Retinal microvascular signs and risk of diabetic kidney disease in asian and white populations.
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ABSTRACT:
SUBMITTER: Nusinovici S
PROVIDER: S-EPMC7921402 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
Retinal microvascular signs and risk of diabetic kidney disease in asian and white populations.
Nusinovici Simon S Sabanayagam Charumathi C Lee Kristine E KE Zhang Liang L Cheung Carol Y CY Tai E Shyong ES Tan Gavin S W GSW Cheng Ching Yu CY Klein Barbara E K BEK Wong Tien Yin TY
Scientific reports 20210301 1
The objective was to examine prospectively the association between retinal microvascular signs and development of diabetic kidney disease (DKD) in Asian and White populations. We analysed two population-based cohorts, composing of 1,221 Asians (SEED) and 703 White (WESDR) adults with diabetes. Retinal microvascular signs at baseline included vascular caliber (arteriolar-CRAE, and venular-CRVE) and diabetic retinopathy (DR). Incident cases of DKD were identified after ~ 6-year. Incident cases wer ...[more]
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Project description:BackgroundRetinal microvascular signs may provide insights into the structure and function of small vessels that are associated with renal disease. We examined the relationship of retinal microvascular signs with both prevalent and incident end-stage renal disease (ESRD) in a multi-ethnic Asian population.MethodsA total of 5763 subjects (aged ? 40 years) from two prospective population-based studies (the Singapore Malay Eye Study and the Singapore Prospective Study) were included for the current analysis. Retinopathy was graded using the modified Airlie House classification system. Retinal vascular parameters were measured using computer-assisted programs to quantify the retinal vessel widths (arteriolar and venular caliber) and retinal vascular network (fractal dimension). Data on ESRD was obtained by record linkage with the ESRD cases registered by National Registry of Diseases Office, Singapore. Multi-variable adjusted regression analyses were performed to assess the associations of baseline retinal vascular parameters and prevalent and incident ESRD.ResultsAt baseline, 21(0.36%) persons had prevalent ESRD. During a median follow-up of 4.3 years, 33 (0.57%) subjects developed ESRD. In our analyses, retinopathy was associated with prevalent ESRD (multi-variable adjusted odds ratio [OR], 3.21, 95% confidence interval [CI]: 1.28-8.05) and incident ESRD (multi-variable adjusted hazard ratio [HR], 2.51, 95%CI: 1.14-5.54). This association was largely seen in person with diabetes (HR, 2.60, 95%CI: 1.01-6.66) and not present in persons without diabetes (HR, 1.65, 95%CI: 0.14-18.98). Retinal arteriolar caliber, retinal venular caliber and retinal vascular fractal dimension were not associated with ESRD.ConclusionRetinopathy signs in persons with diabetes are related to an increased risk of ESRD; however, other microvascular changes in the retina are not associated with ESRD.
| S-EPMC4320082 | biostudies-literature
Project description:Diabetic retinal disease (DRD) remains the most common cause of vision loss in adults of working age. Progress on the development of new therapies for DRD has been limited by the complexity of the human eye, which constrains the utility of traditional research techniques, including animal and tissue culture models-a problem shared by those in the field of kidney disease research. By contrast, significant progress in the study of diabetic kidney disease (DKD) has resulted from the successful employment of systems biology approaches. Systems biology is widely used to comprehensively understand complex human diseases through the unbiased integration of genetic, environmental, and phenotypic aspects of the disease with the functional and structural manifestations of the disease. The application of a systems biology approach to DRD may help to clarify the molecular basis of the disease and its progression. Acquiring this type of information might enable the development of personalized treatment approaches, with the goal of discovering new therapies targeted to an individual's specific DRD pathophysiology and phenotype. Furthermore, recent efforts have revealed shared and distinct pathways and molecular targets of DRD and DKD, highlighting the complex pathophysiology of these diseases and raising the possibility of therapeutics beneficial to both organs. The objective of this review is to survey the current understanding of DRD pathophysiology and to demonstrate the investigative approaches currently applied to DKD that could promote a more thorough understanding of the structure, function, and progression of DRD.
