathies can be
divided into : glomerular and tubulo-interstitial nephropaties.

Primary glomerulonephritis :

 Acute diffuse proliferative glomerulonephritis (nephritic syndrome)

 Rapidly progressive (crescentic) glomerulonephritis
 Lipoid nephrosis (minimal change disease) (nephrotic syndrome)
 Membranous glomerulonephritis (membranous nephropathy) (nephrotic
syndrome)
 Membranoproliferative glomerulonephritis (nephrotic syndrome)
 Focal segmental glomerulosclerosis (nephrotic syndrome)
 IgA nephropathy (Berger's disease)
 Chronic glomerulonephritis
 Secondary glomerulonephritis may appear during some systemic diseases,
such as: systemic lupus erythematosus, diabetes mellitus, amyloidosis,
Goodpasture's syndrome, polyarteritis nodosa, Wegener's granulomatosis,
Henoch-Schonlein purpura, bacterial endocarditis.

 Tubulo-intestitial nephropaties are represented by : acute tubular necrosis

(nephrotoxic or ischemic), inflammatory lesions of the tubules and
interstitium (acute and chronic pyelonephritis, interstitial nephritis, including
drug-induced interstitial nephritis).

 Renal tumors are : benign (cortical adenoma, fibroma, angiomyolipoma,

oncocytoma, urothelial papilloma) and malignant (renal cell carcinoma -
Grawitz tumor, nephroblastoma - Wilms' tumor, urothelial carcinoma,
sarcomas).
is congenital anomaly with
genetic involvement,
characterized by the presence
of multiple kidneys' cysts.
Classification :
 Adult type polycystic kidney disease (autosomal
dominant) = ADPKD
 Infantile type polycystic kidney disease (autosomal
recessive) = ARPKD
Each of these two types have their own pathology and
causes.
 Autosomal-Dominant Polycystic Kidney
Disease (ADPKD)
Polycystic kidney (adult
type) is a manifestation of
autosomal dominant
polycystic kidney disease,
caused by mutations in
genes on chromosome
16p13.3 (PKD1 - producing
protein Polycystin 1) and
4q21 (PKD2 - Polycystin 2)
ADPKD may associate some
other extrarenal
abnormalities, such as:
cysts in the liver (polycystic
liver disease), pancreas,
spleen and lung,
intracranial "berry"
aneurysms and mitral valve
prolapse.
 In ADPKD, both kidneys are
enlarged to impressive size (up to
25 cm and 4 kg, each),
compressing abdominal organs.
The external surface of the kidney
is deformed, bumped. On section,
the cortex and medulla present
numerous spherical cysts, sized
between 0.5-5 cm in diameter,
containing a serous, hemorrhagic
or gelatinous fluid. Between the
cysts, the intervening parenchyma
is reduced, atrophic by
compression. However,
microscopically, this parenchyma is
represented by functional
nephrons.
Cysts (dilated tubuli and colector ducts) lined by cuboidal or flattened epithelium contain
an eosinophilic fluid. The parenchyma between cysts is represented by few atrophic /
compressed but still functional nephrons (glomeruli and tubules), with interstitial fibrosis
and chronic inflammation. (HE, ob. 4x)
Infantile polycystic kidney type:

 is a manifestation of autosomal
recessive polycystic kidney
disease (ARKPD)
Infantile polycystic
 common in newborns and children kidney type

 ARKPD belongs to congenital

hepato-renal fibrocystic syndrome,
cause of morbidity and mortality in
children in the first decade of life
(perinatal, neonatal, infantile and
juvenile type).
Renal disease is characterized by :
 nephromegaly,
 hypertension, and
 varying degrees of renal dysfunction causing renal failure;
 more than 50% of affected children requires renal
transplantation in the first decade of life.

