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Arterial damage and cognitive decline in chronic kidney disease patients.

ABSTRACT: In the general population aortic stiffening, assessed by carotid femoral pulse wave velocity (cf-PWV), is associated with cognitive dysfunction (CO/DY). Data in chronic kidney disease (CKD) are limited. This study tests the hypothesis that large artery stiffness and microvascular damage in CKD patients are related to the damage of brain microcirculation reflected by impaired cognitive function. A cross-sectional study enrolled 151 patients (mean age 58.4 years; 64.5% males; 44 patients with CKD stage 1; 47 with stage 2; 25 with stage 3; and 35 with stage 4). Cognitive impairment, assessed by the Mini Mental State Examination (MMSE), the Clock - drawing test (Clock-test), and the Instrumental Activity of Daily Living (IADL), was considered as primary outcome. We measured systolic and pulse pressures at the brachial and aortic sites and cf-PWV. Our patients revealed a significant linear deterioration in all the domains of cognitive function according to CKD stages. High values of cf-PWV (P = 0.029) and aortic pulse pressure (aPP) (P < 0.026) were independent determinants of cognitive decline assessed by the MMSE. The present trial supports the hypothesis of an interaction between the kidney, large artery damage, central pressure pulsatility, and the injury of brain microcirculation. In clinical practice, cf-PWV and aPP measurements may help to predict cognitive decline. Whether the reduction in aortic stiffness following an aggressive treatment translates into improved cognitive outcomes remains to be determined.

SUBMITTER: Karasavvidou D

PROVIDER: S-EPMC8031195 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Arterial damage and cognitive decline in chronic kidney disease patients.

Karasavvidou Despina D Boutouyrie Pierre P Kalaitzidis Rigas R Kettab Hakim H Pappas Kosmas K Stagikas Dimitrios D Antonakis Nikolaos N Tsalikakis Dimitrios D Elisaf Moses M Laurent Stephane S

Journal of clinical hypertension (Greenwich, Conn.) 20180714 9

In the general population aortic stiffening, assessed by carotid femoral pulse wave velocity (cf-PWV), is associated with cognitive dysfunction (CO/DY). Data in chronic kidney disease (CKD) are limited. This study tests the hypothesis that large artery stiffness and microvascular damage in CKD patients are related to the damage of brain microcirculation reflected by impaired cognitive function. A cross-sectional study enrolled 151 patients (mean age 58.4 years; 64.5% males; 44 patients with CKD ...[more]

PMID: 30006952

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Project description:IntroductionChronic kidney disease (CKD) has been associated with accelerated retinal neurodegeneration. The purpose of this study is to evaluate the association between retinal neurodegeneration and the best-corrected visual acuity (BCVA) decline in patients with CKD.MethodsPost hoc analysis of two prospective studies. Patients with CKD stage ≥ 3 were enrolled. Macular thickness, peripapillary retinal nerve fiber layer (pRNFL) thickness, and macular ganglion cell complex (GCC) thickness were measured by optical coherence tomography. Eyes were classified into three groups: Group 1, no GCC defect; Group 2, GCC defect confined to parafoveal area; and Group 3, GCC defects extending beyond the parafoveal area. Each group was matched for age, sex, axial length, lens status, and cataract grading.ResultsA total of 120 eyes (40 eyes in each group) from 120 patients (age 63.0 ± 10.3 years) were included. The logMAR BCVA was 0.076 ± 0.101, 0.100 ± 0.127, and 0.196 ± 0.191 in Group 1, 2, and 3, respectively. Group 3, but not Group 2, had a significantly worse BCVA than Group 1. In simple linear regression, parafoveal inner retinal thickness, pRNFL thickness, presence of pRNFL defect, GCC thickness, GCC global loss volume, GCC focal loss volume, and GCC defect extending beyond parafoveal area were associated with BCVA. Central subfield retinal thickness (CRT), parafoveal full retinal thickness, and parafoveal outer retinal thickness were not associated with BCVA. In backward stepwise linear regression, age and GCC defects extending beyond the parafoveal area were factors associated with BCVA. Moreover, GCC defect extending beyond parafoveal area was connected with worse BCVA in both phakic and pseudophakic subgroups.ConclusionsGCC defect extending beyond parafoveal area could be an independent biomarker associated with decreased BCVA in patients with CKD. However, macular thinning measured by CRT or parafoveal full retinal thickness might have low discriminative power in determining BCVA.

