Kidney Flashcards
- Which of the following developmental anomalies
has been linked to maternal use of angiotensinconverting
enzyme (ACE) inhibitors and maternal cocaine
abuse?
A. Congenital hydronephrosis
B. Renal dysplasia
C. Renal hypoplasia
D. Renal segmental atrophy
E. Renal tubular dysgenesis
RENAL TUBULAR DYSGENESIS (p. 1850)—This uncommon
cause of neonatal oliguria is due to aberrant development of renal
tubules. It is inherited as an autosomal recessive condition
(family counseling) or in association with prenatal exposure to
several drugs, notably ACE inhibitors and cocaine; a similar renal
abnormality has been linked to in utero exposure to NSAIDs.
Congenital hydronephrosis is due to congenital obstruction at the
ureteropelvic junction. In renal dysplasia, there is an abnormal organization
of metaphrenic elements, usually associated with other
congenital anomalies of the urinary tract. Renal hypoplasia may be
sporadic, due to chromosomal deletion syndromes, or associated
with Down syndrome (15% of cases).
The condition known as renal segmental atrophy (or Ask-
Upmark kidney) is most likely due to:
A. Autosomal dominant genetic defect
B. Autosomal recessive genetic defect
C. Congenital anomaly of ureteral muscle
D. Segmental hypoplasia
E. Vesicoureteral reflux
RENAL SEGMENTAL ATROPHY (p. 1851)—Segmental or lobar
atrophy is an acquired condition due to vesicoureteral and
intrarenal reflux. Vesicoureteral reflux, however, is not always
demonstrable in all cases. The salient macroscopic feature is a
shrunken lobe with effacement of the cortex and medullary pyramid.
In affected lobes, the cortex is virtually devoid of glomeruli: It
contains dilated tubules with intraluminal casts, and the medulla
contains few ducts. The remaining renal parenchyma undergoes
hypertrophy and often develops focal segmental glomerulosclerosis.
Hypertension is the most frequent initial sign.
A 9-month-old infant comes to clinical attention because
of renal insufficiency and enlarged kidneys. Radiologic and
sonographic studies show large and hyperechoic kidneys. A
renal biopsy shows the changes depicted in the photomicrograph.
These findings are consistent with autosomal recessive
polycystic kidney disease (AR-PKD). Which of the following
pathologic lesions is most likely to be associated with this
kidney condition?
A. Angiomas in the retina and cerebellum
B. Angiomyolipoma
C. Cardiac rhabdomyoma
D. Hepatic fibrosis
E. Pancreatic cysts
AUTOSOMALRECESSIVEPOLYCYSTICKIDNEY DISEASE
(p. 1852)—AR-PKD is a hereditary condition characterized by
congenital cystic anomalies of the kidneys and liver. The gene is
located on the short arm of chromosome 6; fibrocystin is the protein
involved. Renal cysts derive from dilated collecting ducts, whereas
hepatic cysts develop from abnormal bile ducts. In the liver, cystically
dilated bile ducts are associated with portal fibrosis, which
progresses with time to a picture mimicking micronodular cirrhosis
and leading to portal hypertension. Hepatic abnormalities
become increasingly severe with age. Cerebellar/retinal angiomas
and pancreatic cysts are seen in von Hippel-Lindau syndrome; angiomyolipomas
and cardiac rhabdomyomas are seen in tuberous
sclerosis.
Which of the following features is not characteristic of
renal pathology in autosomal dominant polycystic kidney
disease (AD-PKD)?
QUESTION 40.3
A. Lithiasis and infection are rare in renal cysts
B. Renal cysts are lined by hyperplastic epithelium with
papillary formations
C. Renal parenchyma between cysts is dysplastic
D. Renal pathology is usually associated with pyelocaliceal
occlusion
E. Virtually all nephrons are affected by cystic dilatation
Correct choice: A
ADULT (AUTOSOMAL DOMINANT) POLYCYSTIC KIDNEY
DISEASE (p. 1854)—About 90% of AD-PKD cases are due
to mutations of a gene on chromosome 16 that encodes polycystin-1,
involved in cell–matrix interactions. A minority of cases are due to
mutations involving two other genes, one of which is on chromosome
4 (coding for polycystin-2), whereas the other has not yet been
mapped. The disease manifests in the fourth or fifth decade with hypertension,
microhematuria, and/or enlarged kidneys. Renal cysts
derive fromvirtually all segments of the nephron. Their wall is lined
by a hyperplastic micropapillary epithelium. Papillary formations
cause luminal obstruction and cause or facilitate cyst development.
