Evidence-Based Clinical Practice Guidelines for Polycystic Kidney
Disease 2014

July 27th, 2015

Authors
Clinical Guidelines for Polycystic Kidney Disease 2014 Advisory Committee
Committee chairman
Shigeo Horie
Committee member
Toshio Mochizuki
Satoru Muto
Kazushige Hanaoka

Juntendo University
Tokyo Women's Medical University
Teikyo University
Jikei University School of Medicine

Yoshimitsu Fukushima
Ichiei Narita
Kikuo Nutahara

Shinshu University
Niigata University
Kyorin University

Ken Tsuchiya
Kazuhiko Tsuruya
Koichi Kamura
Saori Nishio
Tatsuya Suwabe
Yoshifumi Ubara
Eiji Ishimura

Tokyo Women's Medical University
Kyushu University
Chiba-East Hospital
Hokkaido University
Toranomon Hospital
Toranomon Hospital
Osaka City University

Koichi Nakanishi
Collaborator
Keiichi Furukawa

Wakayama Medical University
St. Luke's International Hospital

Chief Chairman of the Clinical Practice Guidelines for Progressive Kidney
Diseases
Kenjiro Kimura
St. Marianna University
Leader of the Research for Progressive Kidney Diseases of the Ministry of
Health, Labour and Welfare
Seiichi Matsuo
Nagoya University

Cooperative Medical Society
The Japanese Urological Association
The Japanese Society for Dialysis Therapy
The Japanese Society for Pediatric nephrology

The Japan Society of Human Genetics
The Japan Neurosurgical society
The Japanese Association for Infectious disease
The Japan Society of Hepatology
The Japanese Society of Interventional Radiology
The Japan Society for Transplantation

Preface
1. Origins of the Guidelines
Autosomal dominant polycystic kidney disease (ADPKD) is the most common
hereditary kidney disease, with approximately half of the patients
experiencing end-stage renal disease by age 60. Bilateral cysts progressively
proliferate and enlarge, even as complications such as hypertension, hepatic
cysts, and intracranial aneurysms lead to more lethal events such as cyst
infections and ruptured intracranial aneurysms prior to end-stage renal
disease. Early-stage diagnosis and intervention are recognized as being vital.
Autosomal recessive polycystic kidney disease (ARPKD) is estimated to occurin 1 in 10,000~40,000 births, with symptoms present neonatally. Due to early
detection and management as well as improvements in end-stage renal
disease treatment, long-term survival is currently possible in patients otherthan neonates with severe pulmonary hypoplasia.
In Japan, Clinical Guidelines for Polycystic Kidney Disease in 1995 waspublished by the Progressive Renal Diseases Research, Research on
intractable disease, from the Ministry of Health, Labour and Welfare of Japan,
followed by a 2002 revision, the ADPKD Guidelines (second edition). Bothserve as protocols for daily treatment of ADPKD in Japan. However,subsequent advancements in PKD expertise led to the 2010 Clinical
Guidelines for Polycystic Kidney Disease, which were aimed at physiciansand other health practitioners. These events provided the backdrop for the2014 Clinical Practice Guidelines for Polycystic Kidney Disease, which weredrawn up to answer the questions of physicians specializing in renal care.
2. The Intended Purpose, Anticipated Users, and Predicted Social
Significance of the Guidelines
The 2014 Clinical Practice Guidelines for Polycystic Kidney Disease weredrawn up to assist renal care specialists with daily diagnosis and treatmentof ADPKD and ARPKD. These Guidelines offer descriptive and exhaustive
coverage of PKD diagnosis and definition, epidemiology, and screening.
Moreover, routine treatment by renal specialists is addressed through clinicalquestions (CQs) and responses. Each response is accompanied by arecommendation grade reflecting the level of evidence the response embodies.
Our objective is to convey standardized care through specific responses torenal specialists’ questions, thereby supporting these professionals as they
face daily clinical decisions. We anticipate that general practitioners using
the current Guidelines along with the 2010 Clinical Guidelines for Polycystic
Kidney Disease will deepen their understanding of PKD and liaise moresmoothly with renal specialists. The Guidelines should also enhance patients’
understanding of the disease and serve as a reference in answering theirquestions concerning current treatments.
Professional literature and international conferences afford renal specialists
fragmented bits of information about the field, while the specialists are
expected to have an integrated understanding of the expertise level andmedical environment in Japan, and to provide optimal care for each patient.
The current Guidelines incorporate the wisdom of experienced specialists,
offering not only evidence, but also practical and standardized views
communicated to readers through the CQ responses. However, the degree towhich information in these Guidelines may be applied to individual patientsrequires the judgment of each specialist. Patients do not expect uniform, rigid
treatment. Indeed, these Guidelines are not intended to restrict thetreatment options available to renal specialists, but rather to facilitate
treatment based on their own flexible insights and expert understanding. We
must also clarify that the Guidelines are not designed for use in resolving
medical practice disputes or as evaluation criteria in malpractice lawsuits.
3. Patients within the Scope of the Guidelines
These Guidelines apply to any and all PKD patients. Sections 1~4 address
ADPKD, whereas Sections 5~9 cover ARPKD. The Guidelines provide an
outline and definition (Sections 1 and 5) for each of the two diseases, alongwith information on diagnosis (Sections 2 and 6), epidemiology (Sections 3
and 7), and treatment (Sections 4 and 9). Each section applies to patients
regardless of gender or age. However, the Guidelines do not generally takepregnancy into account.
4. Preparation procedure
Guidelines on four diseases (IgA nephropathy, nephrotic syndrome, RPGN,
and polycystic kidney disease [PKD]) were created simultaneously by aresearch group on progressive kidney disorders (led by Seiichi Matsuo)
funded by the Ministry of Health, Labour, and Welfare’s research project forovercoming intractable diseases. All of these guidelines have the same
chapter structure. PKD is a genetic disease, so Shinshu University professor
Yoshimitsu Fukushima assisted by serving on the drafting committee as arepresentative of the Japan Society of Human Genetics. Keiichi Furukawa of
the Division of Infectious Diseases in the Department of Internal Medicine at
St. Luke’s International Hospital provided assistance regarding cyst
infections. We would like to take this opportunity to thank these twophysicians for their generous help.
Seventeen CQ were created based on questions the committee members
had from actual clinical practice. These guidelines were completed owing to
the dedication and effort of the physicians who served on the PKD working
group. We thank them again for their efforts. (shown separately: 2014evidence-based PKD clinical guidelines committee)
5. Contents of the guideline
Guidelines on four diseases (IgA nephropathy, nephrotic syndrome, RPGN,
and PKD) with the same format and structure were drafted by a researchgroup on progressive kidney disorders (led by Seiichi Matsuo) funded by the
Ministry of Health, Labour, and Welfare’s research project for overcoming
intractable diseases. As described earlier, the first half (chapters 1–4)
addresses ADPKD and the second half (chapters 5–8) addresses ARPKD.
6. Evidence Levels and Recommendation Grades
Evidence was classified into six levels based on the study design, and wasarranged roughly from the most reliable study type (Level 1) to the least
reliable (Level 6). These levels do not necessarily represent rigorous scientificstandards; they are intended for use as a convenient reference for quickly
assessing the significance of various clinical data during the physician’s
decision-making process.
[Evidence Levels]
Level 1: Systematic review/meta-analysis
Level 2: At least one randomized controlled trial (RCT)
Level 3: A non-RCT
Level 4: An analytical epidemiologic study (cohort study or case-control
study) or a single-arm intervention study (no controls)
Level 5: A descriptive study (case report or case series)

Level 6: Opinion of an expert committee or an individual expert, which is
not based on patient data
However, for a systematic review/meta-analysis, the evidence level was
decided based on the designs of the underlying studies. If the underlying
study designs were mixed, the lowest level underlying study was used todetermine the overall evidence level. For example, a meta-analysis of cohort
studies would be Level 4, but the same Level 4 would also be assigned to ameta-analysis including both RCTs and cohort studies.
In addition, a decision based on committee consensus was that all subanalyses and post-hoc analyses of RCTs should be categorized at evidence
Level 4. Accordingly, it was decided that the evidence level of findings
representing the primary endpoints of an RCT would be Level 2, but theevidence level of findings determined via a sub analysis or post-hoc analysisof that RCT would be Level 4.
When a statement related to a certain treatment was presented,
consideration was given to the level of the evidence serving as the basis ofthat statement, and a recommendation grade was assigned as outlined below:[Recommendation Grades]
Grade A: Strongly recommended because the scientific basis is strong.
Grade B: Recommended because there is some scientific basis.
Grade C1: Recommended despite having only a weak scientific basis
Grade C2: Not recommended because there is only a weak scientific basis
Grade D: Not recommended because scientific evidence shows thetreatment to be ineffective or harmful.
If we found only a weak scientific basis for a certain statement concerning atreatment, the members of the committee discussed the matter and decided
on C1 or C2 for the recommendation grade. Thus, discrimination between C1and C2 statements was based on expert consensus.
7.

