InnovAiT, 13(6), 326–335

Polycystic kidney disease

Dr Soo Oh
Royal Stoke Hospital, University Hospitals West Midlands North
Email: Soo.Oh@uhnm.nhs.uk

Dr Rabeet Khan
John Radcliffe Hospital, Oxford University Hospitals

Dr Ahmed Ziada
Royal Stoke Hospital, University Hospitals West Midlands North

P olycystic kidney disease (PKD) is a monogenic, hereditary disorder of the kidneys

that leads to fluid-filled cysts within the renal tubes. It is one of the most common
causes of end-stage renal failure. There are two types, the more common autosomal
dominant (ADPKD) and the rarer autosomal recessive (ARPKD). ADPKD mostly presents
in adulthood, whereas ARPKD is usually detected during antenatal screening or as a
neonate. This article will focus on key points to understand and consider for the holistic
management of PKD.

The RCGP curriculum and polycystic kidney disease

The role of the GP in the genomic medicine clinical topic guide is to:
. Take and consider family histories in order to identify families with, or at risk of, genetic conditions (including
autosomal and X-linked disorders) and familial clusters of common conditions such as cancer, cardiovascular disease
and diabetes
. Identify patients and families who would benefit from being referred to appropriate specialist services
. Manage the day-to-day care of patients with genetic conditions, even if the patient is under specialist care
. Coordinate care across services, including transitions from paediatric to adult services
. Communicate information about genetics and genomics, including discussing results from antenatal and new-born screen-
ing programmes
. Understand how genomic information is used within the context of routine clinical practice
The role of the GP in the kidney and urological health topic guide is to:
. Identify and manage chronic kidney disease, and understand the interventions that can delay its progression and reduce
the associated increased cardiovascular morbidity and mortality
. Identify and manage acute kidney injury (AKI), including taking early action, such as stopping medications, to reduce the
risk of AKI
. Be alert to possible indicators of urinary tract malignancy
. Know when to refer and when not to refer, avoiding futile investigation and escalation and encouraging sup-
portive care

