The Classification of Renal Cystic Diseases and Other
Congenital Malformations of the Kidney and
Urinary Tract
Stephen M. Bonsib, MD
● Context.—Renal cystic diseases and congenital abnor-
malities of the kidney and urinary tract comprise a hetero-
geneous group of lesions whose pathogenesis has eluded
physicians for centuries. Recent advances in molecular and
genetic understanding of these diseases may provide the
solution to this riddle.
Objective.—The formulation of an effective classifica-
tion system for these disorders has been elusive but is
needed to introduce order while providing a conceptual
framework for diagnosis.
Data sources.—This review discusses the evolution, be-
ginning in the 19th century, of postulates regarding the
pathogenesis of cystic and developmental renal diseases.
Selected classification systems proffered during this period
are discussed in pursuit of an ideal classification schema
that would account for morphologic features and their
clinical importance, with logical links to pathogenesis and
treatment. Although this remains an elusive target, its gen-
R enal cystic diseases (RCDs) and congenital abnormal-
ities of the kidney and urinary tract (CAKUT) com-
prise a group of metanephric and ampullary bud misad-
ventures and acquired lesions that have captured the in-
terest and challenged the imagination of physicians for
centuries. There are several reasons for this medical infat-
uation, including the frequency of these disorders (abnor-
malities in urinary tract development occur in approxi-
mately 10% of the population); their astonishing variety,
which results in an impressive menu of gross abnormali-
ties; and most important, their clinical importance (Figure
1).1–12 Although most patients with some of the more com-
mon forms of maldevelopment, such as bifid ureter and
horseshoe kidney, may have few significant complications,
collectively, RCD/CAKUT represent the most common
Accepted for publication February 26, 2009.
From the Department of Pathology, Louisiana State University Health
Sciences Center, Shreveport.
The author has no relevant financial interest in the products or com-
panies described in this article.
Presented in part at the 4th Annual Renal Pathology Society/Kidney
and Urology Foundation of America satellite meeting held in associa-
tion with the 21st European Congress of Pathology, Istanbul, Turkey,
September 13, 2007.
Reprints: Stephen M. Bonsib, MD, Department of Pathology, LSU
Health Sciences Center, 1541 Kings Hwy, Shreveport, LA 71130-3932
(e-mail: sbonsi@lsuhsc.edu).
554 Arch Pathol Lab Med—Vol 134, April 2010
eral outline is becoming clearer. A classification approach
favored by the author is presented, which incorporates
many of the strengths contained in several previous clas-
sifications.
Conclusions.—Genetic- and molecular-based postulates
regarding the pathogenesis of the renal cystic and devel-
opmental diseases have implicated mutated master genes
and the modification of genes that are crucial in renal de-
velopment and genes that are central to the sensory effects
of the renal tubular primary cilium on cell physiology.
These scientific advances provide pathogenetic links be-
tween morphologically and genetically distinct entities and
certain cystic and neoplastic entities, associations that
seemed implausible not long ago. These advances may
eventually provide the basis for future classification sys-
tems while suggesting targets for therapeutic approaches
in the prevention and treatment of these diseases.
(Arch Pathol Lab Med. 2010;134:554–568)
cause of end-stage renal disease in children, accounting
for 40% to 50% of cases, and includes autosomal dominant
polycystic kidney disease, the most common type of RCD
and the fourth leading cause of end-stage renal disease in
adults.1–5 Furthermore, renal hypoplasia in the form of in-
sufficient nephron endowment has been implicated in a
substantial fraction of individuals with essential hyper-
tension.13–15
The formulation of an effective classification system for
RCD/CAKUT has been an elusive goal driven by the need
to introduce order into this complex arena, and thereby,
provide a conceptual framework as attempts to unravel its
pathogenesis were pursued. Long before abnormalities of
the kidney could be defined, however, was the challenge
of defining the anatomic features and function of the nor-
mal kidney and urinary tract so that deviations from this
blueprint could be recognized. Some of the first and most
primitive assumptions of urinary tract structure and func-
tion were proffered a millennia ago, when Aristotle taught
that urine was formed by the bladder and that kidneys
were present ‘‘not of actual necessity, but as matters of
greater finish and perfection.’’ 16
Details of the normal gross renal and lower urinary
tract (LUT) anatomy were first unveiled in the 16th cen-
tury by Leonardo de Vinci and Vesalius, who generated
drawings of the female and male genitourinary tracts,
thus laying the foundation for the modern day disciplines
Classification of Renal Cystic Diseases and Malformations—Bonsib

of nephrology, urology, and nephropathology (Figure
2).16–18 Centuries later, the invention of the first micro-
scopes by Hans and Zacharias Janssen in the 1590s al-
lowed the 17th century masters of microscopic anatomy,
such as William Bowman and Marcello Malpighi, to
glimpse the complexity of the renal microscopic anatomy
(Figure 3).19–21 Later, Huber and Brödel in the early 20th
century illustrated, in meticulous 3-dimensional serial re-
constructions and captured in elegant drawings, respec-
tively, its embryologic basis (Figures 4 and 5).22,23
THEORIES ON PATHOGENESIS OF RCD/CAKUT
Historically, the authors of most classifications used pre-
vailing concepts of pathogenesis to frame classification
systems. If this is a prerequisite for a useful classification
scheme, then it would appear that the ideal classification
must await a thorough understanding of RCD/CAKUT
pathogenesis, an elusive goal, but one in which much
progress has occurred in the past decade. Interestingly,
some of the earliest theories of pathogenesis appearing
during the 19th century are similar to those that persisted
throughout most of the 20th century.
Two of the earliest reported theories on renal cystogen-
esis were those of Virchow24 and of Rokitanky.25 Virchow,24
in 1869, proposed that obstruction by uric acid crystals or
papillary duct atresia was operative in the pathogenesis
of renal cysts. Conversely, Rokitansky,25 in his 1885 text
Manual of Pathological Anatomy, indicated that the consen-
sus among German pathologists was that renal cysts
formed within the malpighian corpuscle ‘‘when tumified
and gorged with the inflammatory product of these dis-
eases upon the surrounding strata.’’ An obstructive etiol-
ogy was also favored by Danforth26 who wrote in 1888
that the evolution of cysts involved the ‘‘unrolling or un-
folding of the renal structure as it slowly yields to the
pressure of the fluid accumulating in the cysts.’’ The no-
tion that renal cysts were neoplastic surfaced as early as
the late 1800s when Sturm,27 in 1875, and Brigidi and Sev-
eri,28 in 1880, argued that cysts resulted from epithelial
Arch Pathol Lab Med—Vol 134, April 2010
Figure 1. Composite photograph of domi-
nant and recessive polycystic kidney disease,
multicystic dysplasia, renal aplasia, and dys-
plasia associated with lower urinary tract ob-
struction.
proliferations or inclusion of mesonephric elements in the
kidney that subsequently proliferate.