Issues on the preparation of this guideline(1) Paucity of evidence
Little evidence exists for PKD, and only few large clinical studies have been
performed globally, apart from a small number in the United States andEurope. For the most part, little evidence substantiates the recommendationsin the CQ. In particular, almost no evidence comes from Japan. Whether the
results of clinical research from the West can be applied as is to Japan is aquestion that deserves careful consideration. In creating these guidelines, westrove to ensure that they would not deviate greatly from the clinical practicein Japan.
(2) Issues on medical resources
In general, the clinical guideline must consider medical resources associatedwith recommended statements. However, the current guideline did not
discuss issues on medical cost; thus medical financial problems did not affectthe contents of our guideline. In the next guideline, this point may be included.
(3) Guideline reflecting the opinions of patients
During the preparation processes of the clinical guideline, we needed to
introduce the opinions of patients. However, this time, we unfortunately could
not include the opinions of patients. We should refer to the opinions ofpatients in the next guideline, particularly in the case that the guideline isused for patients.
8. Financial sources and conflict of interest
The funds used in creating the guidelines were provided by a research groupon progressive kidney disorders funded by the Ministry of Health, Labour,and Welfare’s research project for overcoming intractable diseases. These
funds were used to pay for transportation to and from meetings, to rent spacefor meetings, and for box lunches and snacks. The committee members
received no compensation. Everyone involved in creating the guidelines(including referees) submitted conflict-of-interest statements based onacademic society rules, which are managed by JSN. Opinions were soughtfrom multiple referees and related academic societies to prevent theguidelines from being influenced by any conflicts of interest. Drafts wereshown to the society members, and revisions were made based on theiropinions (public comments).
9. Publication and Future Revisions
The Guidelines were published in the Japanese-language journal of theJapanese Society of Nephrology and concurrently released as a Japaneselanguage book (by Tokyo Igakusha, Tokyo). The Guidelines were also
uploaded to the homepage of the Japanese Society of Nephrology.
At present, CKD-related evidence is being rapidly accumulated, and this new
evidence will necessitate the preparation of an updated version of theGuidelines in 3-5 years. A certain degree of turnover in the membership of
the revision committee will be required in order to ensure the impartiality of
the Guidelines.

Content
I. Disease concept and definition of Autosomal Dominant Polycystic Kidney
Disease (ADPKD)
II. Diagnosis of ADPKD: Symptoms and laboratory findings
1. Algorithm
2. Diagnostic criteria
3. Comparison of diagnostic criteria between Japan and other countries
4. Testing
5. Diagnostic imaging
6. Differential diagnosis
7. Genetic diagnosis
8. Diagnostic imaging for infants and young adults
9. Initial symptoms
10. Renal symptoms
III. ADPKD: Epidemiology and prognosis (prevalence, incidence, renal
prognosis, and vital prognosis)
IV. ADPKD: Treatment and management of complications
1. Treatment to control the development of ADPKD
1) Antihypertensive treatment
CQ 1. Is antihypertensive treatment recommended as a means of slowing
the deterioration of renal function in patients with ADPKD complicatedwith hypertension?
2) Increased water intake
CQ 2. Does increased water intake have a beneficial effect in ADPKD
patients?
3) Dietary protein restriction
CQ 3. Should we recommend dietary protein restriction to inhibit
progression of renal dysfunction in patients with ADPKD?
4) Tolvaptan
CQ 4. Is tolvaptan recommended for treatment of ADPKD?
5) Aspiration of renal cysts
CQ 5. Aspiration of renal cysts in patients with ADPKD
2. Complications and their managements
1) Cerebral aneurysm and subarachnoid hemorrhage
CQ 6：Does screening of intracranial aneurysms improve the prognosis of

ADPKD patients?
CQ 7. Is treatment recommended for cerebral aneurysms detected during
screening?
2) Cyst infection
CQ 8. Are newer quinolones recommended for the treatment of cyst
infection in ADPKD?
3) Cystic hemorrhage/hematuria
CQ 9. Should we recommend tranexamic acid in the treatment of cystic
hemorrhage in ADPKD?
4) Urolithiasis
CQ 10. Are there any effective pharmacological preventive therapies for
urolithiasis associated with ADPKD?
5) Cardiac complications (including valvular disease)
CQ 11. Is transthoracic echocardiography (TTE) for screening of valvulardisease recommended to improve the mortality of ADPKD patients?
6) The specific treatment of complications
CQ 12. Should ADPKD patients with ESRD undergo renal transarterial
embolization to reduce enlarged kidneys?
CQ 13. Should ADPKD patients with ESRD undergo hepatictransarterial embolization to reduce hepatomegaly?
3. The treatment of ESRD
1) Peritoneal dialysis
CQ 14. Is peritoneal dialysis recommended for patients with ADPKD?
2) Renal transplantation
CQ 15. Is unilateral or bilateral nephrectomy recommended during
ADPKD kidney transplantation?
V. Autosomal Recessive Polycystic Kidney Disease (ARPKD): Disease
concept/definition (etiology and pathophysiological mechanism)
VI. ARPKD: Diagnosis (symptomatology, symptom, and examination
findings)
VII. ARPKD: Epidemiology and prognosis (incidence, prevalence, andtreatment outcome)1. ARPKD: Prenatal diagnosis
2. ARPKD: Treatment and management of complications (treatment ofdisease including adjunct therapy, supportive therapy, and prophylaxis)

CQ 16. Is peritoneal dialysis recommended for the improvement of thevital prognosis and quality of life (QOL) of patients with ARPKD?
CQ 17. Is solitary or simultaneous transplantation of the liver andkidney recommended for the improvement of the vital prognosis and
QOL of patients with ARPKD?
CQ 18. Is antihypertensive therapy recommended for the improvement of
the vital prognosis of patients with ARPKD?

1. Disease concept and definition of ADPKD
ADPKD is the most common hereditary cystic kidney disease. ADPKD is
characterized by the progressive development of fluid-filled cysts derived
from renal tubular epithelial cells and the development of disorders inseveral organs. Bilateral renal cysts enlarge progressively, graduallycompromising renal function, and finally, end-stage renal disease (ESRD)
requiring renal replacement therapy occurs in approximately 50% of
patients by the age of 60 years.
The pattern of transmission in ADPKD is autosomal dominant inheritance.
A male or female with a mutant allele develops the disease. In case thatboth parents are unaffected, disease in the offspring results from new
mutation.
ADPKD is caused by a germ line mutation in PKD1 (16p13.3)(85% of cases)or PKD2 (4q21)(15% of cases).

