The new england journal of medicine

case records of the massachusetts general hospital

Founded by Richard C. Cabot

Nancy Lee Harris, m.d., Editor
Jo-Anne O. Shepard, m.d., Associate Editor Stacey M. Ellender, Assistant Editor
Sally H. Ebeling, Assistant Editor Christine C. Peters, Assistant Editor

Case 40-2004: A 42-Year-Old Woman

with Long-Standing Hematuria
David J.R. Steele, M.D., and Paul J. Michaels, M.D.

presentation of case

A 42-year-old woman visited the nephrology clinic for an evaluation of chronic micro- From the Renal Unit, Department of Med-
scopic hematuria. icine (D.J.R.S.), and the Department of Pa-
thology (P.J.M.), Massachusetts General
Microscopic hematuria had been detected 14 years earlier during an episode of cys- Hospital; and the Departments of Medi-
titis. She subsequently had several episodes of cystitis each year, but the hematuria per- cine (D.J.R.S.) and Pathology (P.J.M.), Har-
sisted after treatment and resolution of the infections; usually there were 10 to 20 red vard Medical School.

cells per high-power field on examination of the urine, but occasionally more than 100, N Engl J Med 2004;351:2851-9.
with findings of trace to 1+ proteinuria. An intravenous pyelogram obtained at the time Copyright © 2004 Massachusetts Medical Society.

of the initial diagnosis of hematuria was said to have shown a urethral stricture. Ten
years before the current evaluation, a urologist prescribed daily nitrofurantoin to pre-
vent recurrent urinary tract infections. A renal ultrasonographic examination prompted
by the persistent microscopic hematuria showed normal-size kidneys, no hydronephro-
sis, and no evidence of renal stones. Cytologic examination of the urine showed no ma-
lignant cells.
Later that year, the patient’s first pregnancy was complicated by gestational diabetes,
which was controlled by diet, and by preeclampsia with a blood pressure of 150/95
mm Hg. Labor was induced, and the delivery was uncomplicated. A second pregnancy
three years later was uncomplicated. Nine months after the second delivery, mild hyper-
tension developed; systolic blood pressure ranged between 120 and 144 mm Hg and di-
astolic pressure ranged between 70 and 96 mm Hg over the next three years. Hematuria
and intermittent proteinuria persisted. Another renal ultrasonogram was obtained and
showed the right kidney to be 9.3 cm long and the left kidney to be 9.4 cm long without
hydronephrosis. No residual fluid was seen within the urinary bladder after voiding.
A nephrology consultation was requested.
The patient was a native of the Philippines and had emigrated to the United States at
26 years of age. She worked as a nurse. When she came to the nephrology clinic, she had
not had an episode of cystitis for three years. A thyroidectomy for goiter was performed
when she was 13 years of age, after which she was prescribed levothyroxine (0.125 mg
per day). Her father had had hypertension and had died at the age of 72 from a stroke.
Her mother was alive and had diabetes. Her brother died at 46 years of age while on di-
alysis, of renal failure that was reportedly caused by the use of analgesic agents for the
treatment of chronic gout. Two sisters were said to have hematuria; one of them had hy-