326 InnovAiT, 2020, Vol. 13(6), 326–335, ! The Author(s) 2020.

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InnovAiT
Epidemiology
Autosomal dominant polycystic kidney
disease
Autosomal dominant polycystic kidney disease (ADPKD)
affects all ethnicities worldwide. Within the UK, it is estimated
that 1 in 2459 individuals are affected by ADPKD (Davies
et al., 1991). A more recent review of epidemiological litera-
ture estimates the prevalence of ADPKD within the European
Union to be at a similar level, around 1 in 2525 (Willey et al.,
2017).
ADPKD is also estimated to be responsible for 10% of
people aged under 65 years being on renal replacement ther-
apy (RRT) (Gilg et al., 2016), with a younger starting age for
RRT (Shaw et al., 2014). The primary cause of death from
ADPKD patients on RRT is from cardiac disease, although sur-
vival has considerably improved due to an overall reduction in
cardiovascular disease mortality (Spithoven et al., 2014).
Autosomal recessive polycystic
kidney disease
The prevalence of autosomal recessive polycystic kidney disease
(ARPKD) is much rarer than ADPKD, estimated at 1 in 20 000 live
births (Hartung and Guay-Woodford, 2014). Neonatal infants
with ARPKD have significant complications and a high mortality
rate associated with conditions such as pulmonary hypoplasia,
however, survival has markedly improved with better ventila-
tion methods and neonatal supportive care (Hartung and
Guay-Woodford, 2014). Long-term prognosis following the
perinatal period is good, with 1-year survival at 85% and
10-year survival estimated at 82% (Bergmann et al., 2005).
Genetics of polycystic kidney disease
ADPKD
The majority of ADPKD cases are a result of mutations in the
gene PKD1 on chromosome 16p13.3 or PKD2 on chromo-
some 4q22.1. PKD1 accounts for 80% of cases and PKD2
15% (Bergmann et al., 2018). As it is inherited in an autosomal
dominant manner, only one parent with a defective copy of
the gene is required for ADPKD to be transmitted. However, to
trigger cyst formation in ADPKD, there must also be another
somatic polycystic kidney disease (PKD) gene inactivating
event or ‘second hit’ that leads to loss of heterozygosity and
inactivation of both copies of the PKD genes (Pei et al., 1999).
Disease severity is dependent on the level of polycystin pro-
tein expression and correlates with the amount of cyst forma-
tion. Less frequently, it can also occur secondary to autosomal
dominant polycystic liver disease (Davila et al., 2004; Drenth
et al., 2003).
ARPKD
ARPKD occurs as a result of mutations in the polycystic kidney
and hepatic disease 1 (PKHD1) gene on chromosome 6p12
that encodes the protein fibrocystin (Halvorson et al., 2010).
Truncated mutations of PKHD1 are associated with the most
severe phenotype of ARPKD with even two truncated muta-
tions capable of causing foetal death (Bergmann et al., 2003).
ARPKD is inherited in an autosomal recessive manner, which
means that both parents must have the defective gene in order
for the child to be affected by ARPKD.
Pathophysiology
Both forms of PKD result in cyst formation and destruction of
the structure and function of the kidneys. Cyst formation is
thought to be linked to primary cilia dysfunction, impairing
primary cilia-mediated signalling (Patel et al., 2009).
The primary cilium is a hair-like organelle that protrudes
from the apical membrane of renal tubular epithelial cells into
the lumen of the nephron. Distributed within these cilia are the
polycystin 1 and polycystin 2 proteins. Genetic mutations that
cause defects in these proteins, as well as the functionally
related fibrocystin protein, lead to cystic cell dedifferentiation,
reduced resorptive capacity and increased cell division and
apoptosis (Halvorson et al., 2010). These changes have been
shown to occur due to aberrancies in cell signalling involving
cyclic AMP (cAMP), Myc and mechanistic target of rapamycin
(mTOR) in both forms of PKD (Bergmann et al., 2018;
Ibraghimov-Beskrovnaya and Bukanov, 2007).
Specifically, in ADPKD, there is also evidence for the
involvement of the calcium, Wnt, vascular endothelial
growth factor (VEGF) and RAS-RAF-ERK signalling pathways
(Bergmann et al., 2018) (Fig. 1). Increased activation of the
RAS-RAF-ERK pathway works in synergy with increased epi-
dermal growth factor receptor (EGFR) expression to trigger
epithelial proliferation and cystic growth (Bergmann et al.,
2018). Ultimately, cystic growth exerts stress on nearby renal
epithelium, triggering apoptosis and increasing the likelihood
of further cyst formation (Leonhard et al., 2014). The gradual
formation of multiple cysts then compresses renal vessels and
triggers apoptosis leading to fibrosis (Halvorson et al., 2010).
The increased external pressure on the vessels triggers the
renin-angiotensin system causing systemic vasoconstriction
and sodium retention, further disrupting renal homeostasis
(Halvorson et al., 2010).
The extra-renal expression of polycystin in hepatocytes
and vascular smooth muscle can explain the development of
hepatic cysts and vascular abnormalities associated with PKD
(Fedeles et al., 2014; Kim et al., 2000). In vascular smooth
muscle, polycystins are involved in sensing shear stress, mod-
ulating muscle tone and regulating vasodilation through nitro-
gen oxide release (Lorthioir et al., 2015). Mutated proteins
therefore lead to reduced tone and poorly regulated dilation
of vessels in response to blood flow, resulting in aneurism
formation in the aorta and the cerebral vessels (Bergmann
et al., 2018).
Clinical manifestations of ADPKD
There is no single classic presentation of ADPKD, which
makes spot diagnosis in a clinic situation difficult. Clinicians
should therefore be aware of the wide range of presenting
327

