What is Polycystic Kidney Disease?
Polycystic kidney disease is typically a genetically inherited disease (Autosomal Dominant Polycystic Kidney Disease; ADPKD) characterized mainly by multiple cysts in both kidneys that cause high blood pressure, bleeding, pain, and ultimately kidney failure (end-stage renal disease).
Polycystic kidneys are more likely to have stones and urinary tract infections. Cysts also usually occur in the liver, and in a minority of patients may occur in the pancreas, spleen, arachnoid membrane covering the brain and spinal cord, and seminal vesicles in men.
There are three main non-cystic complications of ADPKD:
- intracranial aneurysms the likelihood of which is strongly influenced by family history
- abnormalities in certain valves of the heart (usually mitral valve prolapse) in about 1/3 of patients
- a higher frequency of hernias of various types.
What are Cysts?
Cysts are fluid-filled sacs of varying size and complexity. Certain cells in the kidney (tubular cells) are triggered to increase in number, form sacs, and fill with fluid because of abnormalities in several metabolic pathways. Renal cysts can cause massive enlargement of the kidneys that increase from roughly the size of a human fist to the size of a football or larger. Over time enlarging renal cysts lead to kidney failure; liver cysts usually do not seriously impair liver function although in some patients, particularly women, a polycystic liver can be massive.
How is ADPKD Inherited?
There are two established inherited forms of ADPKD, PKD1 and PKD2. A separate type of polycystic kidney disease occurring in children (Autosomal Recessive Polycystic Kidney Disease; ARPKD) has a different form of inheritance and many different clinical features, and it is not discussed here.
In ADPKD an affected parent has a 50% chance of passing the germline mutation to each child. The inheritance pattern is considered "dominant" because it only has to come from one parent, and it does not skip a generation.
PKD1 is based on mutation of its gene located on the 16th chromosome. Approximately 85% of all cases of ADPKD are due to PKD1 mutations. Kidney cysts may be seen when the patients are in their 20s, and there is usually progression to end-stage renal disease (ESRD) when the patients are in their 50s.
PKD2 is based on mutation of its gene located on the 4th chromosome. About 15% of all patients with ADPKD have PKD2. The kidney cysts appear later when patients are in their 30s and progress more slowly to ESRD when patients are in their 70s.
However, the general pattern of inheritance and progression may be modified by at least two factors. First, there may be new mutations (de novo) of the relevant genes, a phenomenon not yet quantified and certainly not understood.
Second, there appears to be an additional mutation called a "second hit" or somatic mutation that damages the "normal" chromosome and is responsible for cyst formation. In other words, the germline mutation for PKD1 or PKD2 is necessary but not sufficient for cyst formation, and a "second hit" is required. It can readily be seen that such "second hits" could accelerate the time course of ADPKD and blur the distinction between PKD1 and PKD2, as well as lead to some cases appearing in childhood. The nature of such "second hits" is not known at this time.
How is the Diagnosis of ADPKD Made?
There are three general ways in which the diagnosis is made:
- First, an imaging study of the kidneys (such as ultrasound, CT, or MRI) may disclose kidney cysts. Sometimes these tests are done specifically because of a family history of ADPKD, and other times in order to evaluate hypertension, kidney stones, blood in the urine, pain, recurrent urinary tract infections, as well as reasons unrelated to the kidneys.
- Second, the number of cysts found (classically by the Ravine criteria using ultrasound) combined with the age of the patient and information about a family history of ADPKD can establish the diagnosis in most cases.
- Third, when there is uncertainty about the diagnosis because of the lack of a family history of ADPKD, or need for additional information, direct DNA sequencing can be done in order to detect a mutation. The interpretation of any mutation requires careful evaluation.
What Are the Common Symptoms of ADPKD?
Early in the disease and often for years there may be no symptoms. However, hypertension is usually the first sign.
Other symptoms or signs include: blood in the urine; kidney stones; pain in the flank, abdomen, or back even without a kidney stone; recurrent urinary tract infections; increased frequency of urination more noticeable at night even without a urinary tract infection.
An excruciating headache ("sentinel" or "thunderclap" headache) can be caused by an intracranial aneurysm (an outpouching of a blood vessel in the brain) that is beginning to rupture. The headache may be located anywhere, but it may be behind the eye or associated with nausea, vomiting, loss of consciousness, or seizure. This type of headache should be immediately managed in the nearest hospital with referral as needed.
What Can I Do to Help Control ADPKD? Is there a Cure?
Currently, there is no cure for ADPKD. However, there is exceptionally promising research in this area, and clinical trials are underway for new treatment modalities.
Early treatment and effective control of hypertension is a major factor in slowing the progression of chronic kidney disease and decreasing its cardiovascular complications such as heart attacks and strokes. The preferred anti-hypertensive medications by consensus are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.
Other key and current approaches to treatment of ADPKD include:
- High water intake (3000 cc/day; 100 ounces) because of data showing that the hormone (vasopressin) produced when a person is dehydrated provokes kidney cyst development, and blocking it reduces cyst formation; high fluid intake may have to modified according to a person's heart, lung, and kidney status;
- Avoiding caffeine because of data showing that the way a cyst-promoting substance in polycystic kidneys (cyclic AMP) is controlled (phosphodiesterase) is interfered with by caffeine;
- Low-sodium diet for several reasons: it is important in blood pressure control, helps to prevent kidney stones, and has been shown in an animal study to decrease the development of kidney cysts.
- Avoiding a high protein diet is useful, but how beneficial a low protein diet is, and exactly what that level should be, has not been clearly established.
- Early treatment of renal complications such as urinary infections and kidney stones is important. Kidney stones have been successfully broken up with lithotripsy in ADPKD. Bleeding and pain cover a wide range of possibilities and often require more individualized treatment. In select circumstances cyst ablation, usually laparoscopically, may be indicated. Routine cyst-reduction surgery is not advised.
