Kidney Function Is Related to Cerebral Small Vessel Disease

Background and Purpose— Poor kidney function, as measured by glomerular filtration rate (GFR), is closely associated with presence of glomerular small vessel disease. Given the hemodynamic similarities between the vascular beds of the kidney and the brain, we hypothesized an association between kidney function and markers of cerebral small vessel disease on MRI. We investigated this association in a population-based study of elderly persons. Methods— We measured GFR using the Cockcroft-Gault equation in 484 participants (60 to 90 years of age) from the Rotterdam Scan Study. Using automated MRI-analysis we measured global as well as lobar and deep volumes of gray matter and white matter, and volume of WML. Lacunar infarcts were rated visually. Volumes of deep white matter and WML and presence of lacunar infarcts reflected cerebral small vessel disease. We used linear and logistic regression models to investigate the association between GFR and brain imaging parameters. Analyses were adjusted for age, sex, and additionally for cardiovascular risk factors. Results— Persons with lower GFR had less deep white matter volume (difference in standardized volume per SD decrease in GFR: −0.15 [95% CI −0.26 to −0.04]), more WML (difference per SD decrease in GFR: 0.14 [95% CI 0.03 to 0.25]), and more often lacunar infarcts, although the latter was not significant. GFR was not associated with gray matter volume or lobar white matter volume. Additional adjustment for cardiovascular risk factors yielded similar results. Conclusions— Impaired kidney function is associated with markers of cerebral small vessel disease as assessed on MRI.

[1]  B. Kestenbaum,et al.  Elevated risk of stroke among patients with end-stage renal disease. , 2003, Kidney international.

[2]  N. Madias,et al.  Serum creatinine as an index of renal function: new insights into old concepts. , 1992, Clinical chemistry.

[3]  Michael F O'Rourke,et al.  Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. , 2005, Hypertension.

[4]  Anne Newman,et al.  Cystatin C and subclinical brain infarction. , 2005, Journal of the American Society of Nephrology : JASN.

[5]  Charles E. McCulloch,et al.  CHRONIC KIDNEY DISEASE AND THE RISKS OF DEATH, CARDIOVASCULAR EVENTS, AND HOSPITALIZATION , 2004 .

[6]  Tien Yin Wong,et al.  Retinal microvascular abnormalities and renal dysfunction: the atherosclerosis risk in communities study. , 2004, Journal of the American Society of Nephrology : JASN.

[7]  Matthijs Oudkerk,et al.  Incidence and Risk Factors of Silent Brain Infarcts in the Population-Based Rotterdam Scan Study , 2003, Stroke.

[8]  R. Thisted,et al.  Predictors of body surface area. , 1992, Journal of clinical anesthesia.

[9]  T. Ohtake,et al.  Asymptomatic cerebral lacunae in patients with chronic kidney disease. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[10]  G. Beck,et al.  The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease , 1994 .

[11]  Wiro J. Niessen,et al.  Brain tissue volumes in the general elderly population The Rotterdam Scan Study , 2008, Neurobiology of Aging.

[12]  L. Truong,et al.  Role of the microvascular endothelium in progressive renal disease. , 2002, Journal of the American Society of Nephrology : JASN.

[13]  S. Greenberg,et al.  Small vessels, big problems. , 2006, The New England journal of medicine.

[14]  Deeb N Salem,et al.  Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. , 2004, Journal of the American Society of Nephrology : JASN.

[15]  Niels D Prins,et al.  Retinal vessel diameters and cerebral small vessel disease: the Rotterdam Scan Study. , 2006, Brain : a journal of neurology.

[16]  J. O'Brien,et al.  White Matter Lesions in an Unselected Cohort of the Elderly: Molecular Pathology Suggests Origin From Chronic Hypoperfusion Injury , 2006, Stroke.

[17]  G. Beck,et al.  The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. , 1994, The New England journal of medicine.

[18]  A. Nissenson,et al.  Prevalence and characteristics of individuals with chronic kidney disease in a large health maintenance organization. , 2001, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[19]  A. Hofman,et al.  Cerebral white matter lesions and the risk of dementia. , 2004, Archives of neurology.

