Polycystic Kidney Disease

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Practice Essentials

Autosomal dominant polycystic kidney disease (ADPKD) is a multisystemic and progressive disorder characterized by cyst formation and enlargement in the kidney and other organs (eg, liver, pancreas, spleen). Up to 50% of patients with ADPKD require renal replacement therapy by 60 years of age.

Essential update: Long-acting somatostatin analogue nephroprotective in polycystic kidney disease

In a 3-year multicenter Italian study, the somatostatin analogue octreotide long-acting release (LAR) provided nephroprotective benefits in adult patients with ADPKD, including reduction of kidney and cyst volume and slowing progression of renal insufficiency (as measured by decline in glomerular filtration rate [GFR]).[1, 2] Seventy-nine patients with an estimated GFR of 40 mL/min/1.73 m2 or greater were randomly assigned to receive two 20-mg intramuscular injections of octreotide-LAR or 0.9% sodium chloride solution every 28 days for 3 years.[1, 2] Clinicians were not blinded to patient allocation, although patients and outcome assessors were.[2]

At 1-year follow-up, in 75 patients evaluable by magnetic resonance imaging (MRI), there was significantly less increase in total kidney volume (TKV) in the active treatment group (46.2 mL) (n = 38) than in the placebo group (143.7 mL) (n = 37).[1, 2] At 3 years, however, although the TKV increase was numerically lower in the octreotide-LAR group (220.1 mL) than in the placebo group (454.3 mL) (n = 35 in each group), the difference was not significant.

All patients had at least 1 adverse event, and incidences of serious adverse events were similar between groups. However, cholelithiasis or acute cholecystitis from octreotide-LAR treatment was likely in 4 patients.[1, 2]

The investigators indicated that these findings suggest somatostatin analogues may protect against renal function loss and progression to end-stage kidney disease in patients with ADPKD.[1, 2]

Signs and symptoms

Pain—in the abdomen, flank, or back—is the most common initial complaint, and it is almost universally present in patients with ADPKD. Dull aching and an uncomfortable sensation of heaviness may result from a large polycystic liver.

The pain can be caused by any of the following:

See Clinical Presentation for more detail.

Diagnosis

Examination in patients with ADPKD may demonstrate the following:

Testing

Routine laboratory studies include the following:

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.[5]

Staging

Staging of renal failure is by GFR, as follows:

Imaging studies

Radiologic studies used in the evaluation of ADPKD include the following:

Ultrasonographic diagnostic criteria for ADPKD1 are as follows[6] :

Ultrasonographic diagnostic criteria for ADPKD in patients with a family history but unknown genotype are as follows[7] :

Fewer than 2 renal cysts in the findings provides a negative predictive value of 100% and can be considered sufficient for ruling out disease in at-risk individuals older than 40 years.

Indications for MRA are as follows[8, 9] :

See Workup for more detail.

Management

No specific medication is available for ADPKD. However, pharmacotherapy is necessary to accomplish the following:

Surgical option

Surgical intervention in ADPKD includes the following:

Patients with ADPKD who progress to end-stage renal disease may require the following procedures:

See Treatment and Medication for more detail.

Image library


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Polycystic kidney.

Background

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited disorders in humans. It is the most frequent genetic cause of renal failure in adults, accounting for 6-8% of patients on dialysis in the United States.

ADPKD is a multisystemic and progressive disorder characterized by the formation and enlargement of cysts in the kidney (as seen in the image below) and other organs (eg, liver, pancreas, spleen). Clinical features usually begin in the third to fourth decade of life, but cysts may be detectable in childhood and in utero.[10]


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Polycystic kidney.

Pain—in the abdomen, flank, or back—is the most common initial complaint, and it is almost universally present in patients with ADPKD (see Clinical). Ultrasonography is the diagnostic procedure of choice (see Workup). Medical therapy is needed to control problems such as hypertension, urinary tract infections, hematuria, and pain. Surgical drainage of cysts may be indicated. Patients who progress to end-stage renal disease (ESRD) may require dialysis or renal transplantation. (see Treatment).