Figure 1. The RAS-RAF-ERK signalling pathway.
Activation of the RAS-RAF-ERK signalling cascade stimulates
nuclear pathways that increase cell proliferation and contribute to
cyst formation.
AC ¼ adenylate cyclase, cAMP ¼ cyclic AMP, RAS ¼ RAS protein,
RAF ¼ RAF protein, ERK ¼ ERK protein.
symptoms and investigate appropriately to minimise compli-
cations and progression of PKD.
Presenting symptoms can be categorised as renal and
extra-renal (Table 1). Renal manifestations include renal
cysts, hypertension, haematuria, urinary tract infection, head-
aches, abdominal pain and/or abdominal mass on examin-
ation. Extra-renal manifestations include cardiac murmurs,
hernias and hepatomegaly.
Clinical manifestations of ARPKD
Although unlikely to be seen within the primary care setting,
neonates with ARPKD typically present with a history of oli-
gohydramnios, enlarged kidneys and the Potter sequence.
Other renal manifestations include renal cysts, polyuria or
polydipsia, hypertension and at advanced stages – chronic
kidney disease (CKD) or end stage renal failure (ESRF).
Extra-renal manifestations can include: liver disease, portal
hypertension, feeding problems or failure to thrive, as well
as the aforementioned Potter sequence (see Table 2).
Investigating PKD in primary care
Further investigation of suspected PKD is dependent on the
patient’s presenting symptoms. Imaging is a key to prompt
diagnosis of PKD, but it is also important to be aware of
the non-specific symptoms to follow up in primary care.
Figure 2 summarises investigations to consider and their
relevance to PKD.
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Diagnostic criteria for PKD
ADPKD
Diagnostic criteria were developed by Ravine et al. (1994).
These are based upon ultrasound (US) findings and the clinical
history of the patient. Currently modified Ravine’s criteria are
used as the diagnostic criteria for ADPKD for those with a
positive family history (referred to as ‘at risk’ patients)
(Pei et al., 2008). It should be noted that this is only for US
modality diagnosis, as use of this criteria for magnetic reson-
ance imaging (MRI) or computed tomography (CT) will result
in false positives.
The original Ravine’s criteria provide an exclusion criterion
for at-risk patients under 30 years in age with PKD1, stating
that fewer than two cysts in each kidney on US imaging is
sufficient to exclude ADPKD (Ravine et al., 1994). However,
as shown in Table 3, the modified Ravine’s criteria show that
there is insufficient evidence to support the use of diagnostic
US for these patients without genetic testing.
For individuals with no family history there are no formal
criteria. However, careful consideration of the clinical history,
radiological investigation detecting greater than 10 cysts in
each kidney, and exclusion of other renal pathology can pro-
vide strong evidence to support a diagnosis of ADPKD without
genetic testing.
ARPKD
The diagnostic criteria for ARPKD are based on imaging and
clinical findings (Table 4). Patients must meet imaging criteria
and at least one clinical criterion (modified from Halvorson
et al. (2010) and Zerres et al. (1996)).
Management of PKD
Management should be aimed at prompt treatment of acute
presentations, early recognition of complications and slowing
the progression of the disease. This section highlights key
points in managing different aspects of PKD.
Hypertension
Target blood pressure for patients with PKD should be 130/
80 mmHg, unless the patient is experiencing proteinuria which
lowers the target further to 125/75 mmHg. Adequate manage-
ment of hypertension has shown to reduce progression of the
underlying disease process.
Advising patients to make dietary and lifestyle changes
should be the first-line management of hypertension in PKD
prior to initiating drug therapy. Advice that should be given
includes:
. Restriction of dietary salt
. Smoking cessation
. Regular exercise
. High water intake and hydration
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Table 1. Clinical manifestations of autosomal dominant polycystic kidney disease.

Renal manifestations Key points
Renal cysts . Seen on different imaging modalities such as ultrasound, Computed Tomography and
Magnetic resonance imaging (see sections Investigations and Diagnostic criteria)

. Highly suggestive of PKD in patients with greater than 10 cysts per kidney, without
family history and evidence of other renal cystic disease
. Results in enlargement of kidneys and drop in renal function. The average rate of
decline is 4.4 to 5.9 mL/minute/year
Hypertension . Very common in patients. Can present before renal function decline is detectable
. More likely to develop with ageOften the first symptom that is picked up in younger
patients aged 20–34 years old without a known cause of secondary hypertension
. Associated with left ventricular hypertrophy and consequently increased cardiovas-
cular morbidity

Haematuria . Can be microscopic or macroscopic.

. Associated with decreased renal function
Abdominal pain . Variety of causes, such as renal cysts, renal stones, pyelonephritis, urinary tract
infection (UTI) and hepatomegaly

. Can present with flank pain

Abdominal mass . Palpable renal/hepatic mass on examination
. Highly suggestive of ADPKD if there is a known family history

Urinary tract infection . Common presenting symptoms of dysuria, urgency, suprapubic pain and fever
. 50–75% of all patients experience one episode
. Monitor for signs of complicated UTI

Headaches . Can suggest a cerebrovascular event or an intracranial bleed.

. Intracranial aneurysms (ICA) or ‘berry aneurysms’ in the anterior cerebral circulation
are associated with ADPKD.

. Symptoms of ICAs:
 Acute onset, severe headache
 Nausea and þ vomiting

 Loss of vision
 Sensitivity to light
 Weakness
 Slurred speech

 Facial pain/paralysis
 Stiff neck
 Seizures

 Loss of consciousness
 Mental confusion
(continued)

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Table 1. Continued.
Extra-renal manifestations Key points
Cardiac murmurs . Common murmurs include mitral regurgitation, aortic regurgitation
. Common cardiac abnormalities include mitral valve prolapse, dilated aortic root

Hernias . Patients commonly present with inguinal, incisional, para-umbilical hernias and/or
rectus abdominis diastasis
Hepatomegaly . Polycystic liver disease causes an enlarged liver due to multiple cysts.

. Patients are usually asymptomatic

. Hepatic cysts express oestrogen receptors in their epithelial lining stimulating cell
proliferation

. Therefore, women present with larger cysts than men. Equally, women who are multi-
parous, on oestrogen-containing hormone replacement or birth control have worse
disease

. More likely to develop with age

Table 2. Clinical manifestations of autosomal recessive polycystic kidney disease.