Bunting29 summarized in detail, in a 1906 publication,
the prevailing theories on cystogenesis. The postulates in
vogue included tubular obstruction attributable to external
compression of tubules by infection-related fibrosis, con-
genital maldevelopment or a neoplasm related to abnor-
mal cell growth, and finally, nonunion of primitive col-
lecting ducts and secretory tubules. The latter postulate
followed the delineation by Kupffer,30 Huber,22 and Brö-
del23 of the dual role of the ampullary bud and renal blas-
tema in renal nephrogenesis. In the 1920s to 1930s, after
the dual origin of ampullary bud and nephrogenic blas-
tema in nephrogenesis was more widely recognized, cyst
formation, resulting from failure of the 2 tissues to unite,
emerged as the most popular theory.
Bunting,29 in his review of cytogenesis, made the in-
sightful comment that his 2 cases of cystic kidney disease
differed morphologically and clinically from many previ-
ous reportedly cases. Bunting29 noted that ‘‘the attempts
to explain pathogenesis of the congenital cystic kidney
have been so numerous and so varied that one is inclined
to question whether pathologists have been dealing
throughout with a single pathological process.’’ Because
the personal experience of these early investigators was
limited to small numbers of cases, with no individual hav-
ing access to the full spectrum of RCD/CAKUT diseases,
his concerns were appropriately insightful. Regardless,
even if these early investigators were fortunate enough to
have exposure to the complete palate of RCD/CAKUT
possibilities, they would not have been able to solve the
puzzle of pathogenesis, which required advances in sci-
entific knowledge and technology only recently achieved.
Kampmeier,31 in 1923, published beautifully illustrated,
histologic pictures of fetal kidney in early gestation and
noted the common occurrence of occasional ectatic (cystic)
tubules as a normal event in embryogenesis. This led him
to offer one of the earliest insights into the possibility of
a molecular basis for many RCDs. He suggested that ec-
Classification of Renal Cystic Diseases and Malformations—Bonsib 555
Figure 2. Genitourinary tract, a diagram by Andreas Vesalius, published in 1541 (Organs of Nutrition and Generation. Marburg, Germany:
Johannes Oporinus, printer. De humani corporis fabrica and libri septum [On the fabric of the human body]; book 5).122
Figure 3. William Bowman’s 1842 illustration of the vascular supply to glomeruli, based on a dye injection study (from Bowman W. On the
structure and use of the malpighian bodies of the kidney, with observations on the circulation through that gland. Philos Trans R Soc Lond Biol.
1842;132:57–80). 19

tatic abnormal tubules could possibly persist and enlarge
to form the grossly visible, simple renal cysts of adults.
He further postulated that ‘‘factors control the degenera-
tion or suppression of abnormal growth,’’ in effect, impli-
cating master genes that regulate and orchestrate normal
embryogenesis or that fail to do so in abnormal embryo-
genesis. He further noted that these ‘‘factors’’ could also
explain coexistent lesions in other organ whose embryo-
genesis was similarly dysregulated.31–33
Anatomic investigations into the site of cyst formation
within the nephron emerged in the mid-20th century, con-
tributing further to our understanding of cystic diseases.
Lambert,34 in 1947, employed serial section reconstruc-
tions of cystic kidneys from 6 adults and 2 children and
showed that cystic dilations could develop in any segment
of the nephron. In the 1950s and 1960s, Potter and Osa-
thanondh and others,35–44 using the newly developed tech-
nique of microdissection, studied normal and congenitally
cystic kidneys. The exhaustive work Potter and Osatha-
nondh41–46 was particularly noteworthy because it formed
the basis of a classification schema known as the Potter
556 Arch Pathol Lab Med—Vol 134, April 2010
Classification, which was predicated on the anatomic dis-
tribution of cysts within the nephron.
In the mid to late 1900s, the obstructive theory of path-
ogenesis for renal dysplasia was popularized. Bern-
stein47,48 noted that more than 90% of dysplastic kidneys
are associated with urinary tract abnormalities that are
invariably obstructive. The renal lesions seem to parallel
the LUT abnormality, whether unilateral versus bilateral
or segmental in a duplex kidney, and that the severity also
appears proportional (Figure 6, A and B). Bernstein47,48 ac-
knowledged, however, that not all dysplastic kidneys are
associated with obstruction because the many familial
multiple malformation syndromes argue for a genetic eti-
ology. Appreciation that these disorders can affect several
members of the same family implicated genetic causation.
Experimental studies, intended to implicate obstructive
etiologies in metanephric dysgenesis, were initiated in the
1970s to 1990s. Extreme experimental maneuvers were
employed, where not only LUT obstruction, urethral or
ureteral obstruction was induced early in embryogenesis
but also unilateral nephrectomy was sometimes per-
Classification of Renal Cystic Diseases and Malformations—Bonsib
Figure 4. G. Carl Huber’s 1905 illustration of his wax model serial reconstructions of nephron differentiation (from Huber GC. On the development
and shape of uriniferous tubules of certain of the higher mammals. Am J Anat. 1905;4(4)(suppl):1–98). 22
Figure 5. Max Brödel’s 1907 illustration of the sequence of nephron induction (from Kelly HA, Burnan CF. Diseases of Kidneys, Ureter, and
Bladder: With Special Reference to the Diseases in Woman. vol 2. New York, NY: D Appleton and Company; 1914).23

formed to further stress to the remaining, developing kid-
ney.49–53 In most species examined, including pigs, chick-
ens, and rabbits, investigators failed to induce changes
typical of cystic dysplasia, instead severe hydronephrosis
was mostly observed.49–53 However, in the fetal lamb mod-
el, convincing cystic dysplasia was produced in some an-
imals, although others developed only severe hydrone-
phrosis.54,55
Experiments of nature indicate that obstruction and
metanephric maldevelopment are not inevitably linked be-
cause a neonate can be born with complete LUT obstruc-
tion and resultant massive hydroureteronephrosis, yet
nephrogenesis can be preserved (Figure 7).56–58 Another
argument against simplistic anatomic causation is the il-
logic of implicating sequential injury, obstruction followed
by metanephric dysgenesis, for a synchronous activity of
ureteral and renal development. This creates a physiologic
conundrum: How can a nonfunctional, disordered meta-
nephric mass produce an ultrafiltrate of sufficient ‘‘toxic-
ity’’ or pressure to perturb the development of subsequent
nephron formation. Especially relevant to this concern are
cases of cystic dysplasia identified in the first trimester.58–60
McKenna and Kampmeier,33 in their 1933 article entitled
‘‘A Consideration of the Development of the Polycystic
Kidney,’’ captured the state of understanding that existed
then, and which persisted until the end of the 20th century
Arch Pathol Lab Med—Vol 134, April 2010
when they wrote: ‘‘There are many theories which begin
as logical deduction, and later without foundation of ob-
servation are handed down from textbook to textbook and
from paper to paper as facts. Such is the hypothesis of the
origin of cystic kidney.’’ 3 Bernstein elaborated further, in
1968, about the challenge investigators faced in this field
when he wrote: ‘‘A classification in a strict taxonomic
sense cannot be devised because pathogenesis remains
unknown and because considerable overlap exists both
clinically and morphologically.’’ 46
Although by the latter decades of the 20th century, the
etiology or etiologies for RCD/CAKUT remained un-
known, implication of an anatomic causation, especially
urinary tract obstruction in severe metanephric maldevel-
opment, remained popular because of the ubiquitous as-
sociation. Knowledge of the embryologic development of
the kidney would appear to provide a logical basis for
explaining departures from normal renal development
and was especially popular for many CAKUT lesions.
