Polycystic Kidney Disease – Causes, Symptoms, Treatment

Polycystic kidney disease is a disorder that affects the kidneys and other organs. Clusters of fluid-filled sacs, called cysts, develop in the kidneys and interfere with their ability to filter waste products from the blood. The growth of cysts causes the kidneys to become enlarged and can lead to kidney failure.

Polycystic kidney disease (ADPKD) is an autosomal dominant disorder. It is a multisystem and progressive disease with cysts formation and kidney enlargement along with other organ involvement (e.g., liver, pancreas, spleen). This activity describes the evaluation and management of polycystic kidney disease and highlights the role of the interprofessional team in improving care for patients with this condition.

Polycystic kidney disease (ADPKD) is an autosomal dominant disorder. It’s a multisystem and progressive disease with cysts formation and kidney enlargement along with other organ involvement (e.g., liver, pancreas, spleen).

Causes of Polycystic Kidney Disease

ADPKD is an autosomal dominant disease, so it is found in males and females equally, and each offspring has a 50% chance of inheriting the disease.

ADPKD involves at least two genes. PKD1 accounts for most ADPKD cases and is located on 16p13.3. PKD2 accounts for 15% of ADPKD cases.

PKD1 codes for polycystin 1, a 4304 amino acid protein. Polycystin 1 interacts with polycystin 2 and is involved in cell cycle regulation and intracellular calcium transport. PKD2 codes for polycystin two, which is structurally similar to polycystin 1. It is a member of the family of voltage-activated calcium channels.

Polycystin 1 and two are located in the epithelial cells of the renal tubules and other areas of the renal cell epithelium. Both form heteromeric complexes and are found in the primary cilium of epithelial cells in kidneys. The primary cilium is considered a mechanical receptor that can sense changes in tubular fluid flow, and that can transduce them into intracellular calcium signaling. ADPKD1 is more severe than ADPKD2.

Mutations in the PKD1PKD2, and PKHD1 genes cause polycystic kidney disease.

Mutations in either the PKD1 or PKD2 gene can cause autosomal dominant polycystic kidney disease; PKD1 gene mutations cause ADPKD type 1, and PKD2 gene mutations cause ADPKD type 2. These genes provide instructions for making proteins whose functions are not fully understood. Researchers believe that they are involved in transmitting chemical signals from outside the cell to the cell’s nucleus. The two proteins work together to promote normal kidney development, organization, and function. Mutations in the PKD1 or PKD2 gene lead to the formation of thousands of cysts, which disrupt the normal functions of the kidneys and other organs. People with mutations in the PKD2 gene, particularly women, typically have a less severe form of the disease than people with PKD1 mutations. The signs and symptoms, including a decline in kidney function, tend to appear later in adulthood in people with a PKD2 mutation.

Mutations in the PKHD1 gene cause autosomal recessive polycystic kidney disease. This gene provides instructions for making a protein whose exact function is unknown; however, the protein likely transmits chemical signals from outside the cell to the cell nucleus. Researchers have not determined how mutations in the PKHD1 gene lead to the formation of numerous cysts characteristic of polycystic kidney disease.

Although polycystic kidney disease is usually a genetic disorder, a small percentage of cases are not caused by gene mutations. These cases are called acquired polycystic kidney disease. This form of the disorder occurs most often in people with other types of kidney disease who have been treated for several years with hemodialysis (a procedure that filters waste products from the blood).

Polycystin-1 (PKD1 protein) and polycystin-2 (PKD2 protein) belong to a subfamily of transient receptor potential (TRP) channels. PKD2 is found in the endoplasmic reticulum and also in the plasma membrane in spindles in cell division and primary cilium. PKD1 inactivation determines the rate of development of the cystic disease. PC1 interacts with PC2 and helps in the maturation of PC2, and vice versa. PC1 and PC2 also interact with additional calcium channel proteins.

A common finding in animal models of PKD has increased levels of cyclic adenosine monophosphate (cAMP), not only in the kidney but also in the liver and vascular smooth muscle. cAMP exerts effects on cell proliferation in different cell types. cAMP and PKA signaling enhances several pro-proliferative pathways in cells derived from polycystic kidneys while inhibiting proliferation in cells derived from the normal human kidney cortex.

Liver cysts arise by excessive proliferation and dilation of biliary ductules and peribiliary glands.

Endothelial vasodilation and constitutive nitric oxide synthase activity are reduced in subcutaneous resistance vessels from patients with ADPKD and normal glomerular filtration rate (GFR), thus causing hypertension.