2. Diagnosis of ADPKD: Symptoms and laboratory findings
1) Algorithm
The diagnostic algorithm for ADPKD is depicted in the figure. Family
history, while important in ADPKD diagnosis, often cannot be assessed.
Moreover, even in the absence of family history, it is important to remainalert to newly reported mutations in PKD1/PKD2 genes responsible fordisease onset. It can be difficult to detect cysts meeting diagnostic criteria inyounger patients, requiring reexamination. Clinical questions (CQs) areappended to these guidelines as a reference in following the algorithm anddetermining treatment and other medical care once a definitive diagnosis
has been made.
Figure2) Diagnostic criteria
Table 1 presents the diagnostic criteria of ADPKD (ADPKD Diagnostic
Guidelines, Second Edition, published by a Grant-in-Aid for Progressive
Renal Diseases Research, Ministry of Health, Labour and Welfare of Japan).
Confirmation or nonconfirmation of family history determines one of two
possible protocols, each requiring its own distinctive cyst assessment based
not only on ultrasonography (US) but also on computed tomography (CT)and magnetic resonance imaging (MRI). In most cases, cysts manifest
bilaterally and diagnosis is uncomplicated; in the remaining cases, diagnosis
should be carefully performed in accordance with the diagnostic criteria
noted herein.

Table 1 the diagnostic criteria of ADPKD (ADPKD Diagnostic Guidelines, Second
Edition, published by a Grant-in-Aid for Progressive Renal Diseases Research,
Research on intractable disease, from the Ministry of Health, Labour and Welfare ofJapan)
1. Confirmation of family history
a. Three or more bilaterally-manifested cysts confirmed with ultrasonographyb. Five or more bilaterally-manifested cysts confirmed with CT and MRI imaging
2. Non-confirmation of family history
a. Patients 15-years old or younger: three or more bilaterally-manifested cysts
confirmed with either CT and MRI imaging or ultrasonographyb. Patients 16-years old or older: five or more bilaterally-manifested cysts confirmedwith either CT and MRI imaging or ultrasonography
Diseases to be excluded
1. Multiple simple renal cyst
2. Renal tubular acidosis
3. Multicystic kidney (multicystic dysplastic kidney)
4. Multilocular cysts of the kidney
5. Medullary cystic disease of the kidney (juvenile nephronophthisis)
6. Acquired cystic disease of the kidney
7. Autosomal recessive polycystic kidney disease3) Comparison of diagnostic criteria between Japan and other countries
Following Bear’s diagnostic criteria in 1984, numerous other versions havebeen reported, each with its own emphasis on, for example, ageclassification or cyst assessment through imaging. Ravine’s criteria, whichwere utilized for some time, were the first guidelines reflecting age as afactor. However, Ravine only incorporated PKD1 family history. Although
PKD1 and PKD2 mutations each result in almost the same clinicalmanifestation of the disease, PKD1 progresses to ESRD more rapidly andproduces more cysts, leading Pei to incorporate both PKD1 and PKD2
families in his diagnostic criteria. Diagnosis in Western countries combining

US with genetic testing is highly credible and should serve as a reference,but its applicability to Japanese patients has not yet been demonstrated.
4) Testing
ADPKD screening should include family history of renal disease (end-stage
and otherwise) and intracranial hemorrhage/cerebrovascular disease; patient
history of hypertension, cerebrovascular disease, urinary tract infection, fever,and lower back pain; subjective symptoms such as macroscopic hematuria,
lower back and/or flank pain, abdominal distension, headache, edema, andnausea; physical examination to determine blood pressure, abdominal girth,
heartbeat, abdominal findings, and edema; blood and urine tests, screening
for urinary sediment, proteinuria, and microalbuminuria; estimatedglomerular filtration rate (eGFR) and other renal function tests; andscreening for intracranial aneurysm through cranial MR angiography. US
represents the simplest form of diagnostic imaging for kidney diseases. Other
tests to be performed, as appropriate, should include measurement of Nacetyl beta-glucosaminidase and urinary beta2 microglobulin values, MRI,
and kidney CT imaging.
5) Diagnostic imaging
US is the standard screening technique for ADPKD diagnosis and evaluation,but evaluation of kidney size, as opposed to function, is reportedly the bettermeasurement in the evaluation of progression, with CT or MRI recommended
for follow-up evaluation. The latter methods surpass US in detecting smaller
cysts; MRI can detect cysts with a diameter of 2 mm through T2-weighted
imaging. Each diagnostic imaging technique (US, CT, and MRI) plays a rolein highlighting the distinctive characteristics of cysts. Diagnostic imaging is
also clinically important in terms of disease complications such as cerebral
aneurysms. As adverse reactions can occur, careful consideration must be
given to the risk–benefit balance before utilizing contrast media. MRA isuseful in screening for cerebral aneurysms and is a noninvasive test with thegreat benefit of not requiring contrast media. If imaging performed after adefinitive ADPKD diagnosis is strictly for follow-up observation, a simple CTonce every 2–5 years would be adequate if total kidney volume (TKV) is≤1,000 mL. If TKV exceeds 1,000 mL, CT once every year or two would beappropriate. For screening purposes, diagnostic imaging at the age of 30 years

is recommended.
6) Differential diagnosis
A patient’s clinical manifestation and diagnostic imaging should be used torule out possibilities such as multiple simple renal cysts, acquired cystic
kidney disease, and tuberous sclerosis (Table 2). Particular caution isneeded when considering tuberous sclerosis, as approximately 30% of
patients with this disease are said to have no typical symptoms other thanrenal cysts, which are mistakenly attributed to ADPKD. Additional diseases
to be ruled out include renal tubular acidosis, multicystic kidney(multicystic dysplastic kidney), multilocular cyst of the kidney, medullary
cystic kidney disease, and oral–facial–digital syndrome. As rare diseases are
difficult to identify and distinguish during normal medical examinations,despite reports on characteristic indicators other than renal cysts, extra careshould be given during differential diagnosis.
Table 2 Major non-ADPKD renal cystic diseases

DiseaseCyst
proliferation

Cyst
distribution/size

Typical life
stage forcyst

Pathophysiologicalcharacteristics

diagnosis
Multiple
simple renal
cyst
Acquiredcystic diseaseof the kidney

ModerateSizediversity/nonuniform
distribution

All ages

Rare under age 30
years; manifestation
increases with age

Moderate to
great

Diffusibility

Adulthood

Cyst formation precedes
ESRD

Tuberous
sclerosis

Moderate to
great

Uniform
distribution ofrelatively small(<1 to 2 cm) cysts

All ages

ARPKD

Great

Diffusibility/small
cysts

Birth

Renal
angiomyolipomas, skinlesions, periungual
fibromas, retinal
hamartomas, andcardiacrhabdomyomas
Greatly enlarged kidney,congenital hepatic
fibrosis7) Genetic diagnosis
ADPKD is an autosomal dominant genetic disease. Responsible genes for
ADPKD were already identified. Diagnosis of ADPKD in typical cases iseasy by detecting multiple cysts in both kidneys.
In Japan, genetic diagnostic tests for ADPKD are only available for basic
research but not for clinical practice. Physicians must consider whether
samples for genetic testing should be sent to foreign laboratories.
8) Diagnostic imaging for infants and young adults
Diagnostic criteria, including imaging, for ADPKD in infants and young
adults have not been established. Screening imaging tests are notrecommended for nonsymptomatic infants and young adults, even if they arechildren of ADPKD patients.
9) Initial symptoms
Cysts are said to form in utero, with most progressing asymptomatically
until the patients are in their 30s or 40s. Subjective symptoms include
abdominal or lower back pain, macroscopic hematuria (including its
posttraumatic form caused by sports activities), or abdominal bloating.
Acute pain is usually attributable to hemorrhagic cysts, infection, or urinary
tract stones. Chronic pain is defined as persistent pain for 4–6-weeks. It
occurs in approximately 60% of ADPKD cases and is usually attributable tocysts. Macroscopic hematuria occurs in approximately 50% of all cases.
Hypertension, diagnosed objectively by physical examination and othermethods, is a significant initial symptom (or findings).
10) Renal symptoms
Both acute and chronic abdominal and/or flank pain is one of the mostprevalent subjective symptoms of ADPKD, whereas many patients do nothave any complaint until their third or fourth decade of life. Anorexia,
gastrointestinal obstruction, and malnutrition are manifestations ofcompression of the gastrointestinal tract by the advanced enlargement of thekidney (and/or the liver). Macroscopic hematuria is observed at least once
during the entire clinical course in almost 50% of the patients. Massive
proteinuria is rare. The first functional abnormality of the kidney is disturbed
concentrating capacity, although it rarely becomes clinically evident unlessthe patient complains of polydipsia and polyuria. Decrease in GFR usually
starts after 40 years of age, and the mean rate of its reduction is 4.4–5.9
mL/(minyear).
The factors associated with rapid progression of GFR decline have beenreported as follows:① Disease-causing gene (worse in cases with PKD1 mutation than in thosewith PKD2 mutation)② Hypertension③ Early development of urinary abnormality (hematuria and proteinuria)④ Male sex⑤ Large size and rapid enlargement of the kidney⑥ Left cardiac hypertrophy⑦ Proteinuria

