Human Pathology (2014) 45, 11001104

www.elsevier.com/locate/humpath

Case study

Four miniature kidneys: supernumerary kidney and

multiple organ system anomalies
Marjan Afrouzian MD, FCAP a,, Joseph Sonstein MD b , Tahereh Dadfarnia MD a ,
J. Nicholas Sreshta MD b , Hal K. Hawkins MD, PhD a
a

Department of Pathology, Division of Surgical Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
Department of Surgery, Division of Urology, University of Texas Medical Branch, Galveston, TX 77555, USA

Received 30 May 2013; revised 24 September 2013; accepted 13 November 2013

Keywords:
Kidney;
Supernumerary;
Anomaly;
Gallbladder

Summary More than 350 years after Martius's first reported case in 1656, supernumerary kidney (SNK)
continues to fascinate the world of medicine, generating new ideas in the domain of embryogenesis.
Association of a normal kidney with a second or third ipsilateral smaller kidney is an extremely rare
anomaly with only a total of 81 cases reported until today. We are reporting a case of SNK, clinically
diagnosed as right hydronephrosis, associated with an ipsilateral ectopic ureter, a contralateral partially
duplicated ureter, and a multiseptate gallbladder. Pathologic examination of the nephrectomy revealed 4
miniature kidneys, joining a dilated ureter through 4 separate conduits. Our patient is the first reported
case of SNK with absent ipsilateral normal kidney, presence of more than 3 kidneys on 1 side, and
associated anomaly in the gallbladder. This case represents a unique combination of rarities, suggesting
insights in the domain of molecular embryology.
Published by Elsevier Inc.

1. Introduction
Supernumerary kidney (SNK) is an extremely rare
anomaly. In 2009, the 81st reported case of SNK was
published. This is 335 years after the first reported case. All
of the cases consist of a normal kidney associated with a
usually smaller, second, or even third kidney on the same
side. This rare anomaly has been associated in few patients
with a second anomaly of the urinary tract, such as renal
artery stenosis, ureteral atresia, or ectopia. Most of the cases
of SNK have originally been diagnosed as hydronephrosis/
pyonephrosis, proving that SNK can be missed by the
Corresponding author. Marjan Afrouzian, MD, FCAP, University of
Texas Medical Branch, Department of Pathology, 2.190 John Sealy Annex,
301 University Boulevard, Galveston, TX 77555-0588 USA.
E-mail address: maafrouz@utmb.edu (M. Afrouzian).
0046-8177/$ see front matter. Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.humpath.2013.11.015

radiologist and the urologist, and for this reason, the

incidence of SNK might be higher than reported. Therefore,
raising awareness regarding SNK could lead to future proper
diagnosis of this anomaly.

2. Materials and methods

2.1. Patient history
A 29-year-old man with history of hypertension presented
to the urology clinic with chronic right back/flank pain, lower
urinary tract symptoms of urgency and frequency, subjective
gross hematuria, and a history of having a swollen kidney
that may require an operation. There was no family history of
kidney disease. Physical examination was unremarkable,
although blood pressure was 191/110 mm Hg.