Symptoms of Polycystic Kidney Disease

Polycystic kidney disease symptoms can include:

  • High blood pressure
  • Back or side pain
  • Blood in your urine
  • A feeling of fullness in your abdomen
  • Increased size of your abdomen due to enlarged kidneys
  • Headaches
  • Kidney stones
  • Kidney failure
  • Urinary tract or kidney infections

Diagnosis of Polycystic Kidney Disease

History and Physical

Renal size increases with age, and renal enlargement eventually occurs in 100% of patients with ADPKD. The severity of the structural abnormality correlates with the manifestations of ADPKD, such as pain, hematuria, hypertension, and renal impairment. Most clinical manifestations are directly related to the enlargement of renal cysts. 

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Episodes of acute renal pain are seen quite often due to cyst hemorrhage, infection, stone, and, rarely, tumors. Visible hematuria may be the initial presenting symptom. Cyst hemorrhage is a frequent complication causing gross hematuria when the cyst communicates with the collecting system. It can manifest with fever, raising the possibility of cyst infection. Occasionally a hemorrhagic cyst will rupture, resulting in a retroperitoneal bleed.

Urinary tract infection (UTI) is common in ADPKD. UTI presents as cystitis, acute pyelonephritis, cyst infection, and perinephric abscesses. Most infections are caused by Escherichia coli, Klebsiella and Proteus species, and other Enterobacteriaceae.

Both CT and MRI are sensitive to detect complicated cysts.

Renal stone disease occurs in about 20% of patients with ADPKD. Most stones are composed of uric acid, calcium oxalate, or both. Stones can be difficult to diagnose on imaging in ADPKD because of cyst wall and parenchymal calcification. CT urography is helpful.

Hypertension is the most common manifestation of ADPKD. Microalbuminuria, proteinuria, and hematuria are more common in hypertensive patients with ADPKD.

In a majority of patients, renal function is within the normal range. By the time renal function starts worsening, the kidneys usually are greatly enlarged. ESRD is not inevitable in ADPKD. Up to 77% of patients are alive with preserved renal function at age 50 years, and 52% at age 73. Kidney and cyst volumes are the strongest predictors of renal functional decline.

Most simple hepatic cysts are solitary, and PLD should be suspected when four or more cysts are present in the hepatic parenchyma.

Lab Test and Imaging

Ultrasound criteria for the diagnosis of ADPKD:

Original Ravine’s PKD1 Diagnostic Criteria

  • Age 15-29 years – two or more cysts unilateral or bilateral
  • Age 30-39 years – two or more cysts in each kidney
  • Age 40-49 years – two or more cysts in each kidney
  • Age 60 years or above – four or more cysts in each kidney

Genetic testing is done when a precise diagnosis is not confirmed enlargement along, and the results of imaging are indeterminate.

Treatment of Polycystic Kidney Disease

  • Flank Pain – Causes of flank pain that may require intervention, such as infection, stone, and tumor, should be excluded. Opioid analgesics should be reserved for the management of acute pain. Reassurance, lifestyle modification, and avoidance of aggravating activities may be helpful. Tricyclic antidepressants are helpful as in other chronic pain syndromes, as they are well tolerated. Cyst aspiration, under ultrasound or CT guidance, can be done if distortion of the kidney by a large cyst is considered the cause of the pain. If multiple cysts are contributing to pain, laparoscopic or surgical cyst fenestration may be of benefit.
  • Cyst hemorrhage – Cyst hemorrhage episodes are self-limited, and patients respond well to conservative management with bed rest, analgesics, and increased fluid intake to prevent obstructing clots. Rarely, bleeding is more severe, leading to hemodynamic instability; this requires hospitalization and transfusions.
  • Cyst and urinary tract infection – Immediate treatment of symptomatic cystitis and asymptomatic bacteriuria is indicated to prevent retrograde seeding of the renal parenchyma. Agents of choice include trimethoprim-sulfamethoxazole and fluoroquinolones. If fever persists after 1 to 2 weeks of appropriate antimicrobial therapy, infected cysts should be drained percutaneously or surgically. In the case of end-stage polycystic kidneys, nephrectomy should be considered.
  • Nephrolithiasis – Potassium citrate is the treatment of choice in stone-forming conditions associated with it, which are uric acid stones, hypo-citraturic calcium oxalate stones, and distal acidification disorders.
  • Hypertension – Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) increase renal blood flow in ADPKD and are antihypertensives of choice.

