Published online before print July 9, 2007
The British Institute of Radiology, doi: 10.1259/bjr/20129205
The British Journal of Radiology
REVIEW ARTICLE
Segmental disorders of the nephron: histopathological and
imaging perspective
1
S R PRASAD, MD, 2V R NARRA, MD, 1R SHAH, MD, 3P A HUMPHREY,
J R CATENA, MD, 1N C DALRYMPLE, MD and 2C L SIEGEL, MD
MD, PhD,
4
J JAGIRDAR,
MD,
1
1
Department of Radiology, University of Texas Health Science Center @ San Antonio, San Antonio, TX, 2Department of
Radiology, Mallinckrodt Institute of Radiology, St Louis, MO, 3Department of Pathology, Washington University in St
Louis, St Louis, MO, and 4Department of Pathology, University of Texas Health Science Center @ San Antonio, San
Antonio, TX, USA
;
ABSTRACT. Recent advances in molecular genetics and immunocytochemistry have
clarified the cell of origin in many renal disorders. Several renal disorders are thought to
involve specific segments of the nephron. Renin-secreting tumours arise from
juxtaglomerular cells. Clear cell and papillary renal cell carcinoma (RCC) recapitulate
the epithelium of the proximal tubules [1]. Oncocytoma and chromophobe RCC
differentiate towards Type A and Type B intercalated cells of the cortical collecting duct,
respectively [1]. Medullary collecting ducts are the target sites for the development of
autosomal recessive polycystic kidney disease, collecting duct carcinoma and medullary
carcinoma [2, 3]. Renal papillae are susceptible to unique changes such as necrosis or
papillitis. The segmental disorders of the nephrons are summarized in a table and
depicted in a figure (Table 1, Figure 1). The purpose of our article is threefold: to illustrate
the imaging findings of renal disorders that show segmental involvement of the nephron,
to describe proximal and distal nephron disorders and to correlate imaging findings of
some entities with histopathological features.
Introduction
The nephron is the structural and functional unit of the
kidney. There are approximately 1.3 million nephrons in
each kidney [4]. There are two types of nephrons based
on their location within the kidney. The cortical
nephrons comprise 85% of nephrons and contain
glomeruli located in the cortex with short loops of
Henle. The juxtamedullary nephrons (15% of nephrons)
have glomeruli in the juxtamedullary regions of the
cortex and long loops of Henle [4]. The anatomical parts
of the nephron include the glomerulus, the juxtaglomerular apparatus, the proximal convoluted tubule
(PCT), the loop of Henle and the distal convoluted tubule
(DCT). The collecting duct is the conduit of formed
urine into the pelvicalyceal system. Embryologically, the
nephrons are derived from the nephrogenic blastema,
and the collecting ducts develop from the ureteric bud.
Background functional histology of the
juxtaglomerular apparatus
The glomerulus serves as a size- and charge-dependant barrier to filtration of proteins and large molecules
Address correspondence to: Dr Srinivasa Prasad, MD, Abdominal
Radiology, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX
78229, USA. E-mail: prasads@uthscsa.edu
Recipient of Silver Medal at the 2005 ARRS meeting (Ref: E 247).
The British Journal of Radiology, Month 2007
Received 22 September
2006
Revised 9 January 2007
Accepted 15 January 2007
DOI: 10.1259/bjr/20129205
’ 2007 The British Institute of
Radiology
[4]. Each glomerulus consists of an anastomosing network of capillaries that invaginates the dilated, proximal
blind end of the nephron, the Bowman’s capsule.
Juxtaglomerular (JG) cells are specialized smooth muscle
cells in the wall of the afferent arteriole that maintain
blood pressure homeostasis. The specialized tubular
(DCT) cells of the macula densa act as chemoreceptors
to detect sodium concentration and influence renin
secretion by the JG cells [4].
Nephronal disorders isolated to the
juxtaglomerular apparatus
Juxtaglomerular cell tumours (‘‘reninomas’’)
Juxtaglomerular cell tumours (JGCTs) are extremely
rare benign renal neoplasms. The cell of origin of JGCTs is
the modified smooth muscle cell termed the ‘‘myoendocrine cell’’ that shows actin and CD34 immunoreactivity
[5]. Since the first description of JGCT by Robertson et al in
1967 [6], less than 100 cases have been reported. JGCTs
commonly affect young people; peak age of incidence is in
the second and third decades. JGCTs are twice as common
in women as in men. Patients usually present with severe
hypertension, hyperaldosteronism and hypokalaemia [7].