However, because of the enormous diversity of malformed
urinary tracts, the limitless combinations of abnormalities
affecting kidney and LUT, and the asymmetry of renal
lesions, the delayed onset of some genetic cystic diseases
in kidneys that were initially normal in form and the ac-
quired nature of others cannot be easily accommodated
by any simplistic anatomic-based approach.3–12,61–66 To
Classification of Renal Cystic Diseases and Malformations—Bonsib 557
Figure 6. Two examples of bilateral dysplasia with extreme degrees of (A) ureteral atresia and (B) ureteral dilation.
quote the time traveler in H. G. Wells’ 67 The Time Machine ,
‘‘Very simple was my explanation, and plausible enough—
as most wrong theories are!’’
Limitation in the understanding of pathogenesis, as not-
ed by Bernstein,47,48 has plagued the classification process,
but has been alleviated in recent years as the molecular
contributions to RCD/CAKUT have been identified.68–100
The list of mutated genes expressed during renal devel-
opment is rapidly growing. These genes code for a variety
of transcription and growth factors required for the reg-
ulation and orchestration of interactions between the ure-
teric bud and the metanephric blastema and its predeces-
sor’s tissues, the mesonephric and pronephric ducts. One
of the most common mutated genes in CAKUT is PAX2,
a gene that serves a central role in renal development.
PAX2 is one of 9 paired-box transcription factors, a master
organizer gene expressed in the nephric duct, metanephric
mesenchyme, ureteric bud, and S-shaped body.65–69 PAX2
performs many functions at early stages of renal devel-
opment. It organizes caudal descent of the nephric duct
with PAX8 and GATA3, emergence of the ureteric bud, and
induces WT1 in metanephric blastema. PAX2 is also in-
volved with branching morphogenesis and the sustained
arborization of the collecting duct. With such extensive
involvement in the early stages of metanephric kidney in-
duction, it is easy to envision how mutations of this crucial
gene, or other similarly critically located genes, could re-
sult in a vast array of maldevelopment.
Table 1 lists several of the most commonly mutated mas-
558 Arch Pathol Lab Med—Vol 134, April 2010
ter genes, displays the various malformations observed,
and reports associated clinical syndromes. It is clear that
the renal consequences of the mutation of a single master
gene can be diverse, dependent upon the specific type of
mutation, missense, nonsense, deletion, and so forth, and
the resultant functionality of the mutated protein pro-
duced. Modifying genes also influence the final phenotype
adding an additional layer of complexity. Furthermore,
based on cDNA microarray analysis comparing the RNA
signature of normal and dysplastic kidneys, the expres-
sion profiles of entire families of genes are affected in
many cases of RCD/CAKUT.
A second major advance in understanding RCD/CAK-
UT pathogenesis has been the explosion in understanding
of the molecular composition and function of the renal
tubule primary cilium.101–110 Cilia are eukaryotic organelles
that project from the cell surface; they can exhibit motile
or sensory functions. The basic structure of nonmotile, pri-
mary cilia of the renal tubular cells consists of 9 peripheral
microtubular doublets that form the axoneme, surrounded
by a lipid bilayer that is continuous with the cell mem-
brane. By contrast, motile cilia of other organs have a cen-
tral doublet of microtubules in addition to the 9 peripheral
microtubular doublets, and the latter are linked by dynein
arms and other structural components. All cilia are an-
chored in the cytosol by the basal body, a microtubular
organizer derived from the older of the 2 centrioles (Fig-
ure 8). Assembly and maintenance of cilia is provided by
a bidirectional microtubular transport system.
Classification of Renal Cystic Diseases and Malformations—Bonsib

Figure 7. Complete urinary tract obstruction secondary to ureteral
atresia with a severely hydronephrotic, but otherwise normal kidney.
The proteins of the primary cilia are ancient and have
been highly conserved evolutionarily; in fact, some cys-
toproteins have been conserved for more than 1.5 billion
years from unicellular organisms to vertebrates. Although
primary cilia have been recognized for decades, they had
previously been regarded as evolutionary vestiges. How-
ever, more recently, it has been recognized that primary
cilia serve important functions in cellular physiology, such
as cell cycle regulation, cell signaling, apoptosis, and ep-
ithelial cell polarization. The list of signaling pathways in-
fluenced by ciliary function is growing and includes plate-
let-derived growth factor receptor ␣ signaling, hedgehog
signaling, epidermal growth factor signaling, and 5-HT6
serotonin signaling.
Mutation of more than 20 molecules that are localized
to primary cilia, basal bodies, and centrosomes, and which
also reside in cell adhesions, have been identified in a
broad range of morphologically and clinically dissimilar
disorders (Table 2). Most of the cytoproteins identified in-
teract with other cystoproteins (Figure 9). Thus, mutations
of these physiologically interactive proteins provide path-
ophysiologic links between RCDs previously regarded as
unrelated because they differ in type of transmission, age
of onset, extrarenal manifestations, and risk of and rate of
progression to end-stage renal disease. Mutated genes of
the primary cilium could provide an approach to the clas-
sification of at least an important subset of RCDs and,
more significant, may allow targeted therapies to be de-
veloped in the future.