Treating polycystic kidney disease involves dealing with the following signs, symptoms, and complications in their early stages:

  • Kidney cyst growth – Tolvaptan therapy may be recommended for adults at risk of rapidly progressive ADPKD. Tolvaptan (Jynarque, Samsca) is a pill that you take by mouth that works to slow the rate of kidney cyst growth and the decline in how well your kidneys work. There’s a risk of serious liver injury when taking tolvaptan, and it can interact with other medicines you take. It’s best to see a doctor who specializes in kidney health (nephrologist) when taking tolvaptan so that you can be monitored for side effects and possible complications.
  • High blood pressure – Controlling high blood pressure can delay the progression of the disease and slow further kidney damage. Combining a low-sodium, low-fat diet that’s moderate in protein and calorie content with not smoking, increasing exercise, and reducing stress may help control high blood pressure. However, medications are usually needed to control high blood pressure. Medications called angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are often used to control high blood pressure.
  • Declining kidney function. To help your kidneys stay as healthy as possible for as long as possible, experts recommend maintaining a normal body weight (body mass index). Drinking water and fluids throughout the day may help slow the growth of kidney cysts, which in turn could slow down a decline in kidney function. Following a low-salt diet and eating less protein might allow kidney cysts to respond better to the increase in fluids.
  • Pain. You might be able to control the pain of polycystic kidney disease with over-the-counter medications containing acetaminophen. For some people, however, the pain is more severe and constant. Your doctor might recommend a procedure using a needle to draw out cyst fluid and inject a medication (sclerosing agent) to shrink kidney cysts. Or you may need surgery to remove cysts if they’re large enough to cause pressure and pain.
  • Bladder or kidney infections. Prompt treatment of infections with antibiotics is necessary to prevent kidney damage. Your doctor may investigate whether you have a simple bladder infection or a more complicated cyst or a kidney infection. For more complicated infections, you may need to take a longer course of antibiotics.
  • Blood in the urine. You’ll need to drink lots of fluids, preferably plain water, as soon as you notice blood in your urine to dilute the urine. Dilution might help prevent obstructive clots from forming in your urinary tract. In most cases, the bleeding will stop on its own. If it doesn’t, it’s important to contact your doctor.
  • Kidney failure. If your kidneys lose their ability to remove waste products and extra fluids from your blood, you’ll eventually need either dialysis or a kidney transplant. Seeing your doctor regularly for monitoring of PKD allows for the best timing of a kidney transplant. You may be able to have a preemptive kidney transplant, which means you wouldn’t need to start dialysis but would have the transplant instead.
  • Aneurysms. If you have polycystic kidney disease and a family history of ruptured brain (intracranial) aneurysms, your doctor may recommend regular screening for intracranial aneurysms.

If an aneurysm is discovered, surgical clipping of the aneurysm to reduce the risk of bleeding may be an option, depending on its size. Nonsurgical treatment of small aneurysms may involve controlling high blood pressure and high blood cholesterol, as well as quitting smoking.

Should people with PKD take a special diet?

  • At present, no specific diet is known to prevent cysts from developing in patients with PKD. Reducing salt intake helps control blood pressure in PKD patients who have high blood pressure. A diet low in fat and moderate in calories is recommended to maintain a healthy weight. Speak to your doctor or a dietitian about other changes to your diet, such as avoiding caffeine.
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Is exercise recommended for people with PKD?

  • Absolutely. However, exercises that are potentially harmful to the kidney, such as contact sports, should be avoided. It is important not to become too dehydrated during any physical activity.

Who is at risk for developing PKD?

PKD runs in families. It is an inherited disorder that is passed from parents to children through genes. Genes are the basic elements of heredity. At conception, children receive a set of genes from each parent. They determine many characteristics such as hair color and eye color. Genes can also determine the likelihood of developing a disease.

A genetic disease can happen if one or both parents pass abnormal genes to a child. This happens through something called dominant inheritance or recessive inheritance.

  • Dominant inheritance – If one parent has the disease and passes an abnormal gene to the child, it is called dominant inheritance. Each child has a 50% chance of getting the disease. The risk is the same for every child, regardless of how many children develop the disease.
  • Recessive inheritance – If both parents carry the abnormal gene, and both parents pass an abnormal gene to the child, it is called recessive inheritance. In this situation, every child has a 25% chance of getting the disease.

Are there different types of PKD?