| S-EPMC8003049 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Small-vessel disease contributes to the pathophysiology of stroke, and retinal microvascular signs have been linked to the risk of stroke. We examined the relationship of retinal signs with incident stroke in a multiethnic cohort. METHODS:The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study that enrolled participants without clinical cardiovascular diseases from 6 US communities between 2000 and 2002. Of the participants, 4849 (71.2%) had fundus photography performed in 2002 to 2004. Retinopathy and retinal vessel caliber were assessed from retinal images. Stroke risk factors including high-sensitivity C-reactive protein, carotid artery intima-media thickness, and coronary artery calcium were measured using standardized protocols. Incident stroke was confirmed from medical record review and death certificates. RESULTS:After 6 years of follow-up, there were 62 incident strokes. Narrower retinal arteriolar caliber was associated with increased risk of stroke after adjusting for conventional cardiovascular risk factors (adjusted incidence rate ratio, 2.83; 95% CI, 1.34-5.95; P=0.006; adjusted hazard ratio, 3.01; 95% CI, 1.29-6.99; P=0.011). Retinopathy in persons without diabetes was associated with increased risk of stroke (adjusted adjusted incidence rate ratio, 2.96; 95% CI, 1.50-5.84; P=0.002; adjusted hazard ratio, 3.07; 95% CI, 1.17-8.09; P=0.023). These associations remained significant after adjusting for high-sensitivity C-reactive protein, carotid intima-media thickness, or coronary artery calcium. CONCLUSIONS:Narrower retinal arteriolar caliber and retinopathy in nondiabetic persons were associated with increased risk of stroke in this relatively healthy multiethnic cohort independent of traditional risk factors and measures of atherosclerosis. The association between narrower retinal arteriolar caliber and stroke warrants further investigation.
| S-EPMC3508325 | biostudies-literature
Project description:ObjectivesTo determine the risk factors for retinal microvascular impairment on optical coherence tomography angiography (OCT-A) in type 2 diabetic patients without clinical diabetic retinopathy (DR).MethodsThis retrospective and cross-sectional study enrolled 74 diabetic patients without clinically evident DR for the study group and 34 healthy subjects for the control group. OCT-A parameters were measured to determine vascular density (VD) and the foveal avascular zone (FAZ) size in the superficial and deep capillary plexuses (SCP/DCP) of the retina. Clinical data were collected on sex, age, diabetes duration, hemoglobin A1c (HbA1c), hypertension, dyslipidemia, low-density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate (eGFR) and smoking status. Multiple linear regression analyses were performed to represent the associated clinical variables with OCT-A parameters in diabetic patients.ResultsIn comparison between the study and control groups, the VD in the SCP and DCP were significantly lower in diabetic patients compared to the controls (P = 0.022 and 0.003, respectively). The FAZ size in the SCP and DCP were significantly greater in diabetic patients compared to the controls (P = 0.035 and <0.001, respectively). In age- and sex-adjusted multiple regression analyses for the diabetic patients, dyslipidemia and hypertension were negatively associated with SCP-VD (β = -0.357, P = 0.002; β = -0.239, P = 0.039, respectively). Current smoking was correlated with lower DCP-VD (β = -0.255, P = 0.043). Greater SCP-FAZ size was associated with dyslipidemia and greater LDL-C (β = 0.254, P = 0.013; β = 0.232, P = 0.029, respectively), and greater DCP-FAZ size, with lower eGFR and greater LDL-C (β = -0.355, P = 0.004; β = 0.235, P = 0.037, respectively).ConclusionsDiabetic patients without clinical DR showed lower VD and greater FAZ size in the SCP and DCP compared to healthy controls. In diabetic patients without clinical DR, dyslipidemia and/or high LDL-C were important risk factors for retinal microvascular impairment. Hypertension, current smoking and lower eGFR also contributed to microvascular impairment.