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pertension, and the other a history of goiter. The pa- renal ultrasound imaging that showed kidneys that
tient’s two daughters were well. appeared normal and no evidence of a renal mass
On physical examination, the patient’s weight lesion. Cytologic examination of the urine was nor-
was 57.2 kg (126 lb), the blood pressure 138/88 mal. Cystoscopy had not been performed, presum-
mm Hg, and the pulse 72 beats per minute. The re- ably because there were no risk factors for bladder
sults of a physical examination were normal, except cancer. Helical computed tomographic (CT) imag-
for scars from thyroid surgery. The results of a com- ing either with or without contrast material — cur-
plete blood count, measurements of glucose and rently the imaging method of choice for diagnos-
electrolyte levels, renal-function tests, measurement ing either a kidney stone or an occult cancer of the
of serum immunoglobulin levels, protein electro- upper urinary tract, and more sensitive than ultra-
phoresis, and tests for cryoglobulins, complement, sonography — had not been done in this patient.
antinuclear antibodies, rheumatoid factor, and uri- The crux of this patient’s initial evaluation was
nary Bence Jones protein were normal. Serologic the microscopical examination of the urine sedi-
tests were positive for hepatitis B antibody, negative ment. The sediment contained dysmorphic red cells
for hepatitis B antigen, and negative for hepatitis C and red-cell casts. These findings help us differen-
antibodies. Urinalysis disclosed 20 to 50 red cells tiate between hematuria arising from a glomerular
per high-power field and 1+ proteinuria. Micro- source and hematuria from a nonglomerular source.
scopical examination of the urinary sediment dis- Dysmorphic red cells, or acanthocytes, are red cells
closed dysmorphic red cells and two cellular casts that have undergone microtrauma while traversing
thought to be red-cell casts. Treatment with lisino- a diseased glomerular basement membrane; such
pril, 5 mg daily, was prescribed. A 24-hour urine col- trauma results in structural changes, including loss
lection of 1600 ml contained 1152 mg of creatinine of biconvexity and the appearance of membrane
and 160 mg of protein. At follow-up examinations, blebs. Dysmorphic red cells are best seen during
five weeks and eight weeks later, the blood pressure phase-contrast microscopical examination of a cen-
was 100/60 and 110/60 mm Hg, respectively. trifuged urine sediment (Fig. 1A and 1B).
A diagnostic procedure was performed. The reliability of dysmorphic red cells — on their
own — as a predictor of glomerular disease in the
differential diagnosis absence of red-cell casts is controversial.3,4 How-
ever, the combination of dysmorphic red cells and
Dr. David J.R. Steele: This patient presented to me in red-cell casts is believed to pinpoint a glomerular
the clinic with long-standing microscopic hematu- origin of hematuria; this diagnosis is more likely to
ria, low-grade proteinuria, a history of mild hy- be valid if proteinuria is present. In this case, the
pertension, preserved renal function, and a family level of proteinuria was below that which is ordinari-
history of renal disease. Microscopic hematuria is ly considered clinically significant (300 mg per 24-
generally defined as more than one to three red cells hour collection, or a protein-to-creatinine ratio of
per high-power field in a centrifuged urine speci- 0.3). Nevertheless, the combination of findings sug-
men. It has a broad differential diagnosis. In pa- gested hematuria of a glomerular origin.
tients with hematuria without proteinuria, approx-
imately 10 percent of cases are due to a glomerular glomerular causes
process and the remaining cases are due to urologic of microscopic hematuria
factors, although estimates vary widely. In many cas- Once the glomerulus has been defined as the source
es, no cause is found despite extensive evaluation.1,2 of hematuria, the differential diagnosis can be nar-
rowed to a limited number of disease processes (Ta-
nonglomerular causes ble 1). The probability that this patient had focal
of microscopic hematuria glomerulonephritis was small, because of her pro-
Nonglomerular causes of microscopic hematuria longed hematuria, the minimal proteinuria, her
involving the kidney and urinary tract include neo- stable normal renal function, and the negative se-
plasms of the kidney, the collecting system, the ure- rologic workup. Her clinical presentation was not
ter, and the bladder; nephrolithiasis; cystic diseases; consistent with a collagen vascular process, anti–
papillary necrosis; hypercalciuria; hyperuricosuria; glomerular basement membrane disease, or vascu-
and sickle cell disease. A urologic workup of this pa- litis. Tests for hepatitis B surface antigen and hepa-
tient included a normal intravenous pyelogram and titis C antibody were negative. The long natural

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 case records of the massachusetts general hospital

Table 1. Differential Diagnosis of Isolated Hematuria

A of Glomerular Origin.

