International Stroke Conference
February 6–8, 2019
Richard Jackson, MD
I’m writing to you from ISC reporting on another difficult topic: chronic kidney disease (CKD) and stroke. From past experience, both with traditional vascular CKD and Fabry’s disease, I know that there is a higher incidence of ICH in CKD; however, I’ve never been able to find a source that goes deep into the subject matter. Enter “Neuro-Nephrology,” a new word I had never heard before introduced to me at this mini-series. I had no idea this was a word, let alone an emerging field. I have always thought that stroke needs a subspecialty field for each subset of disease for proper study. So, welcome to the fray, Neuro-Nephrology.
First Lecture: Epidemiology of CKD and Stroke by Angela Webster, MBBS, MM(Clin Epid), PhD, FRCP, FRACP
Mortality in ESRD is 10%/year all cause and a higher incidence of ICH. Interestingly, she presented the data that most ESRD with strokes don’t go to Stroke Units despite the proven benefits of the units and the proven benefit of the units in ESRD.
She then move on to cognition and showed data that Attention and Memory worsen early in CKD and are dose dependent with decreases in GFR peaking in HD with worsening further still in the non-dialyzed. Interestingly, but not surprisingly, there is improvement after transplant.
Second Lecture: Neuroimaging of CKD by Daniel Chow, MD
There are baseline imaging features seen in CKD, such as basal ganglia hyperintensities in uremia and increased risk of microhemorrhages. There are also common disease with increased incidence in CKD, such as PRES and central and extra-pontine myelinolysis. And then there are common disease presentations made worse by CKD, such as increased hematoma expansion after ICH by 50% and a 1.95 RR of hemorrhagic conversion after ischemic stroke.
He then moved on to another useful topic, which was the risk of contrast induced nephropathy. Something which I don’t think is mainstream knowledge outside of the Nephrology and Radiology subspecialties is that there are actually two terms: post-contrast AKI (PCAKI), which refers to any change in GFR within 48 hours after contrast administration regardless of whether it is contrast induced or not, and contrast-induced nephropathy (CIN), which is a sudden deterioration after contrast administration. CIN is actually a subset of PCAKI and is extremely rare with the only known risk factors being severe renal insufficiency and multiple injections within 24 hours. The threshold which defines severe insufficiency is not well defined, and there is no evidence that NAC or bicarb help prevent CIN. Something to consider is that all of the previous data on CIN was likely contaminated by PCAKI.
Third Lecture: CKD and White Matter Disease (WMD) by Mark Fisher, MD
There is a large overlap of WMD CKD morphology on imaging with HTN, CAA, and CADASIL, and a large overlap of vascular morphology in the kidney and brain. Both receive 20% of the cardiac output by renal has a 7x higher flow with a high flow/low resistance pattern similar to the brain. It is thought that poor autoregulation with BBB breakdown might cause the WMD. Animal models show increasing BBB breakdown with increasing concentrations of uremia.
Specific CKD-related contributions include Hyper-Phosphatemia and loss of calcium regulators which cause vascular remodeling and loss of media elasticity. A new emerging concept is that CKD damages the gut epithelium with an increase in P Cresyl Sulfate and indoxyl sulfate into the systemic circulation. Lacunar infarcts in the brain have a specific histological morphology with adventitial hypertrophy and calcifications not seen in other diseases.
Fourth Lecture: Controversies in Stroke Management by Wei Ling Lau, MD
The BP target is recommended to be <130, but there is limited data and CKD patients have always been excluded from trials. Spring showed a composite MACE outcome decrease in the <120 group compared to the 140 group but no impact on stroke was found. Instead a J-shaped curve was found with <120 increased the risk of stroke by HR 2.6.
There has not been any mortality benefit in CKD with statin treatment for stroke.
CKD patients have a 2.5x increased risk of stroke and 5x higher risk of ICH. Apixiban has been approved based solely on a pharmacological study of <10 patients, but there is little evidence for its use. 2 meta-analyses in 2016 showed no mortality benefit and an increase in bleeding with anticoagulation and an increase in calcemic uremic vasculopathy of 5-10% which is worsened by warfarin. A Circulation paper in 2018 by Konstantinos showed a decreased risk of stroke with 5mg Apixiban, but the optimal dose is unclear and there is a lower risk of stage in CKD stages 1 and 2 but not seen in >3.
A Cochrane meta-analysis showed no decrease in stroke with antiplatelet but an increase in major and minor bleeding at 33% and 49%. There are contrasting findings of secondary prevention but a consistent increase in ICH. No evidence of Plavix benefit, possibly high levels of resistance.
The DOPPS registry shows increased mortality and incidence of stroke in CKD. Standard dose of tPA should be used with higher associated risk of bleeding complications, worse outcomes, and a higher risk of death despite the benefits of tPA. There is a 4x higher risk of dying in the hospital and 10% risk of death at 30 days.