On gross pathology, JGCT appears as a well-circumscribed, yellow-tan, solitary solid tumour [8]. Haemorrhage
is typically seen at the cut surface, and necrosis is notably
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Table 1. Overview of the segmental pathology of the nephron
Pathology
Segment of the nephron implicated
Juxtaglomerular cell tumour
Clear cell renal cell carcinoma (RCC)
Papillary RCC
Proximal renal tubular acidosis
Mucinous tubular and spindle cell carcinoma
Autosomal recessive polycystic kidney disease
Medullary sponge kidney
Chromophobe RCC
Oncocytoma
Collecting duct carcinoma
Medullary carcinoma
Papillary necrosis
Autosomal dominant polycystic kidney disease
Juxtaglomerular cell (glomerulus)
Proximal convoluted tubule
Proximal convoluted tubule
Proximal convoluted tubule
Loop of Henle?
Collecting duct
Ducts of Bellini
Cortical collecting duct; Type B intercalated cell
Cortical collecting duct, Type A intercalated cell
Medullary collecting duct, principal cell
Medullary collecting duct
Medullary loop of Henle and medullary collecting duct
All segments of the nephron
absent. On histological examination, JGCT is composed of
sheets of polygonal or spindle-shaped cells. Both thinwalled and the characteristic thick-walled hyalinized blood
vessels are frequently found [5]. The presence of rhomboid
crystalline forms of protorenin in a renal neoplasm is
considered diagnostic of JGCT [5].
JGCTs appear as expansile, homogeneous, solid renal
cortical neoplasms that typically measure 2–4 cm in
diameter (Figure 2). Although JGCTs are richly perfused,
the tumour vessels may show marked luminal narrowing
secondary to intimal hyperplasia, possibly due to renin
effect [9]. Thus, JGCTs typically appear hypovascular at
angiography and contrast-enhanced CT and MRI (10).
JGCTs may show delayed contrast enhancement on CT
scans [9]. However, imaging findings of JGCTs are indistinguishable from other renal neoplasms on imaging
studies.
Background functional histology of the
proximal convoluted tubule
The proximal convoluted tubule (PCT) is a coiled tube
that is approximately 15 mm long and 55 mm in diameter
[4]. PCT is lined by a simple cuboidal epithelium with a
prominent brush border containing numerous tall
microvilli [11]. The PCT reabsorbs approximately 65%
of the glomerular filtrate via the microvilli [4, 11]. Almost
100% of the filtered glucose and amino acids as well as
60% of the filtered sodium ions are reabsorbed in the
PCT [4]. Small proteins, some peptide hormones and
bicarbonates are reabsorbed in the PCT as well.
Nephronal disorders localized to the proximal
convoluted tubule
Clear cell renal cell carcinoma (conventional renal
cell carcinoma)
Clear cell renal cell carcinoma (RCC) is the most
common sporadic form of RCC, comprising approximately 70% of RCCs. Clear cell RCC recapitulates the
epithelium of the PCTs [1]. Clear cell RCC is seen in
patients with von Hippel–Lindau (VHL) disease [12]. It is
interesting to note that inactivation of tumour suppressor
Figure 1. Schematic diagram representing segmental localization of various renal disorders within the nephron.
Different components of the nephrons including the glomerulus, proximal convoluted tubule (blue), distal convoluted tubule (green) and collecting duct (yellow) and their
associated conditions are demonstrated (courtesy of Robert
Chandler, MD, UTHSCSA, San Antonio, TX).
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Figure 2. Juxtaglomerular cell tumour of the kidney.
Delayed phase, contrast-enhanced CT scan shows an expansile, relatively homogeneous, hypoattenuating mass in the
right kidney (arrows).
The British Journal of Radiology
Segmental disorders of the nephron
when compared with other histological subtypes such as
papillary and chromophobe RCCs [8, 17].
Papillary renal cell carcinoma (chromophil renal cell
carcinoma)
Papillary RCC is the second most frequent RCC
subtype accounting for approximately 10–15% of RCCs.