For a discussion of ADPKD in children, see the Medscape Reference article Pediatric Polycystic Kidney Disease.

Pathophysiology

The main feature of ADPKD is a bilateral progressive increase in the number of cysts, which may lead to ESRD. Hepatic cysts, cerebral aneurysms, and cardiac valvular abnormalities also may occur.[11, 12]

Although ADPKD is a systemic disease, it shows a focal expression because less than 1% of nephrons become cystic. In ADPKD, each epithelial cell within a renal tubule harbors a germ-line mutation, yet only a tiny fraction of the tubules develop renal cysts.

It is currently held that the cells are protected by the allele inherited from the parent without ADPKD. When this allele is inactivated by a somatic event (mutation or otherwise) within a solitary renal tubule cell, the cell divides repeatedly until a cyst develops, with an aberrant growth program causing endless expansion. The severity of ADPKD is thought to be a direct consequence of the number of times and the frequency with which this cystogenic process occurs within the kidneys over the life of the patient. However this hypothesis is hard to understand in neonatal cases.

The hyperplastic cells cause an out-pocketing of the tubule wall, with the formation of a saccular cyst that fills with fluid derived from glomerular filtrate that enters from the afferent tubule segment. Progressive expansion eventually causes most of the emerging cysts to separate from the parent tubule, leaving an isolated sac that fills with fluid by transepithelial secretion. This isolated cyst expands relentlessly as a result of continued proliferation of the mural epithelium together with the transepithelial secretion of sodium chloride and water into the lumen.

The expanding fluid-filled tumor masses elicit secondary and tertiary changes within the renal interstitium evinced by thickening and lamination of the tubule basement membranes, infiltration of macrophages, and neovascularization. Fibrosis within the interstitium begins early in the course of the disease.

Cellular proliferation and fluid secretion may be accelerated by cyclic adenosine monophosphate (cAMP) and growth factors, such as epidermal growth factor (EGF). In summary, cysts function as autonomous structures and are responsible for progressive kidney enlargement in ADPKD.

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.

PKD1 and PKD2 are expressed in most organs and tissues of the human body. The proteins that are encoded by PKD1 and PKD2, polycystin 1 and polycystin 2, seem to function together to regulate the morphologic configuration of epithelial cells. The polycystins are expressed in development as early as the blastocyst stage and are expressed in a broad array of terminally differentiated tissues. The functions of the polycystins have been scrutinized to the greatest extent in epithelial tissues of the kidneys and liver and in vascular smooth muscle (see Etiology).

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.[13]

Bleeding

Renal cysts in ADPKD are associated with excessive angiogenesis evinced by fragile vessels stretched across their distended walls. When traumatized, these vessels may leak blood into the cyst, causing it to expand rapidly, resulting in excruciating pain. If bleeding continues, then the cyst may rupture into the collecting system, causing gross hematuria. Alternatively, the cyst may rupture into the subcapsular compartment and eventually dissect through the renal capsule to fill the retroperitoneal space.

Etiology

ADPKD is a hereditary disorder. The pattern of inheritance is autosomal dominant. Because the disorder occurs equally in males and females, each offspring has a 50% chance of inheriting the responsible mutation and, hence, the disease.

ADPKD is a genetically heterogeneous condition that involves at least 2 genes. PKD1 is located on 16p13.3 and accounts for most ADPKD cases. PKD2 is located on 4q21-q22 and accounts for 15% of ADPKD cases.

Polycystin 1 and 2

PKD1 codes for a 4304–amino acid protein (polycystin 1). The function of polycystin 1 is not yet fully defined, but this protein interacts with polycystin 2 and is involved in cell cycle regulation and intracellular calcium transport. Polycystin 1 localizes in the primary cilia of renal epithelial cells, which function as mechanosensors and chemosensors.

PKD2 codes for a 968–amino acid protein (polycystin 2) that is structurally similar to polycystin 1 and co-localizes to the primary cilia of renal epithelial cells. It is a member of the family of voltage-activated calcium channels.

