Thursday, 9 July 2009

Aneurysms in PKD – should we screen?

Q: Hi Donal, I hope this finds you well. I’m writing from a table outside a Parisian café, on my way back from Zurich after a weekend hosted by a big pharma drug company. An interesting couple of days – I think not a ‘normal’ meeting. It was a facilitated open forum, with 13 transplant patients from Europe and the US, where they seemed to genuinely want to know what they might think of doing – above and beyond producing drugs – that would help patients. I was prompted to write after seeing a post to the PKD email group that Tess Harris runs – which suggested it was standard procedure in France for dialysis-transplant patients to have a brain scan. I’ve been aware for some time that PKD patients have an above average risk of getting aneurysms in the brain. I’d never heard that dialysis patients in general had risks along these lines. It’s possible of course that Michael who posted this, is mistaken (though I know he lives in France, and has been a PKD patient there for many years). I was just wondering what the attitude is to this in the UK. Best wishes, Andy Williamson, Chair, Guys & St Thomas' KPA

A: Dear Andy, I am pleased to hear you are enjoying the pleasures of Paris and that the PKD email group that Tess has established is thriving. Inter-cranial aneurysm rupture is a rare but devastating complication of autosomal dominant PKD. It occurs in about 1 in 20 people with PKD without a family history but in up to nearly 1 in 5 people in whom there is a family history of rupture. This compares with about 1% in the general population. Rupture also occurs on average 10 years younger in people with PKD; the youngest reported case being a 6 year old boy. Aneurysm rupture is associated with a combined mortality or severe residual disability rate of about 35-55%. However, treatment of aneurysms by either neurosurgical clipping or endovascular treatment also carries an unacceptably high combined high mortality – severe disability rate of 21-34%. Some individuals make remarkable recoveries such as Alberto Contador who collapsed following an aneurysm rupture during the Vuelta a Asturias, Spain (May 2004), but who has subsequently gone on to win the Tour de France in 2007 and may possibly in 2009.

In the general population, size greater than 1 cm, location and history of previous rupture are the major risk factors for rupture but in PKD the situation is less certain and it has been suggested that half of all ruptured aneurysms in PKD are under the 1 cm threshold. Aneurysm formation rupture also appears to run in families and there is some early evidence of genetic linkage and risk. Recent studies have concluded that the outlook for asymptomatic aneurysms in PKD is excellent. The only factor that seemed to correlate with development of new aneurysms was a history of previous rupture. Given this uncertainty we really don’t know which patients we should be screening for asymptomatic aneurysms.

Patients who have suffered a previous rupture appear to a higher risk group who require life long screening. For asymptomatic patients, the presence of a strong family history of rupture (at least 2 first degree relatives) remains the best predictor of rupture (it increases risk by 4.4 times) and the case can be made for screening this group. The evidence does not support routine screening of all PKD patients but all PKD patients should have good control of blood pressure, be advised about smoking cessation and limiting alcohol consumption to within health limits as these treatable and lifestyle factors are key determinants of rupture. In the future we may have genetic tests that help us assess risk but at the moment there isn’t a UK wide consensus on the approach that should be taken in people with PKD who might have asymptomatic aneurysms. Best wishes, Donal.

Polycystic Kidney Disease Charity (UK)