Polycystic Kidney Disease
POLYCYSTIC KIDNEY DISEASE
Sumi Ramadhani, Radar Tarigan, Abdurrahim Rasyid Lubis, Ayu Nurul Zakiah
Division of Nephrology-Hypertension
Department of Internal Medicine University of North Sumatera
ABSTRACT
Polycystic Kidney Disease is an inherited condition that causes small, fluidfilled sacs called cysts to develop in the kidneys. The disease can be inherited in
autosomal dominant and recessive forms. Estimates of PKD’s prevalence range
from one in 400 to one in 1,000 people. In many cases, PKD does not cause signs or
symptoms until cysts are half an inch or larger. When present, the most common
symptoms are abdominal pain, haematuria, urinary tract infection, hypertension,
renal stones and renal failure.
We reported one case of a 55 years old male patient, admitted to Adam
Malik Hospital with abdominal distention. He was diagnosed with multiple cysts in
the liver and kidney. Family member whose experienced abdominal distention was
found to his brother and sister but undiagnosed because they were died. Urine
output was 1500 cc/24 hours. On physical examination he was normoweight, blood
pressure 160/100 mmHg, pulse rate, respiratory rate and temperature within normal
limit. Abdominal examination was asymmetrical distension with hepar, spleen and
kidney was hard to define. Examination or other systems were within normal limits.
Investigation showed complete blood count and urinalysis was normal.
Renal function test showed ureum 113 mg/dL and creatinine 6.09 mg/dL (creatinine
clearance 11,63 mL/min). Liver function test was normal. Chest radiography was
normal. Funduscopy showed retinopathy hypertension grade II oculi dextra and
sinistra. Abdominal ultrasonography showed multiple cysts in the liver and kidney
bilateral and CT scan abdomen showed multiple cysts may still be on the hepar and
both kidney accompanied by hepatomegaly and nefromegali ec bilateral Polycystic
disease, suspect nephrolitiasis bilateral and bilateral pleural Effusion.
Keyword : polycystic kidney disease, hypertension
INTRODUCTION
Autosomal-dominant polycystic kidney disease (ADPKD), an inherited kidney disease
that affects 12.5 million people worldwide in all ethnic groups, is responsible for up to 10% of
patients in end-stage renal disease (ESRD) and is a major burden on public health. 1 ADPKD is an
inherited condition that causes small, fluid-filled sacs called cysts to develop in the kidneys. 2 It is
characterized by relentless development and growth of cysts in the kidney and other organs (eg,
liver, pancreas, spleen) causing progressive kidney enlargement associated with hypertension,
abdominal fullness and pain, episodes of cyst hemorrhage, gross hematuria, nephrolithiasis, cyst
infections, and reduced quality of life.1,3
The disease can be inherited in autosomal dominant and recessive forms. Cyst
development and growth is gradual, yet despite the massive growth of the kidneys, the
glomerular filtration rate (GFR) in these patients is typically conserved until ages 30–40,
followed by a rapid, linear decline after this time. By the age of 70, 50% of patients with
ADPKD will require dialysis or kidney transplantation.4
Autosomal recessive polycystic kidney disease (ARPKD), by contrast, typically presents
in a younger patient population. The disease is characterized by cystic dilation of the collecting
ducts of the kidneys, along with dysgenesis of the biliary ductal plate, resulting in congenital
hepatic fibrosis and often death in the perinatal period due to respiratory failure. 4
EPIDEMIOLOGY
Estimates of PKD’s prevalence range from one in 400 to one in 1,000 people. According
to the United States Renal Data System, PKD accounts for 2.2 percent of new cases of kidney
failure each year in the United States. Annually, eight people per 1 million have kidney failure as
a result of PKD.5
Extrarenal manifestations such as multiple liver cysts occur in 60–90% and intracranial
aneurysms in 5–10% of the patients. ADPKD is a leading cause for renal replacement therapy
comprising 5–10% of all patients with end-stage renal failure.6 Approximately 1 per 800-1000
population carries a mutation for this condition. ADPKD is slightly more severe in males than in
females, but the difference is not statistically significant. 3,5
CASE REPORT
55 years old male patient, admitted to Adam Malik Hospital on August 31th 2015 with a
chief complaint is abdominal distention. He experienced this condition for about one year before
hospital admission. Abdominal pain was found in epigastric region until upper right quadran
abdomen but he had no nausea and vomitus. He had no problem with defecation and urinating.