Renal manifestations Key points

Renal cysts . Bilateral enlarged kidneys

. Echogenic þ microscopic cysts with fusiform dilatation of collecting ducts seen on

imaging
Hypertension . Common in children with ARPKD
Polyuria and polydipsia . Risk of dehydration, especially when patients have concomitant illnesses causing
vomiting or diarrhoea
CKD or ESRD . Can occur at various ages

. Most develop kidney failure by 15 to 20 years old

. Will require long-term dialysis and ultimately kidney transplantation

Extra-renal manifestations Key points

Liver disease . Over time may develop polycystic liver disease and hepatic fibrosis

. Fibrosis may contribute to portal hypertension

. Can develop into Caroli’s syndrome (non-obstructed dilatation of the intrahepatic

bile ducts) which occurs in more than 60% of ARPKD patients
Portal hypertension . Common in children with ARPKD

. Can result in development of varices

. Can result in splenomegaly which increases the risk of internal bleeding

Feeding problems and failure to thrive . Feeding may be difficult due to reduced abdominal space from kidney
enlargement.

. This may also result in vomiting after feeds

 May need dietician input and/or feeding tube to prevent malnutrition

Potter’s sequence . Describes a group of facial, ear and limb deformity presenting with pulmonary
hypoplasia

. Leading to respiratory insufficiency as a direct result of oligohydramnios

. Poor prognosis

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Figure 2. First-line investigations to consider.

Imaging Bloods

Renal ultrasound (US) Urea and Electrolytes (U+Es)

•1st line invesgaon •Can be normal
•Non-invasive, widely available •Elevated U+Es are rare in paents less
than 30 years of age in ADPKD
•Diagnosc if posive findings with known family history (see
Diagnosc criteria) •Not sensive
•In children with risk factors, large echogenic kidneys even without •Renal funcon and electrolytes should
macroscopic cysts is diagnosc be monitored in paents on ACE
inhibitors or diurecs

CT abdomen and pelvis

•2nd line invesgaon if US is not diagnosc
•Used especially in paents less than 30 years old with PKD2 Other
mutaon
•In the absence of a family history and no evidence of alternave
cysc renal disease, it is diagnosc when greater than 10 cysts are
seen bilaterally. There should be no evidence supporng an
alternave cysc renal disease. Urine dip and culture
•In the presence of a family history of ADPKD, diagnosis is presumed •Tested in all paents to evaluate
when at least 2 unilateral or bilateral cysts are seen in paents less increased urinary albumin excreon or
than 30 years of age; 2 cysts in each kidney in paents 30 to 59 proteinuria
years of age; and 4 cysts in each kidney in paents 60 years of age or •Increased urinary albumin excreon or
older. proteinuria suggests
•Consideraon must be taken with regards to contrast reacons, •higher risk of progression to CKD
renal funcon and radiaon risk •high incidence of le ventricular
hypertrophy (LVH) in ADPKD
•Common findings of microscopic or
macroscopic haematuria
•If leukocyte posive should send sample
MRI for culture
• 2nd line invesgaon if US is not diagnosc •Culture should be sent when symptoms
•Used especially in paents less than 30 years old with PKD2 mutaon of UTI are present
•Good to use when renal funcon poor or unable to use iodine
contrast
•Use of gadolinium contrast should be avoided in paents with
advanced kidney disease (GFR <30 mL/minute/1.73 m²).
•In the absence of a family history, considered presumpve diagnosis ECG
if >10 cysts in each kidney and there is no evidence supporng •For paents with cardiac murmurs or
alternave cysc renal disease suspected le ventricular dysfuncon

CT Head
•To invesgate sudden-onset, severe, or atypical headaches
•Non-contrast CT is more sensive to MRI for detecng intracranial
bleed

Pharmacological therapy includes different classes of anti-
hypertensives as well as diuretics. Angiotensin converting
enzyme (ACE) inhibitors should be used as first-line agents;
angiotensin-II receptor blockers should be considered when
the patient is not tolerant to ACE inhibitors. Renal function
tests and electrolytes should be closely monitored during ther-
apy. Currently, combination therapy has not proven to be
effective in improvement of overall renal function and total
kidney volume (Schrier et al., 2014).
Beta-blockers may also be considered for patients with
concomitant cardiovascular co-morbidities. Beta-blockers
that have shown to be the most effective in such patients
include non-cardio selective beta-blockers with alpha-block-
ing properties such as:
. Labetalol
. Carvedilol
. Metoprolol
. Nebivolol
Diuretics should be used only in combination with other
classes of drugs, and with caution, as they can trigger a decline
in renal function. Diuretics should be introduced in patients with
volume overload as well as patients with refractory hypertension.
Subarachnoid haemorrhage
Patients with PKD are at increased risk of subarachnoid haem-
orrhage (SAH). Therefore, SAH should be suspected in
patients with sudden onset severe headache with or without
the presence of other neurological manifestations. Patients
with suspected intra-cranial should be urgently referred for a
neurosurgical opinion for consideration of coiling or clipping.
Medical management includes the use of a calcium channel
blocker. Nimodipine 60 mg orally 4 hourly for 21 days has
proven to be effective in improving neurological outcomes,
not cerebral vasospasm (Connolly et al., 2012).
Renal cysts with superimposed infection
Acute onset abdominal pain and fever should raise suspicion
of an infected renal cyst and should be investigated

