Nephrol Dial Transplant (1999) 14: 2234–2244

Nephrology
Dialysis
Continuing Nephrological Education (CNE) Transplantation

The spectrum of renal cysts in adulthood—discussion of eight cases*

Hartmut P. H. Neumann

Department of Nephrology, Albert-Ludwigs-University, Freiburg i. B., Germany

Key words: autosomal dominant polycystic kidney dis- Table 1. Evaluation of adults with renal cysts
ease; autosomal recessive polycystic kidney disease;
nephronophthisis; autosomal dominant medullary 1. What can you see? US, CT, MRI
cystic kidney disease; echinococcosis of the kidney; 2. What can you ask? Age, sex, CRF, Tx, BP, family
3. Laboratory tests: Serum, urine etc.
medullary sponge kidney; tuberous sclerosis complex; 4. Clinical evaluation: BP, liver, eyes, CNS, skin
Von Hippel-Lindau disease 5. Biopsy: Kidney, liver
6. Molecular genetics: Candidate genes

Introduction radiological findings in eight patients ( Figure 1). The

reader may first wish to consider the differential dia-
The diagnosis of cystic renal disease in adults can be gnosis based on the radiographic images, before read-
challenging. In this paper, the spectrum of cystic renal ing the associated text. Important points in the clinical
disease will be illustrated by focusing on the key

Case 2

Case 1

Case 3

Correspondence and offprint requests to: Prof. Dr med. Hartmut

P. H. Neumann, Department of Nephrology, Albert-Ludwigs- Case 4
University, Hugstetter Strasse 55, D-79106 Freiburg i. B., Germany.
* Invited Guest Lecture at the ERA-EDTA Congress, Rimini, 1998. Fig. 1. Radiological findings in eight patients (see over).

© 1999 European Renal Association–European Dialysis and Transplant Association

Renal cysts in adulthood 2235

Case 5

Case 6

Fig. 2. Chromosome 7 and examples of intraexonic mutations.

Case 7
or family history that contribute to the correct dia-
gnosis will be emphasized, and the current molecular
understanding of the disease will be summarized.
The six crucial pieces of information and questions
which can help to find the diagnosis of cystic renal
disease are given in Table 1.
The majority of cystic renal diseases are inherited
and associated with predisposing mutations of suscepti-
bility genes. The nomenclature of localization of the
genes is based on chromosomal bands obtained by
Giemsa staining. Figure 2 shows chromosome 7 with
short (p) and long (q) arms and numbers of bands
with more precise subbands (middle and left). Typi-
cal mutation types of intra-exonic mutations (mis-
Case 8
2236 H. P. H. Neumann

sense, nonsense, frame shift) are shown below the encoding a protein of 4304 AA named polycystin 1.
chromosome. PKD1 is mutated in about 85% of ADPKD. The
PKD2 gene is localized on the long arm of chromosome
4 (4q13-23) with 15 exons encoding a protein of 968
Case 1 AA called polycystin 2. Additional PKD genes have
not yet been identified [2,3].
Figure 3 shows the contrast-enhanced computed tomo- There are four important consequences of knowing
graphy (CT ) scan of a 36-year-old male with normal the underlying PKD1 or PKD2 mutation in a patient
serum creatinine. Both kidneys are enlarged, contain with ADPKD:
abundant cysts, have irregular surface and seem to 1. to make the diagnosis if family history and screen-
have reduced functioning parenchyma indicated by ing investigations are negative,
contrast-enhanced tissue. In addition, the liver shows 2. to differentiate ADPKD 1 and ADPKD 2 since
several cysts. It is important to know whether there is ESRF occurs roughly 15 years later in type 2,
a positive family history of polycystic kidney disease, 3. to exclude a carrier status in a relative who is
consistent with a diagnosis of autosomal dominant willing to serve as a donor for kidney transplanta-
polycystic kidney disease (ADPKD) ( Figure 4). In tion and
ADPKD, extrarenal lesions can include cysts in the 4. for prenatal diagnosis.
liver, pancreas or spleen, CNS aneurysms, heart valve
insufficiency, hernia and diverticula of the colon Due to the gene structure, however, mutation ana-
(Figure 5) [1]. There are at least three susceptibility lysis is still time intensive and not available for clinical
genes for ADPKD. The PKD1 gene is localized on the practice. Linkage analysis which provides only the
short arm of chromosome 16 (16p13) with 46 exons results of likelihood have been used (Figure 4 demon-
strating linkage of allele C with the disease; bold
symbols) [4]. Mutations reported from limited series
of PKD1 and PKD2 patients have shown mutations
of different types in both genes.
Molecular biological and biochemical research has
yielded interesting aspects for understanding the
macro- and micro-pathological features of prolifera-
tion, fluid accumulation and matrix alteration, but
currently no proposals for prevention have emerged
from such pathophysiological analysis [1].

Fig. 3. CT scan of case 1.

Fig. 4. Family tree of case 1.