NOMENCLATURE AND TERMINOLOGY
Before proceeding with a review of the classification
systems for RCD/CAKUT, it would be prudent to list the
nomenclature and terminology employed in the remainder
of this article and included in the most recent classifica-
tions cited later. The RCD/CAKUT diseases are compli-
cated enough without introducing communication obsta-
cles. Although laxity in terminology is understandable for
the pioneers in this field, this is not acceptable today, and
it risks creating confusion about important entities, with
resultant inappropriate clinical responses. For purposes of
this article, the terms used and their definitions are pro-
vided in Table 3. They represent a synthesis of definitions
obtained from several reputable sources: The Committee
on Terminology, Nomenclature, and Classification, Section
on Urology, American Academy of Pediatrics,112 and 2 ar-
ticles published by individuals of stature in this field of
investigation.111–113
CLASSIFICATION SYSTEMS
Although there have been numerous classifications pro-
posed, those that strive to be all-inclusive employ similar
general strategies, strategies that continue today. Prevail-
ing notions of pathogenesis and obvious clinical associa-
tions have been closely linked to classification strategies
from the beginning. Most classification systems distin-
guish entities with intrinsic abnormalities, presumed to
result from developmental miscues that occurred early in
the embryologic formation of the kidney and urinary tract,
placing them in a congenital category. The remaining cat-
egories contain acquired lesions that affect a kidney that
previously developed normally. In these categories, cyst
formation as a consequence of external forces, injuries, and
neoplastic events are often included.
One of the earliest forays into the daunting arena of the
classification of cystic kidney disease was by I. N. Dan-

Table 1. Selected Examples of Genes in Which Mutations can Result in Various Congenital Abnormalities of the Kidney
and Urinary Tract (CAKUT) Lesions
CAKUT PAX2 TCF2 EYA1 SIX1 SALL1 GATA3
Dysplasia ⫻ ⫻ ⫻ ⫻ ⫻ ⫻
Agenesis ⫻ ⫻ ⫻
Hypoplasia ⫻ ⫻ ⫻
UPJ obst ⫻ ⫻ ⫻
VU reflux ⫻ ⫻
GCKD ⫻
Syndrome Renal-coloboma MODY5 BOR BOR Townes-Brock HDR
Abbreviations: BOR, branchial-oto-renal syndrome; GCKD, glomerulocystic kidney disease; HDR, hypoparathyroidism, deafness and renal dyspla-
sia; MODY, maturity onset diabetes type 5; UPJ obst, ureteropelvic junction obstruction; VU, vesicoureteral.

Arch Pathol Lab Med—Vol 134, April 2010 Classification of Renal Cystic Diseases and Malformations—Bonsib 559
Figure 8. Diagram of a primary cilium with location of cystoproteins identified (reprinted with permission from the American Society of Ne-
phrology, Hildebrandt F, Zhou W. Nephronophthisis-associated ciliopathies. J Am Soc Nephrol. 2007;18(6):1855–1871). 108 PC-1, polycystin-1;
PC-2, polycystin-2; OFD1, oral facial digital syndrome 1; BBS, Bardet-Biedl syndrome; BB, basal body; Cem, centriole; ER, endoplasmic reticulum;
TJ, tight junction; Des, desmosome; AJ, adherens junction; FAP, focal adhesion plaque.

forth26 and was published in 1888. The Danforth classifi-
cation contained 5 categories separating congenital forms
from those with clinical associations, such as obstruction,
infection, and trauma (Table 4). Danforth26 acknowledged
the rudimentary nature of the current understanding of
these diseases, which handicapped formation of a satis-
factory classification, at the conclusion of his article, when
he wrote, ‘‘I have to express my regret that so much re-
mains to be learned about cystic disease. . . . [I] hope that
in the near future our knowledge will be more definite
and accurate. . . ’’. Although 120 years has elapsed since
his review, regrettably, our understanding remains incom-
plete and, therefore, so does a completely satisfactory clas-
sification.
As the field of pathology evolved, and more disease en-
tities were identified, classifications became lengthier but
not necessarily crafted more effectively. In 1954, White
and Braunstein114 formulated a classification of renal cys-
tology, based on etiologic groupings not too dissimilar to
many more modern formulations (Table 5). The authors
conceded, in the first paragraph of the article, that they
faced challenges, stating ‘‘The pathogenesis and embryo-
logic development of these cystic formations are quite fan-
tastic and appear to the authors as a constant urological

Table 2. Ciliopathies: Molecular, Genetic, and Pathologic Features

Ciliopathy Protein Inheritance Lesion
Autosomal dominant PKD Polycystin 1 AD Cysts within the entire nephron
Autosomal dominant PKD Polycystin 2 AD Cysts within the entire nephron
Autosomal recessive PKD Fibrocystin AR Collecting duct cysts
Meckel-Gruber syndrome MKS proteins 1, 3 AR Cystic dysplasia
Oral-facial-digital syndrome OFD protein X linked Glomerulocystic kidney disease
Bardet-Beidl syndrome BBS proteins 1-8 Digenic Tubulointerstitial nephritis
Von Hippel–Lindau VHL protein AR Clear cell cysts and cancer
Abbreviations: PKD, polycystic kidney disease; AD, autosomal dominant; AR, autosomal recessive.

560 Arch Pathol Lab Med—Vol 134, April 2010 Classification of Renal Cystic Diseases and Malformations—Bonsib
Figure 9. A through D, the Potter and Osathanondh microdissections of congenital cystic kidneys showing the examples of their 4 types based
on cyst location (reprinted with permission from Osathanondh V, Potter EL. Arch Pathol. 1964;77:466–473, 474–484, 484–501, 502–509). 41–44
imponderable’’ and ‘‘The majority of cysts still defy un-
derstanding and therefore accurate grouping.’’ 114 White
and Braunstein114 focused on etiologic factors, as under-
stood at the time, as the common denominator for their
classification. They were some of the first to discuss ge-
netic causes because of the heredofamilial nature of the
polycystic kidney diseases, which can present at any age but
are usually bilateral and are associated with lesions in oth-
er organs. The authors114 also commented that the simple
cortical cyst can be associated with renal neoplasms. Al-
though this association is likely simply a reflection of the
increasing incidence of both lesions with age, the concept
of dysregulated growth for both cyst formation and neo-
plasia in some cystic diseases now has an established sci-
entific basis, although not for the simple cortical cyst.