[20]  D. Siscovick,et al.  Cystatin C and the risk of death and cardiovascular events among elderly persons. , 2005, The New England journal of medicine.

[21]  G. London,et al.  Cardiovascular disease in renal failure. , 2004, Minerva urologica e nefrologica = The Italian journal of urology and nephrology.

[22]  A Hofman,et al.  A follow‐up study of blood pressure and cerebral white matter lesions , 1999, Annals of neurology.

[23]  P. J. Koudstaal,et al.  Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI , 2003, Diabetologia.

[24]  Wiro J. Niessen,et al.  kNN-based multi-spectral MRI brain tissue classification: manual training versus automated atlas-based training , 2006, SPIE Medical Imaging.

[25]  M. H. Gault,et al.  Prediction of creatinine clearance from serum creatinine. , 1975, Nephron.

[26]  Daniel Rueckert,et al.  Nonrigid registration using free-form deformations: application to breast MR images , 1999, IEEE Transactions on Medical Imaging.

[27]  A. Hofman,et al.  Renal function and risk of myocardial infarction in an elderly population: the Rotterdam Study. , 2005, Archives of internal medicine.

[28]  A. Hofman,et al.  Determinants of disease and disability in the elderly: The Rotterdam elderly study , 1991, European Journal of Epidemiology.

[29]  J. Wetzels,et al.  Assessment of glomerular filtration rate in healthy subjects and normoalbuminuric diabetic patients: validity of a new (MDRD) prediction equation. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[30]  Koen L. Vincken,et al.  Probabilistic segmentation of brain tissue in MR imaging , 2005, NeuroImage.

[31]  C. DeCarli,et al.  Chronic Kidney Disease Is Associated With White Matter Hyperintensity Volume: The Northern Manhattan Study (NOMAS) , 2007, Stroke.

[32]  A. Hofman,et al.  Prevalence and Risk Factors of Silent Brain Infarcts in the Population-Based Rotterdam Scan Study , 2002, Stroke.

[33]  A Hofman,et al.  C-Reactive Protein and Cerebral Small-Vessel Disease: The Rotterdam Scan Study , 2005, Circulation.

[34]  F. Barkhof,et al.  Histopathologic correlates of white matter changes on MRI in Alzheimer's disease and normal aging , 1995, Neurology.

[35]  A. Levey,et al.  A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation , 1999, Annals of Internal Medicine.

[36]  Charles E McCulloch,et al.  Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. , 2004, The New England journal of medicine.

[37]  L. Truong,et al.  A role for uric acid in the progression of renal disease. , 2002, Journal of the American Society of Nephrology : JASN.

[38]  R. D'Agostino,et al.  Association of white matter hyperintensity volume with decreased cognitive functioning: the Framingham Heart Study. , 2006, Archives of neurology.

[39]  Matthijs Oudkerk,et al.  Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam scan study , 2002, Annals of neurology.

[40]  Josien P. W. Pluim,et al.  Comparison of gradient approximation techniques for optimisation of mutual information in nonrigid registration , 2005, SPIE Medical Imaging.

[41]  O. Djurdjev,et al.  Screening for renal disease using serum creatinine: who are we missing? , 2001, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[42]  R. Foley,et al.  Cardiovascular risk factor profiles and kidney function stage in the US general population: the NHANES III study. , 2005, Mayo Clinic proceedings.

[43]  H. Möller,et al.  Reliable manual segmentation of the frontal, parietal, temporal, and occipital lobes on magnetic resonance images of healthy subjects. , 2005, Brain research. Brain research protocols.

[44]  P. Scheltens,et al.  A new rapid landmark-based regional MRI segmentation method of the brain , 2002, Journal of the Neurological Sciences.

[45]  A. Hofman,et al.  Silent Brain Infarcts and White Matter Lesions Increase Stroke Risk in the General Population: The Rotterdam Scan Study , 2003, Stroke.