Table 1.
Characteristics of studies included in the systematic review
| Study and population | Lacunar stroke definition | Imaging | Definition of renal impairment | Lacunar ischaemic stroke impaired/total | Non-lacunar ischaemic stroke impaired/total | |
|---|---|---|---|---|---|---|
| Studies which compared renal function between lacunar and non-lacunar stroke | ||||||
| Beamer [14], 1999 USA | Setting: 2 hospitals | TOAST | not clear | Proteinuria >20 mg/l | 17/54 | 11/42 |
| Included: 96 patients up to 7 days post-stroke | ||||||
| Excluded: UTI and dialysis | ||||||
| Das [10], 2012 Bangladesh | Setting: neurology department | TOAST | CT/MRI | proteinuria 20–200 ml/l | 13/42 | 6/18 |
| Included: 60 patients up to 4 weeks post-stroke | ||||||
| Excluded: known CKD | ||||||
| MacWalter [16], 2002 UK | Setting: teaching hospital | OCSP | CT | eGFR <66 | 121/134 | 302/354 |
| Included: 488 patients 48 h post stroke | ||||||
| Excluded: dialysis | ||||||
| Rodríguez-Yáñez [13], 2006 Spain | Setting: teaching hospital | TOAST | CT | proteinuria <30 mg/l | 4/33 | 45/167 |
| Included: 200 patients within 24 h | ||||||
| Excluded: TPA/trial drug, brainstem stroke or known renal disease | ||||||
| Tsagalis [19], 2009 Greece | Setting: teaching hospital stroke data bank | TOAST | CT | >50% increase in creatinine from baseline | 72/378 | 403/1454 |
| Included: 2,155 patients <48 h post stroke with 2× creatinine measurements | ||||||
| Excluded: previous stroke | ||||||
| Naganuma [21], 2011 Japan | Setting: registry of thrombolysis patients in 10 stroke units | TOAST | CT/MRI | eGFR <60 | 5/28 | 181/550 |
| Included: 578 patients who were thrombolysed for ischaemic stroke | ||||||
| Excluded: patients disabled prior to stroke | ||||||
| Mostofsky [18], 2009 USA | Setting: emergency department | TOAST | CT/MRI | eGFR <60 | 105/339 | 286/836 |
| Included: 1,175 consecutive patients | ||||||
| Excluded: IN-hospital stroke | ||||||
| Ueda [9], 2011 Japan | Setting: stroke unit | TOAST | MRI | eGFR <60 | 12/38 | 44/164 |
| Included: 202 consecutive ischaemic stroke patients | ||||||
| Excluded: acute kidney injury | ||||||
| Putaala [20], 2011 Finland | Setting: Helsinki young stroke registry | TOAST | not clear | eGFR <60 | 17/130 | 26/828 |
| Included: 958 first stroke patients age 15–19 | ||||||
| Excluded: incomplete data or creatinine measured 30 days post-stroke | ||||||
| Hoshino [17], 2012 Japan | Setting: Neurology Department | TOAST | CT | eGFR <60 | 29/92 | 88/235 |
| Included:475 stroke patients | ||||||
| Excluded: severe renal dysfunction, pre stroke disability | ||||||
| Kudo [22], 2012 Japan | Setting: single hospital | TOAST | CT/MRI | eGFR <60 and/or24/60 proteinuria | 168/264 | |
| Included: 525 stroke patients | ||||||
| Excluded: missing data | ||||||
| Tsukamoto [23], 2012 Japan | Setting: neurology department | TOAST | CT/MRI | eGFR <60 | 32/104 | 207/535 |
| Included: 639 consecutive stroke patients | ||||||
| Excluded: dialysis patients | ||||||
| Chinda [15], 2012 Japan | Setting: single hospital | TOAST | CT/MRI | eGFR <60 | 15/65 | 79/224 |
| Included: 451 consecutive stroke patients | ||||||
| Excluded: presented later than 7 days after stroke | ||||||
| Studies which compared renal function in stroke patients with WMH to those without WMH | ||||||
| Oksala [11], 2010 Finland | Setting: single hospital | NA | 1.0T MRI | eGFR <60 | 96/203 | 56/175 |
| Included: 378 consecutive ischaemic stroke patients aged 55–85 | ||||||
| Excluded: patients who were not Finnish or not living in Helsinki | ||||||
| Rost [12], 2010 USA | Setting: Emergency Department | NA | 1.5T MRI | eGFR as a continuous relationship | low eGFR correlated with WMH volume, r = −0.003, p = 0.002 | |
| Included: 523 consecutive ischaemic stroke patients | ||||||
| Excluded: patients without a lesion on MRI | ||||||