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Table 3. US-based modified Ravine’s criteria for kidney injury. Oral or rectal Diclofenac 75–150 mg daily
autosomal dominant polycystic kidney disease. divided into two or three doses is recommended in patients
with renal or ureteric colic.
Number of cysts Patients with the following criteria require urgent referral
Age (years) Positive family history for urology opinion and acute management:
<30 At least three in one or both kidneys . Clinical evidence of infection such as fever

30–39 At least three in each kidney . Shock or sepsis

. Patients with suspected acute kidney injury
40-59 At least two in each kidney
. Dehydration
>60 At least four in each kidney
Management of stones in the secondary care setting
depends on the stone type, size, presence or absence of
Table 4. Diagnostic criteria for autosomal recessive urinary tract obstruction and any contraindications to instru-
polycystic kidney disease. mentation. Stones that are likely to pass spontaneously are
managed conservatively with fluid intake and calcium
Imaging criteria . Enlarged, echogenic kidneys channel blockers or alpha blockers. Stones unlikely to do
with poor cortical medullary so necessitate removal or urological intervention via extra-
differentiation corporeal shock wave lithotripsy, ureteroscopy, percutan-
eous nephrolithotomy or open surgery as indicated
. May or may not have macro-
(NICE, 2019).
scopic cysts
Clinical criteria . Absence of renal cysts in both
parents on US Halting disease progression
. Signs of hepatic fibrosis
Tolvaptan is a vasopressin V2 receptor antagonist that is used
. Pathoanatomical evidence of in a selected group of patients to slow the progression of dis-
ARPKD in affected sibling ease by slowing cyst formation and subsequently improving
overall renal function on the long-term. Patients that may be
. Parenteral consanguinity considered for therapy have chronic kidney disease stage 2 or
Source: Halvorson et al. (2010), US findings as defined by Garel 1984. 3 at the start of treatment with evidence of rapidly progressing
disease. Tolvaptan is commenced in specialist centres and
requires referral from primary care.
accordingly. Cysts can become infected secondary to recurrent
urinary tract infections.
The mainstay in management of infected renal cysts is anti-
biotics. Fluoroquinolones are usually the first-line antibiotics
Monitoring and follow-up
that are used in managing such patients however; local Trust Patients with PKD require regular monitoring and follow-up
antimicrobial guidelines should provide guidance for appro- for treatment complications and disease progression. At min-
priate antibiotic regime. Additionally, infected cysts may also imum, an annual or bi-annual review is essential in primary
require percutaneous or surgical drainage if an adequate care (see Box 1). The frequency of follow-up is largely
response is not achieved by antimicrobials alone. dependent upon the stage of disease and the patient’s co-
morbidities and can be adjusted as necessary:
. Systemic hypertension should be followed up bi-annually
Urinary tract infections or annually to ensure optimum control. Patients without
hypertension can be followed up every 1 to 3 years.
Differentiating between urinary tract infections and cyst infec- Advice regarding healthy diet, exercise and lifestyle modi-
tions remains a challenge in clinical practice. Therefore, it is fications as expected for other patients with hypertension
important to exclude cyst infections in patients with suspected should be re-emphasised
urinary tract infections that are non-resolving. It is advised to
refer to local Trust guidelines for specific regimes, and choice . Renal function monitoring is strongly advised, particularly
of antibiotic should be guided by urine culture results. for patients medically managed for hypertension as medi-
cation dosing may need to be adjusted
. Active nephrolithiasis should be followed up bi-annually or
Renal stones annually to monitor metabolic activity
Patients that present with severe pain secondary to stones in . As renal function declines, referral to a nephrologist may be
the urinary tract should be offered analgesia as early as pos- appropriate to consider starting RRT. Once on RRT, further
sible. Renal function should be assessed to rule out acute monitoring will be required.