Polycystin 1 and polycystin 2 are highly conserved ubiquitous transmembrane proteins. In the kidney, they are located in the epithelial cells of the renal tubules—in particular, in the primary cilia at the luminal side of the tubules, as well as in other areas of the renal cell epithelium.

Polycystin 1 is a large protein with a long extracellular N-terminal region, 11 transmembrane domains, and a short intracellular C-terminal tail. Polycystin 2 is structurally related to the transient receptor potential (TRP) channel family, and it is known to function as a nonselective cation channel permeable to Ca2+.

Polycystin 1 and polycystin 2 form heteromeric complexes and colocalize in the primary cilium of renal epithelial cells. The primary cilium is a long, nonmotile tubular structure located in the apical surface of the epithelial cells in the renal tubules. Its function was unknown for a long time. However, studies now indicate that the primary cilium may be a mechanoreceptor that senses changes in apical fluid flow and that transduces them into an intracellular Ca2+ signaling response.

This model involves the participation of polycystin 1 as a mechanical sensor of ciliary bending induced by luminal fluid flow. Bending of the cilium would cause a conformational change in polycystin 1 that would, in turn, activate the polycystin 2–associated Ca2+ channel, increasing the intracellular Ca2+ concentration and triggering intracellular signaling pathways leading to normal kidney development.[14]

A good genotype-phenotype correlation has not been well established for ADPKD1 and ADPKD2.[15]

ADPKD1 is more severe than ADPKD2. The mean age of ESRD for patients with ADPKD1 is 53 years. The mean age of ESRD for patients with ADPKD2 is 74 years.

The genetic heterogeneity of ADKPD, and the possible contribution of modifier genes, may explain the wide clinical variability in this disease, both within and between families.[16]

Epidemiology

ADPKD is responsible for 6-10% of ESRD cases in North America and Europe. Approximately 1 per 800-1000 population carries a mutation for this condition. Approximately 85-90% of patients with ADPKD have ADPKD1; most of the remaining patients have ADPKD2.[17]

ADPKD is slightly more severe in males than in females, but the difference is not statistically significant.

Symptoms generally increase with age. Children very rarely present with renal failure from ADPKD.

Prognosis

The prognosis in patients with ADPKD covers a wide spectrum. Renal failure has been reported in children; conversely, individuals with ADPKD may live a normal lifespan without knowing that they have the disease. More typically, however, ADPKD causes progressive renal dysfunction, resulting in grossly enlarged kidneys and kidney failure by the fourth to sixth decade of life. There is an inverse association between the size of polycystic kidneys and the level of glomerular filtration.[18, 19]

An early study estimated that approximately 70% of patients with ADPKD would develop renal insufficiency if they survived to age 65 years. Currently, half of all patients with ADPKD require renal replacement therapy by age 60 years. Risk factors for progression include the following:

The presence of more than one risk factor increases the risk of progression to ESRD.

The 2 forms of ADPKD are ADPKD1 and ADPKD2.[21] Although they share similar clinical features, renal prognosis is strikingly different.[22] ADPKD2 is a milder disease, based on the age of onset of ESRD. The median age of renal survival for individuals with ADPKD2 is 68 years, which is significantly older than for those with ADPKD1, in whom the median age of renal survival is 53 years. Although ADPKD2 is milder than ADPKD1, it has an overall impact on survival and shortens life expectancy.

A study of 180 patients with ADPK by Idrizi et al found that recurrent episodes of gross hematuria may increase the risk for more severe renal disease.[20] In the 43 study patients who experienced at least one episode of gross hematuria before age 30 years, renal survival was worse than in the other patients with ADPKD (a 10-year difference in survival). Although 60% of the study patients experienced urinary tract infections (UTIs), appropriate treatment of UTI decreased its frequency and slowed the rate of progression to renal failure.

Cardiovascular pathology and infections account for approximately 90% of deaths of those patients treated by hemodialysis or peritoneal dialysis and after renal transplantation.