Primary glomerulonephritis
IgA nephropathy
Poststreptococcal
Membranoproliferative
Secondary glomerulonephritis
Associated with depletion of immune complex
Lupus nephritis
Hepatitis C–associated nephritis and cryoglobu-
linemia
Bacterial endocarditis
Pauci-immune (no depletion of immune complex)
Antinuclear cytoplasmic antibody–associated
glomerulonephritis
B Anti–glomerular basement membrane disease
Polyarteritis
Hereditary causes
Thin basement membrane nephropathy
Alport’s syndrome (hereditary nephritis)
Fabry’s disease
Nail–patella syndrome

Fabry’s disease, the nail–patella syndrome, and pos-

sibly — in some kindreds — IgA nephropathy.

IgA Nephropathy
IgA nephropathy is a common cause of microscopic
Figure 1. Dysmorphic Red Cells in Urinary Sediment.
hematuria.5 It results from mesangial IgA deposi-
Panel A shows red-cell casts (arrow) similar to the one
seen in this patient. Panel B shows dysmorphic red cells
tion. Although some patients have an elevated IgA
(arrows), indicative of a glomerular lesion. (Photomicro- level, not all do; an increase in IgA level alone is not
graphs from other patients, courtesy of Dirk Hentschel, sufficient to produce this disease. A defect in galac-
Department of Nephrology, Massachusetts General tosylation of IgA1 may play a role. A patient who has
Hospital.) IgA nephropathy may present with hematuria (with
or without proteinuria), hypertension, and a rising
serum creatinine level. The natural history of the
history in the absence of clinically significant pro- condition varies among patients, ranging from
teinuria and hypertension is not consistent with those who have hematuria with stable renal func-
poststreptococcal glomerulonephritis. tion to those (between 15 percent and 40 percent in
The family history of renal disease suggested the reported studies) in whom end-stage renal disease
possibility of a hereditary renal disorder. The patient develops. There are no markers that predict pro-
had two sisters who had hematuria and apparently gressive disease in patients who present with only
normal renal function; one is said to have had hy- minor urinary abnormalities.6 A subgroup of pa-
pertension, although we do not have the details. In tients with IgA nephropathy may have hereditary
addition, her brother died at a young age of end- disease. A linkage of IgA nephropathy to chromo-
stage renal disease, with the cause said to be analge- some 6q22–23 with a dominant mode of inherit-
sics used to treat gout. We have incomplete records ance has been shown.7
of these events, but we should consider alternative
diagnoses, including the possibility that the brother Alport’s Syndrome
had a hereditary renal disease. Hereditary renal dis- Alport’s syndrome is a rare hereditary renal disease
eases associated with hematuria include Alport’s caused by a defect in genes coding for the a5 chain
syndrome (hereditary nephritis), thin-basement- of type IV collagen. The majority of cases are
membrane nephropathy, polycystic kidney disease, X-linked; autosomal recessive inheritance occurs