Only 20% of the nephrons are affected. The remaining ones suffer
from cyst compression, but are structurally normal. Lithiasis and
infections are common in AD-PKD. Pyelocaliceal occlusion and
ureteral agenesis are usually associated with renal dysplasia, suggesting
that urinary obstruction plays a pathogenetic role.
- Electron microscopy on a renal biopsy from a 9-year-old
boy with nephritic syndrome and elevated antistreptococcal
antibody titers reveals subepithelial electron-dense domeshaped
“humps.” The morphologic pattern most probably
demonstrable on light microscopic examination is:
A. Diffuse extracapillary proliferative glomerulonephritis
B. Diffuse intracapillary proliferative glomerulonephritis
C. Focal glomerulonephritis
D. Membranous glomerulopathy
E. Normal glomerular morphology
- Correct choice: B
DIFFUSE (INTRACAPILLARY) PROLIFERATIVE
GLOMERULONEPHRITIS (p. 1867)—The history suggests
a nephritic syndrome secondary to streptococcal infection.
Subepithelial deposits of electron-dense material, called humps,
are characteristic of this glomerulonephritis. On light microscopy,
this condition is characterized by hypercellular glomeruli due to
increased mesangial and intracapillary (inflammatory) cells. The
disease resolves spontaneously with supportive treatment. A useful
algorithm for the diagnosis of glomerular diseases is proposed
(Algorithm ofMorphologic Interpretation of Glomerular Patterns
on p. 1864). Increased glomerular cellularity is usually consistent
with glomerulonephritis (GN). Intracapillary hypercellularity with obliteration of the capillary lumina, if diffuse, suggests
postinfectious GN or membranoproliferative GN. Extracapillary
hypercellularity is diagnostic of crescentic GN.
- A 12-year-old boy has nephrotic syndrome and low complement
levels. The main findings on renal biopsy are as
follows: diffuse mesangial hypercellularity, pronounced accentuation
of glomerular lobules, a double-contour (“tramtrack”)
appearance of glomerular basement membrane on
PAS/silver stains, and mesangial deposition of C3 and IgG.
Which of the following is the most likely diagnosis?
A. Membranoproliferative (mesangiocapillary) glomerulonephritis,
type I
B. Membranoproliferative (mesangiocapillary) glomerulonephritis,
type II
C. Membranous glomerulopathy
D. Minimal change glomerulopathy
E. Postinfectious glomerulonephritis
Correct choice: A
MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
(MPGN),TYPE I (p. 1869)—Clinical presentation (nephritic syndrome
with or without nephrotic syndrome) and progression are
similar for all three types of MPGN. MPGN may manifest at
all ages. Most cases are idiopathic, but some occur in association
with certain systemic conditions (hepatitis B, lupus erythematosus,
sickle cell disease, etc.). The microscopic features outlined
in the question stem are characteristic of MPGN type I, especially
the tram-track appearance of GBM, which is due to the
interposition of mesangium between the glomerular basement
membrane (GBM) and the endothelium. Pronounced lobularity
may mimic diabetic nodular glomerulosclerosis. Immunofluorescence
(IF) usually shows mesangial deposits of C3 and IgG.
- Which of the following is true about rapidly progressive
(crescentic) glomerulonephritis (RPGN)?
A. Crescents consist exclusively of parietal cells of Bowman
capsule
B. Finding 20% of glomeruli with crescents supports the
diagnosis
C. Most cases are associated with a known underlying
condition
D. Most cases are associated with linear deposition of
anti-GBM IgG
E. Prognosis depends
EXTRACAPILLARY PROLIFERATIVE (CRESCENTIC)
GLOMERULONEPHRITIS (p. 1873)—At least 50% of
glomeruli must show crescents for a diagnosis of RPGN. Crescents
are masses of cells and fibrin accumulating into and obliterating
the urinary space of the Bowman capsule. They originate from
the rupture of the GBM and the subsequent extravasation
of inflammatory cells (monocytes and neutrophils) and the
subsequent hyperplasia of visceral and parietal cells. Most cases
are idiopathic. The IF pattern recognizes three different forms:
Minimal or no immune deposits (pauci-immune), often associated
with circulating anti-neutrophil cytoplasmic autoantibodies
(ANCAs). Idiopathic or associated with Wegener’s granulomatosis,
microscopic polyangiitis, and so on. This is the most
common form of RPGN.
Linear deposition of anti-GBM IgG and C3. Idiopathic or associated
with Goodpasture syndrome.
Granular deposition of immune complex. Idiopathic or
associated with postinfectious glomerulonephritis, Henoch-
Sch¨onlein syndrome, systemic lupus erythematosus (SLE), IgA
nephropathy, and so on.
The prognosis of RPGN depends on the extent of crescents and
the IF type.