Another cause of mortality is in ADPKD is subarachnoid hemorrhage from intracranial aneurysms.[23] This complication is rare and severe.

In a retrospective, observational study of 88 patients with ADPKD who died between 1981 and 1999, Rahman et al determined that almost half of the patients died of cardiovascular problems.[24] The median age of death was 60.5 years.

Causes of death included the following:

Patient Education

Ensure that patients are aware that this disease is hereditary and that their children have a 50% chance of acquiring the disease. Patients should also understand that although several treatments are being tested, this disease currently has no cure. Only interventions that slow the progression of renal disease (eg, adequate blood pressure control) are of benefit. Hopefully, effective specific therapy will be available in a few years.

Prenatal diagnosis is available through DNA linkage studies, if enough family members cooperate, or through a mutation search. Suggest that family members who are not screened for ADPKD have annual blood pressure checks and urine screenings for hematuria.

History

Pain— in the abdomen, flank, or back— is the most common initial complaint, and it is almost universally present in patients with autosomal dominant polycystic kidney disease (ADPKD). The pain can be caused by any of the following:

In addition, patients with ADPKD may have abdominal pain related to definitively or presumably associated conditions. Dull aching and an uncomfortable sensation of heaviness may result from a large polycystic liver. Rarely, hepatic cysts may become infected, especially after renal transplantation.

Abdominal pain can also result from diverticulitis, which has been reported to occur in 80% of patients with ADPKD maintained on dialysis, probably from altered connective tissue. However, this rate has not been demonstrated to be higher than the rate among other patients on dialysis.

Patients with ADPKD may be at a higher risk of developing thoracic aortic aneurysms. Abdominal aortic aneurysms are not increased among these patients.

Pain may also develop for reasons completely unrelated to the underlying disease; thus, abdominal pain in patients with ADPKD may be a diagnostic challenge.

Hematuria

Hematuria frequently is the presenting manifestation and usually is self-limited, lasting 1 week or less. Polycystic kidneys are unusually susceptible to traumatic injury, with hemorrhage occurring in approximately 60% of individuals. Mild trauma can lead to intrarenal hemorrhage or bleeding into the retroperitoneal space accompanied by intense pain that often requires narcotics for relief.

Physical Examination

Hypertension is one of the most common early manifestations of ADPKD.[3, 4] Even when renal function is normal, hypertension has been found in 50-75% of patients.

The clinical course of hypertension in ADPKD is very unlike that of hypertension in chronic glomerulonephritis or tubulointerstitial nephropathies. In ADPKD, the hypertension is usually more severe early in the course of the disease and becomes less problematic as the renal insufficiency progresses. A rise in diastolic blood pressure is the rule in ADPKD.

Palpable, bilateral flank masses occur in patients with advanced ADPKD. Nodular hepatomegaly occurs in those with severe polycystic liver disease.

Symptoms related to renal failure (eg, pallor, uremic fetor, dry skin, edema) are rare upon presentation.

Complications

End-stage renal disease (ESRD) is the most frequent complication of ADPKD. The prevalence of hypertension increases with age, with a rate of approximately 85% when patients enter ESRD.

Polycystic liver disease

The presence of cysts in the liver, pancreas, and spleen is a well-known feature of polycystic liver disease, which is a frequent extrarenal manifestation of ADPKD.[11] Pain and infection are the only symptoms that occur from the presence of hepatic cysts. Most frequently, cysts are asymptomatic.

Polycystic liver disease belongs to a family of liver diseases characterized by an overgrowth of biliary epithelium and supportive connective tissue. It is characterized by multiple cysts that may be microscopic or can occupy most of the abdominal cavity. Liver size may range from normal to enlarged.

Women are more likely to have more and larger hepatic cysts than men; this correlates with estrogen exposure and increases with gravidity in women. Liver size in massive polycystic liver disease tends to stabilize after menopause. Hepatic cysts occur in almost 50% of affected patients. Cysts occur in approximately 20% of patients during the third decade of life and in 75% during the seventh decade of life. They are rare in children, and the frequency increases with age. Pancreatic cysts occur at a rate of 9% in patients older than 20 years.

