Chronic kidney disease and glaucoma.
Chronic kidney disease (CKD) is defined as a glomerular filtration rate (GFR) of less than 60 ml/min per 1.73 m2 of body surface area or a urinary albumin excretion greater than 30 mg/g that exists for longer than 3 months and that has implications for health [1]. CKD is a serious worldwide public health problem that affects many people and is associated with adverse cardiovascular and kidney outcomes as well as premature death [2,3]. The prevalence of CKD increases rapidly with aging of the population in both Western and Asian populations. In the United States, the CKD prevalence in adults of 30 years of age or older is estimated to be 14.4% in 2020 and 16.7% in 2030 [4]. In Singapore, the age- and sex-standardized prevalence of CKD was reported to be 12.8% (11.4%, 18.6%, and 17.6% in Chinese, Malays, and Indians, respectively) [5]. In China, the overall prevalence of CKD was found to be 11.4% in adults over 60 years of age [6].
Glaucoma is the worldwide leading cause of irreversible blindness. The global prevalence of glaucoma for the age range 40-80 years is between 3 and 4%, which will result in approximately 110 to 120 million glaucoma patients in 2040 [7]. Glaucoma is characterized by retinal ganglion cell (RGC) degeneration and, related to that, optic nerve head cupping. Glaucoma is related to an increase in intraocular pressure, but its etiology and pathophysiology are poorly understood and, clearly, other factors play a role as well. Examples of other factors are vascular deficits, genetic factors, increased trans-lamina cribrosa pressure, oxidative stress, Helicobacter pylori infections, and metabolic diseases, including CKD.
CKD and glaucoma have been linked to each other in several population-based, cross-sectional studies, as discussed in our recently published review [8]. However, findings are inconsistent and the picture is far from complete. Differences in study population, study design, medical infrastructure, risk profile and prevalence of CKD, management of diseases, as well as survival bias may explain the discrepancies between the different studies. Our proposal aims to explore the association between CKD and POAG in the large-scale population-based Lifelines cohort, which will further our understanding on the relationship between CKD and glaucoma. We will not only focus on CKD as a disease entity, but also on CKD-related endophenotypes. One of these endophenotypes is uric acid. The relationship between uric acid and glaucoma is complex, because uric acid is not only related to CKD, and could thus be considered harmful, but also has neuroprotective properties, and as such it could be protective in POAG.
As demonstrated in our review, kidney disease and glaucoma may also share a common genetic background [8]. However, thus far no significant genetic associations are found between POAG and eGFR in GWAS data [9]. Further studies are needed to convincingly confirm or reject a potential pleiotropic relationship between CKD and glaucoma. One approach to investigate this in more detail is via the construction and application of polygenic risk scores (PRS). For this, we will apply a novel approach for PRS calculation, which has recently been developed by our collaborators [10].
Research question
1. To explore the association between CKD, and related endophenotypes like uric acid, and POAG in the large-scale population-based Lifelines cohort.
2. To explore the genetic associations between CKD and POAG.