A 4-year-old child presents with nephrotic syndrome,
and a renal biopsy shows no light microscopic changes.
Ultrastructural changes are shown here. Which of the following
immunofluorescence findings would most likely be
present?
A. Absence of C3 and immunoglobulin deposits
B. Continuous granular C3 deposition along capillary
wall
C. Granular IgG/C3 deposits along GBM
D. Linear IgG deposition along GBM
E. Mesangial IgA deposits
Correct choice: A
MINIMAL CHANGE DISEASE (p. 1879)—This is the most
common cause of nephrotic syndrome in children, usually presenting
before 6 years of age. On light microscopy, glomeruli lookvirtually normal, but EM reveals diffuse effacement (detachment
and fusion) of epithelial foot processes. Immunuofluorescence is
usually negative. The disease commonly resolves with steroid treatment,
but relapses may occur, and only infrequently does the disease
progress to chronic renal failure. Continuous granular C3 deposition
along the capillary wall is seen in type II MPGN (dense
deposit disease). Granular IgG/C3 deposits along GBM are found
in various glomerular diseases, for example, membranous glomerulonephritis
and postinfectious glomerulonephritis. Linear IgG deposition
along GBM is pathognomonic of Goodpasture syndrome.
Mesangial IgA deposits are associated with Berger disease (IgA
nephropathy).
A clinical evaluation of a young adult with generalized
edema shows heavy proteinuria (4.5 g/day). The past medical
history is unremarkable. In the United States, which of the
following is the mostcommonglomerular disease accounting
for this presentation?
A. Diabetic nephropathy
B. Focal segmental glomerulosclerosis
C. IgA nephropathy (Berger disease)
D. Membranous glomerulonephritis
E. Minimal change disease
FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS; p.
1882)—FSGS is currently the most common glomerular pattern
seen in adults with idiopathic nephrotic syndrome. It is characterized
by the collapse of glomerular basement membrane with the
deposition of hyaline material (sclerosis) in a segmental and focal
distribution. Lipid droplets and foam cells are characteristic.
It may be idiopathic or associated with other conditions such as
heroin abuse, HIV infection, obesity, sickle cell disease, and renal
ablation.
7. Correct
- Focal segmental glomerulosclerosis (FSGS) is the usual
morphological pattern of HIV-associated nephropathy
(HIVAN). Which of the following light microscopic changes
is most characteristic of HIVAN?
A. Argyrophilic spikes on the basement membrane
B. Crescent formation
C. Glomerular collapse and interstitial fibrosis
D. Obsolescent glomeruli
E. None of the above
Correct choice: C
HIVAN (p. 1886)—This AIDS-associated complication is particularly
prevalent in African-American males. Although FSGS is the
predominant pattern of glomerular involvement, there are specific
clinical and morphologic features suggesting that HIVAN may
be a unique entity. Among the morphologic changes characteristic
of HIVAN are the collapse of glomerular loops, interstitial
fibrosis with chronic inflammation, and tubuloreticular inclusions
in endothelial cells (identifiable by EM). Furthermore, podocytes
become conspicuously hypertrophic, resulting in crescentlike formations.
Resorption droplets are particularly abundant. HIVAN
causes rapidly progressive renal failure.
A renal biopsy is performed on a 34-year-old man for the
evaluation of proteinuria in the nephrotic range. A representative
silver-stained section is shown in the photomicrograph.
IF demonstrates finely granular deposits of IgG and
C3 along the capillary wall. EM shows effacement of footprocesses, associated with numerous subepithelial electrondense
deposits, which are separated from each other by extensions
of the basement membrane. Which of the following
is the most likely diagnosis?
A. Focal segmental glomerulosclerosis
B. Membranoproliferative glomerulonephritis, type I
C. Membranoproliferative glomerulonephritis, type II
D. Membranous glomerulonephritis
E. Minimal change glomerulopathy
Correct choice: D
MEMBRANOUS GLOMERULONEPHRITIS (p. 1887)—The
subepithelial deposits detected onEMbetween the basement membrane
and visceral epithelium consist of antigen-antibody complexes,
which are highlighted by IF. In most cases, they result from
in situ production. The basement membrane extensions between
such deposits are stained by silver methods, resulting in the characteristic
spiked appearance, as shown in the picture. Most cases are
idiopathic, but some are associated with infections (hepatitis B and
syphilis), SLE, drugs/toxins (mercury exposure), or cancer (e.g., renal
cell carcinoma). About one-third of idiopathic cases progress to
chronic renal failure, whereas the secondary forms usually abate on
elimination of the inciting factors. Staging does not have prognostic
A 55-year-old woman with a 15-year history of type II
diabetes mellitus is found to have microalbuminuria. All
other renal function tests are normal. At this early stage, the
most likely glomerular change of diabetic nephropathy is:
A. Expansion of the mesangial matrix
B. Fibroepithelial crescents
C. Insudative lesions such as fibrin caps and capsular
drops
D. Mesangial intercapillary nodules (of Kimmelstiel-
Wilson)
E. Thickening of the basement membrane
Correct choice: E
DIABETIC NEPHROPATHY (p. 1890)—This is the most common
cause of end-stage renal disease (ESRD) in the United States.