| S-EPMC6084984 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:We hypothesized that retinal microvascular signs are associated with executive dysfunction, slow gait, and depressive mood, which are characteristic features of microvascular disease affecting frontal subcortical regions of the brain. METHODS:In the Cardiovascular Health Study, 1744 participants (mean age, 78) free of stroke had retinal photographs and carotid ultrasound during the 1997 to 1998 visit. We examined the cross-sectional association of retinal signs with the digit-symbol substitution test (DSST) score, gait speed, the Center for Epidemiologic Studies-Depression score, and depressive mood, defined as Center for Epidemiologic Studies-Depression score >9 or antidepressant use. RESULTS:After adjusting for potential confounders, retinal signs were associated with lower DSST score (generalized arteriolar narrowing and arteriovenous nicking), slower gait (retinopathy), and depressive mood (generalized arteriolar narrowing). A higher number of retinal signs was associated with lower DSST score (-0.76 and -2.79 points for 1 sign and ?2 signs versus none; P<0.001) and slower gait (-0.009 and -0.083 m/s; P=0.047), but not with the square root of Center for Epidemiologic Studies-Depression score (0.079 and -0.208; P=0.072). In addition, coexistence of retinal signs (generalized arteriolar narrowing and arteriovenous nicking) and carotid atherosclerosis was associated with lower DSST score compared with either process alone (P for interaction <0.01). Notably, further adjustment for ventricular size, white matter disease, and infarcts on MRI did not attenuate the association. CONCLUSIONS:Retinal signs are associated with executive dysfunction and slow gait, and possibly with depressive mood, suggesting a common process involving small vessels.
| S-EPMC3127407 | biostudies-literature
Project description:Brain microvascular disease leads to leukoaraiosis and lacunar infarcts and contributes to risk of stroke and cognitive decline. Given a shared pathophysiology, retinal microvascular signs are expected to predict brain microvascular disease progression. We investigated if either leukoaraiosis volume progression measured continuously or combined with incident lacunar infarcts would better demonstrate expected associations with retinal disease than has previously been shown.Eight hundred thirty participants in the Atherosclerosis Risk in Communities (ARIC) study aged ?55 years and without previous stroke received an initial brain magnetic resonance imaging, retinal photography, and, 10 years later, a follow up magnetic resonance imaging. We evaluated retinal vascular sign phenotypes as predictors of (1) leukoaraiosis volume increase, and (2) a new score combining leukoaraiosis volume change and incident lacunar infarcts. Hypertension and diabetes mellitus were evaluated as confounders and effect modifiers.Individuals with any retinopathy (3.34 cm3; 95% confidence interval [CI], 0.74-5.96) or with arteriovenous nicking (2.61 cm3; 95% CI, 0.80-4.42) each had greater progression of leukoaraiosis compared with those without these conditions. Any retinopathy (odds ratio [OR], 3.18; 95% CI, 1.71-5.89) or its components-microaneurysms (OR, 3.06; 95% CI, 1.33-7.07) and retinal hemorrhage (OR, 3.02; 95% CI, 1.27-7.20)-as well as arteriovenous nicking (OR, 1.93; 95%, CI 1.24-3.02) and focal arteriolar narrowing (OR, 1.76; 95% CI, 1.19-2.59), were associated with a higher quartile of a novel brain microvascular disease score combining leukoaraiosis progression with incident subclinical lacunes.A novel scoring method revealed associations of retinal signs with leukoaraiosis progression and brain microvascular disease, which have not been shown before.
| S-EPMC4191897 | biostudies-literature
Project description:IntroductionC-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.MethodsGenome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N?=?2,434) and Malays (N?=?2,542) and South-Asian Indians (N?=?2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.ResultsSerum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ?4.7×10(-8)) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ?0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ?0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).ConclusionsCommon variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease.
| S-EPMC3699653 | biostudies-literature
