Vision Impairment in CKD Patients: Epidemiology, Mechanisms, Differential Diagnoses, and Prevention

Nusinovici, Simon; Sabanayagam, Charumathi; Teo, Boon Wee; Tan, Gavin Siew Wei; Wong, Tien Yin

doi:10.1053/j.ajkd.2018.12.047

Cited by 40 publications

(32 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is worth noting that mechanisms underlying CKD, such as vascular remodeling, endothelial dysfunction, atherosclerosis, inflammation, and oxidative stress are also involved in the development of many eye diseases. Besides diabetes and hypertension, metabolic disorders associated with CKD, such as oxidative stress, uremia, anemia, as well as specific treatment, such as steroids and dialysis may be also involved [43]. Despite this bulk of evidence, screening for vision and hearing impairment is not currently recommended in CKD clinical guidelines and our findings suggest for its potential usefulness in this vulnerable population.…”

Section: Discussionmentioning

confidence: 89%

“…A population study involving 10,033 adults aged 40-80 years showed that the prevalence of vision impairment and ocular disease were significantly higher in participants with (36.1 and 84.7%) compared to those without CKD (12.9 and 54.3%, both p < 0.001) [42]. Diabetic retinopathy and age-related macular degeneration are most consistently associated with CKD [43]. It is worth noting that mechanisms underlying CKD, such as vascular remodeling, endothelial dysfunction, atherosclerosis, inflammation, and oxidative stress are also involved in the development of many eye diseases.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic kidney disease in the context of multimorbidity patterns: the role of physical performance

et al. 2020

View full text Add to dashboard Cite

Background Chronic kidney disease (CKD) is known to be associated with several co-occurring conditions. We aimed at exploring multimorbidity patterns associated with CKD, as well as the impact of physical performance and CKD severity on them in a population of older outpatients. Methods Our series consisted of 2252 patients enrolled in the Screening of CKD among Older People across Europe multicenter observational study. Hypertension, stroke, transient ischemic attack, cancer, hip fracture, osteoporosis, Parkinson’s disease, asthma, chronic obstructive pulmonary disease, congestive heart failure, angina, myocardial infarction, atrial fibrillation, anemia, CKD (defined as GFR < 60, < 45 or < 30 ml/min/1.73 m2), cognitive impairment, depression, hearing impairment and vision impairment were included in the analyses. Physical performance was assessed by the Short Physical Performance Battery (SPPB) and used as stratification variable. Pairs of co-occurring diseases were analyzed by logistic regression. Patterns of multimorbidity were investigated by hierarchical cluster analysis. Results CKD was among the most frequently observed conditions and it was rarely observed without any other co-occurring disease. CKD was significantly associated with hypertension, anemia, heart failure, atrial fibrillation, myocardial infarction and hip fracture. When stratifying by SPPB, CKD was also significantly associated with vision impairment in SPPB = 5–8 group, and hearing impairment in SPPB = 0–4 group. Cluster analysis individuated two main clusters, one including CKD, hypertension and sensory impairments, and the second including all other conditions. Stratifying by SPPB, CKD contribute to a cluster including diabetes, anemia, osteoporosis, hypertension and sensory impairments in the SPPB = 0–4 group. When defining CKD as eGFR< 45 or 30 ml/min/1.73 m2, the strength of the association of CKD with hypertension, sensory impairments, osteoporosis, anemia and CHF increased together with CKD severity in pairs analysis. Severe CKD (eGFR< 30 ml/min/1.73 m2) contributed to a wide cluster including cardiovascular, respiratory and neurologic diseases, as well as osteoporosis, hip fracture and cancer. Conclusions CKD and its severity may contribute significantly to specific multimorbidity patterns, at least based on the cluster analysis. Physical performance as assessed by SPPB may be associated with not negligible changes in both co-occurring pairs and multimorbidity clusters. Trial registration The SCOPE study is registered at clinicaltrials.gov (NCT02691546).