3. ADPKD: Epidemiology and prognosis (prevalence, incidence, renal
prognosis, and vital prognosis)
The number of ADPKD patients in Japan who visited hospitals wasestimated to be 14,594, yielding an ADPKD prevalence of 116.7 cases per
million population at the end of 1994. The total number of ADPKD patients
including those who will visit hospitals in the future was estimated to be
31,000. It was suggested that ADPKD affected 1 individual per 4033
population in Japan. ADPKD was diagnosed in 40 residents of Olmsted
County between 1935 and 1980, resulting in an age- and sex-adjusted annual
incidence rate of 1.38 case per 100,000 person-years. Approximately 50% of
the patients developed ESRD at the age of 60–69 years. The most common
causes of death in ADPKD were infection, sepsis, and cardiac disease(myocardial infarction and congestive heart failure). The survival of ADPKD
patients undergoing dialysis surpasses that of general dialysis patients.

4. ADPKD: Treatment and management of complications
1) Treatment to control the development of ADPKD
CQ 1. Is antihypertensive treatment recommended as a means of slowing
the deterioration of renal function in patients with ADPKD complicatedwith hypertension?

Recommendation Grade: C1
Antihypertensive treatment is recommended for patients with ADPKD
complicated with hypertension to slow the deterioration of renal function.
[Summary]
Hypertension in ADPKD is frequent and develops at a young age, in contrast
to essential hypertension. In addition, it is often detected when renal function
is normal and cysts are still small. Antihypertensive treatment is generally
performed. It is thought that antihypertensive treatment may slow thedeterioration of renal function in ADPKD with hypertension. However,
because the evidence related to the recommended antihypertensive agentsand target blood pressure is inconclusive, we recommend thatantihypertensive treatment in ADPKD should follow that administered forchronic kidney disease (CKD).
CQ 2. Does increased water intake have a beneficial effect in ADPKD
patients?
Recommendation Grade: C1
Human studies of high water intake to affect the progression of renal
dysfunction in ADPKD patients have not been reported; however, drinking
water can affect the progression of ADPKD by suppressing ADH, resulting in
attenuation of cyst growth and proliferation of cystic cells. Thus, 2.5 – 4 L/dayof water intake would be recommended for ADPKD.
[Summary]
A 3-5-cyclic adenosine monophosphate (cAMP)-mediating vasopressin
receptor can stimulate cystic cell proliferation and fluid secretion into cysts
in ADPKD. Thus, a novel treatment of ADPKD that targets the vasopressincAMP axis is currently evaluated and a selective inhibitor of vasopressin 2
receptor is adopted and examined for its effects on ADPKD. Another way tosuppress vasopressin secretion is to increase fluid intake to mediateosmoregulation. Although human studies have not been reported regarding
the effect of high water intake on the renal size and function of ADPKD,
increasing water intake could be recommended to affect the progression of
ADPKD based on the biological properties of the cystic epithelium. A larger
human study is needed to clarify the effect of high water intake; patientswould be advised to avoid stimulating vasopressin secretion by chronic water
depletion.

CQ 3. Should we recommend dietary protein restriction (DPR) to inhibit
progression of renal dysfunction in patients with ADPKD?
Recommendation Grade: C1
Evidence is limited and unclear whether DPR is effective for inhibiting
progression of renal dysfunction in patients with ADPKD; however, it may
considered.
[Summary]
The effect of DPR on ADPKD has been examined by several clinical studies,including small retrospective studies and randomized clinical trials.
However, almost all studies have shown no significant effect of DPR on the
progression of renal dysfunction. Although a meta-analysis showed theefficacy of DPR in patients with CKD, including ADPKD, the effect in
ADPKD patients alone was not evaluated. However, we could not conclude
that DPR is ineffective for those patients because of the many limitations of
those clinical studies, such as a small sample size, low prevalence ofoutcome due to a short observation period, and low adherence to DPR. Thus,
further evidence is required to answer this question.
CQ 4. Is tolvaptan recommended for treatment of ADPKD?
Recommendation Grade: B
Tolvaptan slow the increase in total kidney volume and the decline in kidney
function in ADPKD patients with a relatively-good renal function withcreatinine clearance ≥60 mL/min by Cock-Croft equation and a total kidney
volume of 750 ml or more. Therefore, tolvaptan is recommended for treatmentof ADPKD.
[Summary]
Tolvaptan, a V2-receptor antagonist, selectively blocks the binding ofvasopressin to the V2-receptors and inhibit production of cAMP. To determine
the effect of tolvaptan to suppress the increase in total kidney volume, a phase
3, international multicenter, double-blind, placebo-controlled, 3-year trial(TEMPO3/4) was performed. The results of the trial demonstrated thattolvaptan slowed the increase in total kidney volume and the decline in
kidney function in ADPKD patients with a relatively-good renal function withcreatinine clearance ≥60 mL/min by Cock-Croft equation and a total kidney
volume of 750 ml or more. Due to the lack of other specific and efficacious