Swelling of the extremity and history of having jaundice were not found, but he was diagnosed
with multiple cysts in the liver and kidney. History of hypertension was not found. Family
member whose experienced abdominal distention was found in his brother and sister but
undiagnosed because they were died. Urine output was 1500 cc/24 hours.
On physical examination he was normoweight with body mass index (BMI) 22 kg/m 2,
blood pressure 160/100 mmHg, pulse rate was 90 beats per minute, respiratory rate 20 x/minute
and temperature 36 C. Abdominal examination was asymmetrical distension with hepar, spleen
and kidney was hard to define. Examination or other systems were within normal limits.
Laboratory finding showed Hb 13 mg/dl, WBC count 9980/ul and platelet count was
202.000/mm3. Urine laboratory analysis was normal. Renal function test showed ureum 113
mg/dL and creatinine 6.09 mg/dL (creatinine clearance 11,63 mL/min). Liver function test was
normal, SGOT 25 I/L, SGPT 18 I/L, total bilirubin 0,2 and direct bilirubin 0,06 mg/dl, albumin
3,3 g/dl.
Chest radiography was normal. Funduscopy showed retinopathy hypertension grade II
oculi dextra and sinistra. Abdominal ultrasonography showed multiple cysts in the liver and
kidney bilateral and abdominal CT scan showed multiple cysts may still be on the hepar and both
kidney accompanied by hepatomegaly and nefromegali ec bilateral Polycystic disease, suspect
nephrolitiasis bilateral and bilateral pleural Effusion.
The patient was diagnosed as polycystic kidney disease and hypertension. He was only
treated with antihypertension, captopril 3 x 25 mg and amlodipin 1 x 5 mg and no indication to
had hemodialysis.
PATHOPHYSIOLOGY
ADPKD is characterized by the progressive development and enlargement of multiple
cysts in each kidney. Ultimately, the precise architecture of the kidney (consisting of
approximately 1 million nephrons) is totally replaced by an often greatly enlarged organ,
consisting of a few thousand cysts, separated by fibrotic regions. The cysts are thought to form
from any region of the tubular segment in the kidney, but only a small proportion of nephrons
develops cysts. In rare cases where fetal ADPKD kidneys have been examined, some microcysts
are already evident, indicating the onset of cyst development in the fetus, although cyst initiation
may continue into adult life.7
Microdissection studies show that ADPKD cysts develop as outpouchings of the tubule
and the early stages are associated with abnormalities of the basement membrane and cell
differentiation. Cyst expansion requires epithelial cell proliferation and altered secretory
characteristics of the epithelia, which may be associated with changes in the normally polarized
state of the cells. Normal renal tissue is destroyed by cyst expansion, interstitial fibrosis and
possibly programmed cell death, apoptosis.7
ADPKD should be considered a systemic disease because many disease manifestations
are seen outside the kidney. Cysts are found in many organs, most notably the liver, and
associations are seen with several noncystic lesions (Table 1). Many of these abnormalities are
defects of connective tissue and indicate a role for the ADPKD protein(s) beyond the kidney.7
Table 1. Nonrenal abnormalities associated with
autosomal dominant polycystic kidney disease
Approximately 85-90% of patients with ADPKD have an abnormality on the short arm of
chromosome 16 (ie, ADPKD type 1 [ADPKD1]). A second defect, termed ADPKD type 2
(ADPKD2), is responsible for 10-15% of ADPKD cases and is found on the long arm of
chromosome 4. A third genotype may exist, but no genomic locus is assigned. 3
A decrease in urine-concentrating ability is an early manifestation of ADPKD. The cause
is not known. Plasma vasopressin levels are increased; this increase may represent the body's
attempt to compensate for the reduced concentrating capacity of the kidneys and could contribute
to the development of renal cysts, hypertension, and renal insufficiency. 3
CLINICAL FEATURES
In many cases, PKD does not cause signs or symptoms until cysts are half an inch or
larger.4,5 When present, the most common symptoms are abdominal pain, haematuria, urinary
tract infection (eg, acute pyelonephritis, infected cysts, perinephric abscess), hypertension, renal
stones and renal failure.3,4,7,8 Hypertension is found in the majority of patients, the frequency
increasing with declining renal function.4,7,8
Nephrolithiasis is another common complication of ADPKD, occurring in 20%–30% of
patients. Stone formation should be suspected in any ADPKD patient with an acute onset of pain,
hematuria, or deteriorating kidney function. Stone composition is typically uric acid or calcium