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Chronic kidney disease in the context of multimorbidity patterns: the role of physical performance

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Although the precise etiology of DKD remains unclear, it is clear that hyperglycemia-induced oxidative damage to mitochondrial constituents (DNA, proteins, and lipids) results in mitochondrial dysfunction in DKD ( Forbes and Thorburn, 2018 ). Circumstantial evidence supporting the involvement of mitochondrial dysfunction in DKD has been accumulating from animal and in-vitro studies ( Sun et al, 2008 ; Nusinovici et al, 2019 ). Recent studies have directly demonstrated that mitochondrial dysfunction is present in clinical DKD samples: for example, Czajka et al reported that mitochondrial DNA and mitochondrial RNAs are altered in the blood cells of DKD patients ( Czajka et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Nephroprotective Effects of Tetramethylpyrazine Nitrone TBN in Diabetic Kidney Disease

et al. 2021

View full text Add to dashboard Cite

Diabetic kidney disease (DKD) is the leading cause of end-stage renal failure, but therapeutic options for nephroprotection are limited. Oxidative stress plays a key role in the pathogenesis of DKD. Our previous studies demonstrated that tetramethylpyrazine nitrone (TBN), a novel nitrone derivative of tetramethylpyrazine with potent free radical-scavenging activity, exerted multifunctional neuroprotection in neurological diseases. However, the effect of TBN on DKD and its underlying mechanisms of action are not yet clear. Herein, we performed streptozotocin-induced rat models of DKD and found that TBN administrated orally twice daily for 6 weeks significantly lowered urinary albumin, N-acetyl-β-D-glycosaminidase, cystatin C, malonaldehyde, and 8-hydroxy-2′-deoxyguanosine levels. TBN also ameliorated renal histopathological changes. More importantly, in a nonhuman primate model of spontaneous stage III DKD, TBN increased the estimated glomerular filtration rate, decreased serum 3-nitrotyrosine, malonaldehyde and 8-hydroxy-2′-deoxyguanosine levels, and improved metabolic abnormalities. In HK-2 cells, TBN increased glycolytic and mitochondrial functions. The protective mechanism of TBN might involve the activation of AMPK/PGC-1α-mediated downstream signaling pathways, thereby improving mitochondrial function and reducing oxidative stress in the kidneys of DKD rodent models. These results support the clinical development of TBN for the treatment of DKD.

show abstract

“…Indeed, once Klotho fails to adequately express its proteins and variants, 6,[8][9][10] it is implicated in pathways that drive agerelated chronic disorders such as kidney disease, tissue dysfunction, diabetic retinopathies, neurodegeneration, and impairments in mitochondrial function and muscle regeneration. 4,8,[11][12][13][14][15][16] a-Klotho is often referred to as an ''anti-aging protein.'' 3,6,17,18 When overexpressed in mice, Klotho extends life (20-30%), reduces oxidative stress (OS), and demonstrates other prosurvival properties.…”

Section: Introductionmentioning

confidence: 99%

“…3,18,27,102,183,184 A soluble form of Klotho (sKlotho), primarily secreted from the kidney, circulates in blood, urine, and cerebrospinal fluid, exerting different biological effects in multiple tissues as a humoral factor. 5,6,8,52,[185][186][187][188][189] In the eye, Klotho protects against OS 53,55,58,153,190,191 and is essential to the proper maintenance and function of the ocular system, 12,26,[192][193][194][195] being expressed throughout the retina, with the highest levels in retinal ganglion cells. 196 The retinal pigment epithelium (RPE) is a highly specialized CNS tissue whose function is critical in preserving retinal homeostasis 53,78 and an age-dependent decline of Klotho expression is said to contribute to RPE degeneration and retinal pathology.…”

Section: Introductionmentioning

confidence: 99%

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

Moos

Faller

Glavas

et al. 2020

BioResearch Open Access

View full text Add to dashboard Cite

In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.

show abstract

Vision Impairment in CKD Patients: Epidemiology, Mechanisms, Differential Diagnoses, and Prevention

Cited by 40 publications

References 122 publications

Chronic kidney disease in the context of multimorbidity patterns: the role of physical performance

Chronic kidney disease in the context of multimorbidity patterns: the role of physical performance

Nephroprotective Effects of Tetramethylpyrazine Nitrone TBN in Diabetic Kidney Disease

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

Contact Info

Product

Resources

About