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in 5 percent of cases and autosomal dominant in- turia, but it is likely that thin basement membrane
heritance in a few kindreds. The first sign of the dis- nephropathy occurs in about 1 percent of the gener-
ease is microscopic or occasionally macroscopic he- al population.10 Patients present with hematuria;
maturia. Alport’s syndrome occurs predominantly there may be proteinuria, although usually urinary
in men, and affected male patients classically have protein excretion is less than 500 mg per day, and hy-
hematuria, proteinuria (urinary protein excretion, pertension is rare. There are no extrarenal manifes-
less than 1 to 2 g per day), progressive renal failure, tations. Renal failure occurs rarely and, for unclear
and sensorineural deafness. Lenticonus of the an- reasons, often in association with other glomeru-
terior lens capsule, retinopathy, and leiomyomato- lonephritides. Focal segmental glomerulosclerosis
sis are sometimes associated with the disease. Deaf- is reported to occur in at least 5 percent of patients.
ness occurs in approximately 55 percent of patients. IgA nephropathy may occur together with thin base-
The urine sediment is likely to contain dysmorphic ment membrane nephropathy — probably more of-
red cells and red-cell casts. Patients with Alport’s ten than by chance alone.11 The diagnosis is based
syndrome lack a component of glomerular base- on the combination of hematuria and characteristic
ment membrane, and anti–glomerular basement changes on renal biopsy and on the finding of he-
membrane glomerulonephritis may develop after maturia in multiple family members without a his-
kidney transplantation. The disorder is clinically tory of end-stage renal disease. Treatment is non-
variable, probably reflecting the complexity of col- specific and includes control of hypertension, use of
lagen genetics.8,9 angiotensin-converting–enzyme inhibitors if pro-
Heterozygous females in families with Alport’s teinuria or hypertension is present, and modest di-
syndrome may have intermittent or persistent mi- etary protein restriction.10,12
croscopic hematuria with no other manifestations
of renal disease; about 10 percent of heterozygous differential diagnosis of alport’s
female patients have no hematuria. Proteinuria is syndrome and thin basement membrane
uncommon, as is hypertension. The prognosis for nephropathy
affected girls and women is generally good, but The distinction between thin basement membrane
end-stage renal disease develops in some women. nephropathy and Alport’s syndrome is not always
In such cases, gross hematuria in childhood, ne- easy to make. It is important to distinguish between
phrotic-range proteinuria, and thickening of the the two when possible, because of the different
glomerular basement membrane (identified by the prognoses of these conditions and because of the
use of electron microscopy) are associated with pro- implications for the offspring of the female carriers
gressive nephritis. Hearing loss and lenticonus, al- of Alport’s syndrome. Since hearing loss, lentico-
though rare, are also associated with an adverse out- nus, and retinopathy are found in fewer than 10 per-
come in heterozygous female patients. Pregnancy cent of female carriers of Alport’s syndrome, thin
does not appear to have an adverse effect on renal basement membrane nephropathy and Alport’s
function in patients with mild disease but may ac- syndrome are difficult to distinguish on clinical
celerate the decline in renal function in those with grounds alone in women who have hematuria as
severe disease. their only clinical abnormality.13,14
The family history may be useful. A family histo-
Thin Basement Membrane Nephropathy ry of hematuria without renal failure supports a di-
In thin basement membrane nephropathy, also agnosis of thin basement membrane nephropathy.
known as benign familial hematuria or thin base- If the nature of renal failure in a family member is
ment membrane disease, the glomerular basement unknown, then information regarding hearing loss
membrane is uniformly thinned to about half its or eye disorders may be useful. In the case under
normal thickness. Many cases follow an autosomal discussion, there was no history of either in the
dominant mode of inheritance and, as with Alport’s brother who had end-stage renal disease. The ab-
syndrome, are caused by mutations in the type IV sence of hearing loss or optical abnormalities, how-
collagen gene — in this case the a3 and a4 chains. ever, does not rule out Alport’s syndrome as the
There is a female-to-male ratio of 1.6. The preva- cause of end-stage renal disease in his case, since
lence of this disease cannot be accurately estimated these extrarenal abnormalities are not present in all
because of the reluctance of nephrologists to per- cases. In questionable cases, a renal biopsy may be
form a renal biopsy in patients with isolated hema- helpful.10,12,15-17

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 case records of the massachusetts general hospital