White and Braunstein114 proclaim in their conclusion
concerning the subject of renal cystology, that ‘‘embryonic
origin has been thoroughly modernized with advanced
embryologic knowledge and a clearer and more compre-
hensive classification has been suggested.’’ Unfortunately,
Arch Pathol Lab Med—Vol 134, April 2010
their classification failed this claim. The pathologic fea-
tures of many of the RCDs that had become clearer by
that time permitted morphologic separation of major cat-
egories, such as renal dysplasias versus the hereditary
polycystic diseases. However, these authors114 lumped
those entities into a single category: 1A polycystic disease.
Conversely, other primary categories contained entities
that are not actually cystic diseases, such as their category
II, obstructive; category IV, vascular; and category V, in-
flammatory and infections. Inclusion of noncystic diseases
in cystic disease classifications is a persistent problem that
continues to plague many classification schema.
Failure to employ the known morphologic differences
that exist between several of the major RCDs, such as
dominant and recessive polycystic kidney disease and re-
nal dysplasia, was prevalent in the early RCD classifica-
tion literature. Another example is provided by the clas-
sification of Stubitz et al.115 In their 1963 study,115 restricted
to pediatric cases, they proposed a classification that em-
ployed age of onset and laterality while excluding major
Classification of Renal Cystic Diseases and Malformations—Bonsib 561
 Table 3.
Acquired renal cystic disease
Cystic kidney
Cystogen
Dysmorphic kidney
Glomerulocystic kidney
Heritable renal cystic disease
Induced renal cystic disease
Medullary sponge kidney
Multicystic kidney
Polycystic kidney
Renal adysplasia
Renal agenesis
Renal aplasia
Renal cyst
Renal cystic disease
Renal dysgenesis
Renal dysplasia
Renal hypoplasia
Renal Cystic Disease (RCD) Nomenclature and Terminology
The spontaneous, idiopathic, bilateral development of multiple cysts in previously noncystic kidneys
A kidney containing 3 or more cysts
An agent capable of inducing renal cyst formation or RCD
A misshapen kidney and calyceal system; implies a congenital lesion without any histologic or etiologic
implications
Glomerular cysts as a dominant finding; glomerulocystic kidney disease is a primary disease; glomerulo-
cystic kidney is a kidney with glomerular cysts but of diverse etiologies
Renal cystic disease in a kindred, in a pattern predicted by Mendelian theory
Renal cystic disease produced by exposure to drugs or chemicals
A usually sporadic, medullary cystic abnormality that is commonly diagnosed by radiology
Multiple cystic lesions, most frequently sporadic; they can be small, segmental, unilateral, or bilateral
A genetically determined cystic lesion of either the autosomal-dominant form or autosomal-recessive
form
Where findings of either combined renal agenesis and renal dysplasia or a hereditary syndrome occur
Absent kidney
An extreme form of dysplasia, in which a nubbin of dysplastic kidney caps a normal or an abnormal
ureter
An enclosed or communicating segment of nephron or duct that is dilated to a diameter of ⱖ200 ␮mol
Morbidity attributable to the presence of renal cysts
Abnormal development of the kidney in size, shape, or structure; forms of renal dysgenesis include dys-
plasia, hypoplasia, aplasia, agenesis, and dysmorphism
Abnormal metanephric differentiation diagnosed histologically; it can be diffuse, segmental, or focal
A small kidney or segment with less than a reference range number of nephrons; dysplastic elements are
not present

secondary causes, such as infectious causes, neoplastic its application. In a practical sense, it would difficult or
causes, and chronic glomerulonephritis (Table 6). Al- impossible to know where nephron cysts reside within
though they proclaimed, ‘‘There is widespread confusion any individual cystic kidney without actually performing
among both clinicians and pathologists concerning the a microdissection on each case, an impossible task. Their
classification of cystic disease,’’ and stated, ‘‘It is only re- classification had an eventual lethal failing—lack of clini-
cently that the true etiology and significance of the uni- cal utility—because of the heterogeneity of some catego-
lateral multicystic disease and polycystic kidney may have ries. For instance, their type III cystic kidney combines
been understood’’; they grouped obvious cases of reces- cases of dominant polycystic kidney disease with renal
sive polycystic kidney disease and multicystic renal dys- dysplasias, a similar flaw afflicting previous classifica-
plasias associated with LUT anomalies into congenital tions.
polycystic kidney diseases in the newborn. Two classifications, both comprehensive and clinically
The first influential classification of RCDs, embraced by
many for several decades, was formulated by Potter and
Osanthanondh in the 1964.41–45 Their classification was the Table 5. The White and Braunstein114 (1954)
first formulation predicated on data derived from a sys- Classification of Renal Cystology
tematic, anatomic analysis (Table 7). Potter and Osatha- I. Congenital or developmental
nondh41–45 performed a series of elegant microdissection A. Polycystic disease
studies of the normal developing kidney and on congen- B. Serous cysts
itally cystic kidneys in which the entire nephron was dis- C. Lymphatic cysts
sected (Figure 9, A through D). They identified 4 patterns II. Obstructive
of cyst localization within the nephron that formed the A. Diverticula
B. Parapelvic
basis for the Potter Classification of 4 types of RCD. C. Hydrocalycosis
Although, in subsequent years, pathologists and clini- III. Neoplastic
cians attempted to place all cystic kidneys into one of the A. Cystadenoma
4 Potter types, Potter46 states in her book Normal and Ab- B. Cystadenocarcinoma
normal Development of the Kidney: ‘‘The majority of cysts C. Angioma
found in children and infants beyond the newborn period D. Dermoid
IV. Vascular
fall outside of the four major categories that result from A. Hemangioma
abnormalities during the formative years.’’ Thus, their B. Aneurysm
classification was not intended to be all-encompassing in C. Embolism
D. Infarction
V. Inflammatory and infectious
Table 4. The Danforth26 (1888) Classification of A. Pyogenic
Renal Cystic Diseases B. Tuberculous
C. Chronic nephritis
Diathetic causes VI. Parasitic
Congenital causes A. Echinococcus
Mechanical obstruction, consequent upon disease of the pel- B. Tinea
vic organs C. Trichina
Traumatic causes Reprinted with permission from 114White EW, Braunstein L. Renal cystic
Pathogenic cysts disease. J Urol. 1954;71(1):17–27. Copyright Elsevier 1954.