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. Health providers should be aware of the high prevalence of
depression in this cohort of patients. Consideration should
be given to actively monitor patient’s ideas, concerns and
expectations at every consultation
Genetic counselling and testing
As with all genetic conditions, there are serious implications
for the families of those affected. Genetic counselling should
be offered and GPs should refer patients to the nearest NHS
regional genetic centre. GPs should advise patients that the
counselling will aim to provide accurate and clear information
regarding PKD to them and their family. The process of coun-
selling should involve detailed advice on the natural history
of the disease, inheritance patterns, recurrence risk and
prognosis.
Genetic counselling is particularly important for those plan-
ning a family. Before pregnancy, patients may have many ques-
tions surrounding fertility, risk of PKD for the future baby and
impact on the pregnancy itself. These questions should be
answered fully with the help of the multidisciplinary team invol-
ving the GP, midwife or obstetrician. Information should be
given on options for pre-implantation genetic diagnosis and
in vitro fertilisation, amniocentesis, and chorionic villous sam-
pling prior to pregnancy. Reassurance should be given that
many women with PKD go on to have healthy babies.
Genetic testing is not routinely used for diagnosis of PKD.
However, testing can be considered in situations where
patients with a positive family history are:
. Asymptomatic or other tests have been unequivocal
. Planning to donate a kidney to a relative with PKD
. Planning a family
For children of affected families, genetic testing is offered at
any age, as it is useful in the early prevention of PKD compli-
cations. Testing for either adults or children is available on the
NHS when referred by a specialist nephrologist or geneticist.
Genetic testing of the general population is not routine and
will not be offered.
Psychosocial impact on patients and
their families
PKD has significant immediate and longer-term sequelae.
It is important for primary care doctors to recognise the
psychological and social impact for patients and their
families. Previous studies have noted a relationship between
PKD and the onset of depression and anxiety. The depres-
sive symptoms may originate due to a combination of
family guilt relating to the transmission of genetic disease
or the isolation associated with lifestyle modifications required
to comply with renal disease treatment, e.g. dialysis
(De Barros et al., 2011; Pérez et al., 2011). Clinicians should
be aware that these symptoms can be more common
when commencing dialysis, as patients feel an acute loss of
Box 1. Annual review of polycystic kidney disease in
primary care.
What can we do on annual review of PKD?
Annual review of patients with PKD is important to assess
the progression of disease, presence or absence of compli-
cations and overall quality of life
. Take a thorough history
Patients can develop new symptoms as the disease pro-
gresses. It is important to enquire about any symptoms
suggestive of UTI, haematuria, abdominal pain or disten-
sion. A focused cardiac history should be obtained to look
for evidence of heart failure
. Examine the patient
Physical examination should aim to identify palpable cysts,
hepatomegaly or flank tenderness on abdominal examin-
ation. Cardiovascular examination should be focused on
identifying left ventricular hypertrophy, murmurs or evi-
dence of heart failure
. Blood pressure monitoring
Blood pressure should be measured to ensure adequate
control within target levels. A review of the patient’s medi-
cation should be undertaken to optimise management.
Patients can also be advised to monitor their blood pres-
sure at home and to keep a record of their readings
. Renal function monitoring
Renal function blood tests should be assessed to look
for decline in renal function with possible referral to specialist
services if required. In addition, severe anaemia may be an
indication to commence erythropoietin-stimulating agents
and therefore would also warrant referral to a nephrologist
. Provide psychosocial support
Anxiety and depression can be common in patients with
PKD. Clinicians should take every opportunity to enquire
about the patient’s overall wellbeing and available support
at home
control and independence over their health (Watnick et al.,
2003).
Provision of psychosocial support can also be the key to
preventing deterioration of kidney function, as depressive
symptoms in patients with kidney disease have been correlated
with a faster decrease in kidney function and an increased risk