Yes. The three main types of PKD are

    • Autosomal Dominant PKD – (also called PKD or ADPKD)This form of the disease is passed from parent to child by dominant inheritance. In other words, only one copy of the abnormal gene is needed to cause the disease. Symptoms usually begin between the ages of 30 and 40, but they can begin earlier, even in childhood. ADPKD is the most common form of PKD. In fact, about 90 percent of all PKD cases are ADPKD.
    • Infantile or Autosomal Recessive PKD(also called ARPKD) – This form of the disease is passed from parent to child by recessive inheritance. Symptoms can begin in the earliest months of life, even in the womb. It tends to be very serious, progresses rapidly, and is often fatal in the first few months of life. This form of ARPKD is extremely rare. It occurs in 1 out of 25,000 people.
    • Acquired Cystic Kidney Disease (also called ACKD) – ACKD can happen in kidneys with long-term damage and severe scarring, so it is often associated with kidney failure and dialysis. About 90 percent of people on dialysis for 5 years develop ACKD. People with ACKD usually seek help because they notice blood in their urine. This is because the cysts bleed into the urinary system, which discolors urine.
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Complications

Complications associated with polycystic kidney disease include:

  • High blood pressure – Elevated blood pressure is a common complication of polycystic kidney disease. Untreated, high blood pressure can cause further damage to your kidneys and increase your risk of heart disease and strokes.
  • Loss of kidney function – Progressive loss of kidney function is one of the most serious complications of polycystic kidney disease. Nearly half of those with the disease have kidney failure by age 60. PKD can interfere with the ability of your kidneys to keep wastes from building to toxic levels, a condition called uremia. As the disease worsens, end-stage kidney (renal) disease may result, necessitating ongoing kidney dialysis or a transplant to prolong your life.
  • Chronic pain – Pain is a common symptom for people with polycystic kidney disease. It often occurs in your side or back. The pain can also be associated with a urinary tract infection, a kidney stone or a malignancy.
  • Growth of cysts in the liver – The likelihood of developing liver cysts for someone with polycystic kidney disease increases with age. While both men and women develop cysts, women often develop larger cysts. Female hormones and multiple pregnancies might contribute to liver cyst development.
  • Development of an aneurysm in the brain – A balloon-like bulge in a blood vessel (aneurysm) in your brain can cause bleeding (hemorrhage) if it ruptures. People with polycystic kidney disease have a higher risk of aneurysms. People with a family history of aneurysms seem to be at the highest risk. Ask your doctor if screening is needed in your case. If screening reveals that you don’t have an aneurysm, your doctor may recommend repeating the screening exam in a few years or after several years as a follow-up. The timing of repeat screening depends on your risk.
  • Pregnancy complications – Pregnancy is successful for most women with polycystic kidney disease. In some cases, however, women may develop a life-threatening disorder called preeclampsia. Those most at risk have high blood pressure or a decline in kidney function before they become pregnant.
  • Heart valve abnormalities – As many as 1 in 4 adults with polycystic kidney disease develops mitral valve prolapse. When this happens, the heart valve no longer closes properly, which allows blood to leak backward.
  • Colon problems –  Weaknesses and pouches or sacs in the wall of the colon (diverticulosis) may develop in people with polycystic kidney disease.

Make lifestyle changes

  • Be active for 30 minutes or more on most days. Regular physical activity can help you reduce stress, manage your weight, and control your blood pressure. If you are not active now, ask your health care provider about how much and what type of physical activity is right for you. If you play contact sports, such as football or hockey, a health care provider should do a magnetic resonance imaging (MRI) test to see whether these sports are safe for you. Trauma to your body, especially to your back and sides, may cause kidney cysts to burst.
  • Lose weight. Being overweight makes your kidneys work harder. Losing weight helps protect your kidneys.
  • Aim for 7 to 8 hours of sleep each night. Getting enough sleep is important to your overall physical and mental health and can help you manage your blood pressure and blood glucose, or blood sugar.
  • Reduce stress. Long-term stress can raise your blood pressure and even lead to depression. Some of the steps you take to manage your PKD are also healthy ways to cope with stress. For example, getting enough physical activity and sleep helps reduce stress.
  • Quit smoking. Cigarette smoking can raise your blood pressure, making your kidney damage worse. Quitting smoking may help you meet your blood pressure goals, which is good for your kidneys and can lower your chances of having a heart attack or stroke. Quitting smoking is even more important for people with PKD who have aneurysms. An aneurysm is a bulge in the wall of a blood vessel.

Prevention

If you have polycystic kidney disease and you’re considering having children, a genetic counselor can help you assess your risk of passing the disease to your offspring.

Keeping your kidneys as healthy as possible may help prevent some of the complications of this disease. One of the most important ways you can protect your kidneys is by managing your blood pressure.

Here are some tips for keeping your blood pressure in check:

  • Take the blood pressure medications prescribed by your doctor as directed.
  • Eat a low-salt diet containing plenty of fruits, vegetables, and whole grains.
  • Maintain a healthy weight. Ask your doctor what the right weight is for you.
  • If you smoke, quit.
  • Exercise regularly. Aim for at least 30 minutes of moderate physical activity most days of the week.
  • Limit alcohol use.

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