 Liver disease is characterized by biliary abnormalities (dilated

intrahepatic biliary ducts), which causes progressive
hepatomegaly and portal hypertension in 40 -60 % of cases. In
almost all cases, the cysts are associated with portal fibrosis
and proliferation of portal bile ducts.
Both kidneys are enlarged and have a smooth external surface, with preserved fetal
lobulation. On the cut surface, it reveals a sponge-like appearance with numerous cysts
(dilated nephron tubules) round or fusiform, with sero-citrin content and sizes that
varies from 0.1 to 1 cm. They extend radially in cortex and medulla, completely
replacing the renal parenchyma.
Liver parenchyma shows round cysts similar to those described in the kidney.
 Acute postinfectious (poststreptococcal)
diffuse proliferative glomerulonephritis is a
primary glomerulonephritis, which produces
nephritic syndrome (hematuria, oliguria,
uremia, hypertension and mild proteinuria).
 "Acute" - because it occurs 2 weeks after a
streptococcal (group A beta-hemolytic)
pharyngitis. It becomes chronic only in 10 - 15 Poststreptococcal
% of cases, especially in adults. acute diffuse
 "Diffuse" - because almost all the glomeruli are proliferative
affected (about 80 %). glomerulonephritis
 "Proliferative" - due to proliferation of
endothelial cells and mesangial cells.
 The mechanism of poststreptococcal acute
diffuse proliferative glomerulonephritis is
immune : granular deposits of IgG and C3
("humps") on the external (subepithelial) side
of the basement glomerular membrane. These
humps can be seen in electron microscopy and
immunofluorescence microscopy.
 Acute postinfectious
diffuse proliferative
glomerulonephritis. Almost
all glomeruli are enlarged
(hypercellular) due to
proliferation of endothelial
cells and mesangial cells,
swelling of endothelial cells
and inflammatory infiltrate
(neutrophils and
monocytes). This will result
in compression of
capillaries and Bowman
space, which is reduced in
size. Initially, tubules are
not affected, but with
evolution, they may
present hydropic change.
(H&E, ob. x10)
 Rapidly progressive ("crescentic")
glomerulonephritis is a primary
glomerulonephritis, which produces
nephritic syndrome (hematuria, oliguria,
uremia, hypertension and mild
proteinuria). The prognosis is severe, Rapidly progressive
with rapid and irreversible evolution to ("crescentic")
renal failure.
glomerulonephritis
 Etiology of rapidly progressive crescentic
glomerulonephritis : streptococcal
infection, systemic lupus, vasculitis,
Goodpasture's syndrome, idiopathic.
 Rapidly progressive
("crescentic")
glomerulonephritis - the
majority of glomeruli
present "crescents".
Formation of crescents is
initiated by passage of fibrin
into the Bowman space as a
result of increased
permeability of glomerular
basement membrane. Fibrin
stimulates the proliferation
of parietal cells of Bowman
capsule, and an influx of
monocytes. Rapid growing
and fibrosis of crescents
compresses the capillary
loops and decreases the
Bowman space which leads
to renal failure within weeks
or months. (H&E, ob. x20)
Chronic glomerulonephritis represents the end-stage of all glomerulonephritis with
unfavorable evolution. This general (glomerular, vascular and interstitial) affection
constitutes the so-called "end stage kidney". In most cases, it is associated with systemic
hypertension.
Chronic glomerulonephritis.

 The majority of the glomeruli are affected.

 Depending on the stage of the disease, they may present different degrees of
hyalinization (hyalinosclerosis - total replacement of glomeruli and Bowmann's
space with hyaline).
 The hyaline is an amorphous material, pink, homogenous, resulted from
combination of plasma proteins, increased mesangial matrix and collagen.
 Totally hyalinised glomeruli are atrophic (smaller), lacking capillaries, hence
these glomeruli are non-functional.
 Few glomeruli may still present changes which permit to discern the etiology
of chronic glomerulonephritis.
 Obstruction of blood flow will produce secondary tubular atrophy, interstitial
fibrosis and thickening of the arterial wall by hyaline deposits.
 In the interstitium is present an abundant inflammatory infiltrate (mostly with
lymphocytes). (Hematoxylin-eosine, ob. x20)
Chronic glomerulonephritis. Functional nephrons have dilated tubules, often with
hyaline casts in the lumens. (Hematoxylin-eosine, ob. x20)
 In diabetes, basement membranes of majority
of capillaries in the body are thickened by
deposits of nonenzymatic glycosilated proteins
(diabetic microangiopathy): retinopathy,
coronary arteries, and peripheral vessels.
In kidney, diabetic nephropathy includes :
diabetic glomerulosclerosis, arteriolosclerosis
and papillary necrosis, with an increased risk for
pyelonephritis.

 Diabetic glomerulosclerosis is characterized by

thickening of glomerular basement membrane
with increased permeability. With time, the
mesangial space becomes larger by deposits of
proteins (collagen IV), initially diffuse, then
nodular.
Diffuse diabetic glomerulosclerosis. The deposits appear diffusely on the basement
membranes of capillary loops of the glomeruli, as well as on basement membranes of
tubules and arterioles. (PAS, ob. x40)
In nodular diabetic glomerulosclerosis, PAS-positive nodular deposits (containing
mucopolysaccharides, fibrils and collagen) may appear in the mesangial space, at the
periphery of the glomerulus, pushing the capillaries. The lesion is focal (glomeruli are
not entirely affected), and some of them are spared. This pattern is also called
Kimmelstiel-Wilson lesion. (PAS, ob. x20)
 Amyloid (an abnormal protein) accumulates
as extra-cellular deposits, nodular or diffuse,
as pink, amorphous material.
Initially, the deposits appear in the glomeruli:
within the mesangial matrix and along the
basement membranes of the capillary loops. Amyloidosis
Continuous accumulation of the amyloid will (kidney)
compress and obliterate the capillary tuft.
With progression, amyloid deposits appear
also peritubular and within the arteriolar
wall, narrowing them.
Congo red is a special staining, elective for
amyloid. (Congo Red, ob. x20)
Acute tubular necrosis is a pathological entity
characterized by destruction of tubular epithelial
cells, followed by acute renal failure (oliguria,
proteinuria, blood retention of urea and
creatinine).