| Study | Patients | Imaging | Definition SVD | Measure of renal function | Subjects with SVD impaired/total | Subjects without SVD impaired/total |
| Studies of patients with MR imaging features of SVD, but no symptomatic stroke | ||||||
| Uzu [38], 2010 Japan | Setting: diabetic outpatient clinic | 1.5T MRI | 1+ SBI definition not given | micro albuminuria (30–299 ml/1) | 95/1772 | 188/431 |
| Included: 608 type 2 diabetic | ||||||
| Excluded: IHD, cancer, steroid use, heavy proteinuria 300 ml/l+, renal impairment | ||||||
| Ikram [30], 2008 Netherlands | Setting: Rotterdam study: population based study of 7,983 participants over 50 | 1.5T MRI | automated measurement of WMH volume | eGFR | for each SD decrease in eGFR there was a significant increase in OR of WMH 0.16 (0.04–0.29) | |
| Included: subgroup of 484 participants aged 60–90 stratified by sex and age | ||||||
| Excluded: patients with known dementia, or who could not have MRI | ||||||
| de Bresser [27], 2010 Netherlands | Setting: patients aged 56–80 with diabetes recruited though their General Practitioners | 1.5T MRI | automated measurement of WMH volume | albuminuria >0.03 g/1 | baseline albuminuria was associated with a non-significant increase in WMH at 2 years | |
| Included: 122 patients with Type 2 diabetes | ||||||
| Excluded: patients with psychiatric and neurological disorders, heavy alcohol use and dementia | ||||||
| Seliger [34], 2005 USA 40 | Setting: Cardiovascular Health Study 5,888 individuals over 65 selected randomly from medicare lists | not clear | 1+ infarct-like lesion ≥3 mm in a patient without a history of stroke | eGFR <60 | 237/789 | 484/1,9952 |
| Included: 2,784 participants selected for MRI | ||||||
| Excluded: previous stroke and TIA | ||||||
| Giele [29], 2004 Netherlands | Setting: second manifestations of ARTertial disease (SMART) study | 1.5T MRI | 1+ CSF filled lesion ≥3 mm | mild renal impairment: eGFR 80–50 Severe renal impairment eGFR <50 | age adjusted OR for presence of silent infarcts in: mild renal impairment 1.6 (0.7–3.5) | |
| Included: 308 patients with first presentation of atherosclerotic disease | ||||||
| Excluded: previous stroke or TIA | Severe renal impairment 7.3 (2.1–25.2) | |||||
| Wada [39], 2007; [40], 2008; [41], 2010 Japan | Setting: population study of all 61 and 72 year olds from two towns | 0.3 & 0.5T MRI | Fazekas score of either 2 or 3 (not specified whether deep or periventricular) | presence of micro albuminuria: cut off not clear | 95/177 | 188/431 |
| Included: 608 participants | ||||||
| Excluded: history of stroke, current UTI | ||||||
| eGFR <60 or urinary ACR <30 | 70/143 | 157/508 | ||||
| Cystatin C | OR of moderate or severe WMH, per SD increase in cystine C 1.48 (1.22–1.78) (unadjusted) | |||||
| Weiner [42], 2009 USA | Setting: clients of a home care service for low income people over 60 | 1.5T MRI | a score of 2/10 or more on an unvalidated qualitative WMH rating scale | microalbuminuria (17 mg/g+ in men and 25 mg/g+ in women) | 88/214 | 29/105 |
| Included: 319 participants | ||||||
| Excluded: participants who were unable to consent, non-English speakers, had a visual or hearing disability, on dialysis or unable to provide a urine specimen | ||||||
| Otani [32], 2010 Japan | Setting: population study of one town | 0.5T MRI | at least 1 hyperintensity on T2 between 3 and 15 mm | eGFR <60 | 100/286 | 186/722 |
| Included: 1,008 participants aged over 55 | ||||||
| Excluded: previous stroke or TIA | ||||||
| Bouchi [25], 2010 Japan | Setting: patients with type 2 diabetes who had an MRI for any reason at a single hospital | 1.5T MRI | T2 hyperintensity ≥3 mm | eGFR <60 | 182/415 | 75/371 |
| Included: 786 participants | ||||||
| Excluded: patients with type 1 DM, pregnancy, infection, cancer, or eGFR under 15 | ||||||
| Chou [26], 2011 Taiwan | Setting: healthy volunteers from Taipai City | 1.5T MRI | T2 hyperintensity ≥3 mm | eGFR 30–60 | 10/62 | 37/1,250 |