Fig. 6. CT scan of case 2.

Fig. 5. Extrarenal lesions in the Freiburg ADPKD-register (n=298)

and angiography of a cerebral aneurysm in ADPKD. Fig. 7. Family tree of case 2.
Renal cysts in adulthood 2237

Case 2

This CT showed abundant cysts scattered all over the

renal parenchyma, and the 18-year-old patient with CRF
was considered to have ADPKD (Figure 6). The young
age of the patient, and the family history (only a sister
had PKD) were atypical, leading to the possible dia-
gnosis of ARPKD (Figure 7). In such a situation further
investigations should be performed including renal sono-
graphy of the parents, paternity test and liver biopsy of
the patient (Figure 8). Liver fibrosis is a classical feature
of ARPKD [5]. The gene has been mapped on chromo-
some 6p21-cen, but is not identified [6 ]. The diagnosis
has important implications, since offspring have a very
Fig. 8. Liver biopsy of case 2. low risk of developing the disease. Interestingly, this
patient subsequently required surgery for multiple cereb-
ral aneurysms (Figure 9), lesions usually associated with
ADPKD [7]. ARPKD is most frequently diagnosed in
very young children based on clinical findings.

Case 3

This CT of a 17-year-old male patient showed bilateral

renal cysts which were localized in the cortico-
medullary boundary area, consistent with juvenile
nephronophthisis (NPH ) ( Figure 10). Patients develop
symptoms of renal failure in the first and second
decade (serum creatinine 2.4 mg/dl in the given case).
Family information, particularly renal ultrasound
findings of the parents, are important. The family
history in this disease can be consistent with either
autosomal recessive ( Figure 11) or autosomal domin-
ant (see later) inheritance.

Fig. 9. Cerebral aneurysm in ADPKD (case 2).

Fig. 11. Family tree of case 3.

Fig. 10. CT scan of case 3.

2238 H. P. H. Neumann

a b
Fig. 12. Renal biopsy results of case 3.

Fig. 13. Analysis of the NPHP 1 gene (20 exons) on 2p13 (taken from ref. 9).
Renal cysts in adulthood 2239

a b

Fig. 14. Ophthalmological investigation of case 3.

ings and in absence of ocular changes, the diagnosis

juvenile NPH can be established [8].
Mutations predisposing for NPH have been identi-
fied in the NPHP1 gene which is localized on the short
arm of chromosome 2 (2p13) [9]. An example is shown
in Figure 13. The father has hemizygous deletion of a
gene, the mother a TA mutation causing a stop
codon, and both affected chromosomes (alleles) have
been inherited by the child. The autosomal recessive
form of this disease is important, since the offspring
of affected individuals are unlikely to develop nephro-
nophthisis. The protein encoded by the NPHP1 gene
is called nephrocystin.
Every patient in whom the diagnosis of NPH
is suspected should undergo ophthalmological in-
Fig. 15. Histology of NPH/ADMCKD. vestigation (Figure 14) [10,11]. Retinitis pigmentosa
associated with NPH constitutes the Senior Loken
syndrome (SLS ). Retinoscopy reveals pigmented spots
( Figure 14a). Visual fields can be bilaterally reduced
to the central area and a sickle-like region in the
periphery (Figure 14b). Night blindness may be caused
by reduced rod function. The susceptibility gene for
SLS remains still unknown.
NPH and SLS can occur as isolated and thus
seemingly sporadic cases, possibly explained by the
Fig. 16. Family tree of ADMCKD (see discussion of case 3). small size of the family. Increasing availability of
genetic laboratories and research progress are expected
Both histological findings and molecular genetic to permit classification of most patients within the
testing can be crucial for establishing the diagnosis. near future.
Classical findings are low number of nephrons, All findings including histology (Figure 15) of NPH
shrunken parenchyma, corticomedullary cysts, signs can be present also in patients whose family pedigree is
of inflammation and fibrosis in the interstitium consistent with autosomal dominant inheritance of the
(Figure 12a and b). High power magnification shows disease, as shown in Figure 16. Such a patient become
alterations of the tubular basement membrane with mostly symptomatic at the end of the 3rd decade and
splitting and peritubular sclerosis. Based on such find- can in fact not be distinguished from NPH except by
2240 H. P. H. Neumann

b
a

Fig. 17. CT scans of case 4.

c

a. Scolices b. Hookes
Fig. 18. Microscopy of cyst fluid.
Renal cysts in adulthood 2241

pedigree analysis. This entity is autosomal dominant

medullary cystic kidney disease (ADMCKD) [12]. The
susceptibility gene has not been mapped or identified yet.