treatments for ADPKD at present time, with particular attention to serious
adverse events such as drug-induced liver injury, tolvaptan is recommend fortreatment of ADPKD patients with a relatively-good renal function and a
total kidney volume of 750 ml or more. However, the safety of tolvaptan
therapy for adult patients with creatinine clearance <60 mL/min or total
kidney volume less than 750 mL or children is not established.
CQ 5. Aspiration of renal cysts in patients with ADPKD
Recommendation Grade: C1
Aspiration of renal cysts for ADPKD is not recommended for improving renal
function. The procedure would be considered in the management of diseaserelated chronic pain or abdominal distention, as well as for diagnostic
purposes and the treatment of infected cysts.
[Summary]
A review of cyst aspiration and surgical cyst decortication for symptomatic
ADPKD was performed. The impact of renal cyst aspiration or surgical cyst
decortication on renal function and hypertension in patients with ADPKD is
controversial, but these procedures are highly effective in the management ofdisease-related chronic pain. The duration of pain relief is shorter in cyst
aspiration than surgical cyst decortication.
The cyst aspiration technique for simple renal cysts can be used for ADPKD.
Cyst aspiration followed by instillation of a sclerosing agent (most commonly
ethanol) is indicated when the symptoms are caused by one or few dominant
or strategically located cysts. Cyst aspiration and sclerosis for multiple cysts
need further investigation.
Cyst aspiration for diagnostic purposes and the treatment of infected cysts
has been the standard procedure.
CQ 6. Does screening of intracranial aneurysms improve the prognosis of
ADPKD patients?
Recommendation Grade: B
The prevalence of unruptured intracranial aneurysms in ADPKD patients ishigher than that in the general population. Intracranial hemorrhage, either
cerebral or aneurysmal subarachnoid hemorrhage (SAH), confers high risks
for mortality and morbidity in ADPKD patients. Screening of intracranialaneurysms improves prognosis.
[Summary]
The high incidence of intracranial aneurysms in patients with ADPKD haslong been recognized. Rupture of an intracranial aneurysm resulting in SAH
is the most devastating extrarenal complications and often results inpremature death or disability. The prevalence rate of unruptured intracranial
aneurysms in patients with ADPKD is higher than that in people without
comorbidity. First-degree relatives (parents, siblings, and children) of
patients with subarachnoid hemorrhage have a 3–7 times higher risk for SAH
than the general population.
Aneurysm size correlates with the presence of symptoms and the risk of
bleeding, and aneurysms may rupture more often and at a younger age thansporadic aneurysms. However, there is no correlation between the risk ofrupture and sex, renal function and blood pressure. Hence, it is difficult topredict intracranial aneurysm rupture.
Intracranial hemorrhage, either cerebral hemorrhage or aneurysmal SAH,
confers high risks for mortality and morbidity in PKD patients. Screening of
intracranial aneurysms improves prognosis.
CQ 7. Is treatment recommended for cerebral aneurysms detected during
screening?
Recommendation Grade: C1Treatment of a cerebral aneurysm is determined by a comprehensive
examination of factors such as location, shape, and size of the aneurysm, andgeneral conditions, age, and medical history of the patient. Decisions
regarding treatment advisability and method should follow consultation witha neurosurgeon.
[Summary]
Considering that a ruptured cerebral aneurysm is a life-threatening
complication, detection of an unruptured cerebral aneurysm during screening
should receive all due attention. However, there is no particular treatment
for the latter, which is specific to ADPKD. Detection of a cerebral aneurysm
during screening should be followed by careful control of smoking, alcohol
consumption, and blood pressure. Treatment of a cerebral aneurysm issurgery, involving a craniotomy and endovascular treatment, with specifics
determined following comprehensive investigation of the location, shape, andsize of the aneurysm, and general conditions, age, and medical history of thepatient. As treatment options have their respective strengths and weaknesses,
decisions should follow consultation with a neurosurgeon. If conservative
observation is chosen, biannual—or at the very least, annual—monitoring ofaneurysm size is recommended.
CQ 8. Are newer quinolones recommended for the treatment of cyst infectionin ADPKD?
Recommendation Grade: C1
Administration of the newer quinolones is recommended for the treatment ofcyst infection in ADPKD.
[Summary]
Cyst infection is a frequent and serious complication of ADPKD and is often
refractory and difficult to treat. Most causative bacteria originate from theintestine, and many are gram-negative rods. Fluoroquinolones, which havebroad effectiveness against gram-negative rods and good penetration of cysts,
is recommended for the treatment of infected cysts in ADPKD. Having said
this, however, there has not been an adequate level of study to investigate theactual effectiveness of fluoroquinolones for treating cyst infection in ADPKD.
Few studies have compared fluoroquinolones with other antibiotics for thetreatment of cyst infection in ADPKD.
CQ 9. Should we recommend tranexamic acid in the treatment of cystic
hemorrhage in ADPKD?
Recommendation Grade: C1
Tranexamic acid may be considered when cystic hemorrhage does not improveby conservative treatment.
[Summary]
Hematuria is a common problem in patients with polycystic kidney disease.
It can be spontaneous or result from trauma, renal calculi, tumor, or
infection. These episodes are normally managed with conservative medical
treatment and rarely require surgery or embolization. Only a few publishedstudies have investigated the use of tranexamic acid for the treatment of
cystic hemorrhage in ADPKD. However, these studies demonstrated thattranexamic acid can be used safely and is effective for selected ADPKD

patients with severe or intractable cystic hemorrhage that does not respondto conventional treatment.
Thus, tranexamic acid may be considered when cystic hemorrhage does not
improve by conservative treatment.
CQ 10. Are there any effective pharmacological preventive therapies for
urolithiasis associated with ADPKD?
Recommendation Grade: C1
Because of the lack of data about the prophylactic efficacy for urolithiasis inpatients with ADPKD, we cannot recommend any medical treatment toprovide a prophylactic benefit. We may recommend, however, the standard
prophylactic treatment in patients with metabolic disorder.
[Summary]
Renal calculi were detected in 21% of male and 13% of female patients withADPKD. Anatomical urinary retention and metabolic disturbance in patientswith ADPKD tend to cause development of renal stones. The main componentof the stones is uric acid, and the most common metabolic abnormality is
hyperoxaluria. Medical preventive treatments are not recommended becauseof the lack of studies that prove their efficacy. General preventive measures
are recommended for fluid intake and diet.
CQ 11. Is transthoracic echocardiography (TTE) for screening of valvulardisease recommended to improve the mortality of ADPKD patients?
Recommendation Grade: C1
We suggest a TTE study for valvular disease only if the patients have heartmurmur to evaluate the severity of valvular diseases.
[Summary]
Mitral valve prolapse and mitral regurgitation (MR) are the common cardiac
complications in ADPKD. Twenty-one percent of Japanese ADPKD patients
have MR. However, solid data on the natural history of valvular disease in
ADPKD are currently lacking, and studies with long-term follow-up periods arealso very few.
According to the reports regarding non-ADPKD patients, mild or trivial MR
carries better prognosis and is thought not to affect the loss of cardiac function
and mortality in cardiovascular diseases.
For patients with a heart murmur, it is uncertain whether the disease is mild orsevere. TTE might be useful to evaluate indications for surgical treatments andimprove the mortality of these ADPKD patients.
CQ 12. Should ADPKD patients with ESRD undergo renal transarterial
embolization to reduce enlarged kidneys?
Recommendation Grade: C1
Renal transarterial embolization in ADPKD patients with ESRD is effective
in reducing the size of enlarged kidneys and is therefore recommended.
[Summary]
As ADPKD patients age, kidney enlargement becomes increasingly
pronounced, with some patients experiencing considerable abdominal
bloating. Such patients are unable to eat properly, leading to malnutrition
and an overall deterioration of health. However, there is no clear treatment
for massively enlarged kidneys. The literature remains sparse on renaltransarterial embolization in ADPKD patients with enlarged kidneys, andreports differ as to the embolism type. However, as renal transarterial
embolization was demonstrated to reduce kidney swelling in all existing
reports, the procedure is believed to be effective for ADPKD patients and istherefore recommended despite the paucity of evidence.
CQ 13. Should ADPKD patients with ESRD undergo hepatic transarterial
embolization to reduce hepatomegaly?
Recommended Grade: C1
Hepatic transarterial embolization in ADPKD patients with ESRD is effective
in reducing hepatomegaly and is therefore recommended.
[Summary]
As ADPKD patients age, liver cysts proliferate and hepatomegaly becomesincreasingly pronounced, with some patients experiencing extreme
abdominal bloating. Such patients are unable to eat properly, leading tomalnutrition and an overall deterioration of health. However, there is no clear
treatment for a massively enlarged liver. There are limited reports of hepatictransarterial embolization in ADPKD patients with hepatomegaly, but they
are individual or collected case reports, as opposed to scientific studies. The
evidence presented in these reports is meager, but as there is some suggestionthat hepatic transarterial embolization may be effective in ADPKD patientswith enlarged livers, the procedure is recommended.
CQ 14. Is peritoneal dialysis recommended for patients with ADPKD?
Recommended Grade: C1
Peritoneal dialysis is recommended for patients with ADPKD.
[Summary]
Peritoneal dialysis is not considered appropriate or suitable in ADPKD
patients because of the limited peritoneal space due to enlarged kidneys.
However, according to the recent European Renal Best Practice Guidelines,
initiation of dialysis with peritoneal dialysis should not be considered acontraindication. Which of the two modalities, hemodialysis or peritoneal
dialysis, is better for patients’ long survival? Although there have been
several studies concerning this question that examined different populations
and situations of dialysis patients, there is no definite conclusion orconsensus on this matter. The dialysis modalities, hemodialysis orperitoneal dialysis, should be decided by patients themselves according to
the suitability of the modality for the patients.