| Included: 1,312 participants | ||||||
| Excluded: previous stroke, current fever, eGFR <30 | ||||||
| Anan [24], 2008 Japan | Setting: outpatient endocrinology clinic | 1.5T MRI | the presence of WMH with Fazekas score ≥2 – unclear if deep or periventricular | urinary albumin in the range of 30–299 mg/24 h | 27/34 | 20/56 |
| Included: 90 patients with type 2 diabetes | ||||||
| Excluded: patients with IHD, macro-albuminuria, high creatinine, or insulin use | ||||||
| Eguchi [28], 2004 Japan | Setting: asymptomatic patients having an annual health check | 0.5T MRI | at least 1 hyperintensity on T2 between 3 and 15 mm | correlation between serum creatinine and no of WMH | serum creatinine correlated with number of WMH, r = 0.2, p < 0.006 | |
| Included: 170 patients aged 42–89 with 3 or more vascular risk factors | ||||||
| Excluded: renal or liver failure, secondary or malignant hypertension | ||||||
| Khatri [31], 2007 USA | Setting: randomly selected residents of Manhattan | 1.5T MRI | automated measurement of WMH volume | correlation between creatinine clearance and WMH volume | creatinine clearance of 15–60 ml/linked to log WMH volume (0.322; 95% CI, 0.095–0.550) | |
| Included: 615 participants over 40 who had a telephone and could consent | ||||||
| Excluded: those with a history of stroke or eGFR <15 | ||||||
| Takahashi [35], 2012 Japan | Setting: asymptomatic patients presenting for a ‘brain check’. | 1.5T MRI | score of ≥2 on Fazekas score – deep and periventricular lesions analysed separately | eGFR <60 | deep WMH 89/465 | deep WMH 156/1,571 |
| Included: 2,043 healthy volunteers. | ||||||
| Excluded: participants with a history of stroke, neurological, or heart diseases | ||||||
| periventricular WMH: 51/221 | periventricular WMH: 194/1,822 | |||||
| Takami [36], 2012 Japan | Setting: outpatient hypertension clinic | 1.5T MRI | deep WMH: cases if Fazekas score ≥2. Periventricular WMH cases if Fazekas score ≥1 | eGFR <60 | deep WMH 31/75 | deep WMH 16/1102 |
| Included: 185 participants | ||||||
| Excluded: patients with AF | ||||||
| periventricular WMH 36/102 | periventricular WMH 10/832 | |||||
| Turner [37], 2011 USA | Setting: members of sibling pairs where one was hypertensive | 1.5T MRI | automated measurement of WMH volume on FLAIR | correlation between serum creatinine and WMH volume | correlation between serum creatinine and WMH volume. Age adjusted correlation coefficient = 0.54 | |
| Included: 1,585 participants | ||||||
| Excluded: secondary hwypertension, known CKD and previous stroke | ||||||
| Ravera [33], 2002 Italy | Setting: patients from one centre who were enrolled in a large study on complications of microalbuminuria in untreated patients with mild-moderate hypertension | 1.5T MRI | a count of number of lacuanes: 3–15 mm lesion dark on T1, light on T2 | no of lacunes in 11 patients with microalbuminuria against the number of lacunas in 11 patients without microalbuminuria 82 of patients with microalbuminuria had incident lacunes vs. 27% of patients without | ||
| Included: 22 patients with microalbuminuria, 22 controls without | ||||||
| Excluded: patients with cancer, liver disease, IHD, diabetes, obesity, and Dementia | ||||||
1All studies excluded patients unable to have MRI
2
Calculated from mean and SD assuming a normal distribution. UTI = Urinary tract infection; TOAST = trial of org 10,172 in acute stroke treatment; CKD = chronic kidney disease; CT = computerised topography; MRI = magnetic resonance imaging; OCSP = oxfordshire community stroke project; eGFR = estimated glomular filtration rate; TPA = tissue plasminogen antigen; WMH = white matter hyperintensities; SD = standard deviation; IHD = ischaemic heart disease; TIA = transient ischaemic attack; CSF = cerebrospinal fluid; OR = odds ratio; ACR = albumin creatinine ratio.