562 Arch Pathol Lab Med—Vol 134, April 2010 Classification of Renal Cystic Diseases and Malformations—Bonsib
 Table 6. The Staubutz, Jewett, and Pletman115 (1963)
Classification of Pediatric Cystic Diseases
Group 1: Congenital polycystic kidney disease
In the newborn
In the adult
Group 2: Congenital polycystic kidney in infants and chil-
dren
Group 3: Congenital unilateral multicystic kidney
Group 4: Simple or solitary cysts
Data derived from Staubitz WJ, Jewett TC Jr, Pletman RJ. Renal cystic
disease in childhood. J Urol. 1963;90:8–12.
relevant, were formulated by Kissane,116 in 1966, in the first
edition of Heptinstall’s Pathology of the Kidney and by Elkin
and Bernstein118 in 1969 (Tables 8 and 9). Both the Kis-
sane116 and the Elkin and Bernstein118 classification provide
the basic framework employed in classification scheme of
today. They include expanded categories of the 2 major
genetic polycystic diseases, dominant and recessive poly-
cystic kidney disease and the renal dysplasias, accom-
modating the expanding spectrum of those diseases. Kis-
sane116 also included other CAKUT abnormalities, such as
abnormalities of position, form, and orientation, whereas
Elkin and Bernstein118 added categories of other genetic
disorders complicated by renal cysts, such as the trisomy
syndromes and the tuberous sclerosis complex.
Another example of a comprehensive classification of
RCD/CAKUT, which is so large that it resembles more of
a tabulation of entities than a classification system, was
recently been published by Bisceglia et al113 in their ex-
cellent 2006 review of RCD (Table 10). This classification
represents an expansion on the strategy of Kissane116 and
Elkin and Bernstein,118 employing key groupings of ge-
netic disorders, such as the 2 polycystic kidney diseases,
and entities with similar morphologic findings, such as
metanephric dysgenesis of renal dysplasias, without mix-
ing pathogenetically unrelated entities, such a medullary
sponge kidney with the genetic medullary cystic diseases
and nephronophthisis
Unfortunately, the Elkin and Bernstein,118 and the Bri-
sceglia et al113 formulations suffer from unnecessary ad-
ditional complexity by inclusion of diseases that lack true
cyst formation or maldevelopment as defined in the glos-
sary of terms in Table 3. These include the Elikin and
Table 7. The Potter46 (1964) Classification of Renal
Cystic Diseases of the Newborn
Type I kidney Enlargement of the cortical- and medullary-
collecting ducts of both kidneys; usually
causes death soon after birth.
Type II kidney The ampullae of the collecting ducts are
profoundly altered and incapable of pro-
ducing functioning nephrons; death results
if bilateral.
Type III kidney Cysts are located in collecting duct or any
segment of the nephron; is almost always
bilateral and principally affects adults.
Type IV kidney Cysts are present at birth and produced dur-
ing distention of the terminal portion of
the S-stage nephron because of urethral
obstruction.
Data derived from 46Potter EL. Cystic kidneys: age distribution and ré-
sumé of pathogenesis. In: Normal and Abnormal Development of the
Kidney. Chicago, IL: Year Book Medical Publishers, Inc; 1972:289–295.
Arch Pathol Lab Med—Vol 134, April 2010
Table 8. Kissane116 (1966) Classification of
Congenital Malformations of the Kidney
I. Abnormalities in amount of renal tissue
A. Deficient definitive renal parenchyma
a. Bilateral renal agenesis
b. Unilateral renal agenesis
c. Renal hypoplasia
B. Excess renal tissue (supernumerary kidney)
II. Anomalies of position, form and orientation
A. Renal ectopia
a. Simple
b. Crossed
B. Renal fusion
C. Anomalies of rotation
III. Anomalies of differentiation
A. Renal dysplasia
a. Total
b. Segmental
c. Focal
d. Associated with congenital obstruction
B. Polycystic kidney disease
a. Adult type
b. Infantile type
C. Medullary cystic disease
a. The sponge kidney
b. Uremic medullary cystic disease
D. Simple renal cyst
E. Multilocular renal cyst
F. Miscellaneous cysts of renal origin
a. Retroperitoneal cysts of nephric origin
b. Dysontogenic cysts of nephric origin
i. Renal teratodermoids
ii. Endometrial cysts of the kidney
G. Cysts in renal fossa of other nephric origin
a. Pyelocalyceal cysts
b. Pericalyceal lymphangiectasis
c. Perinephric pseudocysts
Reprinted with permission from 116Kissane JM. Congenital malforma-
tion. In: Heptinstall RH, ed. Pathology of the Kidney. 1st ed. Boston,
MA: Little, Brown & Co; 1966:63–117.
Bernstein118 medullary necrosis, inflammatory and trau-
matic categories, and cystic degeneration of carcinomas,
and the Brisceglia et al113 renal tumors with cystic necrosis
and some pseudocystic diseases, such as pyelocalyceal
cysts and lymphocele. The justification for inclusion of
noncystic entities in a classification of cystic diseases is
that some noncystic lesions produce a space-occupying le-
sion that, when imaged, elicit a cystic disease in the dif-
ferential diagnosis. However, the list of truly cystic dis-
eases is long enough that including noncystic and non-
maldevelopment diseases clutter the process unnecessari-
ly.