The neoplastic cells are reminiscent of the PCT epithelium [1]. Papillary RCC is commonly bilateral and tends
to occur more frequently in patients with end-stage renal
disease [18].
Papillary RCC appears as a well-circumscribed solid
mass. It is histologically characterized by a tubular or
papillary growth pattern. Delahunt et al [19] classified
papillary RCC into Type 1 and Type 2 based on histology
and biological behaviour; Type 2 tumours portend a
poorer prognosis than Type 1 tumours.
Papillary RCC commonly appears hyperechoic on
ultrasound. In contradistinction to most clear cell RCC,
papillary RCC typically appear homogeneous and hypovascular, showing a lesser degree of contrast enhancement
on dynamic CT and MRI [20, 21] (Figure 4a,b). The
presence of byproducts of haemorrhage and necrosis
presumably result in low signal intensity of papillary
RCC on T2 weighted MRI [22]. Papillary RCC shows a
better prognosis than clear cell RCC [17]. It is interesting to
note that, despite a common putative origin from the PCT,
clear cell RCC and papillary RCC demonstrate different
histology, clinicobiological behaviour, imaging findings
and prognosis, possibly because of the involvement of
distinct oncological pathways [14].
Figure 3. Clear cell renal cell carcinoma. Contrast-enhanced
CT scan during corticomedullary phase shows a heterogeneous, hypervascular right renal mass (arrows) with areas
of necrosis and haemorrhage (arrowhead).
genes such as VHL and fragile histidine triad (FHIT)
genes located on chromosome 3 are seen in up to 96% of
sporadic clear cell RCCs [13].
Clear cell RCC classically appears golden yellow on
gross pathology owing to the presence of abundant
intracellular lipid. Histopathologically, clear cell RCC is
characterized by glycogen- and lipid-rich clear cells and
sinusoidal morphology of thin-walled blood vessels [8].
VHL gene inactivation leading to activation of the
hypoxic response (including synthesis of vascular
growth factors) is seen in approximately 60–75% of
sporadic clear cell RCCs [14]. A majority of clear cell
RCCs thus show hypervascularity on catheter angiography and contrast-enhanced CT/MRI [15] (Figure 3).
Based on the degree of contrast enhancement of RCCs
on helical CT scans (more than 84 Hounsfield units (HU)
in the corticomedullary phase and 44 HU in the excretory
phase), Kim et al [15] diagnosed clear cell RCC with a
specificity of 100% and 91%, respectively. The presence
of intracellular fat, a common finding in clear cell RCC,
may be documented on opposed phase MRI [16]. Cysts,
necrosis, haemorrhage and foci of calcification are
frequently seen and contribute to tumour heterogeneity
(Figure 4). Calcification is seen in 10–15% of neoplasms.
Clear cell RCC exhibits poor prognosis (stage-for-stage)
The British Journal of Radiology, Month 2007
Background functional histology of the loop
of Henle
The thin limbs of the loop of Henle are lined by a
simple squamous epithelium; the thick ascending limb is
lined by low cuboidal epithelium. The loop of Henle
plays a major role in maintaining an osmotic gradient
between the cortex and the medulla via the countercurrent multiplier mechanism [4]. Free, passive diffusion
of water occurs in the thin limb, while active transport
occurs through the cuboidal epithelium of the thick limb.
The vasa recta reabsorb the interstitial water enhancing
the medullary gradient.
Nephronal disorder that may be linked to the
loop of Henle
Mucinous tubular and spindle cell carcinoma
Mucinous tubular and spindle cell carcinoma
(MTSCC) is a low-grade polymorphic epithelial carcinoma associated with non-aggressive behaviour and a
favourable prognosis [8, 23]. Although the precise
histogenesis of the neoplasm is still not established,
MTSCC may differentiate towards the loop of Henle [24].
MTSCC was recently recognized as a subtype of RCC.
Macroscopically, MTSCC appears as well-circumscribed
tumours with uniform, grey or light tan colour [8].
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Figure 4. (a) Papillary renal cell carcinoma. Contrast-enhanced CT scan during the corticomedullary phase shows a left renal
hypoattenuating solid mass (arrow) with foci of calcification (arrowhead). (b) Papillary renal cell carcinoma. Coronal gadoliniumenhanced T1 weighted GRE MRI shows a uniform, hypovascular solid mass (arrow) in the upper pole of the left kidney.