Project description:Background: Widespread neural and microvascular injuries are common in chronic kidney disease (CKD), increasing risks of neurovascular complications and mortality. Early detection of such changes helps assess the risks of neurovascular complications for CKD patients. As an extension of central nervous system, the retina provides a characteristic window to observe neurovascular alterations in CKD. This study aimed to determine the presence of retinal neurovascular impairment in different stages of CKD. Methods: One hundred fifteen non-diabetic and non-dialytic CKD patients of all stages and a control group of 35 healthy subjects were included. Retinal neural and microvascular parameters were obtained by optical coherence tomography angiography (OCTA) examination. Results: CKD 1-2 group (versus control group) had greater odds of having decreased retinal ganglion cell-inner plexiform layer thickness (GC-IPLt) (odds ratio [OR]: 0.92; 95% confidence interval [CI]: 0.86-0.98), increased ganglion cell complex-focal loss volume (GCC-FLV) (OR: 3.51; 95% CI: 1.27-9.67), and GCC-global loss volume (GCC-GLV) (OR: 2.48; 95% CI: 1.27-4.82). The presence of advanced stages of CKD (CKD 3-5 group versus CKD 1-2 group) had greater odds of having decreased retinal vessel density in superficial vascular plexus (SVP)-WholeImage (OR: 0.77, 95% CI: 0.63-0.92), SVP-ParaFovea (OR: 0.83, 95% CI: 0.71-0.97), SVP-ParaFovea (OR: 0.76, 95% CI: 0.63-0.91), deep vascular plexus (DVP)-WholeImage (OR: 0.89, 95% CI: 0.81-0.98), DVP-ParaFovea (OR: 0.88, 95% CI: 0.78-0.99), and DVP-PeriFovea (OR: 0.90, 95% CI: 0.83-0.98). Besides, stepwise multivariate linear regression among CKD patients showed that β2-microglobulin was negatively associated with GC-IPLt (β: -0.294; 95% CI: -0.469 ∼ -0.118), and parathyroid hormone was positively associated with increased GCC-FLV (β: 0.004; 95% CI: 0.002∼0.006) and GCC-GLV (β: 0.007; 95% CI: 0.004∼0.01). Urine protein to creatinine ratio was positively associated with increased GCC-FLV (β: 0.003; 95% CI: 0.001∼0.004) and GCC-GLV (β: 0.003; 95% CI: 0.001∼0.006). Conclusion: Retinal neuronal impairment is present in early stages of CKD (stages 1-2), and it is associated with accumulation of uremic toxins and higher UACR, while retinal microvascular hypoperfusion, which is associated with worse eGFR, was only observed in relatively advanced stages of CKD (stages 3-5). The results highlight the importance of monitoring retinal neurovascular impairment in different stages of CKD.
| S-EPMC8639216 | biostudies-literature
Project description:Importance:The association of diabetic microvascular complications such as diabetic retinopathy (DR) and diabetic kidney disease (DKD) with mortality in populations is not clear. Objective:To examine the association of DR and DKD separately and jointly with all-cause and cardiovascular disease (CVD) mortality in a multiethnic Asian population. Design, Setting, and Participants:A population-based cohort study was conducted including 2964 adults between the ages of 40 and 80 years with diabetes who participated in the Singapore Epidemiology of Eye Diseases study (baseline, 2004-2011). Data analysis was performed from January to May 2018. Exposures:Diabetic retinopathy ascertained from retinal photographs and DKD from estimated glomerular filtration rate. Main Outcomes and Measures:All-cause and CVD mortality obtained by linkage with the National Registry of Births and Deaths until May 2017. Results:Of the 2964 adults (mean [SD] age, 61.8 [10.0] years; 1464 [49.4%] female; 592 Chinese, 1052 Malay, and 1320 Indian), 29.9% of the participants had DR, while 20.7% had DKD. Over a median (interquartile range) follow-up of 8.8 (7.2-11.0) years, 610 deaths occurred (20.6%), of which 267 (9.0%) were due to CVD. In separate models, the multivariable hazard ratios for all-cause and CVD mortality were 1.54 (95% CI, 1.24-1.91) and 1.74 (95% CI, 1.27-2.40), respectively, for DR and 2.04 (95% CI, 1.64-2.56) and 2.29 (95% CI, 1.64-3.19), respectively, for DKD. In models including both DR and DKD, the subgroup with DKD alone (27.1% and 12.6%) followed by DR alone (6.5% and 5.2%) contributed substantially to the excess risk of all-cause and CVD mortality. Compared with those with no DR and DKD, the hazard ratios of all-cause and CVD mortality were 1.89 (95% CI, 1.40-2.57) and 2.26 (95% CI, 1.42-3.61), respectively, for DKD alone and 1.38 (95% CI, 1.03-1.86) and 1.64 (95% CI, 1.06-2.56), respectively, for DR alone. Hazard ratios for all-cause and CVD mortality were 2.76 (95% CI, 2.05-3.72) and 3.41 (95% CI, 2.19-5.32), respectively, for those with both DKD and DR. The relative excess risk associated with the interaction was 0.49 (95% CI, -0.29 to 1.27; P = .20) for all-cause mortality and 0.51 (95% CI, -0.83 to 1.85; P = .50) for CVD mortality. Conclusions and Relevance:These results suggest that risks of all-cause and CVD mortality were significantly higher in those with DKD and DR, but DKD was more strongly associated with excess risk. The findings underscore the importance of early identification and close monitoring and management of patients with DR and DKD to reduce the risk of death.
| S-EPMC6450319 | biostudies-literature
Project description:The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg.
| S-EPMC7724636 | biostudies-literature