IMAGING AND BIOPSY
Renal biopsy
Alan D Salama
Abstract
The renal biopsy is of fundamental importance in nephrology and trans-
plantation. Using appropriate guidelines for including or excluding
patients it is generally safe with the commonest complication being
bleeding. The adequacy and safety have been improved using real-time
ultrasound imaging and automated biopsy needles. To fully interpret
the pathological findings and understand their significance, discussion
between clinicians and pathologists is required. The biopsy must be pro-
cessed and stained for standard haematoxylin and eosin sections as well
as for immunohistochemistry and electron microscopy so as to provide
a complete picture of the underlying pathological process.
Keywords complications; indications; interpretation; methods;
processing; renal biopsy
Why should clinicians consider requesting a renal biopsy?
The renal biopsy is an essential tool in the diagnosis and
management of renal disease in native and transplanted kidneys.
It allows clinicians to establish a histological diagnosis and give
the most accurate prognosis. It may reveal a clinically unsus-
pected diagnosis and allows clinical presentations with many
possible causes to be treated most appropriately; for example,
distinguishing membranous glomerulonephritis, minimal change
and focal segmental glomerulosclerosis as the cause of nephrotic
syndrome in an adult. This is especially important in patients
where multiple aetiologies are being considered, such as
a patient with diabetes mellitus who has nephrotic-range
proteinuria. In addition, it allows us to make predictions
regarding patient (and renal) outcome by correlating pathological
entities with established clinical outcome and treatment data.
Lastly, it allows the degree of acute (reversible) or chronic
(irreversible) damage to be assessed, so that clinicians can
balance the risks and benefits of treatment, based on the likeli-
hood of success or failure. For example, in anti–glomerular
basement membrane (anti-GBM) disease, a presentation with
dialysis dependency and a renal biopsy demonstrating that all of
the glomeruli contain crescents is associated with a very low
probability of recovering renal function; this would prompt many
clinicians to avoid immunosuppression in such patients.
Similarly, in transplantation, renal biopsy has enabled clinicians
to establish a cause for graft dysfunction, assess the degree of
chronic damage, define new disease entities (such as BK virus
nephropathy), and gain a better understanding of the patho-
physiology of transplantation biology (e.g. the appreciation of
antibody-mediated rejection through C4d expression). Following
Alan D Salama MBBS MA PhD FRCP is a Reader and Honorary Consultant
Nephrologist, University College London, Royal Free Hospital, London,
UK. Competing interests: none declared.
MEDICINE 39:6
renal transplant biopsy, management is altered in over 40% of
cases, indicating the benefit of the procedure.1 Indications for
renal biopsy are shown in Table 1, while absolute and relative
contraindications are shown in Table 2.
Diversity of renal biopsy diagnoses
Examples of the diagnoses obtained from native and transplant
biopsies are shown in Figures 1 and 2. These represent the
diagnoses in over 1350 native and 1409 transplant renal biopsies
over a 5-year period from a single institution. The proportions of
each diagnosis will obviously vary between institutions and
depend on the relative case mix, patient population and
threshold for biopsy in each centre. In some cases more than one
diagnosis has been made on a single biopsy. For example, one in
three biopsies showing diabetic glomerulosclerosis also showed
a secondary diagnosis, most commonly interstitial nephritis,
acute tubular necrosis (ATN) or membranous glomerulopathy.
Development of the procedure
The first attempts at percutaneous renal biopsies, over 50 years
ago, used intravenous pyelography to localize the kidneys with
the patient either sitting or prone. Descriptions of successful
biopsies, which frequently resulted in resolution of diagnostic
uncertainty, established the benefit of such an approach.2 Since
then, the introduction of real-time ultrasound for localization and
the wider use of automated biopsy needles has increased the
chances of obtaining sufficient amounts of renal cortex and
minimized the risks of complications following the procedure3
(Figure 3).
Complications
The main adverse effects of percutaneous biopsy are bleeding and,
less commonly, formation of arterio-venous (AV) fistulas and
infection. Self-resolving haematomas and macroscopic haematuria
are variably reported to occur in under 10% of biopsies, whereas
AV fistulas (if sought) may be present in up to 9% of cases,
although wide ranges are reported4e6 (see Table 3). Complication
rates in transplant kidneys appear lower than in native kidneys.7
The majority of AV fistulas resolve spontaneously, while those
that produce significant steal or ischaemic problems can be
successfully embolized using percutaneous intervention.8 Very
rarely, undiagnosed perinephric bleeding may lead to death.7,9
Careful screening of patients before biopsy, partial correction of
anaemia (target Hb >10 g/dl), normalization of coagulation indices
and careful assessment of renal anatomy will minimize complica-
tions. In addition, treatment of hypertension and withholding
Indications for renal biopsy
Significant proteinuria (>1 g/day)
Microscopic haematuria
Unexplained renal impairment
Renal manifestations of systemic disease
Table 1
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 IMAGING AND BIOPSY

Contraindications for percutaneous renal biopsy Diagnoses in biopsies taken over a 5-year period

Relative contraindication Absolute contraindication

Single kidney Uncorrected bleeding diathesis
Anatomic abnormalities Uncontrolled hypertension
Antiplatelet agents Uncooperative patient
Bilateral small kidneys
Obstructed kidney
Bilaterally thinned cortices

In the presence of sepsis consider delay until treated.