Bilateral nephrectomy in patients with massively enlarged livers may cause portal hypertension. This typically manifests as severe ascites or esophageal varices. The enlarged liver may also cause malnutrition, and in such cases, patients may need a partial resection of the liver or hepatic transplantation.

Cerebral aneurysms

Cerebral aneurysms are among the most serious complications of ADPKD; they occur in 4-10% of patients with ADPKD. In the study by Rahman et al, the mortality rate from cerebrovascular events in ADPKD was approximately 7%.[24]

Rupture usually occurs in patients younger than 50 years who have uncontrolled hypertension; however, a stroke from hypertension and intracerebral hemorrhage is more common. There is no relationship between the risk of rupture and the severity of renal disease.

Nephrolithiasis

Nephrolithiasis occurs in 20-30% of patients with ADPKD. Consider this condition in patients with acute pain and hematuria. In contrast to kidney stones in the general population, which most often consist of calcium oxalate, uric acid stones form in as many as 50% of patients with ADPKD. Metabolic abnormalities (eg, decreased urinary citrate) contribute to uric acid stone formation.

Establishing a diagnosis by ultrasonogram is often difficult because of the presence of large cysts. An intravenous pyelogram or a CT scan is the preferred imaging modality.

Approach Considerations

Ultrasonography is the procedure of choice in the workup of patients with autosomal dominant polycystic kidney disease (ADPKD). It is also ideal for screening patients' family members. Computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA) are useful in selected cases. For more information, see the Medscape Reference article Imaging inAutosomal Dominant Polycystic Kidney Disease.

Other studies to perform include the following:

An increased hematocrit may result from increased erythropoietin secretion from cysts. A decrease in urine-concentrating ability is an early manifestation of the disease. Microalbuminuria occurs in 35% of patients with ADPKD. However, nephrotic-range proteinuria is uncommon.

Urinary proteomic biomarkers may have the potential for diagnosis and prognosis of ADPKD. In a large clinical proteomic study, investigators reported that the performance of urinary peptidomic biomarker scores in ADPKD is superior to that of other biochemical markers in young patients with this disease and that proteomic profiling is potentially useful in the diagnosis and risk stratification of ADPKD.[25] In the study, urine samples from 1,048 patients were analyzed to characterize the urinary peptidomic pattern of patients with early stage ADPKD.[25]

Genetic testing

Genetic testing may be performed. The major indication for genetic screening is in young adults with negative ultrasonographic findings who are being considered as potential kidney donors.[5] Genetic testing by means of DNA linkage analysis has an accuracy rate greater than 95% for ADPKD1 and ADPKD2. Mutation screening is commercially available.

Staging by glomerular filtration rate

Staging of renal failure is as follows:

Other studies

Intravenous urography was once widely used in the diagnosis of ADPKD. Among its disadvantages are that it involves contrast medium and it is diagnostic only in advanced-stage ADPKD when distortion of calyces has developed . It is no longer indicated to establish a diagnosis of the disease. Barium enema may be used to help diagnose colonic diverticula. Doppler studies and 2-dimensional echocardiography are used to exclude mitral prolapse, which is often associated with ADPKD.

Ultrasonography

Ultrasonography is the most widely used imaging technique to help diagnose ADPKD.[26] It can detect cysts from 1-1.5 cm. This study avoids the use of radiation or contrast material, is widely available, and is inexpensive. The sensitivity of ultrasonography for ADPKD1 is 99% for at-risk patients older than 20 years; however, false-negative results are more common in younger patients. Sensitivity for ADPKD2 is lower and is still not well defined.

Ultrasonography is also useful for exploring abdominal extrarenal features of ADPKD (eg, liver cysts, pancreatic cysts).The presence of hepatic or pancreatic cysts supports the diagnosis of ADPKD.