Four miniature kidneys

Urinalysis showed 56 white blood cells per high-power
field and 10 mg/dL of protein. Urine cytology revealed
marked pyuria, necrosis, and abundant bacterial cocci in
chains. Interestingly, urine culture was negative. The patient
had normal overall renal function with a calculated creatinine
clearance of 148 mL/min.
The patient underwent a computed tomography (CT) of the
abdomen/pelvis with and without contrast, which showed him
to have a severe right hydroureteronephrosis, with presumed
atrophy of the renal parenchyma along with an ectopic right
ureter with termination in the prostatic urethra. The left kidney
was noted to have incidental findings of partial duplication of
the left ureters. In addition, the patient's gallbladder was noted
to be multicystic with areas of curvilinear calcifications.
Lastly, the patient was noted to have numerous polyps in the
stomach and small and large bowel.
Because of the bowel findings on CT, the patient was
evaluated by gastroenterology and underwent a colonoscopy,
esophagogastroduodenoscopy, and push enteroscopy. The
only finding on these studies was a hyperplastic polyp in the
rectum. A right upper quadrant ultrasound revealed a septate
gallbladder, without wall thickening, pericholecystic fluid or
stones, and a normal common bile duct. The patient
underwent a laparoscopic nephrectomy. Cystoscopy was
performed at the time of surgery and showed a small mucosal
lesion at the bladder neck, possibly consistent with the
ectopic implantation of the right ureter. The patient was also
noted to have a right ureteral orifice at its orthotopic position,
within the bladder. The left ureteral orifice was observed in
its orthotopic position, draining clear fluid.
A laparoscopic simple nephrectomy was performed with
partial ureterectomy. During the procedure, the adrenal gland
was identified attached to the kidney and was removed with
the kidney. The gross appearance of the kidney intraoperatively was consistent with a chronically hydronephrotic
kidney. The ureter was also massively dilated. There were
significant adhesions to surrounding structures including the
vena cava, psoas muscle, and diaphragm, consistent with
previous inflammation and/or infection. A diaphragmatic
injury occurred during the procedure requiring primary
closure and chest tube thoracostomy. Postoperatively, the
patient had no significant change in overall renal function,
and urinalysis revealed resolution of the pyuria. Blood
pressure 2 weeks postoperatively was 161/98 mm Hg.

2.2. Macroscopic findings

Gross examination in the surgical pathology service
revealed that the specimen designated as right kidney was a
hollow and cystic mass weighing 232 g, measuring 15 12
4 cm, and covered with perinephric fat. The cystic area
appeared to be a dilated ureter to which 4 small and miniature
kidneys were connected through separate minuscule conduits
(Fig. A). Kidneys 1, 2, and 3 were found and photographed at
fresh state, and kidney 4 was found after fixation with
formalin. These kidneys were covered by perinephric fat and

1101
separated from each other by a thin-walled cystic tissue,
resembling a dilated ureter, and were situated at different
locations at the periphery of the dilated ureter, which had a
shiny and focally red mucosal surface. The outlet of the
cystic mass was a segment of ureter measuring 4 cm in length
and 1 cm in diameter, at the end of which a surgical clamp
mark was evident. No stones were found. The sizes of the 4
kidneys (kidneys 1, 2, 3, and 4) were as follow: 4 3.5 1
cm (Fig. B), 3 2 0.5 cm (Fig. C), 2 1.5 0.5 cm (Fig.
D), and 1.1 1 0.4 cm (Fig. E), respectively. On
sectioning, each kidney had a normal-appearing capsule, the
corticomedullary junction was well demarcated, and the
cortex appeared to be thicker than expected, especially when
compared with the size of the kidney and relative to the
thickness of the medulla. In order of kidneys 1 to 4, the
cortex measured 0.4, 0.4, 0.6, and 0.4 cm, respectively, and
cortex/medulla ratio was 4:1, 5:1, 4:1, and 3:1, respectively.
An adrenal gland, measuring 5.0 2.0 0.3 cm, was
identified on the superior pole of the kidney 1. Further
dissection of each kidney revealed a shiny pyelocalyceal
system, attached to a miniature conduit measuring 1.8 cm in
length and 0.2 cm in diameter, independently joining the
cystic ureter.

2.3. Microscopic findings

Sections from 4 small kidneys showed well-developed
cortical tissue overlying the relatively thin medullary
parenchyma. In the cortical parenchyma, globally sclerotic
glomeruli appeared to be restricted to the subcapsular area
and represented less than 5% of total glomeruli. Few
glomeruli showed a mild increase in size, but the glomeruli
in general appeared mature and unremarkable with patent
peripheral capillary loops (Fig. B, inset). There was no
evidence of increase in mesangial matrix or cellularity, and
segmental sclerosis was absent, except for 1 glomerulus
adjacent to the area of thyroidization in kidney 2. By special
stains (Periodic acidSchiff and Jones silver stains), the
glomerular basement membrane showed normal contour and
thickness, with no wrinkling or other abnormality. Mild focal
periglomerular fibrosis was evident in a minority of
glomeruli. In each kidney, few dilated tubules close to the
pyelocalyceal system were present, showing features of
thyroidization including tubular dilatation and atrophy and
presence of Periodic acidSchiffpositive hyaline casts with
scattered mononuclear inflammatory cells infiltrating between the atrophic tubules. Focal interstitial fibrosis
occupying up to 5% of the total parenchymal surface area
was present and was mainly located in the area of
thyroidization. Remaining kidney parenchyma showed no
evidence of inflammation or tubular atrophy. Arteries,
especially the ones located close to the area of thyroidization,
showed mild-to-moderate fibrous intimal thickening accompanied by reduplication of the elastic lamina. By Verhoeff's
elastin stain, fibroelastosis was found in the arteries. No
fibroplasia was noted. Some of the arterioles close to the area