Table 2

drugs that promote bleeding (such as the antiplatelet agents

aspirin and clopidogrel) should be undertaken before elective
procedures. There is debate about the benefits of intravenous
desmopressin, although this treatment has been shown to correct
bleeding time in uraemia. There is disagreement about the ideal
post-procedure observation time on the ward; day-case procedures
are becoming more popular although a small but significant Focal segmental Normal
number of complications occur between 8 and 24 hours after the glomerulosclerosis Chronic allograft
Infections
biopsy9 (see Table 3). nephropathy
Thrombosis Calcineurin inhibitor effect
Acute glomerulopathy Dysfunction ? Cause
Acute vascular rejection Acute rejection cellular
BK virus Acute tubular necrosis
Diagnoses in biopsies taken over a 5-year period Rejection borderline HT
Ischaemia
Graft glomerulonephritis

Figure 2 Primary diagnoses in 1409 renal transplant biopsies taken over

a 5-year period from Hammersmith Hospital.

Approaches other than percutaneous renal biopsy

If the percutaneous approach is unsuitable, biopsies can be
obtained using open, laparoscopic or a transjugular approaches.
Open or laparoscopic biopsies are safe, nearly always result in an
adequate yield of tissue, but require a general anaesthetic.10 A
transjugular approach does not always yield sufficient renal cortex
and can result in capsular haemorrhage, but is an alternative that
can be used in patients with refractory bleeding diatheses.11,12

Sample adequacy
The quantity of material available for examination affects the
likelihood of an accurate diagnosis. Although not a strict
Amyloid 1999 B cell dyscrasias requirement, native kidney samples should ideally contain more
HSP Crescentic glomerulonephritis than 20 glomeruli to exclude focal disease processes and assess
TBM/Alports Minor abnormal/normal
the degree of glomerular involvement. In transplant biopsies, the
HIV ATIN
more recent Banff classification requires more than 10 glomeruli
TMA Membranous
and two arteries to be present to be considered adequate, with
CTIN Focal segmental
glomerulosclerosis
a minimum of seven glomeruli and one artery.13 Assessment of
Mesangiocapillary
glomerulonephritis DM two cores rather than one also increases diagnostic sensitivity.14
Acute tubular necrosis IgA
Minimal change Systemic lupus erythematosus Processing of the biopsy sample

Figure 1 Primary diagnoses in 1357 native renal biopsies taken over the Complete assessment of the renal biopsy material requires
last 5 years from Hammersmith Hospital. examination by light microscopy, immunohistochemistry and

MEDICINE 39:6 340 Ó 2011 Elsevier Ltd. All rights reserved.

 IMAGING AND BIOPSY

Figure 3 a Ultrasound-guided image of a native kidney prior to biopsy. The white arrow indicates the path of the biopsy needle. b Computed tomography
image at the level of the kidneys demonstrating (white arrow) the posterior-lateral approach taken to obtain the biopsy.

6,7,9
Complications of ultrasound-guided renal biopsies. Adapted from Refs.

Whittier et al.9 Hergesell et al.6 Preda et al.7

Number of biopsies 750 1090 515
% Native/Transplant 100/0 89.6/10.4 33/67
Overall complication rate 98 (13%) 38 (3.5%) 63 (12.2%)
Major complication 48 (6.4%) 4 (0.36%) 14 (2.7%)
Minor complication 50 (6.7%) 34 (3.1%) 49 (9.5%)
Arterio-venous fistula 48/533 (9%) 3 (0.6%)
Death 1 (0.1%) NR 1 (0.2%)
Risk factors for complications Baseline creatinine >440 mmol/litre gives NR Native vs transplant

2.3 risk of complication
Those with complications were older and had
lower haemoglobin 11  2 g/dl vs
12  2 g/dl
Time to notice complication 42% @ 4 hours NR NR
67% @ 8 hours
85% @ 12 hours
89% @ 24 hours
Inadequate tissue 1% 1.2% 4.7%

Minor complication defined as visible haematuria or self-resolving perinephric haematoma. Major complication defined as blood transfusion, invasive procedure,
septicaemia or death. NR ¼ Not reported.

Table 3

electron microscopy. Apart from the standard haematoxylin and
eosin, and periodic acid Schiff stains, specialist stains that
provide superior definition of certain structures are also required
(such as methenamine silver stains for basement membranes,
congo red for amyloid and Masson trichrome for matrix deposi-
tion and scarring). Immunohistochemistry (immunoperoxidase
or immunofluorescence) is required to demonstrate deposits of
immunoglobulins and complement components, and can be used
to evaluate the nature of infiltrating cells. Electron microscopy
may reveal features not seen on light microscopy, such as
abnormalities of basement membranes, tubuloreticular inclu-
sions (in systemic lupus erythematosus or HIV) or fibril deposits.
Clearly, biopsy processing and examination should be done in
laboratories and by pathologists with sufficient experience, and
a close dialogue between nephrologists, transplant physicians
and the pathologist is essential for an accurate interpretation of
the pathological findings. A
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342 Ó 2011 Elsevier Ltd. All rights reserved.