Ultrasonographic diagnostic criteria for ADPKD1 were established by Ravine et al in 1994 and are as follows[6] :

Ultrasonographic diagnostic criteria for ADPKD in patients with a family history but unknown genotype were established by Pei et al in 2009 and are as follows[7] :

Fewer than 2 renal cysts in the findings provides a negative predictive value of 100% and can be considered sufficient for ruling out disease in at-risk individuals older than 40 years of age.

CT, MRI, and MRA

CT is more sensitive than ultrasonography and can detect cysts as small as 0.5 cm. However, it exposes the patient to radiation and is more expensive; therefore, it is not used routinely for diagnosis or for follow-up studies of ADPKD. CT may be useful in doubtful cases in children or in complicated cases (eg, kidney stone, suspected tumor).

MRI is more sensitive than either ultrasonography or CT scanning. It may be more helpful in distinguishing renal cell carcinoma from simple cysts. MRI is the best imaging tool to monitor kidney size after treatment to assess progress. However, it is not routinely used because it is expensive and tedious. It should not be used unless the patient is in a protocol or similar situation. MRI is the criterion standard to help determine renal volume for clinical trials when testing drugs for ADPKD.

Magnetic resonance angiography (MRA) is the preferred imaging technique for diagnosing intracranial aneurysms (ICAs). It is used selectively rather than routinely. Indications for this study are as follows[8, 9] :

Approach Considerations

Pharmacologic therapy is necessary to accomplish the following:

Patients with autosomal dominant polycystic kidney disease (ADPKD) who progress to end-stage renal disease may require hemodialysis, peritoneal dialysis, or renal transplantation. For more information, see the Medscape Reference articles Chronic Kidney Disease and Renal Transplantation.

In patients with heart murmurs, institute routine American Heart Association antibiotic prophylaxis.

A study by Torres et al identified serum high-density lipoprotein (HDL) cholesterol, urine sodium excretion (UNa V), and 24-hour osmolality as having a likely effect on ADPKD progression.[27] Whether modification of these components influences the clinical course of ADPKD remains unclear.

Several classes of drugs have been identified as having potential benefit in ADPKD (eg, vasopressin-2-receptor antagonists, somatostatin analogues).[28, 29] Clinicians may wish to refer patients for inclusion of clinical trials.[30, 31]

Metabolic problems related to renal failure that need to be controlled include the following:

Diet and activity

Although a low-salt diet is recommended when hypertension or renal failure is present, no other special diet reportedly is of benefit.

Patients should avoid contact sports in which direct trauma to the back or abdomen is likely. This is especially important with larger, palpable kidneys in order to minimize the risk of rupture.

Blood Pressure Control

In patients with renal disease, the goal is a blood pressure of less than 130/88 mm Hg. If more than 1 g/day of urinary protein is present, the target blood pressure is less than 125/75 mm Hg. Achieving good blood pressure control helps slow the progression of renal disease.[32] A study by Patch et al showed that when intensity and coverage of antihypertensive therapy were increased, mortality decreased for patients with ADPKD.[33]

The drugs of choice for this condition are angiotensin-converting enzyme (ACE) inhibitors (ie, captopril, enalapril, lisinopril) or angiotensin II receptor blockers (ARBs) such as telmisartan, losartan, irbesartan, and candesartan. These agents remain the most recommended drugs to treat hypertension in patients with ADPKD, although studies of the renin-angiotensin-aldosterone system have not convincingly demonstrated that it plays an important role in its pathogenesis. Calcium channel blockers are not recommended.

In patients with advanced renal disease, ACE inhibitors and ARBs can exacerbate renal failure or increase serum potassium levels; therefore, regularly monitor use with serum chemistry values.

Infectious and Other Disorders

Urinary tract infections (UTIs) occur in 30-50% of ADPKD patients and most frequently in women. Gram-negative bacteria are the most common pathogens.

Distinguishing between infections of the bladder, renal parenchyma, and cysts is important because the treatment for each condition is different. Treating infected cysts requires antibiotics that penetrate into the cyst. Useful agents are ciprofloxacin, trimethoprim-sulfamethoxazole, clindamycin, and chloramphenicol.