Depending on etiology, there are two types of Toxic tubular

acute tubular necrosis :
necrosis
1. toxic acute tubular necrosis, after ingestion or
inhalation of toxic substance ethylene glycol,
mercury, lead, carbon tetrachloride, methyl
alcohol, nephrotoxic drugs

2. ischemic acute tubular necrosis - in shock

Toxic acute tubular necrosis is
characterized by proximal tubular
epithelium necrosis (no nuclei,
intense eosinophilic homogenous
cytoplasm, but preserved shape) due
to interference of ingested toxic
agents (poisons, organic solvents,
drugs, heavy metals) with epithelial
cell metabolism.

Necrotic cells fall into the tubule

lumen, obliterating it, and
determining acute renal failure
(oligo-anuria).

Basement membrane is intact, so the

tubular epithelium regeneration is
possible, if the patient survives.
The interstitium and glomeruli are
not affected. (H&E, ob. x20)
Acute pyelonephritis is an exudative
purulent localized inflammation of kidney
and renal pelvis.

The renal parenchyma presents in the

interstitium abscesses (suppurative Acute
necrosis), consisting in purulent exudate pyelonephritis
(pus): neutrophils, fibrin, cell debris and
central germ colonies (hematoxylinophils).

Tubules are damaged by exudate and may

contain neutrophil casts. In the early
stages, glomeruli and vessels are normal.
(Hematoxylin-eosine, ob. x10)
• Is a malignant epithelial tumor resulted
from proliferation of tubule cells.
• Tumor cells form cords, papillae, tubules
or nests, and are atypical, polygonal and
large.
• Because these cells accumulate glycogen
and lipids, their cytoplasm appears
"clear", lipid-laden, the nuclei remain in Renal cell
the middle of the cells, and the cellular
membrane is evident. carcinoma
• Some cells may be smaller, with (Grawitz tumor)
eosinophilic cytoplasm, resembling
normal tubular cells.
• The stroma is reduced, but well
vascularized.
• The tumor grows in large front,
compressing the surrounding
parenchyma, producing a pseudocapsule.
(H&E, ob. x20)
 Wilms' tumor (nephroblastoma) is a
malignant mixed tumor containing
metanephric blastema, stromal and
epithelial derivatives. It is the most frequent
renal tumor in children before age of 5
years (peak of incidence: 2 year-old). Nephroblastoma
(Wilms' Tumor)
 Etiology of Wilms' tumor (nephroblastoma)
: mutations of WT1 gene on chromosome
11 and nephroblastematosis (persistence of
renal blastema in kidney tissue).
Wilms' tumor (nephroblastoma). The tumor consists in tumor epithelial component
(abortive tubules and glomeruli) surrounded by metanephric blastema and tumor
immature spindled cell stroma. The stroma may include differentiated (muscle, cartilage,
bone, fat tissue, fibrous tissue) or anaplastic elements. The tumor (photo, left)
compresses the normal kidney parenchyma ( photo, right) (H&E, ob. x10)
 Nephroblastoma
(Wilms' Tumor)
(detail)

Wilms' tumor (nephroblastoma) : metanephric blastema,

stromal and epithelial components. (H&E, ob. x20)
Ureteral Duplication

 Ureteral Duplication (bifid ureters) is a

congenital malformation of the urinary tract,
quite common in women, affecting about 1 %
of the general population.

 Ureteral development begins around the 4th Urinary Tract

week of embryonic life, when the ureteral bud
arises from the mesonephric ducts and gives Pathology
rise to the ureter as well as other parts of
collective system.
 In ureteral duplication the ureteral bud is
splitting or arises twice before metanephric
blastema formation, causing multiple forms of
abnormalities of the ureters or of the renal
pelvis (duplication of ureters is often associated
with duplication of the renal pelvis).
Ureteral Duplication - Classification :
 unilateral : affects only one kidney
 bilateral : both kidneys are affected
 partial ("Y" shape or incomplete) : ureter shows duplication only in the upper /
proximal segment, which merge before opening into the bladder
 complete (total) : the two ureters are separated, one drains from the upper pole,
the other from the lower pole of the kidney. The two ureters can merge very close
to the opening point in the bladder, or one of them can drain into an ectopic point,
most commonly, into the vagina or the urethra.

Clinical manifestations range from asymptomatic (in most cases) to signs of urinary
tract infection (because of a vesicoureteral reflux), urinary incontinence, especially in
females, in cases of ectopic ureter reaching the vagina or the urethra.
Macroscopy
Complete and bilateral ureteral duplication

The ureters had a normal length

about 25 - 30 cm and an outer
diameter of about 5 - 9 mm. They
emerge separately from the renal
pelvis, one draining from the
upper pole, the other from the
lower pole of the kidney, with
separate courses.
The two ureters merge at a point
above the junction with the
urinary bladder.
Both kidney and urinary bladder
have normal size without
macroscopically visible
pathological changes.