Histologically, MTSCC consists of tightly packed, elongated tubules separated by pale mucinous stroma [8]. The
spindle cells are characteristic; chronic inflammation, foam
cell deposits and areas of necrosis are seen in some cases.
MTSCC was previously mistaken for sarcomatoid RCC
and other renal sarcomas. Distinct imaging characteristics of MTSCC have not been described in literature.
Background functional histology of the
collecting duct
The collecting tubules and ducts descend into the
medullary rays and eventually merge to form the
collecting ducts of Bellini, which subsequently enter
the pelvicalyceal system. The primary role of the collecting
tubules is urinary concentration through passive reabsorption of water that is regulated by antidiuretic hormone
(ADH) [4]. The epithelium is simple columnar and
contains three cell types, principal cells and Type A and
B intercalated cells. The principal cells are involved in
ADH-stimulated water reabsorption and sodium reabsorption [4]. Type A intercalated cells contain an adenosine
triphosphate (ATP)-dependent hydrogen–potassium ion
exchanger that enables secretion of acid against a gradient.
Type B intercalated cells contain an apical chloride/
bicarbonate antiporter that allows bicarbonate secretion.
Nephronal disorders localized to the cortical
collecting duct
Oncocytoma
Renal oncocytoma is a benign neoplasm thought to
differentiate towards Type A intercalated cells of the
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cortical collecting duct [1, 25]. Oncocytomas constitute 3–
5% of all adult primary renal epithelial neoplasms. There
is no specific sex predilection.
Typically,
oncocytomas
are
well-encapsulated
tumours with a characteristic mahogany-brown cut
surface and a central stellate fibrous scar [8]. Necrosis
is extremely rare; haemorrhage may be found in up to
20% of cases. Histologically, oncocytomas are composed
of uniform polygonal, mitochondria-rich cells arranged
in nests, tubules and acini [8]. Immunocytochemistry
techniques, staining with Hale’s colloidal iron and
cytogenetics help to distinguish oncocytomas from
chromophobe RCCs [13].
On cross-sectional modalities, oncocytomas appear as
well-circumscribed, homogeneous, smooth-marginated
neoplasms (Figure 5). Oncocytoma is usually a solitary
lesion with a median size of 4–5 cm [8]. Bilateral and
multicentric oncocytomas are seen in renal oncocytosis.
A central stellate scar is a characteristic finding seen in
up to 54% of oncocytomas (Figure 5) [26]. Central scar
and the tumour capsule may be better seen with MRI
[27]. A characteristic ‘‘spoke-wheel’’ pattern of vascularity has been described on catheter angiography [26,
28]. In contradistinction to RCC, arteriovenous shunts or
contrast puddling are typically absent [28]. However,
there is considerable overlap in the imaging findings of
oncocytoma and RCC subtypes [29].
Chromophobe renal cell carcinoma
Thoenes et al [30] first described chromophobe RCC
(CRCC) in 1985 as a distinct variant of RCC on the basis
of morphological criteria. CRCC represents between 5%
and 7% of adult RCCs [8].
The British Journal of Radiology
Segmental disorders of the nephron
Figure 5. Bilateral renal oncocytomas. Delayed phase contrast-enhanced CT scan shows bilateral, hypoattenuating
solid renal masses (arrows). While the right renal mass is
uniformly hypoattenuating, the left renal mass shows the
characteristic central stellate scar (arrowhead).
CRCC typically appears as solitary, well-circumscribed solid neoplasms. CRCC cells resemble the Type
B intercalated cells of the cortical collecting duct [1, 31].
Histopathologically, CRCC displays solid sheets of large
polygonal cells with pale reticular cytoplasm, perinuclear clearing and prominent cell membranes. Most
CRCC demonstrates diffuse staining with Hale’s colloidal iron.
CRCC typically appears hypovascular on contrastenhanced CT and MRI despite the large size [32]
(Figure 6). CRCC may appear hypointense on T2 weighted
MRI. At catheter angiography, CRCC is commonly
hypovascular. A spoke-wheel pattern of contrast enhancement on CT scan has been described recently [33]. CRCC
demonstrates a more favourable prognosis and biological
behaviour than clear cell RCC [17].