of starting dialysis therapy at a higher eGFR (Tsai et al., 2012).
There are many charitable groups that offer face-to-face
meetups, information evenings, and guidance on living with
PKD. British organisations such as the UK Renal
Psychosocial Workforce operate to support patients through
interventions such as psychological counselling, organising
access to social workers and encouraging engagement in
music and play therapy. Patients should feel supported
and be encouraged to seek advice when needed and clin-
icians should be aware of services available in the local area
(see Box 2).
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Box 2. A list of organisations that offer patient
support.
. Polycystic disease charity (UK based):
www.pkdcharity.org.uk/
. PKD International (Switzerland based): https://
pkdinternational.org/
. PKD Australia (Australia based): https://
pkdaustralia.org/
. PKD Foundation (US based): https://pkdcure.org/
. National Kidney Foundation (US based):
www.kidney.org/
KEY POINTS
. ADPKD is an autosomal dominant variant of PKD, usu-
ally due to a mutation in PKD1/2 and presents in
adulthood
. ARPKD is an autosomal recessive variant of PKD due to
a mutation in PKHD1 and presents in childhood
References and further information
Bergmann C, Guay-Woodford L, Harris P, et al. (2018) Polycystic
kidney disease. Nature Reviews Disease Primers 4(1DOI:
10.1038/s41572-018-0047-y.
Bergmann C, Küpper F, Dornia C, et al. (2005) Algorithm for effi-
cient PKHD1mutation screening in autosomal recessive poly-
cystic kidney disease (ARPKD). Human Mutation 25(3):
225–231. DOI: 10.1002/humu.20145.
Bergmann C, Senderek J, Sedlacek B, et al. (2003) Spectrum of
mutations in the gene for autosomal recessive polycystic
kidney disease (ARPKD/PKHD1). Journal of the American
Society of Nephrology 14(1): 76–89. DOI: 10.1097/
01.asn.0000039578.55705.6e.
Connolly E, Rabinstein A, Carhuapoma J, et al. (2012) Guidelines
for the management of aneurysmal subarachnoid hemorrhage.
Stroke 43(6): 1711–1737. DOI: 10.1161/STR.0b013e3182587839.
Davies F, Cole G, Harper P, et al. (1991) Polycystic kidney disease
re-evaluated: A population-based Study. QJM: An International
Journal of Medicine 79(290): 459–460.
Davila S, Furu L, Gharavi A, et al. (2004) Mutations in SEC63 cause
autosomal dominant polycystic liver disease. Nature Genetics
36(6): 575–577. DOI: 10.1038/ng1357.
De Barros BP, Nishiura JL, Heilberg IP, et al. (2011) Anxiety,
depression, and quality of life in patients with familial glomer-
ulonephritis or autosomal dominant polycystic kidney disease.
J Bras Nefrol 33(2): 120–128. DOI: 10.1590/S0101-
28002011000200002.
Drenth J, te Morsche R, Smink R, et al. (2003) Germline mutations in
PRKCSH are associated with autosomal dominant polycystic liver
disease. Nature Genetics 33(3): 345–347. DOI: 10.1038/ng1104.
Fedeles S, Gallagher A and Somlo S (2014) Polycystin-1: A master
regulator of intersecting cystic pathways. Trends in Molecular
Medicine 20(5): 251–260. DOI: 10.1016/j.molmed.2014.01.004.
334
InnovAiT
. GPs should recognise the wide range of presenting
symptoms and be aware of red flags such as SAH and
intracranial aneurysms that require urgent medical care
and escalation
. Genetic testing is not routinely necessary and diagnosis
is based on clinical history and imaging in patients with
positive family history
. Treatment is symptom based and consistent monitoring
of complications to optimise management is advised in
primary care
. The role of GPs in understanding the impact of PKD on
patients and families is crucial in providing appropriate
genetic counselling and support
ORCID iDs
Soo Oh https://orcid.org/0000-0002-2449-7926
Rabeet Khan https://orcid.org/0000-0001-7081-530X
Garel L (1984) Sonography of renal cystic disease and dysplasia in
infants and children. In: Brodehl J, Ehrich JHH (eds). Paediatric
Nephrology. Berlin: Springer.
Gilg J, Caskey F and Fogarty D (2016) UK Renal Registry 18th
Annual Report: Chapter 1 UK renal replacement therapy inci-
dence in 2014: National and centre-specific analyses. Nephron
132(1): 9–40. DOI: 10.1159/000444815.
Halvorson C, Bremmer M and Jacobs S. (2010) Polycystic kidney
disease: Inheritance, pathophysiology, prognosis, and treat-
ment. International Journal of Nephrology and Renovascular
Disease 3: 69–83. DOI: 10.2147/ijnrd.s6939.
Hartung E and Guay-Woodford L (2014) Autosomal recessive poly-
cystic kidney disease: A hepatorenal fibrocystic disorder with
pleiotropic effects. Pediatrics 134(3): e833–e845. DOI: 10.1542/
peds.2013-3646.
Ibraghimov-Beskrovnaya O and Bukanov N (2007) Polycystic
kidney diseases: From molecular discoveries to targeted thera-