oxalate, with decreased ammonia excretion, low urinary pH, low citrate concentration, and
urinary stasis thought to contribute to stone formation. The presence of stones can be confirmed
with either renal ultrasonography (US) or CT scanning, with the latter being better at detecting
stones given the limitations of US in the presence of parenchymal or cyst wall calcifications.4
DIAGNOSIS
Examination in patients with ADPKD may demonstrate the following :3
-
Hypertension: One of the most common early manifestations of ADPKD, in which
increased diastolic BP is the rule; clinical course in ADPKD is usually more severe early
on, then becomes less problematic as the renal insufficiency progresses
-
Palpable, bilateral flank masses: In advanced ADPKD
-
Nodular hepatomegaly: In severe polycystic liver disease
-
Rarely, symptoms related to renal failure (eg, pallor, uremic fetor, dry skin, edema)
Testing3
Routine laboratory studies include the following :
-
Serum chemistry profile, including calcium and phosphorus
-
CBC count
-
Urinalysis
-
Urine culture
Imaging studies3
Radiologic studies used in the evaluation of ADPKD include the following:
-
Ultrasonography: Technique of choice for patients with ADPKD and for screening
patients' family members; useful for exploring abdominal extrarenal features of ADPKD
(eg, liver cysts, pancreatic cysts)
-
CT scanning: Not routine; useful in doubtful pediatric cases or in complicated cases (eg,
kidney stone, suspected tumor)
-
MRI: Not routine; helpful in distinguishing renal cell carcinoma from simple cysts;
criterion standard to help determine renal volume for clinical trials when testing drugs for
ADPKD; best imaging tool to monitor kidney size after treatment to assess progress
-
MRA: Not routine; preferred imaging technique for diagnosing intracranial aneurysms
For at-risk adults the potential benefits of presymptomatic diagnosis usually outweigh the
risks, and it is most commonly performed by ultrasonography (US), which is inexpensive and
widely available.1 Genetic testing may be performed, in which the major indication is for genetic
screening in young adults with negative ultrasonographic findings who are being considered as
potential kidney donors.1,3
TREATMENT
Treatments that extend kidney survival in ADPKD do not currently exist. Ideally,
treatment should start early, when kidney parenchyma is relatively preserved. 7
Management of Hypertension
Hypertension is a common and early manifestation of disease in ADPKD and, when
uncontrolled, is associated with an earlier progression to end-stage renal disease and
cardiovascular complications, compared to normotensive ADPKD patients. 1,5 Data supporting
disease-specific blood-pressure (BP) targets are limited. The general advice of the 2012 KDIGO
Clinical Practice Guideline for the Management of BP in chronic kidney disease can therefore be
followed, suggesting a BP target ≤ 140/90 mmHg. BP control can be achieved by lifestyle
modification and medical treatment. Agents that interfere with the renin-angiotensin-aldosterone
system (RAAS) are first-line BP-lowering agents in combination with a sodium-restricted diet.
There is controversy as to which second-line BP-lowering agents should be used. Large
randomized controlled trials (RCTs) in non-ADPKD populations suggested that calcium channel
blockers and diuretics may be preferred over beta-blockers for cardiovascular protection.1
Treatment of hypertension with b-blockers and angiotensin converting enzyme inhibitors is
important, as cardiovascular complications are a frequent cause of death in patients with
ADPKD.7
Regardless of the agent utilized, tight blood pressure control has been shown to delay the
progression of disease in ADPKD. Other currently-accepted treatment strategies in ADPKD
include salt-restriction (no more than 6 grams of sodium chloride daily), low protein intake (no
more than 1 gram per kilogram of body weight per day), regular exercise, maintenance of a
healthy body weight, and frequent water intake.4
Hematuria and Cyst Hemorrhage
Cyst hemorrhage and gross hematuria are frequent complications of ADPKD. Gross
hematuria can result from cyst hemorrhage, nephrolithiasis, infection, and, rarely, from renal cell
or urothelial carcinoma. Cyst hemorrhage can be associated with fever, and differentiation from
cyst infection may be difficult. Episodes of cyst hemorrhage or gross hematuria are usually selflimited and resolve within 2–7 days. If symptoms persist, a possible neoplasm should be
excluded. Rarely, bleeding can be persistent or severe, sometimes with extensive subcapsular or