Project description:Background and objectivesThe independent link between arterial stiffness and CKD remains unknown. We investigated the association of indicators of arterial stiffness with decline in kidney function.Design, setting, participants, & measurementsWe studied 3666 participants (mean age =65 years old; 58% women) from the Rotterdam Study. Pulse pressure (PP), carotid stiffness, and pulse wave velocity (PWV) were measured. We created genetic risk scores for PP and PWV. Annual declines in kidney function and incident CKD were assessed using eGFR. To put our findings in context of the literature, we performed a meta-analysis of the available population-based studies.ResultsAfter a median (interquartile range) follow-up time of 11 (10.7-11.3) years, 601 participants with incident CKD were recognized. In the model adjusted for age, sex, mean arterial pressure, heart rate, and baseline GFR, each SD higher PP was associated with 0.15-ml/min per 1.73 m(2) steeper annual eGFR decline (95% confidence interval [95% CI], 0.10 to 0.20) and 11% higher risk of incident CKD (95% CI, 1.05 to 1.18). Each SD greater carotid stiffness was associated with 0.08-ml/min per 1.73 m(2) steeper annual eGFR decline (95% CI, 0.04 to 0.13) and 13% higher risk of incident CKD (95% CI, 1.05 to 1.22). Each SD higher PWV was associated with 7% higher risk of incident CKD (95% CI, 1.00 to 1.14). Incorporating our findings in a meta-analysis, each SD higher PP and PWV were associated with 16% (95% CI, 1.12 to 1.21) and 8% (95% CI, 1.03 to 1.14) higher risks of incident CKD. Each SD higher PP genetic risk score was associated with 0.06-ml/min per 1.73 m(2) steeper annual eGFR decline (95% CI, 0.01 to 0.10) and 8% higher risk of incident CKD (95% CI, 1.03 to 1.14). There was no association between PWV genetic risk score and kidney function decline.ConclusionsHigher indices of arterial stiffness are associated with steeper decline in kidney function. This suggests that vascular stiffness could be considered as a target for delaying decline in kidney function.

Project description:BackgroundArterial medial calcification (AMC) is a common complication in individuals with chronic kidney disease (CKD), which can lead to cardiovascular morbidity and mortality. The progression of AMC is controlled by a key transcription factor called runt-related transcription factor 2 (RUNX2), which induces vascular smooth muscle cells (VSMCs) transdifferentiation into an osteogenic phenotype. However, RUNX2 has not been targeted for therapy due to its essential role in bone development. The objective of our study was to discover a RUNX2 coactivator that is highly expressed in arterial VSMCs as a potential therapy for AMC.MethodsWe employed transcriptomic analysis of human data and an animal reporter system to pinpoint four and a half LIM domains 2 (FHL2) as a potential target. Subsequently, we investigated the mRNA and protein expression patterns of FHL2 in the aortas of both human and animal subjects with CKD. To examine the role of FHL2 in the RUNX2 transcription machinery, we conducted coimmunoprecipitation and chromatin immunoprecipitation experiments. Next, we manipulated FHL2 expression in cultured VSMCs to examine its impact on high phosphate-induced transdifferentiation. Finally, we employed FHL2-null mice to confirm the role of FHL2 in the development of AMC in vivo.ResultsAmong all the potential RUNX2 cofactors, FHL2 displays selective expression within the cardiovascular system. In the context of CKD subjects, FHL2 undergoes upregulation and translocation from the cytosol to the nucleus of arterial VSMCs. Once in the nucleus, FHL2 interacts structurally and functionally with RUNX2, acting as a coactivator of RUNX2. Notably, the inhibition of FHL2 expression averts transdifferentiation of VSMCs into an osteogenic phenotype and mitigates aortic calcification in uremic animals, without causing any detrimental effects on the skeletal system.ConclusionThese observations provide evidence that FHL2 is a promising target for treating arterial calcification in patients with CKD.

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Arterial damage and cognitive decline in chronic kidney disease patients.

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Arterial damage and cognitive decline in chronic kidney disease patients.

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