Nephronal disorders localized to the
medullary collecting duct
Collecting duct carcinoma
Collecting duct carcinoma (CDC) is a highly aggressive malignant neoplasm that comprises , 1% of all
RCCs [8, 34]. CDC is thought to differentiate towards the
principal cells of the medullary collecting duct (a
derivative of the ureteral bud).
CDC appears as a grey-white infiltrative neoplasm
with a medullary epicentre. Histologically, classic CDC
is histologically characterized by a tubulopapillary
growth pattern, marked desmoplasia and variable mucin
production [34].
CDC demonstrates a variegated appearance on crosssectional imaging modalities [3, 35]. Although CDC may
appear as expansile masses, it typically exhibits a diffuse
infiltrating growth pattern. At sonography, CDC may be
hyperechoic or hypoechoic to the renal parenchyma [3, 35]
(Figure 7). Typically, CDC appears as a diffusely infiltrative, hypovascular mass on contrast-enhanced CT scan
(Figure 8). Calcification may be seen in up to 25% of
patients [35]. CDC is frequently hypointense on T2
The British Journal of Radiology, Month 2007
Figure 6. Chromophobe renal cell carcinoma. Coronal,
gadolinium-enhanced T1 weighted GRE image of the right
kidney during nephrographic phase shows a large, expansile
mass (arrows) that shows heterogeneous contrast enhancement (arrowhead).
weighted MRI. Imaging findings of a hypovascular,
infiltrative mass with a medullary epicentre may suggest
the diagnosis of CDC [35]. Most CDCs are clinicobiologically aggressive neoplasms with resultant poor prognosis.
Renal medullary carcinoma
Renal medullary carcinoma (RMC) is an extremely
aggressive malignant neoplasm that develops almost
exclusively in young patients with sickle cell trait. First
described by Davis et al [2] in 1995, RMC is considered
the seventh sickle cell nephropathy. Histological features
of RMC mostly mimic those of CDC. It is hypothesized
that RMC develops in a background of transitional cell
hyperplasia in the renal medulla resulting from chronic
hypoxia [2, 36].
At gross pathology, RMC shows a central location and
is poorly circumscribed with frequent haemorrhage and
necrosis [8]. Histopathologically, RMC is characterized
by sheets of poorly differentiated tumour cells that may
show reticular and adenoid cystic growth patterns [8].
At imaging, RMC typically appears as ill-defined,
infiltrative masses that arise in the renal medulla and
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caliectasis is a frequent associated finding [37]. RMC is
typically hypovascular at catheter angiography. Extrarenal
metastases to lymph nodes, lung, adrenal gland and liver
are frequently seen and carry a poor prognosis [8].
Autosomal recessive polycystic kidney disease
Autosomal recessive polycystic kidney disease
(ARPKD) is an autosomal recessive renal disorder
characterized by a variable degree of renal cyst formation
and hepatic fibrosis [38]. Patients with infantile disease
present at birth with severe renal impairment. At the
other end of the spectrum, juvenile patients manifest
with liver disease and portal hypertension. Renal disease
is not always clinically apparent as only about 10% of the
collecting tubules are affected. ARPKD is caused by
mutations involving the PKHD1 (polycystic kidney and
hepatic disease 1) gene on chromosome 6p [39]. The gene
product called polyductin or fibrocystin is presumably
involved in cell adhesion or proliferation [40].
Renal cysts are the result of hyperplasia of the
secretory epithelia leading to fusiform dilatation of the
collecting ducts [38]. The cysts are arranged radially,
Figure 7. Collecting duct carcinoma of the kidney.
Transverse, right renal sonogram shows an expansile,
uniformly hypoechoic solid neoplasm (arrowheads). Arrow
shows the right kidney.
invade the renal sinus [3, 37] (Figure 9). Uncommonly,
RMC may manifest as expansile masses. It is difficult to
ascertain the medullary location of large RMC. Isolated
Figure 8. Collecting duct carcinoma of the kidney.
Nephrographic phase, contrast-enhanced CT scan demonstrates a hypoattenuating, infiltrating neoplasm in the right
kidney (arrow) with associated retroperitoneal lymphadenopathy (arrowhead).
