Polycystic Kidney Disease
What is Polycystic Kidney Disease? What causes PKD?
Polycystic kidney disease (PKD) is a genetic disorder that causes multiple cysts to develop in the kidneys and potentially other organs such as the liver and pancreas. The disease is usually inherited in a dominant pattern. This means if the one of the parents have the gene, this will likely be passed onto his or her children. However the severity varies based on the gene mutation. For instance, those with the PKD1 gene mutation end up with renal failure earlier than those with PKD2 gene mutation. Severity of disease is also different between families with PKD, and even within families with the same gene mutation.
The prevalence of ADPKD is estimated to be 1/400 to 1/1000 individuals worldwide.
What are the symptoms of PKD?
With age, kidney size increases, up to more than 4kg (a normal kidney weighs around 100g)! This causes a few issues, including:
· Pain – From a cyst bleed, infection
· Cyst bleed – Frequently a cyst can burst. This causes pain, which usually lasts up to a week. Sometimes it can also causes blood in the urine. Bleeding may be so severe to require transfusion
· Infections – These can occur in the cysts or urinary system due to the abnormal anatomy. Patients may experience flank pain, fever, and burning or frequency of urine
· Kidney stones – This occurs relatively frequently, due to urine pooling in the kidney because of cyst disruption to the normal kidney anatomy
· High blood pressure – This is a major contributor to progression of kidney disease and heart attacks in patients. It is unclear why this occurs. The gene product itself may disrupt normal functioning of the blood vessels. Also, the cysts push on the normal kidney tissue, triggering a signal to increase blood pressure in attempt to restore blood flow.
Hernias and diverticular disease (a gut issue) are also more common in those with PKD.
How is PKD diagnosed?
Diagnosis is usually made with imaging (usually ultrasound) looking for cysts. For instance in a patient under 40 years old who has a known history of PKD, 3 cysts in either kidney would be enough to clinch a diagnosis. By contrast for those with a family history, having no cysts by the age of 40 means they are very unlikely to have PKD. If there is unsurety around the diagnosis (for example a person who wants to donate to a kidney to their sibling with PKD), genetic testing can done looking for mutations.
Screening for other complications is usually also done when the diagnosis is made. These include looking for:
· Liver cysts – Usually these do not cause many symptoms. However if the liver enlarges this can push upwards onto the chest, causing shortness of breath, reflux, or back pain. It may also compromise liver blood flow causing jaundice. Similar to kidney cysts, liver cysts can also bleed and become infected
· Brain aneurysms – This is especially important in those with a family history of brain aneurysms, high risk jobs (eg pilots), about to start blood thinners or major surgeries. These can cause seizures and weakness if they enlarge, and can be fatal if they rupture (especially those >1cm diameter).
· Heart disease – Some heart valves can be affected in those with PKD. An echocardiogram (an ultrasound of the heart) is used to diagnose this.
Is there a cure for PKD?
There is no silver bullet to stopping the progression of PKD. Strategies that you can consider include:
· Increasing fluid intake – Aiming at around 3 litres per day. This aims to suppress vasopressin (a hormone involved in water retention), which is involved in cyst enlargement
· Limiting caffeine intake – This theoretically decreases the cyst growth chemical signallers
· Limiting salt – This decreases high blood pressure associated with PKD.
The most studied drug so far is tolvaptan, which acts against vasopressin. It has been PBS approved for those with rapidly progressing PKD (eg a drop in kidney function of around 5% in one year). If started early for instance in young patients with a good kidney function, it may delay kidney failure by around 5 years. There are significant side effects however. It causes significant urinary frequency, and the need to drink sometimes more than 5 litres a day. My patients know all the bathrooms on the way to work and carry a drink bottle wherever they go. Further, tolvaptan may cause possible liver toxicity which needs careful monitoring on starting it.
Trials are ongoing. Your kidney specialist will be able to refer you to the closest site. In my local area, there are trials ongoing at Westmead and Nepean Hospital
If the kidneys fail, transplantation is the treatment of choice in the right patient. Thankfully the disease does not recur in the graft.
How does PKD impact kidney function?
Around 50% of those with PKD will progress to kidney failure. Those with a PKD1 mutation on average reach this stage in their 50s-60s , while those with a PKD2 mutation reach this stage in their 70s.
Another way we gauge risk of kidney failure is risk calculators, for instance the Mayo Classification. This is based on how quickly the kidneys are growing, and how quickly the kidney function is declining. Those in the least severe category of the Mayo Classification have a risk of less than 2.5% of end stage kidney failure after 10 years. This compares with those in the most severe category, who have a 67% risk of the same.
Sources:
Colbert, G. B., Elrggal, M. E., Gaur, L., & Lerma, E. V. (2020). Update and review of adult polycystic kidney disease. Disease-a-Month, 66(5), 100887–100887.
Johnson Richard J John Feehally and Floege Jürgen. 2019. Comprehensive Clinical Nephrology (version Sixth edition) Sixth ed. Edinburgh: Elsevier. http://www.engineeringvillage.com/controller/servlet/OpenURL?genre=book&isbn=9780323479097>