retroperitoneal hematomas, requiring hospitalization. Temporary discontinuation of RAAS
inhibitors and diuretics to avoid acute kidney injury during an episode of acute cyst hemorrhage
has been suggested.1
Management Renal Cyst Infection
Recent meta-analyses highlight the course and successful management of both renal and
liver cyst infections. The presence of fever, abdominal pain, and high sedimentation rate or level
of C-reactive protein should raise the suspicion of a cyst infection, but the differential diagnosis
is broad. Blood and urine cultures may be negative. 18 F-fluorodeoxyglucosepositron emission
tomography may be helpful in identifying infected cysts.1 Lipid-permeable anti-microbial agents
such as fluoroquinolones and trimethoprim-sulfamethoxazole, depending on sensitivity (if
available), remain the standard treatment for cyst infections. 1,4
Treatment options for severe polycyctic liver disease (PLD) include surgical and medical
therapy. Surgical options encompass aspiration/sclerotherapy, fenestration, partial or segmental
hepatectomy, and liver transplantation. Somatostatin analogs were shown to reduce or stabilize
liver volume in severe PLD though their use is currently restricted to either clinical trials or
compassionate use. A prolonged course of a fluoroquinolone, combined with early, percutaneous
cyst drainage, provides the best treatment results. Recurrence of liver cyst infection is frequent.1
Management of Chronic Pain
Kidney pain is the most common renal manifestation in ADPKD. It may develop after an
episode of acute pain and is likely maintained by aberrant activity of sensory and autonomic
neurons innervating the kidney.1 Pain management can be difficult in these patients as standard
approaches, including use of non-steroidal agents, should be avoided, given their effect on the
kidneys. Use of narcotic analgesics should be reserved for acute episodes to minimize the
potential for dependence. Despite these strategies, anywhere from 50%–70% of patients with
ADPKD have pain that is uncontrolled with oral analgesics. Accordingly, when conservative
measures fail, surgical options are available.4
These include cyst decortication, which is now performed laparoscopically and has been
found in a study of 29 ADPKD patients to result in a greater than 50% improvement in pain in
73%, 52%, and 81% of patients, at 12, 24, and 36 months, respectively. Similarly, a different
study of 15 ADPKD patients treated with laparoscopic decortication revealed that pain decreased
an average of 62% in 73% of cases at a mean follow-up of 2.2 years (range 0.5–5). An additional
option that holds promise in treating symptoms associated with the mass effect of the kidneys
includes renal artery embolization. This procedure involves embolization of the main renal
artery, although selective embolization has been attempted. It is typically performed only on
dialysis-dependent patients as it eliminates any remaining renal function, essentially decreasing
GFR to zero.4
Thoracoscopic sympathosplanchnicectomy may be helpful in some patients with
disabling pain, but it is invasive and has potential complications such as pneumothorax and
orthostatic hypotension. Laparoscopic renal denervation has been helpful in a small series of
patients. In recent times, percutaneous transluminal catheter–based denervation has also been
shown to be effective in case reports and deserves further evaluation. 1
Management of ESRD
Dialysis
Dialysis is a common means of renal replacement therapy for patients with PKD awaiting
kidney transplants. Options for PKD patients include both hemodialysis and peritoneal dialysis,
though the latter is commonly thought to lead to poor outcomes due to concerns of abdominal
wall complications, including leaks and intestinal perforation, in part due to increased
intraabdominal pressure resulting from large kidney volumes. Hemodialysis has also been shown
to be an effective and safe means of renal replacement in ADPKD patients, with a 5-year
survival 10%–15% higher than non-ADPKD controls, most likely related to decreased cardiac
mortality in this group of patients.4
Transplantation
ADPKD is a common cause of ESRD, requiring renal transplantation.4 Transplantation is
the optimal choice of renal replacement therapy in appropriate patients with ADPKD. Living
kidney donation, ideally preemptive, is likely to be associated with best outcomes. 1
CONCLUSION
We reported one case of polycystic kidney disease, hypertension and acute kidney injury
stadium failure. The diagnosis is based on anamnesis, physical examination, laboratories and
imaging studies. Patient was treated with antihypertension, captopril 3 x 25 mg and amlodipin 1
x 5 mg.