CQ 15. Is unilateral or bilateral nephrectomy recommended during ADPKD
kidney transplantation?
Recommendation Grade: C1
If native kidney enlargement seems sufficiently massive to jeopardize
accommodation of the donor kidney, unilateral or bilateral nephrectomy isrecommended.
[Summary]
Renal transplantation for ADPKD patients proceeds routinely as it does forother patients, including incorporation of immunosuppressive therapy.
Posttransplant survival is more favorable for ADPKD than for other ESRD
patients. However, patients should be monitored postoperatively for possible
complications such as thromboembolism, hyperlipidemia, postoperative
diabetes onset, and hypertension. Careful screening is required to ensure thatany kidney from a living donor is free of ADPKD. If the patient has a cerebral
aneurysm, treatment is preferable prior to renal transplantation. If native
kidney enlargement seems sufficiently massive to jeopardize accommodationof the donor kidney, unilateral (or rarely, bilateral) nephrectomy isrecommended. However, there is no professional consensus on issues such as
nephrectomy timing (simultaneous or heterochronic), scope (unilateral orbilateral), or method (open or laparoscopic).
5. Autosomal Recessive Polycystic Kidney Disease (ARPKD): Disease
concept/definition (etiology and pathophysiological mechanism)
ARPKD is a hereditary cystic kidney disease and inherited as an autosomal
recessive trait. It is characterized by cystic dilation of renal collecting ducts
and varying degrees of hepatic abnormalities consisting of biliary
dysgenesis, and periportal fibrosis and bile duct proliferation in the liver.
Generally, the hepatic lesion in ARPKD is clinically called congenital
hepatic fibrosis if it presents alone, and is associated with the histologicalfeature called ductal plate malformation. ARPKD is caused by mutations in

PKHD1, located on chromosome 6p21.1-p12, and linkage analysis indicatesthat this disorder involves a single defective gene despite the wide
variability in clinical presentation. It is found that causative gene proteinsin three human PKDs (PKD1, PKD2, and ARPKD) are associated withprimary cilia and the related structures, and it is inferred that structuralabnormality and dysfunction of the primary cilia cause disease, and it is atheoretical rationale for the common pathophysiological mechanism of
ARPKD and ADPKD.
6. ARPKD: Diagnosis (symptomatology, symptom, and examination finding)
Renal ultrasonographic findings and a sibling with a history of ARPKD areimportant for the diagnosis of ARPKD. Cysts are usually small, and havemainly diffuse dilatations rather than a round shape. Renal
ultrasonography demonstrates markedly enlarged echogenic kidneys, not a
hubble-bubble low-echogenic appearance, and this recognition is importantfor diagnosis. Sonographic features of ARPKD may manifest in the second
trimester but usually are not apparent until after 30 weeks’ gestation. Manydiseases present with kidney cysts, all of which can be differential
diagnoses. Among hereditary cystic kidney diseases, ADPKD is an
important differential diagnosis. Occasionally, even in ARPKD, dilatation of
the collecting ducts is not detected and macrocysts are present, which is afeature to notice. In advanced cases of ARPKD, it is sometimes difficult tomorphologically distinguish ARPKD from ADPKD. Although ARPKD
presents in infancy in most patients, a subset presents later in childhoodand even adulthood, with abdominal distension related to renal
enlargement or splenohepatomegaly.
7. ARPKD: Epidemiology and prognosis (incidence, prevalence, andtreatment outcome)The incidence of ARPKD is inferred to be 1 case per 10,000–40,000 births.
Prognosis is difficult to assess, although now it becomes clear that survivalof all but the most severely affected neonates who demonstrate pulmonary
hypoplasia is possible. It is expected that the prognosis will be improved in
the future through improvement in the treatment of end-stage renal failureand disease management in infants early after birth.

8. ARPKD: Prenatal diagnosis
In ARPKD, considering that patients often show severe clinical features
early after birth, the prenatal diagnosis is useful in disease management.
Prenatal diagnosis involves fetal ultrasonography and MRI, and there is no
doubt of the clinical significance of performing these diagnostic imaging
methods when required in present conditions of perinatal medical care.
However, the precision of imaging techniques such as ultrasonography islow, and cysts of ARPKD are usually inapparent until 30 weeks’ gestation.
Prenatal diagnosis of ARPKD by genetic analysis is established technically,
and its enforcement is considered when a sibling is diagnosed with ARPKD.
However, the request for a genetic examination from an overseas laboratory
as an option may be subjected to genetic counseling because theenforcement of prenatal genetic diagnosis in Japan is difficult.
9. ARPKD: Treatment and management of complications (treatment ofdisease including adjunct therapy, supportive therapy, and prophylaxis)
CQ 16. Is peritoneal dialysis recommended for the improvement of the vital
prognosis and quality of life (QOL) of patients with ARPKD?
Recommendation Grade: C1
Peritoneal dialysis may be considered for the improvement of the vital
prognosis and QOL of patients with ARPKD.
[Summary]
Peritoneal dialysis is considered for the improvement of the vital prognosis
and QOL of patients with ARPKD. End-stage renal failure is often seen in
ARPKD, and a replacement therapy for the kidney is required for thosecases. Generally, hemodialysis is often unsuitable for children, andperitoneal dialysis is recommended when there are no special
circumstances. It is a consensus that peritoneal dialysis is recommended forthe improvement of the vital prognosis and QOL of patients with ARPKD
considering the present conditions in the medical care of renal failure.

CQ 17. Is solitaryor simultaneous transplantation of the liver and kidney
recommended for the improvement of the vital prognosis and QOL ofpatients with ARPKD?
Recommendation Grade: C1
Solitary or simultaneous transplantation of the liver and the kidney may beconsidered for the improvement of the vital prognosis and QOL of patientswith ARPKD. However, its adaptation should be decided carefully according
to individual cases.
[Summary]
Although solitary or simultaneous transplantation of the liver and thekidney should be considered for the improvement of the vital prognosis and
QOL of patients with ARPKD, its adaptation should be decided carefully
according to individual cases. In ARPKD, because patients often show
severe renal failure early after birth, a replacement therapy for the kidney
is required. Generally, the best replacement therapy method for the kidney
in children is thought to be renal transplantation, and its early enforcement
is recommended. When the management of portal hypertension or recurrent
bacterial cholangitis is difficult in the case of liver disorder in ARPKD
patients, liver transplantation is considered. Although solitary or
simultaneous transplantation of the liver and kidney should be considered
for the improvement of the vital prognosis and QOL of patients with
ARPKD considering the present conditions of transplantation medical care,
its enforcement does not necessarily result in the improvement of vital
prognosis and QOL in each case.
CQ 18. Is antihypertensive therapy recommended for the improvement of
the vital prognosis of patients with ARPKD?
Recommendation Grade: C1
Antihypertensive therapy improves the vital prognosis of patients with
ARPKD.

[Summary]
Antihypertensive therapy improves the vital prognosis of patients with
ARPKD. Therefore, it may be considered a management option for ARPKD.
Hypertension is often found in infants and subsequent childhood in ARPKD,
and it can be the only symptom. Hypertension is also seen in patients withnormal renal function and is manifested in almost all children with ARPKD.
If hypertension is not treated effectively, hypercardia or congestive heart
disorder may occur. The pathogenesis of hypertension in ARPKD is
unknown. It is a consensus that antihypertensive therapy should beconsidered for the improvement of the vital prognosis of patients with
ARPKD.