Hematuria

Hematuria is frequent in patients with ADPKD. It usually results from cyst rupture or stone passage. Instruct the patient to drink large amounts of water, to rest, and to take a pain killer if necessary. Hematuria is usually self-limited. Hospitalization is necessary if the patient is still bleeding after several days or if the amount of blood is substantial.

Abdominal pain from enlarged kidneys

Avoid nonsteroidal anti-inflammatory drugs (NSAIDs), because they can worsen renal function and potentiate hyperkalemia. Treatment involves surgical cyst decompression which is effective for pain relief in 60-80% of patients. See Surgical Drainage, below.

Surgical Drainage

If infected renal or hepatic cysts do not respond to conventional antibiotic therapy, surgical drainage may be necessary. This procedure is usually performed with ultrasonographically guided puncture.[34]

Cysts may become large enough to cause abdominal discomfort or pain. Typically, acute pain is from cyst hemorrhage or an obstruction by a clot, stone, or infection.[35] When one or more cysts can be identified as causing the pain, the symptoms can often be abated by open- or fiberoptic–guided surgery to excise the outer walls and to drain them.

Approximately 25% of patients with the most severe pain do not gain relief from surgery or pharmacologic therapy with narcotics. These individuals usually have inaccessible cysts in the medullary portions of the kidneys. Nephrectomy is used as a last resort to control the pain in these patients. Nephrectomy is often necessary when there is not enough room for a kidney graft.

Severe polycystic liver disease can result in massive hepatomegaly (see image below). When the liver becomes so large that it prevents the patient from obtaining normal nutrition or causes severe abdominal discomfort, a surgical procedure is necessary. Surgical intervention may range from unroofing several cysts to a partial hepatectomy.


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Polycystic kidney disease and massive polycystic liver disease.

Partial hepatectomy is difficult because of the characteristics of the polycystic liver. Only very expert surgeons should proceed with this surgical procedure.

When the polycystic liver causes portal hypertension or is very large with nonresectable areas, liver transplantation may be necessary.

Special attention should be paid when bilateral nephrectomy has to be carried out in patients with severe liver involvement. Several cases of refractory ascites after bilateral nephrectomy have been reported in these patients.

Consultations and Long-Term Monitoring

Consultations may be indicated under the following circumstances:

Ensure that a patient with ADPKD who is nonhypertensive and has normal renal function undergoes blood testing and ultrasonography of the kidneys every 1-2 years.

Schedule more frequent follow-up studies for patients with high blood pressure. Hypertension is common, occurring in as many as 50-70% of patients before the onset of renal failure.

Patients with renal failure require more frequent monitoring, based on the severity of their condition.

Medication Summary

No specific medication is available for autosomal dominant polycystic kidney disease (ADPKD); however, clinical trials with vasopressin 2 receptor antagonists (Tolvaptan), somatostatin analogs, and other drugs are ongoing. A 2012 phase III, double-blind, 3-year trial suggests that tolvaptan may modify the natural course of ADPKD. A significant reduction in the increase of renal volume and decline of glomerular filtration rate (GFR) was demonstrated among patients randomized to tolvaptan. There was a high rate of discontinuation due to side effects of the drug that were mainly related to polyuria and elevation of liver enzymes. Further studies may be necessary and tolvaptan should not be prescribed to patients until it gets the approval of the FDA. The drugs of choice for hypertension are angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Do not treat abdominal pain with nonsteroidal anti-inflammatory drugs (NSAIDs) because of their potentialnephrotoxic effect.

Cyst infections require gyrase inhibitors (eg, ciprofloxacin, chloramphenicol, clindamycin). Trimethoprim-sulfamethoxazole is also an effective antibiotic for reaching the inner cavity of the cyst.