role of renal biopsy

A renal biopsy is not routinely recommended in the A
evaluation of patients with isolated microscopic he-
maturia, unless there is evidence of clinically signif-
icant proteinuria or a progressive deterioration in
renal function. In their review of microscopic hema-
turia in the Journal, Cohen and Brown18 recom-
mended against performing a renal biopsy in cases
of isolated glomerular microscopic hematuria,
since available data suggest that identification of
the specific disease does not make a difference in
management or outcome. Complications of renal
biopsy are infrequent but must be borne in mind.
Major bleeding occurs in 1 to 2 percent of the pa- B
tients who undergo biopsy, and mortality is about
0.1 percent. We accept that not having a tissue di-
agnosis is valid in most patients with isolated he-
maturia whose disease is following a benign course.
In this case, however, I favored performing a biopsy
because of increasing concern on the part of a
medically sophisticated patient and our desire to
define her underlying diagnosis in the context of
her strong family history. The hope was that prog-
nostic information would be obtained that would
be reassuring to the patient and her family and that
further evaluations could be avoided. C
Dr. Nelson Goes (Nephrology): Does the fact that
the patient comes from the Philippines alter the
evaluation? Are there any tropical diseases that could
cause chronic hematuria?
Dr. Steele: In tropical regions there is a high inci-
dence of schistosomiasis, which may be manifest-
ed in the patient by lower urinary tract bleeding. It
certainly is a consideration under appropriate cir-
cumstances.

dr. david j.r. steele’s diagnosis

Thin basement membrane nephropathy or X-linked
Alport’s syndrome or IgA nephropathy.

Figure 2. Examination of Renal-Biopsy Specimen

pathological discussion by Light and Electron Microscopy.
The glomerulus shows a slight increase in the mesangial
Dr. Paul J. Michaels: The diagnostic procedure was matrix, with focal mesangial hypercellularity (Panel A)
a percutaneous renal biopsy. The glomeruli were (hematoxylin and eosin). On electron-microscopical
normal when examined by light microscopy, except examination, the glomerular basement membrane ap-
for focal, mild mesangial hypercellularity (Fig. 2A). pears diffusely thin (Panel B). Focally, small electron-
The interstitium, renal tubules, and vessels were dense granules (microparticles) are present (arrowheads),
and the endothelial portion of the basement membrane
normal. Immunofluorescent staining of the glo- is scalloped (Panel C, arrows).
meruli showed slight segmental linear staining for
IgG and albumin. Only very focal, trace granular

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 The new england journal of medicine

staining for IgA and IgM was noted in the mesan- membranes in combination with focal membrane
gium, excluding a diagnosis of IgA nephropathy. thickening, scalloping, and microparticles sug-
Electron-microscopical examination showed dif- gests that the patient is a carrier of X-linked Alport’s
fusely thin glomerular basement membranes (Fig. syndrome. However, although full-blown Alport’s
2B). Some segments were thickened, scalloped, syndrome is therefore excluded, the pathological
and contained electron-dense granules (“micro- findings alone are not sufficient to distinguish
particles”), but no definite laminations were seen with certainty between thin basement membrane
(Fig. 2C). Ultrastructural morphometric analysis nephropathy and heterozygosity for an Alport
revealed a harmonic mean (±SD) glomerular-base- mutation.
ment-membrane thickness of 219±20 nm, with a The genetic mutations responsible for the phe-
range of 121 to 328 nm. The normal glomerular- notypic abnormalities seen in both X-linked and
basement-membrane thickness in women as mea- autosomal recessive or dominant Alport’s syndrome
sured by this method is 326±45 nm. and thin basement membrane nephropathy have
These histologic, immunofluorescent, and ultra- been characterized (Table 3).20,21 These discoveries
structural findings are consistent with a diagnosis have enabled pathologists to use ancillary diagnos-
of either thin basement membrane nephropathy or tic techniques to narrow the differential diagnosis
a carrier state of X-linked Alport’s syndrome (Table in patients with thin glomerular basement mem-
2). Thin glomerular capillary basement membranes branes. The three clinical entities have in common
are the only pathological abnormality in the kidneys abnormalities in the a chains of type IV collagen
of patients with thin basement membrane nephrop- (COL4), specifically the a3, a4, and a5 chains,
athy.19 However, thin glomerular basement mem- which form a triple helical protomer found in the
branes are found in Alport’s syndrome and may be glomerular basement membrane (Fig. 3).8 X-linked
the only finding in early Alport’s syndrome and in Alport’s syndrome is typically caused by mutations
female carriers of X-linked Alport’s syndrome. In in the a5 chain of type IV collagen (COL4A5).20 In
carriers of X-linked Alport’s syndrome, however, contrast, autosomal Alport’s syndrome, which can
there may also be areas of splitting and thickening be inherited in both a recessive and a dominant
of the basement membrane, which worsen over fashion, is the result of defects in the genes encod-
time; these abnormal areas are not seen in thin ing for either the a3 (COL4A3) or the a4 (COL4A4)
basement membrane nephropathy. In this case, the subunits of type IV collagen.21 The mutations seen
presence of widespread thin glomerular basement in thin basement membrane nephropathy also fre-