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Figure 9. Renal medullary carcinoma. Nephrographic phase
contrast-enhanced CT scan demonstrates a hypoattenuating,
infiltrating neoplasm in the right kidney (arrow) with
associated low-density retroperitoneal lymphadenopathy
(arrowhead).
The British Journal of Radiology
Segmental disorders of the nephron
perpendicular to the renal capsule. Liver involvement is
universally present and is characterized by proliferation
and dilatation of small intrahepatic bile ducts as well as
periportal fibrosis [38].
The renal findings are summarized here. Sonographic
findings include smoothly enlarged kidneys, diffuse,
increased echogenicity and loss of the corticomedullary
differentiation [41]. High resolution sonography may show
dilated, radially oriented medullary tubules, macroscopic
cysts and intratubular crystalline foci [42]. Intravenous
urography demonstrates decreased excretion of contrast
material, enlarged kidneys and striated nephrograms
secondary to dilated collecting tubules [41]. Contrastenhanced CT shows striated nephrograms [41]. Fetal MRI
demonstrates nephromegaly with high water content and
radial striations related to fluid-filled ectatic ducts.
Medullary sponge kidney
Also referred to as Lenarduzzi–Cacchi–Ricci disease (in
the Mediterranean literature), medullary sponge kidney
(MSK) is an idiopathic, congenital, developmental abnormality characterized by diffuse or focal ectasia and cyst
formation in the intrapyramidal or intrapapillary portion of
the medullary collecting duct [43]. Although MSK is mostly
sporadic, familial forms of MSK with an autosomal
dominant inheritance pattern have been described [44].
MSK is hypothesized to result from disruption of the
embryonic interface between the developing ureteral bud
and the metanephric blastema [45]. MSK may be associated
with other renal conditions such as hemihypertrophy and
Beckwith–Wiedemann syndrome [46].
MSK is twice as frequent in women. Patients with
MSK may be asymptomatic, and the condition is often
discovered incidentally on imaging studies. MSK is
usually diagnosed in the third or fifth decades of life
during the evaluation of nephrocalcinosis, urinary tract
infection or calculus disease.
MSK is characterized by multiple, variably shaped
subcentimetre cysts within the papillae. Usually, both
kidneys and most of the renal pyramids are involved
[38]. The cysts are lined by cuboidal, columnar or
transitional epithelium. Cysts containing calcific material
Figure 11. Medullary sponge kidney. Intravenous urography
shows the characteristic medullary ‘‘brush’’ configuration of
the dilated collecting ducts in the right kidney (arrows).
may show squamous metaplasia. Complications include
haematuria, urinary tract infection and calculi [43].
Recurrent calcium nephrolithiasis is a result of complex
factors, including urinary stasis, and associated abnormalities such as hypercalciuria, distal renal tubular
acidosis and acidification defects [43].
Medullary nephrocalcinosis is a characteristic finding of
MSK (Figure 10). Clusters of retained contrast medium
within the dilated papillae on intravenous urography (IVU)
are diagnostic of MSK [47]. On IVU, radial linear streaking in
the renal papillae due to ductal ectasia confers a characteristic ‘‘medullary brush’’ configuration (Figure 11). In severe
cases, beaded or striated cavities and associated calculi
distort the calyces. Echogenic medullary pyramids due to
nephrocalcinosis may be seen on sonography [48]. CT is
helpful in evaluating complications including nephrolithiasis, obstruction and pyelonephritis.
Nephronal disorders localized to pyramid/
papilla
Figure 10. Renal medullary nephrocalcinosis. Longitudinal
right renal sonogram demonstrates hyperechoic pyramids
(arrows) consistent with medullary nephrocalcinosis.
The British Journal of Radiology, Month 2007
Papillary necrosis
As the name implies, papillary necrosis is pathologically characterized by ischaemic, coagulative necrosis of
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Figure 12. (a) Autosomal dominant polycystic kidney disease complicated by the development of a renal cell carcinoma.
Coronal T2 weighted MRI shows innumerable cysts that replace both the kidneys (arrowheads). Incidentally seen is a
hypointense mass in the upper pole of the right kidney (arrows). (b) Autosomal dominant polycystic kidney disease complicated
by the development of a renal cell carcinoma. Coronal, gadolinium-enhanced T1 weighted two-dimensional GRE MRI shows
predominantly peripheral contrast enhancement of the mass in the upper pole of the right kidney (arrowheads).
the renal papillae. Common predisposing risk factors
include urinary obstruction, infection, diabetes mellitus,
sickle cell disease and analgesic abuse nephropathy [49].
