Serum Cystatin C Level, Kidney Disease Markers, and Incidence of Age-Related Macular Degeneration

Klein, Ronald; Knudtson, Michael D.; Lee, Kristine E.; Klein, Barbara E. K.

doi:10.1001/archophthalmol.2008.551

Cited by 56 publications

(60 citation statements)

References 56 publications

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“…There is a significant association between the CFH genotype, and incidences of AMD and chronic renal disease 29,30 and these two seemingly disparate diseases may have a clinical and biological relationship. This fits very well with our hypothesis that FH internalization has an important role in facilitating opsonization, particularly in tissues such as kidneys and eyes.…”

Section: Discussionmentioning

confidence: 99%

Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes

et al. 2016

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Factor H (FH) binds apoptotic cells to limit the inflammatory potential of complement. Here we report that FH is actively internalized by apoptotic cells to enhance cathepsin L-mediated cleavage of endogenously expressed C3, which results in increased surface opsonization with iC3b. In addition, internalized FH forms complexes with nucleosomes, facilitates their phagocytosis by monocytes and induces an anti-inflammatory biased cytokine profile. A similar cytokine response was noted for apoptotic cells coated with FH, confirming that FH diminishes the immunogenic and inflammatory potential of autoantigens. These findings were supported by in vivo observations from CFH − / − MRL-lpr mice, which exhibited higher levels of circulating nucleosomes and necrotic cells than their CFH +/+ littermates. This unconventional function of FH broadens the established view of apoptotic cell clearance and appears particularly important considering the strong associations with genetic FH alterations and diseases such as systemic lupus erythematosus and age-related macular degeneration. Factor H (FH), one of the most abundant plasma proteins, is the major soluble inhibitor of the alternative complement pathway. Apoptotic cells bind FH while triggering complement activation by binding of C1 complex, which ensures efficient opsonization and removal of apoptotic debris but prevents excessive complement activation and inflammation. 1,2 Dysregulation of complement contributes significantly to the pathology of many diseases. 3 Recently, novel roles and intracellular location for complement have been identified suggesting that its functions exceed our current understanding. 4 After previously identifying the ligands for FH on the apoptotic cell surface as dsDNA, histones and annexin A2, 5 we sought to explore the functional consequences of the FH-apoptotic cell interaction in the context of the chronic autoimmune disorder systemic lupus erythematosus (SLE) and age-related macular degeneration (AMD). Aberrant apoptosis and impaired clearance of apoptotic cells are of central importance in the pathogenesis of SLE and lead to formation of autoantibodies. 6-8 Anti-chromatin autoantibodies are a hallmark of SLE and anti-annexin A2 autoantibodies are also frequently observed in SLE patients. 9 Interestingly, the corresponding autoantigens are exactly those that we identified as ligands for FH on the apoptotic cell surface, suggesting a possibility of disturbance of FH function in SLE. Glomerulonephritis is one typical manifestation of human SLE 10 and mutations in FH and another complement inhibitor CD46 are associated with earlier onset of nephritis in SLE patients. 11 FH-deficient (CFH − / − ) mice spontaneously develop membranoproliferative glomerulonephritis, which is dependent on C3 activation. 12 When crossed with the MRL-lpr mouse strain, a model of lupus, the originated CFH − / − MRLlpr mice exhibit accelerated lupus nephritis and die at younger age than their CFH +/+ MRL-lpr littermates. 13,14 AMD is the leading cause of visual impairm...

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Section: Discussionmentioning

confidence: 99%

Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes

et al. 2016

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“…These 9 population-based studies comprised 2 studies using a nationwide health insurance database [38,39], 3 nationwide surveys [42,46,47], and 4 community-based surveys [35,41,43,45]. The setting of the 3 hospital-based studies included 1 renal clinic [36] in a teaching hospital, 1 health examination center [40], and 1 health promotion center [37] in hospitals.…”

Section: The Characteristics Of the Included Studiesmentioning

confidence: 99%

“…Seven [35-37, 42, 43, 46, 47] studies compared the risk ratio of "estimated glomerular filtration rate (eGFR) < 60" vs. "eGFR > 60"; 2 [41,45] compared the risk ratio of "eGFR < 45 or 45-60" vs. "eGFR > 60"; and 1 [40] compared the risk ratio of "eGFR < 60 or the presence of proteinuria" vs. "eGFR > 60 without proteinuria". One study [38] compared the risk ratio of "ESRD on dialysis" vs. "no ICD-9 diagnosis code for kidney disease (ICD-9-CM 580-589)".…”

Section: Outcome Measurementsmentioning

confidence: 99%

“…In addition to the above CKD indicators, per SD change in eGFR [35], per SD change in creatinine [35], high serum cystatin vs. low cystatin [43], proteinuria vs. no proteinuria (in different types of AMD) [41,45,47], per SD change in log serum cystatin C [45], per SD change in log BUN [45], and per unit change in creatinine [46] were also used as renal function indicators in several studies. Data pooling was not undertaken for these renal function indicators because only 1-2 studies were available for each type of effect estimate.…”

Section: Outcome Measurementsmentioning

confidence: 99%

“…Several studies [37][38][39][40] also supported a positive association between CKD and AMD. However, other evidences have been conflicting both between [41][42][43][44] and within [41,[45][46][47] studies. Thus, whether an association exists between CKD and AMD remains undetermined.…”

Section: Introductionmentioning

confidence: 99%

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Age-Related Macular Degeneration in Chronic Kidney Disease: A Meta-Analysis of Observational Studies

et al. 2018

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Background: Age-related macular degeneration (AMD) is an important cause of blindness in aged people. Chronic kidney disease (CKD) was reported to be associated with a higher risk of AMD. However, supporting evidence was inconsistent between studies. This work intends to examine whether a positive association exists between CKD and AMD by systematic review and meta-analysis. Methods: A systematic search of electronic databases (Medline, PubMed, Cochrane and EMBASE) and reference lists on June 2017. The key inclusion criteria were controlled trials that investigated the relationship between AMD and CKD. The outcome measures included risk ratios and/or occurrence rates of AMD in CKD vs. non-CKD population. Data were pooled according to the type of AMD by random effect model. Results: Twelve observational studies (3 cohorts, 2 case controls, and 7 cross-sectionals) with a total 335,601 participants were included. Eleven studies reported risk ratios and 9 reported occurrence rates. Pooled prevalence for early, advanced, and any AMD were all higher in the CKD population than in the non-CKD population. The pooled multivariate adjusted OR of CKD vs. non-CKD was 1.49 (95% CI 1.11–2.02) for early, 1.55 (95% CI 1.05–2.27) for exudative, 1.58 (95% CI 1.12–2.23) for advanced, and 1.35 (95% CI 1.05–1.73) for any AMD. However, high statistical heterogeneity and methodological diversity existed. Moreover, results were inconsistent between different study designs. Conclusions: The overall results support a positive association between CKD and AMD, although some limitations exist. Given the risk that AMD is increased in CKD, regular eye screenings for the CKD population is recommended for an early detection and intervention.

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Complement, Age-Related Macular Degeneration and a Vision of the Future

Gehrs¹

2010

Arch Ophthalmol

147

115

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Serum Cystatin C Level, Kidney Disease Markers, and Incidence of Age-Related Macular Degeneration

Cited by 56 publications

References 56 publications

Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes

Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes

Age-Related Macular Degeneration in Chronic Kidney Disease: A Meta-Analysis of Observational Studies

Complement, Age-Related Macular Degeneration and a Vision of the Future

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