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M. Afrouzian et al.

Fig. A, Nephrectomy specimen showing kidneys 2, 3, and 4 (thin arrows) and ureteral outlet (thick arrow). Kidney 1 and its attached adrenal
gland are on the posterior aspect of the mass and not shown in this picture. B, Kidney 1 with attached adrenal gland (Masson's Trichrome stain
1). Cortex/medulla ratio is 4:1. Glomeruli and the cortical tubulointerstitium and the adrenal gland show normal histology (inset 2). C,
Kidney 2. D, Kidney 3. E, Kidney 4 (arrows) bisected and fixed in formaldehyde.

of thyroidization appeared hyperplastic. Moderate arteriolar

hyalinosis was observed in the remaining arterioles of the
renal parenchyma. The morphology of the adrenal gland was
unremarkable.

3. Discussion
SNK is an extremely rare anomaly. Since the first
described case in 1656 by Martius [1] and then the second
case reported by Blasius in 1677 [1], a total of 81 cases of
SNK have been published until 2009 [2]. Three hundred
thirty-five years after Martius's first report, a rare entity, such

as SNK, continues to fascinate the medical world. The

presence of a normal kidney associated with a smaller,
second, or even third kidney on the same side is a rare
anomaly by itself. Our case is a combination of multiple
rarities, not reported previously in the literature: 4 miniature
kidneys with absence of an ipsilateral normal kidney,
associated anomalies such as ectopia of the ipsilateral ureter
terminating in the prostate gland, partial duplication of
contralateral ureter, and septation of the gallbladder.
Despite the significant anomaly, all 4 kidneys were
relatively well preserved, with functioning nephrons and
expanded cortex and normal glomeruli: cortex/medulla ratio
was remarkably increased in all 4 kidneys. Although

Four miniature kidneys

thyroidization was present in all 4 kidneys, it appeared to be
a focal phenomenon. Areas of thyroidization along with the
abnormal main ureter and the findings of numerous white
blood cells and chronic pain in the patient with lower urinary
tract symptoms and chronic right back/flank pain seem
highly suggestive of possible chronic pyelonephritis or
reflux, albeit affecting small areas. Arterial fibroelastosis and
arteriolar hyalinosis were findings that would have been
considered premature for a 29-year-old white man but
correlate well with patient's history of hypertension. It is also
possible that the latter vascular changes are due to the genetic
defects causing SNK, as cases of renal artery stenosis
associated with SNK have been reported in the past.
Another important lesson from this case is in the domains
of clinical diagnosis and imaging: our case, as all other
reported cases, was originally diagnosed as hydronephrosis,
both clinically and radiologically, and only after careful
examination of the specimen in the pathology laboratory, the
diagnosis of SNK was made. This experience and other
published articles [3] suggest that cases of SNK can be
mislabeled as hydronephrosis. The limited number of reports
of this entity and the tendency to mislabel it as hydronephrosis suggest that the true incidence of this condition might
be much higher than previously thought, and it is unclear
how many cases of SNK remain undiagnosed.
We questioned whether there may have been some
radiographic evidence of the presence of SNK on his
preoperative CT scan. On discussion and review with an
experienced genitourinary radiologist, there were no obvious
radiographic signs on CT scan of the presence of an SNK.
Even with knowledge of the diagnosis, the radiologist felt that
the preoperative CT scan was consistent with a chronically
obstructed, hydronephrotic, nonfunctioning kidney.
On the clinical side, although our patient's signs and
symptoms were consistent with hydronephrosis, we believe
that presence of multiple anomalies in the genitourinary
system, especially when accompanied by anomalies in other
organ systems, should raise the possibility of SNK.
The main impact of this case study is in the domain of
pathology: during gross examination of hydronephrotic
specimens, it is quite easy to miss the miniature kidneys, not
only due to their small size but also due to the fact that there
is little awareness about this entity in the world of
pathology. We suggest that hydronephrotic specimens
should be examined with diligence, having in mind that
an entity such as SNK could present itself as hydronephrosis. Only after recognizing and collecting more cases of
SNK macroscopically, more progress can be made in the
domains of clinical diagnosis, imaging, and molecular
pathology of SNK.
In an effort to aid understand the likely pathogenesis of
our case, a short review of the molecular pathology and
embryogenesis of the kidney is provided below.
The ultimate organ known as the kidney derives from the
metanephros and its Wolffian duct (WD). In mice, around
midgestation, the caudal part of the WD starts to swell, and