REFERENCES
1. Chapman AB, Devuyst O, Eckardt KU, Gansevoort RT, Harris T, et al. Autosomaldominant polycystic kidney disease (ADPKD): executive summary from a Kidney
Disease: Improving Global Outcome (KDIGO) Controversies Conference. International
Society of Nephrology;2015;1-8. Available at : www.kidney-international.org
2. NHS Choices. 2014. Available at : www.nhs.uk
3. Torra, R. Polycystic kidney disease. 2014. Available at : www.medscape.com
4. Halvorson CS, Bremmer MS, Jacobs SC. Polycystic kidney disease : inheritance,
pathophysiology, prognosis and treatment. International journal of nephrology and
renovascular disease;2010;3;69-83
5. Polycystic kidney disease. National Institutes of Diabetes and Digestive and Kidney
Diseases;2014;1-12
6. Neumann HP, Jilg C, Bacher J, Nabulsi Z, Malinoc A, et al. Epidemiology of autosomaldominant polycystic kidney disease: an in-depth clinical study for south-western
Germany. Nephrol Dial Transplant (2013) 28: 1472–87
7. Harris, PC. Polycystic disease of the kidney. Encyclopedia of life sciences;2001;1-7.
Available at www.els.net
8. Polycystic kidney disease. National Kidney Foundation. 2015. Available at :
www.pkdcure.org
-
Sumi Ramadhani, Radar Tarigan, Abdurrahim Rasyid Lubis, Ayu Nurul Zakiah
Division of Nephrology-Hypertension
Department of Internal Medicine University of North Sumatera
ABSTRACT
Polycystic Kidney Disease is an inherited condition that causes small, fluidfilled sacs called cysts to develop in the kidneys. The disease can be inherited in
autosomal dominant and recessive forms. Estimates of PKD’s prevalence range
from one in 400 to one in 1,000 people. In many cases, PKD does not cause signs or
symptoms until cysts are half an inch or larger. When present, the most common
symptoms are abdominal pain, haematuria, urinary tract infection, hypertension,
renal stones and renal failure.
We reported one case of a 55 years old male patient, admitted to Adam
Malik Hospital with abdominal distention. He was diagnosed with multiple cysts in
the liver and kidney. Family member whose experienced abdominal distention was
found to his brother and sister but undiagnosed because they were died. Urine
output was 1500 cc/24 hours. On physical examination he was normoweight, blood
pressure 160/100 mmHg, pulse rate, respiratory rate and temperature within normal
limit. Abdominal examination was asymmetrical distension with hepar, spleen and
kidney was hard to define. Examination or other systems were within normal limits.
Investigation showed complete blood count and urinalysis was normal.
Renal function test showed ureum 113 mg/dL and creatinine 6.09 mg/dL (creatinine
clearance 11,63 mL/min). Liver function test was normal. Chest radiography was
normal. Funduscopy showed retinopathy hypertension grade II oculi dextra and
sinistra. Abdominal ultrasonography showed multiple cysts in the liver and kidney
bilateral and CT scan abdomen showed multiple cysts may still be on the hepar and
both kidney accompanied by hepatomegaly and nefromegali ec bilateral Polycystic
disease, suspect nephrolitiasis bilateral and bilateral pleural Effusion.
Keyword : polycystic kidney disease, hypertension
INTRODUCTION
Autosomal-dominant polycystic kidney disease (ADPKD), an inherited kidney disease
that affects 12.5 million people worldwide in all ethnic groups, is responsible for up to 10% of
patients in end-stage renal disease (ESRD) and is a major burden on public health. 1 ADPKD is an
inherited condition that causes small, fluid-filled sacs called cysts to develop in the kidneys. 2 It is
characterized by relentless development and growth of cysts in the kidney and other organs (eg,
liver, pancreas, spleen) causing progressive kidney enlargement associated with hypertension,
abdominal fullness and pain, episodes of cyst hemorrhage, gross hematuria, nephrolithiasis, cyst
infections, and reduced quality of life.1,3
The disease can be inherited in autosomal dominant and recessive forms. Cyst
development and growth is gradual, yet despite the massive growth of the kidneys, the
glomerular filtration rate (GFR) in these patients is typically conserved until ages 30–40,
followed by a rapid, linear decline after this time. By the age of 70, 50% of patients with
ADPKD will require dialysis or kidney transplantation.4
Autosomal recessive polycystic kidney disease (ARPKD), by contrast, typically presents
in a younger patient population. The disease is characterized by cystic dilation of the collecting
ducts of the kidneys, along with dysgenesis of the biliary ductal plate, resulting in congenital
hepatic fibrosis and often death in the perinatal period due to respiratory failure. 4
EPIDEMIOLOGY
Estimates of PKD’s prevalence range from one in 400 to one in 1,000 people. According
to the United States Renal Data System, PKD accounts for 2.2 percent of new cases of kidney
failure each year in the United States. Annually, eight people per 1 million have kidney failure as
a result of PKD.5
Extrarenal manifestations such as multiple liver cysts occur in 60–90% and intracranial
aneurysms in 5–10% of the patients. ADPKD is a leading cause for renal replacement therapy
comprising 5–10% of all patients with end-stage renal failure.6 Approximately 1 per 800-1000
population carries a mutation for this condition. ADPKD is slightly more severe in males than in
females, but the difference is not statistically significant. 3,5
CASE REPORT
55 years old male patient, admitted to Adam Malik Hospital on August 31th 2015 with a
chief complaint is abdominal distention. He experienced this condition for about one year before
hospital admission. Abdominal pain was found in epigastric region until upper right quadran
abdomen but he had no nausea and vomitus. He had no problem with defecation and urinating.