Case 4
This CT of a 27-year-old female patient shows a single
cyst of 10–15 cm in diameter ( Figure 17). Other renal
findings were normal—as can be expected in unilateral
renal disease. Most of such cysts are assumed to be
simple cysts and do not require therapy. Hypertension
was present in this patient. Blood pressure values may
return to the normal range once the cyst has been
removed by puncture (or other means). In cases of
Fig. 19. CT scan of case 5.
unilateral cystic disease, echinococcosis should be con-
sidered as the underlying disease, as was present in
this patient. Echinococcal cysts often exhibit calcifica-
tions in the membrane and inhomogeneous internal
structures, although these were not present in this case.
It is necessary to evaluate the cyst fluid ( Figure 18a
and b) by microscopy immediately after it has been
obtained [13].

Case 5

These CT findings of a 33-year-old male patient had

initially been interpreted as polycystic kidney disease
(Figure 19). The patient was admitted with impaired
renal function (serum creatinine 2.2 mg/dl ). Renal
tubular acidosis and the disseminated microcalci- Fig. 20. CT scan of case 6.
fication are consistent with the diagnosis of medullary
sponge kidney. This disease causes deceleration of
urine flow in i.v. pyelography or magnetic resonance
angiography. The etiology remains to be clarified. The
family history was negative [14].

Case 6

The numerous bilateral spheroid lesions in the CT of

a 36-year-old female patient are not cysts (Figure 20).
Radiological density reveals negative Hounsfield units
which is consistent with fat tissue. These lesions are
multiple angiomyolipomas (AML) [15]. Patients with
AML, however, can have in addition renal cysts as
shown in Figure 21. Such lesions are highly suggestive
of the tuberous sclerosis complex (TSC ), whereas
isolated AML mainly occur as sporadic lesions [16 ].
Renal manifestations are essential for the diagnosis
Fig. 21. CT scan showing bilateral renal cysts and angiomyolipoma
of TSC. The spectrum of involved organs is broad in a TSC patient.
and variable. Classical features are facial angio-
fibroma, subependymal calcifications, retinophacoma
(Mulberry tumour), and periungual fibromas encoding the protein hamartin, the TSC2 gene 1784
(Figure 22) [17,18]. amino acids encoding the protein tuberin). A limited
Mutations in two genes, the TSC1 gene, localized series of TSC2 patients showed mutations of different
on chromosome 9 (9q34) [19], and the TSC2 gene on types scattered over many of the 41 exons of the TSC2
chromosome 16 (16p13) [20] can independently lead gene [21]. Possibly because of a high spontaneous
to the syndrome without phenotypic differences. Both mutation rate, the TSC patients, family history is
TSC genes are very large ( TSC1 1164 amino acids frequently negative in TSC patients.
2242 H. P. H. Neumann

Fig. 22. Classic extrarenal features of TSC.

and 24) [22]. Similarly to TSC, cysts of different size

occur, and renal function is not impaired. Again sim-
ilarly to TSC, multiple solid lesions are typically seen.
In contrast to TSC, there is no fatty tissue component
in VHL, and the tumours are renal clear cell carcin-
omas (RCC ). Most of the VHL-associated RCCs have
a marked fibrous ‘capsula’, and a cystic growth pattern
( Figure 25) which can in some cases be recognized
based on their radiologic pattern [23].
VHL is an autosomal dominant disorder, and VHL-
associated lesions occur in many organs. Most can be
treated effectively, if the patients are recognized in
time. The VHL gene, localized on the short arm of
chromosome 3 (3p25-26), was identified through posi-
Fig. 23. MRI scan of case 7 with bilateral VHL-associated renal cell tional cloning and subsequently identified [24]. The
carcinomas ( T ) and cysts (C ). VHL gene contains three exons, and more than 200
distinct mutations spread all over the three exons have
Case 7 been reported [25–27]. Analysis for germline mutations
should be performed in all subjects with candidate
This MRI with i.v. Gadolinium contrast of a 38-year- lesions of the kidney. This includes multiple and bi-
old male patient showed bilateral renal cysts (C ) and lateral RCC with or without uni- or bilateral renal
bilateral tumours (T ). Together with TSC, the second cysts in predominantly younger patients (<50 years)
important cystic and tumorous disease of the kidneys with or without extrarenal VHL-associated lesions with
is Von Hippel-Lindau syndrome ( VHL) ( Figures 23 or without family history.
Renal cysts in adulthood 2243

Fig. 26. MRI scan of case 8.

Fig. 24. Features of Von Hippel-hindau syndrome. Note the various

expressions of the disease with symptomatic (solid) and asympto- Fig. 27. Oncocytoma from Histological typing of kidney tumours,
matic (hatched symbols); lesions of the eye (upper left), CNS (upper Mostofi FK, Davis CJ Jr (eds), WHO/Springer, 1998.
right), kidney ( lower left), and pancreas (central ).

( Figure 27) [28]. Thus, some patients with cystic and

tumorous renal lesions may be difficult to classify.
Such patients may lead to the identification of new
syndromes and the identification of novel tumour
predisposition genes [29].
Acknowledgements. The author appreciates the editorial assistance
of Elizabeth Petoi Henske, MD, Philadelphia.

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