1103
an epithelial condensation called the ureteric bud (UB) is
formed. The UB composed of a stalk and a tip invades the
adjacent metanephric mesenchyme (MM), which by this
stage has acquired the necessary properties to form nephrons
[2]. This phenomenon occurs as the result of a complex
interaction between multiple signaling pathways. The
molecular signals induce mesenchymal cell condensation
around the tip of the UB. Subsequently, through a process
called mesenchymal-to-epithelial transition, a selected pool
of condensed mesenchymal cells acquires epithelial capabilities to assemble nephrons [4,5]. Therefore, UB branching
occurs as a result of mesenchymal-to-epithelial transition,
while the tip of the UB becomes a strategic point, where
orchestration of complex interactions between multiple
molecular pathways insures that the branching morphogenesis progresses correctly [6].
Our case of SNK shows evidence of some defect at the
level of UB branching. The cell movement and the molecular
interactions of the signals, agonist and antagonists, participating in kidney epithelial branching morphogenesis have
been beautifully summarized in an article published by
Michos in 2009 [6], showing that signaling pathways
involved in the formation of the UB and further development
of ureteric branching occur in 3 locations: in ureteric stalk, at
the tip of the UB, and in the MM surrounding and flanking
the tip of the UB.
Among different genes involved in the process of UB
formation and ureteric branching, a few are of particular
interest in our case:
(1) Gdnf (the glial cell line-derived neurotrophic factor) and
its receptor Ret: Gdnf/Ret signaling is crucial for the initiation
of kidney organogenesis in that it regulates UB development
[7,8]. It has been shown that ectopic Gdnf signaling can induce
bud formation from the WD [9]. (2) Wnt11 is another player
and is necessary for Gdnf expression, whereas Ret signaling
regulates Wnt11 expression [10]. (3) In the UB, Sprouty
proteins normally express inductive signals that have an
impact on the future size of the kidney [10]. SPRY2 is
expressed in both the UB and the surrounding MM [11].
Ectopic human SPRY2 reduces the expression of 2 important
genes: Gdnf and Fff. This reduction is associated with
formation of fewer ureteric tips [12]. (4) Deficiency in bone
morphogenetic protein 4 (Bmp4) and human SPRY2 expression can induce a complete second collecting duct system both
in vitro and in vivo. (5) Exposure of the WD to Fgf7 and Gdnf
generates supernumerary epithelial buds in the transgenic
kidney. Hence, kidneys expressing human SPRY2 appear to be
sensitized to generate ectopic buds from the WD in response to
Fgf7 and Gdnf signaling [12].
We suggest that, in our case, the kidney and ureteral
anomalies observed might be the results of an imbalance of
multiple gene expression between SPRY2 and WNT11/
mesenchymal Gdnf/stromal Fgf7 and Bmp4. This imbalance has created the molecular environment for multiple
budding and formation of a complete but reduced-in-size
SNK as well as double and ectopic ureters. The authors

1104
have not investigated these possible pathways in the
current patient as much of the above genetic information
has been generated from either in vitro experiments or
from studies on knockout animal models. The relationship
between this imbalance and the septate gallbladder is not
clear at this point, and therefore, molecular studies in the
domain of gallbladder morphogenesis would be needed to
elucidate this relationship.

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