Swelling of the extremity and history of having jaundice were not found, but he was diagnosed
with multiple cysts in the liver and kidney. History of hypertension was not found. Family
member whose experienced abdominal distention was found in his brother and sister but
undiagnosed because they were died. Urine output was 1500 cc/24 hours.
On physical examination he was normoweight with body mass index (BMI) 22 kg/m 2,
blood pressure 160/100 mmHg, pulse rate was 90 beats per minute, respiratory rate 20 x/minute
and temperature 36 C. Abdominal examination was asymmetrical distension with hepar, spleen
and kidney was hard to define. Examination or other systems were within normal limits.
Laboratory finding showed Hb 13 mg/dl, WBC count 9980/ul and platelet count was
202.000/mm3. Urine laboratory analysis was normal. Renal function test showed ureum 113
mg/dL and creatinine 6.09 mg/dL (creatinine clearance 11,63 mL/min). Liver function test was
normal, SGOT 25 I/L, SGPT 18 I/L, total bilirubin 0,2 and direct bilirubin 0,06 mg/dl, albumin
3,3 g/dl.
Chest radiography was normal. Funduscopy showed retinopathy hypertension grade II
oculi dextra and sinistra. Abdominal ultrasonography showed multiple cysts in the liver and
kidney bilateral and abdominal CT scan showed multiple cysts may still be on the hepar and both
kidney accompanied by hepatomegaly and nefromegali ec bilateral Polycystic disease, suspect
nephrolitiasis bilateral and bilateral pleural Effusion.
The patient was diagnosed as polycystic kidney disease and hypertension. He was only
treated with antihypertension, captopril 3 x 25 mg and amlodipin 1 x 5 mg and no indication to
had hemodialysis.
PATHOPHYSIOLOGY
ADPKD is characterized by the progressive development and enlargement of multiple
cysts in each kidney. Ultimately, the precise architecture of the kidney (consisting of
approximately 1 million nephrons) is totally replaced by an often greatly enlarged organ,
consisting of a few thousand cysts, separated by fibrotic regions. The cysts are thought to form
from any region of the tubular segment in the kidney, but only a small proportion of nephrons
develops cysts. In rare cases where fetal ADPKD kidneys have been examined, some microcysts
are already evident, indicating the onset of cyst development in the fetus, although cyst initiation
may continue into adult life.7
Microdissection studies show that ADPKD cysts develop as outpouchings of the tubule
and the early stages are associated with abnormalities of the basement membrane and cell
differentiation. Cyst expansion requires epithelial cell proliferation and altered secretory
characteristics of the epithelia, which may be associated with changes in the normally polarized
state of the cells. Normal renal tissue is destroyed by cyst expansion, interstitial fibrosis and
possibly programmed cell death, apoptosis.7
ADPKD should be considered a systemic disease because many disease manifestations
are seen outside the kidney. Cysts are found in many organs, most notably the liver, and
associations are seen with several noncystic lesions (Table 1). Many of these abnormalities are
defects of connective tissue and indicate a role for the ADPKD protein(s) beyond the kidney.7
Table 1. Nonrenal abnormalities associated with
autosomal dominant polycystic kidney disease
Approximately 85-90% of patients with ADPKD have an abnormality on the short arm of
chromosome 16 (ie, ADPKD type 1 [ADPKD1]). A second defect, termed ADPKD type 2
(ADPKD2), is responsible for 10-15% of ADPKD cases and is found on the long arm of
chromosome 4. A third genotype may exist, but no genomic locus is assigned. 3
A decrease in urine-concentrating ability is an early manifestation of ADPKD. The cause
is not known. Plasma vasopressin levels are increased; this increase may represent the body's
attempt to compensate for the reduced concentrating capacity of the kidneys and could contribute