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IV. ADPKD: Treatment and management of complications
1. Treatment to control the development of ADPKD
1) Antihypertensive treatment
CQ 1. Is antihypertensive treatment recommended as a means ofslowing the deterioration of renal function in patients with ADPKD
complicated with hypertension?
1. Cadnapaphornchai MA, et al. Clin J Am Soc Nephrol 2009；4：820—9.
(Level 2)
2. Schrier RW, et al. Kidney Int 2003；63：678—85. (Level 2)
3. Jafar TH, et al. Kidney Int 2005；67：265—71. (Level 1)
4. Maschio G, et al. N Engl J Med 1996；334：939—45. (Level 2)
5. van Dijk MA, et al. Nephrol Dial Transplant 2003；18：2314—20. (Level
2)
6. Ecder T, et al. Am J Kidney Dis 2000；35：427—32. (Level 2)
7. Schrier R, et al. J Am Soc Nephrol 2002；13：1733—9. (Level 2)
8. Kanno Y, et al. QJM 1996；89：65—70. (Level 4)
9. Nutahara K, et al. Nephron Clin Pract 2005；99：c18—23. (Level 2)
10. Mitobe M, et al. Clin Exp Nephrol 2010；14：573—7. (Level 4)
11. Zeltner R, et al. Nephrol Dial Transplant 2008；23：573—9. (Level 2)
12. Ecder T, et al. Am J Nephrol 2001；21：98—103. (Level 3)

13. Sarnak MJ, et al. Ann Intern Med 2005；142：342—51. (Level 2)2) Increased water intake
CQ 2. Does increased water intake have a beneficial effect in ADPKD
patients?
1. Wang X, et al. J Am Soc Nephrol 2008；19：102—8. (Level 4)
2. Nagao S, et al. J Am Soc Nephrol 2006；17：2220—7. (Level 4)
3. Gabow PA, et al. Kidney Int 1989；35：675—80. (Level 3)
4. Zittema D, et al. Clin J Am Soc Nephrol 2012；7：906—13. (Level 3)
5. Ho TA, et al. Kidney Int 2012；82：1121—9. (Level 3)
6. Torres VE, et al. Clin J Am Soc Nephrol 2009；4：1140—50. (Level 6)
7. Barash I, et al. Clin J Am Soc Nephrol 2010；5：693—7. (Level 4)
8. Wang CJ, et al. Clin J Am Soc Nephrol 2011；6：192—7. (Level 4)3) Dietary protein restriction
CQ 3. Should we recommend dietary protein restriction to inhibit
progression of renal dysfunction in patients with ADPKD?
1. Locatelli F, et al. Lancet 1991；337：1299—304. (Level 2)
2. Choukroun G, et al. J Am Soc Nephrol 1995；6：1634—42. (Level 4)
3. Klahr S, et al. J Am Soc Nephrol 1995；5：2037—47. (Level 2)
4. Levey AS, et al. Am J Kidney Dis 2006；48：879—88. (Level 2)
5. Oldrizzi L, et al. Kidney Int 1985；27：553—7. (Level 3)
6. Fouque D, et al. Cochrane Database Syst Rev 2009；3：CD001892. (Level
1)4) Tolvaptan
CQ 4. Is tolvaptan recommended for treatment of ADPKD?
1. Torres VE, et al. N Engl J Med 2012；367：2407—18. (Level 2)
2. Higashihara E, et al. Clin J Am Soc Nephrol 2011；2499—507. (Level 3)
3. Irazabal MV, et al. Kidney Int 2011；80：295—301. (Level 4)5) Aspiration of renal cysts
CQ 5. Aspiration of renal cysts in patients with ADPKD
1. Skolarikos A, et al. BJU Int 2012；110：170—8. (Level 4)
2. Millar MB, et al. J Endourol 2013；27：528—34. (Level 4)
3. Higashihara E, et al. J Urol 1992；147：1482—4. (Level 4)
4. Bennett WM, et al. J Urol 1987；137：620—2. (Level 4)

5. Uemasu J, et al. Nephrol Dial Transplant 1996；11：843—6. (Level 4)
6. Kim SH, et al. Korean J Radiol 2009；10：377—83. (Level 4)
7. Lee YR, et al. Korean J Radiol 2003；4：239—42. (Level 4)
8. Chapman AB, et al. Am J Kidney Dis 1990；16：252—5. (Level 5)
9. Gupta S, et al. Acta Radiol 2000；41：280—4. (Level 4)
10. Fleming TW, et al. J Urol 1998；159：44—7. (Level 4)
2. Complications and their managements
1) Cerebral aneurysm and subarachnoid hemorrhage
CQ 6：Does screening of intracranial aneurysms improve the prognosisof ADPKD patients?
1. Chauveau D, et al. Kidney Int 1994；45：1140—6. (Level 4)
2. Schievink WI, et al. J Am Soc Nephrol 1992；3：88—95. (Level 4)
3. Vlak MH, et al. Lancet Neurol 2011；10：626—36. (Level 4)
4. Irazabal MV, et al. Clin J Am Soc Nephrol 2011；6：1274—85. (Level 4)
5. Xu HW, et al. Stroke 2011；42：204—6. (Level 4)
6. Gieteling EW, et al. J Neurol 2006；250：418—23. (Level 4)
7. Morita A, et al. N Engl J Med 2012；366：2474—82. (Level 4)
CQ 7. Is treatment recommended for cerebral aneurysms detectedduring screening?
1. Rinkel GJ. J Neuroradiol 2008；35：99—103. (Level 6)
2. Hughes PD, et al. Nephrology（Carlton）2003；8：163—70. (Level 6)2) Cyst infection
CQ 8. Are newer quinolones recommended for the treatment of cyst
infection in ADPKD?
1. Alam A, et al. Clin J Am Soc Nephrol 2009；4：1154—5. (Level 6)
2. Sallée M, et al. Clin J Am Soc Nephrol 2009；4：1183—9. (Level 4)
3. Suwabe T, et al. Nephron Clin Pract 2009；112：157—63. (Level 4)
4. Schwab SJ, et al. Am J Med 1987；82：714—18. (Level 4)
5. Muther RS, et al. Kidney Int 1981；20：519—22. (Level 5)
6. Bennet WM, et al. Am J Kidney Dis 1985；6：400—4. (Level 5)
7. Schwab SJ, et al. Am J Kidney Dis 1983；3：63—6. (Level 5)
8. Elzinga LW, et al. Kidney Int 1987；32：884—8. (Level 5)
9. Elzinga LW, et al. Antimicrob Agents Chemother 1988；32：844—7.