Table 2. Common Renal-Biopsy Findings in Conditions Causing Microscopic Hematuria.

Method of Thin Basement Membrane Early X-Linked Female Carrier of X-Linked

Examination IgA Nephropathy Nephropathy Alport’s Syndrome Alport’s Syndrome
Light microscopy Normal or mild glomeru- Normal or mild increase in Normal or mild podocyte Normal or mild mesangial
lar mesangial prolifer- mesangium hypertrophy with focal hypercellularity
ation; with or without rigid and thickened
mesangial deposits capillary walls
on trichrome and
silver staining
Immunofluores- Mesangial deposition of Usually negative for immu- Usually negative for immu- Usually negative for immu-
cence staining IgA and C3; less ex- noglobulin and comple- noglobulin and com- noglobulin and com-
tensive deposition ment; occasional granu- plement; loss of stain- plement; either linear
of IgM and IgG lar C3 deposition; linear ing for a3–a5 chains or segmental staining
staining for a3–a5 chains of type IV collagen for a3–a5 chains of
of type IV collagen type IV collagen
Electron microscopy Electron-dense deposits Diffusely thin glomerular Thin glomerular basement Diffusely thin glomerular
in the mesangium basement membrane membrane; varying basement membrane;
degrees of thickening, focal areas of splitting,
splitting, laminations, laminations, and elec-
and electron-dense tron-dense granules
granules

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 case records of the massachusetts general hospital

syndrome. Different mutations in these same genes

Table 3. Conditions Associated with Thin Basement
Membrane on Electron Microscopy and Corresponding
occasionally lead to the less common autosomal
Mutations of Type IV Collagen. dominant Alport’s syndrome.
The mutations in Alport’s syndrome lead to a
Thin basement membrane nephropathy segmental reduction in the amount of both a3 and
COL4A3
COL4A4 a5 collagen in the glomerular basement membrane;
Autosomal recessive Alport’s syndrome
this defect can be detected by immunofluorescence
COL4A3 staining with antibodies to these proteins. In con-
COL4A4 trast, the mutations in the a3 chain in thin base-
Autosomal dominant Alport’s syndrome ment membrane nephropathy do not produce this
COL4A3 pattern. Segmental loss of glomerular staining for
COL4A4
the a5 chain of type IV collagen suggests a carrier
X-linked Alport’s syndrome
COL4A5 state for X-linked Alport’s syndrome; however, nor-
COL4A6 mal staining does not necessarily rule out the diag-
nosis.23 Additional diagnostic tests include immu-
nofluorescence staining of a skin-biopsy specimen
for the a5 chain of type IV collagen. Interrupted
quently involve both the a3 and a4 chains of type staining in a female patient suggests a carrier status
IV collagen, suggesting that autosomal Alport’s syn- for X-linked Alport’s syndrome, whereas even, lin-
drome and thin basement membrane nephropathy ear staining supports the diagnosis of thin base-
may represent points on a spectrum of a single dis- ment membrane nephropathy.24 Finally, sequenc-
ease process.22 Thus, some persons with thin base- ing of the gene for the a5 chain of type IV collagen
ment membrane nephropathy may have a single can be performed to confirm or rule out X-linked
copy of a mutated gene in either the a3 or a4 chain Alport’s syndrome, since this gene is usually unaf-
of type IV collagen that, when present in a homozy- fected in patients with thin basement membrane
gous form, leads to autosomal recessive Alport’s nephropathy.