to the development of renal cysts, hypertension, and renal insufficiency. 3
CLINICAL FEATURES
In many cases, PKD does not cause signs or symptoms until cysts are half an inch or
larger.4,5 When present, the most common symptoms are abdominal pain, haematuria, urinary
tract infection (eg, acute pyelonephritis, infected cysts, perinephric abscess), hypertension, renal
stones and renal failure.3,4,7,8 Hypertension is found in the majority of patients, the frequency
increasing with declining renal function.4,7,8
Nephrolithiasis is another common complication of ADPKD, occurring in 20%–30% of
patients. Stone formation should be suspected in any ADPKD patient with an acute onset of pain,
hematuria, or deteriorating kidney function. Stone composition is typically uric acid or calcium
oxalate, with decreased ammonia excretion, low urinary pH, low citrate concentration, and
urinary stasis thought to contribute to stone formation. The presence of stones can be confirmed
with either renal ultrasonography (US) or CT scanning, with the latter being better at detecting
stones given the limitations of US in the presence of parenchymal or cyst wall calcifications.4
DIAGNOSIS
Examination in patients with ADPKD may demonstrate the following :3
-
Hypertension: One of the most common early manifestations of ADPKD, in which
increased diastolic BP is the rule; clinical course in ADPKD is usually more severe early
on, then becomes less problematic as the renal insufficiency progresses
-
Palpable, bilateral flank masses: In advanced ADPKD
-
Nodular hepatomegaly: In severe polycystic liver disease
-
Rarely, symptoms related to renal failure (eg, pallor, uremic fetor, dry skin, edema)
Testing3
Routine laboratory studies include the following :
-
Serum chemistry profile, including calcium and phosphorus
-
CBC count
-
Urinalysis
-
Urine culture
Imaging studies3
Radiologic studies used in the evaluation of ADPKD include the following:
-
Ultrasonography: Technique of choice for patients with ADPKD and for screening
patients' family members; useful for exploring abdominal extrarenal features of ADPKD
(eg, liver cysts, pancreatic cysts)
-
CT scanning: Not routine; useful in doubtful pediatric cases or in complicated cases (eg,
kidney stone, suspected tumor)
-
MRI: Not routine; helpful in distinguishing renal cell carcinoma from simple cysts;
criterion standard to help determine renal volume for clinical trials when testing drugs for
ADPKD; best imaging tool to monitor kidney size after treatment to assess progress
-
MRA: Not routine; preferred imaging technique for diagnosing intracranial aneurysms
For at-risk adults the potential benefits of presymptomatic diagnosis usually outweigh the
risks, and it is most commonly performed by ultrasonography (US), which is inexpensive and
widely available.1 Genetic testing may be performed, in which the major indication is for genetic
screening in young adults with negative ultrasonographic findings who are being considered as
potential kidney donors.1,3
TREATMENT
Treatments that extend kidney survival in ADPKD do not currently exist. Ideally,
treatment should start early, when kidney parenchyma is relatively preserved. 7
Management of Hypertension
Hypertension is a common and early manifestation of disease in ADPKD and, when
uncontrolled, is associated with an earlier progression to end-stage renal disease and
cardiovascular complications, compared to normotensive ADPKD patients. 1,5 Data supporting
disease-specific blood-pressure (BP) targets are limited. The general advice of the 2012 KDIGO
Clinical Practice Guideline for the Management of BP in chronic kidney disease can therefore be
followed, suggesting a BP target ≤ 140/90 mmHg. BP control can be achieved by lifestyle
modification and medical treatment. Agents that interfere with the renin-angiotensin-aldosterone
system (RAAS) are first-line BP-lowering agents in combination with a sodium-restricted diet.
