title: Cerebral small vessel disease and renal function: systematic review and meta-analysis.
abstract: BACKGROUND
  The small vessel disease (SVD) that appears in the brain may be part of a multisystem disorder affecting other vascular beds such as the kidney and retina. Because renal failure is associated with both stroke and white matter hyperintensities we hypothesised that small vessel (lacunar) stroke would be more strongly associated with renal failure than cortical stroke. Therefore, we performed a systematic review and meta-analysis to establish first if lacunar stroke was associated with the renal function, and second, if cerebral small vessel disease seen on the MRI of patients without stroke was more common in patients with renal failure.
  
  
  METHODS
  We searched Medline and EMBASE for studies in adults with cerebral SVD (lacunar stroke or white matter hyper intensities (WMH) on Magnetic Resonance Imaging (MRI)), in which renal function was assessed (estimated glomerular filtration rate (eGFR) or proteinuria). We extracted data on SVD diagnosis, renal function, demographics and comorbidities. We performed two meta-analyses: first, we calculated the odds of renal impairment in lacunar (small vessel) ischaemic stroke compared to other ischaemic stroke subtypes (non-small vessel disease); and second, we calculated the odds of renal impairment in non-stroke individuals with WMH on MRI compared to individuals without WMH. We then performed a sensitivity analysis by excluding studies with certain characteristics and repeating the meta-analysis calculation.
  
  
  RESULTS
  After screening 11,001 potentially suitable titles, we included 37 papers reporting 32 studies of 20,379 subjects: 15 of stroke patients and 17 of SVD features in non-stroke patients. To diagnose lacunar stroke, 13/15 of the studies used risk factor-based classification (none used diffusion-weighted MRI). 394/1,119 (35%) of patients with lacunar stroke had renal impairment compared with 1,443/4,217 (34%) of patients with non-lacunar stroke, OR 0.88, (95% CI 0.6-1.30). In individuals without stroke the presence of SVD was associated with an increased risk of renal impairment (whether proteinuria or reduced eGFR) OR 2.33 (95% CI 1.80-3.01), when compared to those without SVD. After adjustment for age and hypertension, 15/21 studies still reported a significant association between renal impairment and SVD.
  
  
  CONCLUSIONS
  We found no specific association between renal impairment and lacunar stroke, but we did find that in individuals who had not had a stroke, having more SVD features on imaging was associated with a worse renal function, which remained significant after controlling for hypertension. However, this finding does not exclude a powerful co-associate effect of age or vascular risk factor exposure. Future research should subtype lacunar stroke sensitively and control for major risk factors.
authors.affiliation: Clinical Research Fellow, Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Stephen D J
authors.initials: SD
authors.lastname: Makin
authors.forename: F A B
authors.initials: FA
authors.lastname: Cook
authors.forename: Martin S
authors.initials: MS
authors.lastname: Dennis
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
mesh_terms: D059345:Cerebral Small Vessel Diseases / Q000453:epidemiology* / Q000473:pathology; D005919:Glomerular Filtration Rate; D006801:Humans; D008279:Magnetic Resonance Imaging; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000378:metabolism; D059409:Stroke, Lacunar / Q000453:epidemiology* / Q000473:pathology; D066127:White Matter / Q000473:pathology