Figure 3. Structure of the a Chains of Type IV Collagen and Mutations in Renal Disease.
Six distinct a chains (left) are arranged into three triple helical protomers composed of different chains (right). Each protomer has a 7S triple
helical domain at the N-terminal; a long, triple helical, collagenous domain in the middle of the molecule; and a noncollagenous (NC1) trimer
at the C-terminal. The a1, a1, a2 protomer is found in all basement membranes, whereas the a3, a4, a5 and a5, a5, a6 protomers are differ-
entially distributed in various tissues (box). This heterogeneous distribution probably accounts for the variety of overlapping clinical syn-
dromes associated with mutations in different chains. (The illustration has been adapted from Hudson et al. 8)

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 The new england journal of medicine

In the patient under discussion, staining of the

A renal-biopsy specimen with antibodies to the a3
and a5 chains of type IV collagen revealed segmen-
tal reduction in the normal linear staining along the
glomerular basement membranes for both proteins,
as compared with a control glomerulus (Fig. 4A and
4B). This segmental reduction in staining for the
a3 and a5 chains of type IV collagen further sug-
gests a carrier state for X-linked Alport’s syndrome.
Dr. Steele: Since her evaluation, the patient has
been seen in annual follow-up visits. Two years af-
ter the diagnostic biopsy, she remains well, with no
evidence of progressive renal disease. She contin-
ues to receive treatment for hypertension and has
B
microscopic hematuria and stable mild proteinuria.
She reports that her daughters have been tested and
do not have hematuria. She is in the process of re-
viewing her diagnosis and its implications with oth-
er family members.
Dr. Lynn D. Cornell (Pathology): In the future, with
a patient such as this one, would you consider do-
ing a skin biopsy instead of a renal biopsy?
Dr. Steele: Skin biopsy is a much less invasive pro-
cedure than renal biopsy and would therefore be a
desirable alternative. If clinicopathological studies
show that it is reliable for distinguishing between
Figure 4. Immunofluorescence Staining of Renal-Biopsy Alport’s syndrome and thin basement membrane
Specimens with Antibody for a3 Chains of Type IV nephropathy, then it represents a good alternative.
Collagen. Dr. Michaels: A renal biopsy may still be impor-
Immunofluorescence staining of a specimen from a kid- tant when IgA nephropathy is in the differential di-
ney without disease (Panel A) reveals bright, uninter- agnosis, which it often is.
rupted linear staining for the a3 chain of type IV colla-
gen. However, staining of a specimen from the patient’s
glomerulus with the same monoclonal antibody reveals anatomical diagnosis
an overall decrease in staining intensity, with further
segmental reduction of staining in the capillary loops Nephropathy with thin and focally disrupted glo-
(Panel B, arrows). A similar pattern was seen with the merular basement membranes and decreased a3
use of an antibody to the a5 chain.
and a5 chains of type IV collagen, consistent with a
carrier state of X-linked Alport’s syndrome.

refer enc es
1. Ahmed Z, Lee J. Asymptomatic urinary uniquely shaped red cell. Nephron 1993;64: Goodpasture’s syndrome, and type IV col-
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Med Clin North Am 1997;81:641-52. 5. Topham PS, Harper SJ, Furness PN, 9. Kashtan CE, Michael AF. Alport syn-
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Robson RA, Gardner J. Clinical audit of the disease as a cause of isolated microscopic 10. Savige J, Rana K, Tonna S, Buzza M,
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115-20. Nat Genet 2000;28:354-7. lar basement membrane disease and hem-
4. Kitamoto Y, Tomita M, Akamine M, et 8. Hudson BG, Tryggvason K, Sundara- orrhage into renal tubules. Kidney Int 1996;
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 case records of the massachusetts general hospital

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Nephrol 1996;16:412-6. 1024-33. Copyright © 2004 Massachusetts Medical Society.

35-millimeter slides for the case records

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