Renal failure requires drugs to maintain electrolyte levels (eg, calcium carbonate, calcium acetate, sevelamer, lanthanum carbonate, calcitriol [possibly], diuretics, blood pressure medications). Approximately 62% of patients with renal insufficiency require at least 2 antihypertensive agents for optimal blood pressure control.

Enalapril (Vasotec)

Clinical Context:  Enalapril is a competitive inhibitor of ACE. It reduces angiotensin II levels, decreasing aldosterone secretion.

Lisinopril (Prinivil, Zestril)

Clinical Context:  This agent prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Captopril

Clinical Context:  Captopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Class Summary

ACE inhibitors suppress the renin-angiotensin-aldosterone system.

Valsartan (Diovan)

Clinical Context:  Valsartan is a prodrug that produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from the AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses.

Valsartan may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors, it does not affect response to bradykinin, and it is less likely to be associated with cough and angioedema. It is for use in patients unable to tolerate ACE inhibitors.

Losartan (Cozaar)

Clinical Context:  Losartan is an ARB that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, it does not affect the response to bradykinin, and it is less likely to be associated with cough and angioedema. It is used for patients unable to tolerate ACE inhibitors.

Candesartan (Atacand)

Clinical Context:  Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce more complete inhibition of renin-angiotensin system than ACE inhibitors, it does not affect response to bradykinin, and it is less likely to be associated with cough and angioedema. It is used in patients unable to tolerate ACE inhibitors.

Olmesartan (Benicar)

Clinical Context:  Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking binding of angiotensin II to the AT-1 receptor in vascular smooth muscle. Its action is independent of pathways for angiotensin II synthesis.

Class Summary

ARBs interfere with the binding of formed angiotensin II to its endogenous receptor. These agents reduce blood pressure and proteinuria, protecting renal function and delaying onset of end-stage renal disease (ESRD).

Ciprofloxacin (Cipro)

Clinical Context:  Ciprofloxacin inhibits bacterial DNA synthesis and, consequently, growth. It is a fluoroquinolone with activity against pseudomonads, streptococci, methicillin-resistant Staphylococus aureus (MRSA), S epidermidis, and most gram-negative organisms, but no activity against anaerobes. Levofloxacin (Levaquin) overcomes many of these limitations. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms have disappeared.

Levofloxacin (Levaquin)

Clinical Context:  Levofloxacin inhibits growth of susceptible organisms by inhibiting DNA gyrase and promoting breakage of DNA strands.

Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)

Clinical Context:  This agent inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Clindamycin (Cleocin)

Clinical Context:  Clindamycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Chloramphenicol

Clinical Context:  Chloramphenicol binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. It is effective against gram-negative and gram-positive bacteria.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Calcium Acetate ( PhosLo, Eliphos)

Clinical Context:  Calcium acetate reduces the phosphorus load.

Lanthanum carbonate (Fosrenol)

Clinical Context:  Lanthanum is a noncalcium, nonaluminum phosphate binder indicated for reduction of high phosphorus levels in patients with ESRD. It directly binds dietary phosphorus in the upper GI tract, thereby inhibiting phosphorus absorption.

Sevelamer hydrochloride (Renagel, Renvela)

Clinical Context:  This polymeric phosphate binder for oral administration does not contain aluminum. Thus, aluminum intoxication is not a concern.

Class Summary

Administer phosphate binders to maintain phosphate levels in renal failure.

Author

Roser Torra, MD, PhD, Consulting Staff, Hereditary Renal Diseases, Department of Nephrology, Fundacio Puigvert, Spain

Disclosure: Nothing to disclose.

Specialty Editors

Laura Lyngby Mulloy, DO, FACP, Professor of Medicine, Chief, Section of Nephrology, Hypertension, and Transplantation Medicine, Glover/Mealing Eminent Scholar Chair in Immunology, Medical College of Georgia

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

George R Aronoff, MD, Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Disclosure: Nothing to disclose.

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Polycystic kidney.

Polycystic kidney.

Polycystic kidney disease and massive polycystic liver disease.

Polycystic kidney.

Polycystic kidney disease and massive polycystic liver disease.