peutic strategies. . Cellular and Molecular Life Sciences 65(4):
605–619. DOI: 10.1007/s00018-007-7362-x.
Kim K, Drummond I, Ibraghimov-Beskrovnaya O, et al. (2000)
Polycystin 1 is required for the structural integrity of blood ves-
sels. Proceedings of the National Academy of Sciences 97(4):
1731–1736. DOI: 10.1073/pnas.040550097.
Leonhard W, Zandbergen M, Veraar K, et al. (2014) Scattered dele-
tion of PKD1 in kidneys causes a cystic snowball effect and
recapitulates polycystic kidney disease. Journal of the
American Society of Nephrology 26(6): 1322–1333. DOI:
10.1681/ASN.201308086.
Lorthioir A, Joannidès R, Rémy-Jouet I, et al. (2015) Polycystin defi-
ciency induces dopamine-reversible alterations in flow-
mediated dilatation and vascular nitric oxide release in
humans. Kidney International 87(2): 465–472. DOI: 10.1038/
ki.2014.241.
InnovAiT
NICE (2019) Clinical knowledge summaries. Renal or ureteric colic
– acute. Available at: https://cks.nice.org.uk/renal-or-ureteric-
colic-acute#!scenario (accessed 04 August 2019).
Patel V, Chowdhury R and Igarashi P (2009) Advances in the patho-
genesis and treatment of polycystic kidney disease. Current
Opinion in Nephrology and Hypertension 18(2): 99–106. DOI:
10.1097/MNH.0b013e3283262ab0.
Pei Y, Obaji J, Dupuis A, et al. (2008) Unified criteria for ultrasono-
graphic diagnosis of ADPKD. Journal of the American Society of
Nephrology 20(1): 205–212.
Pei Y, Watnik T, He N, et al. (1999) Somatic PKD2 mutations in
individual kidney and liver cysts support a ‘‘two-hit’’ model of
cystogenesis in type 2 autosomal dominant polycystic kidney
disease. Journal of the American Society of Nephrology 10(7):
1524–1529.
Perez TS, Rodriguez A, Buset N, et al. (2011) Psychonephrology:
Psychosocial aspects in autosomal dominant polycycstic kid-
ney disease. Nefrologia 31(6): 716–722. DOI: 10.3265/
Nefrologia.pre2011.Jul.10847.
Ravine D, Sheffield L, Danks D, et al. (1994) Evaluation of ultra-
sonographic diagnostic criteria for autosomal dominant polycys-
tic kidney disease 1. The Lancet 343(8901): 824–827. DOI:
10.1016/s0140-6736(94)92026-5.
RCGP. Clinical topic guide: Genomic medicine. Available at:
www.rcgp.org.uk/training-exams/training/gp-curriculum-over-
view/document-version.aspx (accessed 29 January 2020).
Schrier R, Abebe K, Perrone R, et al. (2014) Blood pressure in early
autosomal dominant polycystic kidney disease. New England
Journal of Medicine 371(24): 2255–2266. DOI: 10.1056/
NEJMoa1402685.
AKT question relating to polycystic kidney disease
Single Best Answer
You see a 42-year-old man with known polycystic kidney
disease. He has been checking his blood pressure at home
which is 150/100. He is otherwise well and asymptotic.
Which SINGLE antihypertensive is the first-line
choice? Select ONE option only.
Dr Anish Kotecha
GP Partner, Cwmbran Village Surgery, Wales
Shaw C, Simms R, Pitcher D, et al. (2014) Epidemiology of patients
in England and Wales with autosomal dominant polycystic
kidney disease and end-stage renal failure. Nephrology
Dialysis Transplantation 29(10): 1910–1918. DOI: 10.1093/
ndt/gfu087.
Spithoven E, Kramer A, Meijer E, et al. (2014) Renal replacement
therapy for autosomal dominant polycystic kidney disease
(ADPKD) in Europe: Prevalence and survival–an analysis of
data from the ERA-EDTA Registry. Nephrology Dialysis
Transplantation 29(suppl 4): iv15–iv25. DOI: 10.1093/ndt/
gfu017.
Tsai Y, Chiu Y, Hung C, et al. (2012) Association of symptoms of
depression with progression of CKD. American Journal of
Kidney Diseases: The Official Journal of the National Kidney
Foundation 60(1): 54–61. DOI: 10.1053/j.ajkd.2012.02.325.
Watnick S, Kirwin P, Mahnensmith R, et al. (2003) The prevalence
and treatment of depression among patients starting dialysis.
American Journal of Kidney Diseases 41(1): 105–110. DOI:
10.1053/ajkd.2003.50029.
Willey C, Blais J, Hall A, et al. (2016) Prevalence of autosomal
dominant polycystic kidney disease in the European Union.
Nephrology Dialysis TransplantationDOI: 10.1093/ndt/gfw240.
Yoder B (2007) Role of primary cilia in the pathogenesis of poly-
cystic kidney disease. Journal of the American Society of
Nephrology 18(5): 1381–1388. DOI: 10.1681/ASN.2006111215.
Zerres K, Rudnik-Schöneborn S, Deget F, et al. (1996) Autosomal
recessive polycystic kidney disease in 115 children: Clinical
presentation, course and influence of gender.
Arbeitsgemeinschaft für Pädiatrische, Nephrologie 85(4):
437–445. DOI: 10.1111/j.1651-2227.1996.tb14056.x.
DOI: 10.1177/1755738020912359
A. Angiotensin converting enzyme inhibitor
B. Alpha-blocker
C. Beta-blocker
D. Calcium channel blocker
E. Diuretic
Answer DOI: 10.1177/1755738020913193
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