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Choroidal and retinal thinning in chronic kidney disease independently associate with eGFR decline and are modifiable with treatment.

ABSTRACT: In patients with chronic kidney disease (CKD), there is an unmet need for novel biomarkers that reliably track kidney injury, demonstrate treatment-response, and predict outcomes. Here, we investigate the potential of retinal optical coherence tomography (OCT) to achieve these ends in a series of prospective studies of patients with pre-dialysis CKD (including those with a kidney transplant), patients with kidney failure undergoing kidney transplantation, living kidney donors, and healthy volunteers. Compared to health, we observe similar retinal thinning and reduced macular volume in patients with CKD and in those with a kidney transplant. However, the choroidal thinning observed in CKD is not seen in patients with a kidney transplant whose choroids resemble those of healthy volunteers. In CKD, the degree of choroidal thinning relates to falling eGFR and extent of kidney scarring. Following kidney transplantation, choroidal thickness increases rapidly (~10%) and is maintained over 1-year, whereas gradual choroidal thinning is seen during the 12 months following kidney donation. In patients with CKD, retinal and choroidal thickness independently associate with eGFR decline over 2 years. These observations highlight the potential for retinal OCT to act as a non-invasive monitoring and prognostic biomarker of kidney injury.

SUBMITTER: Farrah TE

PROVIDER: S-EPMC10697963 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Choroidal and retinal thinning in chronic kidney disease independently associate with eGFR decline and are modifiable with treatment.

Farrah Tariq E TE Pugh Dan D Chapman Fiona A FA Godden Emily E Balmforth Craig C Oniscu Gabriel C GC Webb David J DJ Dhillon Baljean B Dear James W JW Bailey Matthew A MA Gallacher Peter J PJ Dhaun Neeraj N

Nature communications 20231205 1

In patients with chronic kidney disease (CKD), there is an unmet need for novel biomarkers that reliably track kidney injury, demonstrate treatment-response, and predict outcomes. Here, we investigate the potential of retinal optical coherence tomography (OCT) to achieve these ends in a series of prospective studies of patients with pre-dialysis CKD (including those with a kidney transplant), patients with kidney failure undergoing kidney transplantation, living kidney donors, and healthy volunt ...[more]

PMID: 38052813

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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:Importance:Parapapillary choroidal microvasculature dropout (MvD) is considered one of pathophysiological manifestations of glaucomatous damage. Objective:To evaluate the longitudinal change in the parapapillary choroidal MvD in patients with primary open-angle glaucoma (POAG), and to determine whether this change is associated with progressive retinal nerve fiber layer (RNFL) thinning. Design, Setting, and Participants:This prospective observational case series was conducted at a tertiary referral center in Korea and included 68 patients with POAG who exhibited parapapillary choroidal MvD in en face optical coherence tomography (OCT) angiography (OCTA) images who were enrolled from the ongoing Investigating Glaucoma Progression Study from January 1, 2016, through July 31, 2018. The mean (SD) follow-up period was 2.5 (0.2) years and observers were masked to the clinical characteristics of the participants for measurements. The OCTA images were obtained twice at an interval of at least 2 years, during which the RNFL thickness was measured at least 4 times in serial OCT examinations. Microvasculature dropout was defined as a focal sectoral capillary dropout with no visible microvascular network identified in the choroidal layer. The MvD area was measured in the OCTA images obtained at the baseline and the final follow-up. The significance of changes in the MvD area was defined using the 95% Bland-Altman limits of agreement. The rate of RNFL thinning was determined by linear regression of the serial OCT RNFL thickness measurements. Main Outcomes and Measures:The association between the change in the MvD area and the rate of RNFL thinning. Results:Of 68 Korean participants, 37 (54.5%) were women, and the mean (SD) age was 54.3 (13.1) years. Among 68 eyes, 22 (32.4%) showed increases in the MvD area during the follow-up. Faster global RNFL thinning was associated with a larger baseline parapapillary atrophy β-zone (β = -0.55; 95% CI, -0.96 to -0.14; P = .01), disc hemorrhage detection during the follow-up period (β = -0.75; 95% CI, -1.67 to -0.34; P = .001), and a larger increase in the MvD area (β = -4.74; 95% CI, -7.72 to -1.75; P = .002). The MvD area was not associated with the rate of RNFL thinning at baseline or the final follow-up. Conclusions and Relevance:Microvasculature dropout enlargement was associated with progressive RNFL thinning in POAG.

Project description:Data on risk factors predicting rapid progression to end-stage renal disease (ESRD) or short-term kidney function decline (i.e., within 1 year) in chronic kidney disease (CKD) are rare but urgently needed to plan treatment. This study describes the association and predictive value of urinary uromodulin (uUMOD) for rapid progression of CKD.We assessed uUMOD, demographic/treatment parameters, estimated glomerular filtration rate (eGFR), and proteinuria in 230 CKD patients stage I-V. ESRD and 25% decline of eGFR was documented at the end of follow-up period and used as a composite endpoint. Association between logarithmic uUMOD and eGFR/proteinuria was calculated using linear regression analysis, adjusting for age, gender, and body mass index. We performed multivariable Cox proportional hazard regression analysis to evaluate the association of uUMOD with the composite endpoint. Therefore, patients were categorized into quartiles. The predictive value of uUMOD for the above outcomes was assessed using receiver-operating characteristic (ROC) curve analysis.Follow-up was 57.3 ± 18.7 weeks, baseline age was 60 (18;92) years, and eGFR was 38 (6;156) mL/min/1.73 m. Forty-seven (20.4%) patients reached the composite endpoint. uUMOD concentrations were directly associated with eGFR and inversely associated with proteinuria (β = 0.554 and β = -0.429, P < .001). In multivariable Cox regression analysis, the first 2 quartiles of uUMOD concentrations had a hazard ratio (HR) of 3.589 [95% confidence interval (95% CI) 1.002-12.992] and 5.409 (95% CI 1.444-20.269), respectively, in comparison to patients of the highest quartile (≥11.45 μg/mL) for the composite endpoint. In ROC-analysis, uUMOD predicted the composite endpoint with good sensitivity (74.6%) and specificity (76.6%) at an optimal cut-off at 3.5 μg/mL and area under the curve of 0.786 (95% CI 0.712-0.860, P < .001).uUMOD was independently associated with ESRD/rapid loss of eGFR. It might serve as a robust predictor of rapid kidney function decline and help to better schedule arrangements for future treatment.

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Choroidal and retinal thinning in chronic kidney disease independently associate with eGFR decline and are modifiable with treatment.

Publications

Choroidal and retinal thinning in chronic kidney disease independently associate with eGFR decline and are modifiable with treatment.

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