Urinary obstruction results in compression of thinwalled blood vessels that compromises the papillary
perfusion. The incidence of papillary necrosis in patients
with sickle cell disease and diabetes mellitus is 65% and
24%, respectively [50]. Patients with papillary necrosis
present with a wide spectrum of non-specific symptoms
and signs including haematuria, pyuria, bacteriuria,
polyuria and electrolyte imbalances [51]. Papillary
necrosis is bilateral in three-quarters of the cases.
The renal medulla is relatively hypoperfused and
receives between 2.5 ml min21 g21 (outer medulla) and
0.6 ml min21 g21 tissue (inner medulla) [4]. Compared
with this, the renal cortex receives 5 ml min21 g21 tissue.
Renal medulla, especially the papillae, are thus at
increased risk of ischaemic necrosis. The ischaemic
process may be reversible or irreversible. Persistent
ischaemia leads to coagulation necrosis, tubular fibrosis,
lobar infarcts and sloughing of the papilla [52]. Regional
distribution of the medullary vasa rectae and the
peripapillary plexus determines the location and degree
of papillary necrosis.
IVU is a sensitive test to detect papillary necrosis. The
peripheral or central portions of the papillae may be
involved. The findings on IVU include persistent contrast collections and cavitations within the pelvicalyceal
system. Dystrophic calcification of the necrosed papillae
may ensue in chronic cases. Sloughed papillae appear as
filling defects that may cause obstruction in the urinary
system. CT findings of papillary necrosis include illdefined medullary areas of contrast non-enhancement,
persistent contrast collections, filling defects in the
collecting system and, in late cases, calcification [51,
52]. Multiphase CT may be useful in the detection of
early papillary necrosis and to document papillary
healing following treatment [51, 52]. Ultrasound may
demonstrate urinary obstruction in patients with acute
urinary obstruction secondary to sloughed papillae [53].
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Necrosed papillae may appear as soft tissue masses
within the collecting system or the ureter on ultrasound
[53].
Polysegmental nephronal disorders
Pan-nephronal disorder: autosomal dominant
polycystic kidney disease
Autosomal dominant polycystic kidney disease
(ADPKD) is the most common hereditary renal cystic
disease that is characterized by multiple expansile,
bilateral renal cysts that ultimately lead to renal failure
[38]. The cysts are derived from all segments of the
nephrons [38].
Eighty-five per cent of ADPKD is a result of genetic
mutations in the PKD1 gene located on chromosome 16p
[38]. The less common mutation involving the PKD2
gene located on chromosome 4q is seen in 15% of
patients [38]. The PKD1 gene product polycystin-1
interacts with polycystin-2, a voltage-activated calcium
channel that is encoded by the PKD2 gene, to regulate
the cell cycle and intracellular calcium transport. Both
proteins are involved in cell–cell and cell–matrix interactions that determine tubular morphogenesis [54].
Cyst formation is focal in ADPKD, affecting , 5% of
the nephrons [38]. The cyst growth leads to replacement
of the normal parenchyma and interstitial fibrosis.
Systemic complications of ADPKD include hypertension,
renal failure and intracranial haemorrhage from rupture
of berry aneurysms [38].
At imaging, multiple, bilateral, variable-sized renal
cysts are identified with some showing haemorrhage
[55]. Associated liver cysts are seen in about 70% of
patients. In advanced stages, both kidneys are enlarged
with loss of reniform shape and near complete replacement of parenchyma. Renal complications include
pyelonephritis, calculus disease, kidney failure and
malignancy [38] (Figure 12a,b).
The British Journal of Radiology
Segmental disorders of the nephron
Summary
To summarize, recent advances in cytogenetics and
molecular biology have shed fresh light on the cells of
origin and the pathogenesis of renal disorders. Many
renal disorders are now postulated to arise from specific
segments of the nephrons and demonstrate characteristic
biology and clinical findings. Although there is considerable overlap in the imaging findings of renal
disorders arising from different nephronal segments,
some disorders exhibit characteristic findings that permit
accurate diagnosis.
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The British Journal of Radiology