Polycystic Kidney Disease (PKD): The Basics

Polycystic kidney disease, or PKD, is a specific genetic form of kidney disease. As the term suggests, "poly"-cystic refers to the presence of multiple cysts (closed, empty sacs, sometimes filled with fluid) in the kidney. Kidney cysts, in general, are not uncommon, but a diagnosis of cysts in the kidney is not necessarily PKD.

PKD is, in fact, one of many reasons why a person could develop cysts in the kidney. It is the specific genetic inheritance and the course of PKD that makes it a very specific entity. It is not a benign disease, and many patients could see their kidneys decline to failure, necessitating dialysis or a kidney transplant.

Other Types of Cysts

The other kind of kidney cysts (which are not PKD-related cysts) include:

• Simple benign cysts, which are usually a benign result of the aging process. Nearly 12% of individuals aged 50 to 70 and 22.1% of all individuals aged over 70 will have at least one cyst in the kidney.
• Malignant (when cysts could be representative of cancer in the kidneys, sometimes called complex cysts).
• Acquired, as in patients with chronic kidney disease (CKD).

Hence, once cysts are noted in a kidney, the next step is to differentiate whether it is a benign age-related finding, PKD, or something else.

Genetics

PKD is a relatively common genetic disorder, affecting almost 1 in 500 people, and remains a leading cause of kidney failure. The disease is usually inherited from one of the parents (90 percent of cases), or, more rarely, develops "de-novo" (called spontaneous mutation).

Understanding the genetics of PKD is essential to understanding the disease' symptoms and course. The mode of inheritance from parent to child differentiates between the two types of PKD.

Autosomal Dominant PKD (AD-PKD) is the most common inherited form and 90% of PKD cases are this type. Symptoms usually develop later in life around the ages of 30 to 40, although presentation in childhood in not unknown.

The abnormal genes could be the so-called PKD1, PKD2, or PKD3 genes. Which of these genes has the mutation and what type of mutation it might be has a huge effect on the expected outcome of PKD. For instance, the PKD1 gene, which is located on chromosome 16, is the most common mutation site seen in 85% of cases of ADPKD. Defects in the gene (as is the case with other mutations as well) lead to increased growth of epithelial cells in the kidney and subsequent cyst formation.

Autosomal Recessive PKD (AR-PKD) is much rarer and could begin early, even while the baby develops during pregnancy. One of the reason this type of PKD is rare is because the affected patients will usually not live long enough to procreate and pass on the mutation to their kids.

Again, to summarize, 90% of PKD cases are inherited, and of the inherited types, 90 percent are autosomal dominant. Hence, patients with PKD will most often have autosomal dominant PKD (AD-PKD).

Severity and Mutation Location

The site of the mutation will have an impact on the disease course. With PKD2 mutation, cysts develop much later, and renal failure typically does not occur until as late as the mid 70s. Contrast this with PKD1 gene mutations, where patients could develop kidney failure in their mid 50s.

Patients with PKD2 mutations will often not even be aware of any family history of PKD. In this case, it is always entirely possible that the ancestor carrying the mutation died before the disease was severe enough to cause symptoms or require dialysis.

Symptoms

A variety of symptoms can be seen in PKD. Common examples include:

• Flank pain due to enlarging kidneys
• Urinary tract infections
• Kidney stones (because of slow urine flow in cysts) 
• Cysts could be present in other organs like the liver and pancreas as well 
• Patients tend to have high blood pressure given the kidneys' role in blood pressure regulation 

Diagnosis

Although mutations for PKD are usually present at birth, kidney cysts might not be apparent at the time. These cysts grow into appreciable fluid filled sacs over the first couple of decades, at which time they may begin to cause symptoms or signs by the time someone reaches the age of 30. However, advancement of kidney disease to the point of failure could take decades from then on.

Most people who know of a family history of PKD have a low threshold of being diagnosed with PKD since both patients and physicians are well aware of the strong familial nature of the disease. In cases where family history might not be known or is seemingly "normal," diagnosis is more challenging and requires evaluation by a nephrologist. In this case, the affected parent could have died before the disease ever had the chance to progress to end stage kidney disease. Finally, if it is a case of "spontaneous mutation," there might not be any PKD present in either parent.

Initial diagnosis of PKD is made using imaging studies like ultrasound or CT scan. However, just because someone has multiple cysts in the kidneys does not necessarily mean that they have PKD. It could just be a case of one-too-many simple cysts, or other possibilities like medullary cystic kidney disease (not the same as PKD). Lately, MRI scans have also started playing a role in measuring the volume and growth of the cysts in PKD.

When diagnosis is in doubt, genetic testing can confirm or refute the diagnosis. Genetic testing does tend to be expensive though and so is mostly used when the diagnosis is equivocal.

Disease Course

How long do those with PKD take to develop kidney failure? ​This is perhaps the number one question that people newly diagnosed with PKD will have. It is not easy to answer this question. The rate of deterioration of kidney function is dependent upon multiple factors including the age hypertension developed, sex of the patient (males have faster progression of disease) and presence of proteinuria.

Note that not every patient with PKD will necessarily decline to complete kidney failure. What still needs to be emphasized is that not everyone with PKD will necessarily progress to the point where they need dialysis. Patients with PKD2 gene mutation obviously stand a better chance of avoiding complete renal failure. This is why, as a whole, less than one-half of PKD cases will be diagnosed during the patient's lifetime, as the disease could be clinically silent.