As evident in Kissane,116 Elkin and Bernstein,118 and
Brisceglia et al113 classifications, our recognition and cat-
aloguing of RCD/CAKUT lesions has evolved so that
comprehensive classification systems are becoming daunt-
ingly large. There are approaches, however, that can make
this problem more manageable. One approach is to deal
more selectively with subsets of entities as exemplified by
a series of classifications published by Bernstein and col-
leagues118–120 through the years. These more focused clas-
sifications (not shown for economy of space) are useful
when interest is limited to a certain key pathologic vari-
ables or clinical aspects. Examples would include their
1968 classification of renal hypoplasias and dysplasias,48
their 1989 classification of glomerulocystic kidney diseas-
Classification of Renal Cystic Diseases and Malformations—Bonsib 563
 Table 9. The Elkin and Bernstein117 (1969) Table 11. The Liapis and Winyard121 (2006)
Classification of Renal Cystic Diseases Classification of Renal Cystic Disease
I. Renal dysplasia A. Polycystic kidney disease
A. Multicystic kidney 1. Autosomal-dominant polycystic kidney disease
B. Focal and segmental cystic dysplasia Classic ADPKD
C. Multiple cysts associated with lower urinary tract ob- Early onset ADPKD in children
struction 2. Autosomal-recessive polycystic kidney disease
II. Polycystic kidney disease Classic ARPKD in neonates and infants
A. Infantile polycystic disease Medullary duct ectasia in older children with hepatic
1. Polycystic disease of the newborn fibrosis
2. Polycystic disease of childhood 3. Glomerulocystic kidney disease
a. Congenital hepatic fibrosis Familial GCKD
b. Medullary tubular ectasia Renal hypoplasia and UROM mutation
B. Adult polycystic disease Associated with HNFB1 mutations
III. Cortical cysts Hereditary GCKD
A. Trisomy syndromes Associated with ADPKD/ARPKD/TSC
B. Tuberous sclerosis complex Syndromic nonhereditary GCKD
C. Simple cysts Sporadic GCKD
a. Solitary Acquired GCKD
b. Multiple B. Renal medullary cysts
IV. Medullary cysts 1. Nephronophthisis
A. Medullary sponge Nephronophthisis, autosomal recessive
B. Medullary cystic diseases Juvenile nephronophthisis
C. Medullary necrosis NPH1, NPH4
D. Pyelogenic cyst NPH1, NPH5 associated with Senior-Loken syndrome
V. Miscellaneous intrarenal cysts Infantile NPH2
A. Inflammatory 2. Medullary cystic diseases
a. Tuberculosis Autosomal dominant MCKD
b. Calculus disease MCKD associated with hyperuricemia
c. Echinococcus disease 3. Medullary sponge kidney
B. Neoplastic—cystic degeneration of carcinoma C. Cysts in hereditary cancer syndromes
C. Traumatic—intrarenal hematoma 1. von Hippel-Lindau disease
VI. Extraparenchymal cysts 2. Tuberous sclerosis
A. Parapelvic D. Multilocular renal cyst
B. Perinephric E. Localized cystic disease
Reprinted with permission from 117Elkin M, Bernstein J. Cystic diseases F. Simple cortical cysts
of the kidney—radiological and pathological considerations. Clin Ra- G. Acquired (dialysis-induced) cysts
diol. 1969;20(1):65–82. H. Miscellaneous
1. Pyelocaliceal diverticula
2. Perinephric pseudocysts
3. Hygroma renalis
es,118 and their 1993 classification of congenital nephrop- Abbreviations: ADPKD, autosomal dominant polycystic kidney disease;
athies.120 ARPKD, autosomal recessive polycystic kidney disease; GCKD, glom-
erulocystic kidney disease; MCKD, medullary cystic kidney disease;
A second ‘‘divide and conquer’’ approach, especially NPH, nephronophthisis; TSC, tuberous sclerosis complex.
suited to discussions of RCD/CAKUT, uses the textbook
Reproduced with permission from 121Liapis H. Winyard P. Cystic dis-
chapter format. An excellent example of this is the chapter eases and developmental kidney defects. In: Jennette JC, Olson JL,
by Liapis and Winyard,121 appearing in the sixth and most Schwartz MM, Silva FG, eds. Heptinstall’s Pathology of the Kidney, 6th
ed. New York NY; Lippincott Williams & Wilkins; 2007.

Table 10. The Brisceglia, Galliani, Senger, Stallone,

and Sessa (2006) Classification of Renal Cystic
Disease—Abridged
1. Autosomal-dominant polycystic kidney disease
2. Autosomal-recessive polycystic kidney disease
3. Unilateral, localized, segmental cystic disease
4. Solitary and multiple, simple renal cysts
5. Dysplastic kidney
6. Pluricystic kidney of multiple malformation syndromes
7. Juvenile nephronophthisis and medullary cystic disease
8. Medullary sponge kidney
9. Glomerulocystic kidney disease
10. Multilocular renal cysts—cystic nephroma and congeners
11. Renal cysts in hereditary syndromes
12. Renal lymphangioma/peripelvic-peripcalyceal lymphanges-
tasia
13. Pyelocalyceal cyst, parapelvic cyst, perinephric pseudocyst,
lymphocele
14. Acquired renal cystic disease
15. Renal cell carcinomas with cystic change
Reprinted with permission from 113Brisceglia M, Galliani CA, Senger C,
Stallone C, Sessa A. Renal cystic disease: a review. Adv Anat Pathol.
2006;13(1):26–56.
564 Arch Pathol Lab Med—Vol 134, April 2010
recent edition of Heptinstall’s Pathology of the Kidney (Table
11). This beautifully written and illustrated chapter pro-
vides a classification of RCD (see ‘‘Table 16.1’’ in Liapis
and Winyard121) and offers additional tables that display
entities within the differential diagnosis of glomerulocys-
tic kidney disease and the developmental defects within
the CAKUT spectrum and a lengthy tabulation of many
genetic syndromes complicated by CAKUT (see ‘‘Table
26.4,’’ ‘‘Table 26.5,’’ and ‘‘Table 26.6’’ in Liapis and Win-
yard121). In their classification of RCDs, Liapis and Win-
yard121 introduce additional genetic information in the
glomerulocystic disease category and the renal medullary
cyst categories, an approach that will likely expand in fu-
ture formulations by them and others.