Thickening of the glomerular and tubular basement membranes
has been observed as early as 1 to 2 years following the onset
of diabetes. It appears before the second most frequent glomerular
change, that is, the expansion of the mesangial matrix (diffuse
glomerulosclerosis). Nodular glomerulosclerosis (Kimmelstiel-Wilson
disease) is less commonly associated with, but more specific of, diabetic
nephropathy and consists of spherical deposits of PAS-positive
material within the peripheral mesangium. Insudative lesions,including fibrin caps and capsular drops, are less specific and result
from exudation of plasma proteins and lipids.
Which of the following is the most common form of
glomerulonephritis worldwide and manifests with recurrent
gross or microhematuria?
A. Alport syndrome
B. IgA nephropathy (Berger disease)
C. Pauci-immune crescentic glomerulonephritis
D. Postinfectious glomerulonephritis
E. Thin membrane disease
Correct choice: B
IgA NEPHROPATHY p. 1894)—Berger disease is related to the
mesangial deposition of IgA. It is probably the most common form
of glomerulonephritis worldwide. Recurrent hematuria, often discovered
incidentally, is the most frequent presentation, sometimes
associated with mild proteinuria. IgA deposits can be demonstrated
by IF in the mesangium. Overproduction of IgA in response to infectious
agents is the most likely underlying mechanism. Episodes
of hematuria manifest transiently following respiratory or gastrointestinal
infections. Light microscopic alterations are highly variable,
but mesangial expansion and hypercellularity without interstitial
changes represent the earliest stage. Most cases tend to have a remission/
relapsing course, but approximately 30% will eventually
progress to renal failure over a 20-year period. Glomerular changes
of Henoch-Sch¨onlein purpura are indistinguishable from those of
Berger disease.
Microscopic hematuria is discovered in an otherwise
healthy 20-year-old man. There is a family history of similar
abnormality. A renal biopsy appears normal on light
microscopy, but the glomerular basement membrane is less
than 200nmthick on EM. Which of the following extrarenal
abnormalities is most likely associated with this condition?
A. Deafness
B. Hypoplasia of patella
C. Lens dislocation
D. Nail dysplasia
E. None of the above
Correct choice: E
THIN BASEMENT MEMBRANE DISEASE (p. 1896)—
Clinical symptomatology and ultrastructural findings are consistent
with thin basement membrane disease.Note thatGBMthickness
varies with age and sex: A value of 300 to 480 nm is considered
normal in adults. Some authors suggest using a value of 264 nm
as a low cutoff for diagnosis of thin basement membrane disease.
This condition is benign and does not progress to renal failure.
No associated extrarenal abnormalities have been reported. Alport
syndrome initially manifests with ultrastructural features of thin
basement membrane disease.
A 35-year-old man presents with nephritic syndrome.
Several years prior to this, he suffered from an episode
of generalized purpura due to cryoglobulinemia. Which
of the following ultrastructural changes is most characteristic
of glomerular disease secondary to cryoglobulinemia?
A. Diffuse vacuolization of glomerular endothelial cells
B. Laminated intraepithelial inclusions called “zebra
bodies”
C. Subendothelial deposits with a fingerprint-like pattern
D. Subepithelial electron-dense “humps”
E. Tubulovesicular inclusions in endothelial cells
Correct choice: C
CRYOGLOBULINEMIC GLOMERULONEPHRITIS (p.
1903)—This condition is due to the formation of cryoglobulins,
which precipitate at 4◦ C and become soluble at 30◦ C. One-third
of cases are idiopathic, whereas the remaining cases are associated
with various conditions (collagen vascular diseases, liver disease,
lymphomas, etc.). The acute manifestation consists of an
acute syndrome characterized by purpura, joint inflammation,
hepatosplenomegaly, and lymphadenopathy. Intracapillary proliferative
GN may develop in the acute phase or years thereafter.
Cryoglobulin thrombi are evident within the capillary lumen on
PAS staining. EM demonstrates subendothelial accumulation of
fibrillary material showing a microtubular/cylindrical substructure
often described as a fingerprint-like pattern.