(Level 5)
10. Telenti A, et al. Mayo Clin Proc 1990；65：933—42. (Level 5)
11. Rossi SJ, et al. Ann Pharmacother 1993；27：38—9. (Level 5)
12. Hiyama L, et al. Am J Kidney Dis 2006；47：E9—13. (Level 5)3) Cystic hemorrhage/hematuria
CQ 9. Should we recommend tranexamic acid in the treatment of
cystic hemorrhage in ADPKD?
1. Johnson AM, et al. J Am Soc Nephrol 1997；8：1560—7. (Level 4)
2. Peces R, et al. Nefrologia 2012；32：160—5. (Level 5)
3. Vujkovac B, et al. Blood Coagul Fibrinolysis 2006；17：589—91. (Level 5)
4. Alameel T, et al. J Int Nephrol 2011；203579. (Level 5)4) Urolithiasis
CQ 10. Are there any effective pharmacological preventive therapies
for urolithiasis associated with ADPKD?
1. Higashihara E, et al. J Urol 1992；147：329—32. (Level 4)
2. Grampsas SA, et al. Am J Kidney Dis 2000；36：53—7. (Level 4)
3. Nishiura JL, et al. Clin J Am Soc Nephrol 2009；4：838—44. (Level 4)
4. Torres VE, et al. Am J Kidney Dis 1988；11：318—25. (Level 4)5) Cardiac complications (including valvular disease)
CQ 11. Is transthoracic echocardiography (TTE) for screening ofvalvular disease recommended to improve the mortality of ADPKD
patients?
1. Ecder T, et al. Nat Rev Nephrol 2009；5：221—8. (Level 6)
2. Koren MJ, et al. Ann Intern Med 1991；114：345—52. (Level 3)
3. Gabow PA, et al. Kidney Int 1992；41：1311—9. (Level 4)
4. Chapman AB. J Am Soc Nephrol 1997；8：1292—7. (Level 3)
5. Hossack KF, et al. N Engl J Med 1988；319：907—12. (Level 3)
6. Flack JM, et al. Am Heart J 1999；138：486—92. (Level 3)
7. Freed LA, et al. N Engl J Med 1999；341：1—7. (Level 3)
8. Avierinos JF, et al. Circulation 2002；106：1355—61. (Level 3)
9. Enriquez—Sarano M, et al. N Engl J Med 2005；352：875—83. (Level 4)
10. Bonow RO, et al. J Am Coll Cardiol 2006；48：e1—e148. (Level 1)
11. Zoghbi WA, et al. J Am Soc Echocardiogr 2003；16：777—802. (Level 6)12. Lumiaho A, et al. Am J Kidney Dis 2001；38：1208—16. (Level 3)
13. Adeola T, et al. J Natl Med Assoc 2001；93：282—7. (Level 5)
14. Hadimeri H, et al. J Am Soc Nephrol 1998；9：837—41. (Level 5)
15. Ecder T, et al. Nephrol Dial Transplant 1999；14：1113—6. (Level 4)6) The specific treatment of complications
CQ 12. Should ADPKD patients with ESRD undergo renaltransarterial embolization to reduce enlarged kidneys?
1. Harley JD, et al. AJR Am J Roentgenol 1980；134：818—20. (Level 5)
2. Hahn ST, et al. Cardiovasc Intervent Radiol 1999；22：422—4. (Level 5)
3. Ubara Y, et al. Am J Kidney Dis 1999；34：926—31. (Level 5)
4. Ubara Y, et al. Am J Kidney Dis 2002；39：571—9. (Level 5)
5. Sakuhara Y, et al. J Vasc Interv Radiol 2008；19：267—71. (Level 5)
6. Rim H, et al. Korean J Radiol 2010；11：574—8. (Level 5)
7. Morishita H, et al. J Vasc Interv Radiol 2011；22：1631—3. (Level 5)
8. Mukai T, et al. Acta Med Okayama 2011；65：347—51. (Level 5)
CQ 13. Should ADPKD patients with ESRD undergo hepatictransarterial embolization to reduce hepatomegaly?
1. Ubara Y, et al. Am J Kidney Dis 2004；43：733—8. (Level 5)
2. Takei R, et al. Am J Kidney Dis 2007；49：744—52. (Level 5)
3. Park HC, et al. J Korean Med Sci 2009；24：57—61. (Level 5)
4. Wang MQ, et al. Abdom Imaging 2013；38：465—73. (Level 5)
3. The treatment of ESRD
1) Peritoneal dialysis
CQ 14. Is peritoneal dialysis recommended for patients with ADPKD?
1. Covic A, et al. Nephrol Dial Transplant 2010；25：1757—9. (Level 4)
2. Fenton SS, et al. Am J Kidney Dis 1997；30：334—42. (Level 3)
3. Schaubel DE, et al. Perit Dial Int 1998；18：478—84. (Level 3)
4. Collins AJ, et al. Am J Kidney Dis 1999；34：1065—74. (Level 3)
5. Heaf JG, et al. Nephrol Dial Transplant 2002；17：112—7. (Level 3)
6. Moist LM, et al. J Am Soc Nephrol 2000；11：556—64. (Level 3)
7. Foley RN, et al. J Am Soc Nephrol 1998；9：267—76. (Level 3)
8. Vonesh EF, et al. Kidney Int 2004；66：2389—401. (Level 3)
9. Liem YS, et al. Kidney Int 2007；71：153—8. (Level 3)
10. Stack AG, et al. Kidney Int 2003；64：1071—9. (Level 3)

11. Ganesh SK, et al. J Am Soc Nephrol 2003；14：415—24. (Level 3)3) Renal transplantation
CQ 15. Is unilateral or bilateral nephrectomy recommended during
ADPKD kidney transplantation?
1. Jacquet A, et al. Transpl Int 2011；24：582—7. (Level 4)
2. Kramer A, et al. J Urol 2009；181：724—8. (Level 4)
3. Sulikowski T, et al. Transplant Proc 2009；41：177—80. (Level 4)
4. Hadimeri H, et al. Nephrol Dial Transpl 1997；12：1431—6. (Level 4)
5. Fuller TF, et al. J Urol 2005；174：2284—8. (Level 4)
6. Patel P, et al. Ann R Coll Surg Engl 2011；93：391—5. (Level 4)
7. Cohen D, et al. Prog Urol 2008；18：642—9. (Level 4)
8. Yamamoto T, et al. Transplantation 2012；93：794—8. (Level 4)
9. Desai MR, et al. BJU Int 2008；101：94—7. (Level 4)
10. Gill IS, et al. J Urol 2001；165：1093—8. (Level 4)
11. Jenkins MA, et al. Urology 2002；59：32—6. (Level 4)
12. Dunn MD, et al. Am J Kidney Dis 2000；35：720—5. (Level 4)
13. Bendavid Y, et al. Surg Endosc 2004；18：751—4. (Level 4)
V. Autosomal Recessive Polycystic Kidney Disease (ARPKD): Disease
concept/definition (etiology and pathophysiological mechanism)
1. Ward CJ, et al. Nat Genet 2002；30：259—69.
2. Onuchic LF, et al. Am J Hum Genet 2002；70：1305—17.
VI. ARPKD: Diagnosis (symptomatology, symptom, and examination
findings)
1. Guay—Woodford LM, et al. Pediatrics 2003；111：1072—80.
2. Capisonda R, et al. Pediatr Nephrol 2003；18：119—26.
3. Zerres K, et al. Acta Paediatr 1996；85：437—45.
4. Kääriäinen H, et al. Pediatr Radiol 1988；18：45—50.
5. Gagnadoux MF, et al. Adv Nephrol Necker Hosp 1989；18：33—57.
6. Roy S, et al. Pediatr Nephrol 1997；11：302—6.
VII. ARPKD: Epidemiology and prognosis (incidence, prevalence, andtreatment outcome)
1. Zerres K, et al. Am J Med Genet 1998；76：137—44.
2. Guay—Woodford LM, et al. Pediatrics 2003；111：1072—80.
3. Bergmann C, et al. Kidney Int 2005；67：829—48.
1.

ARPKD: Prenatal diagnosis

1. Zerres K, et al. Am J Med Genet 1998；76：137—44.
2. Zerres K, et al. Clin Genet 2004；66：53—7.
3. Guay—Woodford LM, et al. Am J Hum Genet 1995；56：1101—7.
4. Gigarel N, et al. Reprod Biomed Online 2008；16：152—8.
2. ARPKD: Treatment and management of complications (treatment ofdisease including adjunct therapy, supportive therapy, and prophylaxis)
CQ 16. Is peritoneal dialysis recommended for the improvement of thevital prognosis and quality of life (QOL) of patients with ARPKD?
1. Bergmann C, et al. Kidney Int 2005；67：829—48. (Level 5)
2. Beaunoyer M, et al. Pediatr Transplant 2007；11：267—71. (Level 5)
3. Spechtenhauser B, et al. Pediatr Transplant 1999；3：246—8. (Level 5)
CQ 17. Is independent or simultaneous transplantation of the liverand kidney recommended for the improvement of the vital prognosis and
QOL of patients with ARPKD?
1．Bergmann C, et al. Kidney Int 2005；67：829—48. (Level 5)
2. Beaunoyer M, et al. Pediatr Transplant 2007；11：267—71. (Level 5)
3. Spechtenhauser B, et al. Pediatr Transplant 1999；3：246—8. (Level 5)
4. Gunay-Aygun M, et al. Clin J Am Soc Nephrol 2010；5：972—84. (Level
5)
5. De Kerckhove L, et al. Transpl Int 2006；19：381—8. (Level 5)
6. Davis ID, et al. Pediatr Transplant 2003；7：364—9. (Level 5)
7. Khan K, et al. Am J Transplant 2002；2：360—5. (Level 5)
CQ 18. Is antihypertensive therapy recommended for the improvementof the vital prognosis of patients with ARPKD?
1. Bergmann C, et al. Kidney Int 2005；67：829—48. (Level 5)
2. Loghman—Adham M, et al. J Histochem Cytochem 2005；53：979—88.
(Level 5)