The classification I would propose combines the land-
mark strategies of Kissane116 and Elkin and Bernstein,117
and the more detailed formulation of Brisceglia et al113 and
Liapis and Winyard,121 into 4 major categories, with a fifth
miscellaneous category that could include other rare en-
Classification of Renal Cystic Diseases and Malformations—Bonsib
 Table 12. Bonsib (2009) Classification of Renal
Cystic Diseases and Congenital Anomalies of the
Kidney and Urinary Tract
I. Polycystic renal diseases
A. Autosomal-recessive polycystic kidney disease
Classic in neonates and infants
Childhood with hepatic fibrosis
B. Autosomal-dominant polycystic kidney disease
Classic adult form
Early onset childhood form
C. Acquired renal cystic disease
D. Glomerulocystic kidney diseases
A. Familial GCKD
Renal hypoplasia and UROM mutation
Associated with HNFB1 mutations
B. Hereditary GCKD
Associated with ADPKD/ARPKD/TSC
C. Syndromic nonhereditary GCKD
D. Sporadic GCKD
E. Acquired GCKD
II. Congenital anomalies of the kidney and urinary tract
A. Renal agenesis and dysplasia
Agenesis
Sporadic: unilateral or bilateral
Syndromic
Nonsyndromic, multiple malformation syndromes
Renal dysplasias
Sporadic: unilateral or bilateral
Syndromic
Nonsyndromic, multiple malformation syndromes
Hereditary adysplasia
B. Renal hypoplasias
Simple hypoplasia: unilateral or bilateral
Oligomeganephronic hypoplasia
Reduced nephron generations (‘‘cortical hypoplasia’’)
Reduced nephron numbers (premature and low birth
weight risk of hypertension)
C. Abnormalities in form, position, and number
Rotation anomaly
Renal ectopias
Renal fusions
Supernumerary kidney
In combination with A, B, or D
D. Ureteral and urethral abnormalities
Ureteropelvic junction obstruction
Ureteral duplication/bifid ureter
Vesicoureteral reflux
Primary megaureter
Ureteral ectopia
Posterior urethral valves
In combination with A, B, or C
III. Tubulointerstitial syndromes ⫾cysts
A. Renal tubular dysgenesis
Autosomal recessive
Secondary twin-twin transfusion
ACE inhibitor
B. Nephronophthisis: types 1–6
C. Medullary cystic diseases:
Type 1
Type 2/familial juvenile hyperuricemic nephropathy
D. Bardet-Biedel syndromes, types 1–12
IV. Cystic neoplasms and neoplastic cysts
A. Cystic nephroma
B. Cystic partially differentiated nephroblastoma
C. Mixed epithelial and stromal tumor
D. Multilocular cystic renal cell carcinoma
E. Tubulocystic renal cell carcinoma
F. Von Hippel–Lindau disease
G. Lymphangioma/hygroma renalis
V. Miscellaneous cysts
A. Simple cortical cysts
Arch Pathol Lab Med—Vol 134, April 2010
Table 12. Continued
B. Medullary sponge kidney
C. Localized renal cystic disease
Abbreviations: ACE, angiotensin converting enzyme; ADPKD, autoso-
mal dominant polycystic kidney disease; ARPKD, autosomal recessive
polycystic kidney disease; GCKD, glomerulocystic kidney disease; TSC,
tuberous sclerosis complex.
tities not listed. The first category groups the major clinical
forms of the genetic polycystic kidney diseases and glom-
erulocystic kidney diseases with acquired RCD into a
polycystic renal disease category (Table 12). Although ge-
netic and nongenetic diseases are grouped in this category,
these entities have in common the initial normal nephron
formation complicated by diffuse cystic alterations when
fully expressed.
The diverse entities characterized by the metanephric
dysgenesis and LUT abnormalities of CAKUT are clus-
tered together into the second category that accommo-
dates their occurrence in sporadic, syndromic, and mul-
tiple malformation syndromes, while allowing for combi-
nations of renal and LUT defects that can affect the same
kidney. This grouping accounts for the major possibilities
but does not attempt to list the numerous syndromic en-
tities that it includes because of their large number and
because many syndromes would fall in multiple categories
of this grouping.
The third category includes entities that are predomi-
nately interstitial diseases; some of the entities may have
coexistent cysts with renal tubular dysgenesis, the major
exception. The various forms of nephronophthisis and
medullary cystic diseases are clustered together, but med-
ullary sponge kidney is kept separate in a final miscella-
neous category. The fourth major category is cystic renal
neoplasms and neoplastic cysts. Only intrinsically cystic
renal neoplasms are listed. Their number has expanded
greatly in the past few years. Neoplasms with cystic de-
generation and necrosis are not included in this grouping
because this finding is not only common in renal neo-
plasms but also occurs in nearly every type of renal tumor.
The many noncystic diseases that clutter previously men-
tioned formulations are excluded.
CONCLUSION
In the 21st century, the genetic/molecular-based pos-
tulates in the pathogenesis of the complex RCD/CAKUT
family implicate mutated master genes and modifying
genes crucial in renal development and in cell physiology.
This insight has minimized the importance of anatomic-
based postulates that relate urinary tract obstruction to
developmental misadventures by placing them within a
larger paradigm of sequential intrinsic genetic and molec-
ular defects that culminate in the malformed kidney and
LUT and in progressive lesions developing in normally
formed kidneys. With the burst of information on mole-
cules that reside in the primary cilium of renal tubules,
there are now pathogenetic links among morphologically
and genetically distinct entities and among select mixed
cystic and neoplastic entities; such exciting associations
would have seemed implausible not too many years ago.
These advances may ultimately explain not only the
pathogenesis of most cystic renal diseases, whether con-
genital, acquired, or neoplastic, but also may, when fully
Classification of Renal Cystic Diseases and Malformations—Bonsib 565
delineated, provide a molecular basis for targeted thera-
pies to prevent or ameliorate some diseases. Despite im-
pressive scientific advances, it remains difficult to develop
a completely satisfactory classification of the diverse array
of anomalies that affect the urinary tract. Although clas-
sifications incorporating genetic and molecular data are
now emerging, there are complicating factors that are dif-
ficult to accommodate. These include the polygenetic na-
ture of some disorders, the accumulation of multiple ge-
netic defects that can affect susceptibility and influence the
nature of the malformation expressed, and different types
of mutations in a single master gene that can clearly alter
the phenotypic expression.
Contributing to this challenge is that a classification
suitable for one discipline, such as pathology, may not be
optimized to serve the interests of another discipline.
When pathologists encounter an anatomic abnormality, we
strive to place it within a diagnostic category that will
satisfy and initiate the proper clinical responses. Con-
versely, formulating a purely molecular-based or mecha-
nistic classification can serve the interests of a basic re-
searcher striving to develop targeted therapies, for in-
stance, to affect the function of a mutated ciliary protein,
but can fail to meet the diagnostic needs of the patholo-
gist.
The ideal classification scheme would account for mor-
phologic features and their clinical importance, with log-
ical links to pathogenesis, while providing a basis for ther-
apeutic interventions. Although such a comprehensive
classification remains an elusive target, its general outline
is becoming clearer but remains a lofty goal yet to be
achieved. The classification listed in Table 12 strives to
meet the first 2 objectives cited above, but likely falls short
in some respects, and with the pace of discovery in RCD/
CAKUT, it will soon be obsolete. In the final analysis, our
infatuation with these diseases derives from the impossi-
ble challenge their complexity creates. This is nicely cap-
tured in the quote by Potter when she stated in 1972, ‘‘The
more complicated an organ in its development, the more
subject it is to maldevelopment, and in this respect the
kidney outranks most other organs.’’ 46
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