There is controversy as to which second-line BP-lowering agents should be used. Large
randomized controlled trials (RCTs) in non-ADPKD populations suggested that calcium channel
blockers and diuretics may be preferred over beta-blockers for cardiovascular protection.1
Treatment of hypertension with b-blockers and angiotensin converting enzyme inhibitors is
important, as cardiovascular complications are a frequent cause of death in patients with
ADPKD.7
Regardless of the agent utilized, tight blood pressure control has been shown to delay the
progression of disease in ADPKD. Other currently-accepted treatment strategies in ADPKD
include salt-restriction (no more than 6 grams of sodium chloride daily), low protein intake (no
more than 1 gram per kilogram of body weight per day), regular exercise, maintenance of a
healthy body weight, and frequent water intake.4
Hematuria and Cyst Hemorrhage
Cyst hemorrhage and gross hematuria are frequent complications of ADPKD. Gross
hematuria can result from cyst hemorrhage, nephrolithiasis, infection, and, rarely, from renal cell
or urothelial carcinoma. Cyst hemorrhage can be associated with fever, and differentiation from
cyst infection may be difficult. Episodes of cyst hemorrhage or gross hematuria are usually selflimited and resolve within 2–7 days. If symptoms persist, a possible neoplasm should be
excluded. Rarely, bleeding can be persistent or severe, sometimes with extensive subcapsular or
retroperitoneal hematomas, requiring hospitalization. Temporary discontinuation of RAAS
inhibitors and diuretics to avoid acute kidney injury during an episode of acute cyst hemorrhage
has been suggested.1
Management Renal Cyst Infection
Recent meta-analyses highlight the course and successful management of both renal and
liver cyst infections. The presence of fever, abdominal pain, and high sedimentation rate or level
of C-reactive protein should raise the suspicion of a cyst infection, but the differential diagnosis
is broad. Blood and urine cultures may be negative. 18 F-fluorodeoxyglucosepositron emission
tomography may be helpful in identifying infected cysts.1 Lipid-permeable anti-microbial agents
such as fluoroquinolones and trimethoprim-sulfamethoxazole, depending on sensitivity (if
available), remain the standard treatment for cyst infections. 1,4
Treatment options for severe polycyctic liver disease (PLD) include surgical and medical
therapy. Surgical options encompass aspiration/sclerotherapy, fenestration, partial or segmental
hepatectomy, and liver transplantation. Somatostatin analogs were shown to reduce or stabilize
liver volume in severe PLD though their use is currently restricted to either clinical trials or
compassionate use. A prolonged course of a fluoroquinolone, combined with early, percutaneous
cyst drainage, provides the best treatment results. Recurrence of liver cyst infection is frequent.1
Management of Chronic Pain
Kidney pain is the most common renal manifestation in ADPKD. It may develop after an
episode of acute pain and is likely maintained by aberrant activity of sensory and autonomic
neurons innervating the kidney.1 Pain management can be difficult in these patients as standard
approaches, including use of non-steroidal agents, should be avoided, given their effect on the
kidneys. Use of narcotic analgesics should be reserved for acute episodes to minimize the
potential for dependence. Despite these strategies, anywhere from 50%–70% of patients with
ADPKD have pain that is uncontrolled with oral analgesics. Accordingly, when conservative
measures fail, surgical options are available.4
These include cyst decortication, which is now performed laparoscopically and has been
found in a study of 29 ADPKD patients to result in a greater than 50% improvement in pain in
73%, 52%, and 81% of patients, at 12, 24, and 36 months, respectively. Similarly, a different
study of 15 ADPKD patients treated with laparoscopic decortication revealed that pain decreased
an average of 62% in 73% of cases at a mean follow-up of 2.2 years (range 0.5–5). An additional
option that holds promise in treating symptoms associated with the mass effect of the kidneys
includes renal artery embolization. This procedure involves embolization of the main renal
artery, although selective embolization has been attempted. It is typically performed only on
dialysis-dependent patients as it eliminates any remaining renal function, essentially decreasing
GFR to zero.4
Thoracoscopic sympathosplanchnicectomy may be helpful in some patients with
disabling pain, but it is invasive and has potential complications such as pneumothorax and
orthostatic hypotension. Laparoscopic renal denervation has been helpful in a small series of
patients. In recent times, percutaneous transluminal catheter–based denervation has also been
shown to be effective in case reports and deserves further evaluation. 1
Management of ESRD
Dialysis
Dialysis is a common means of renal replacement therapy for patients with PKD awaiting
kidney transplants. Options for PKD patients include both hemodialysis and peritoneal dialysis,
though the latter is commonly thought to lead to poor outcomes due to concerns of abdominal
wall complications, including leaks and intestinal perforation, in part due to increased
intraabdominal pressure resulting from large kidney volumes. Hemodialysis has also been shown
to be an effective and safe means of renal replacement in ADPKD patients, with a 5-year
survival 10%–15% higher than non-ADPKD controls, most likely related to decreased cardiac
mortality in this group of patients.4
Transplantation
ADPKD is a common cause of ESRD, requiring renal transplantation.4 Transplantation is
the optimal choice of renal replacement therapy in appropriate patients with ADPKD. Living
kidney donation, ideally preemptive, is likely to be associated with best outcomes. 1
CONCLUSION
We reported one case of polycystic kidney disease, hypertension and acute kidney injury
stadium failure. The diagnosis is based on anamnesis, physical examination, laboratories and
imaging studies. Patient was treated with antihypertension, captopril 3 x 25 mg and amlodipin 1
x 5 mg.
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