Inflammatory Skin Diseases and the Risk of Chronic Kidney Disease - Cross-sectional and Cohort Studies

Date of ISAC Approval: 
25/01/2019
Lay Summary: 
Chronic kidney disease is common with one in ten people affected. It often has no symptoms until late in the disease process (kidney failure requiring dialysis or kidney transplantation), with resulting poor quality of life and increased risk of death. Diabetes and high blood pressure are well-established risk factors for kidney disease, but the full reasons for developing chronic kidney disease are not completely understood. Emerging evidence suggests that there may be a link between chronic inflammation and kidney damage, and inflammation might cause kidney disease. Chronic inflammation is also a feature of several common non-infectious skin diseases (e.g. atopic eczema, psoriasis, rosacea, hidradenitis suppurativa). Recent work suggests a possible association between more common inflammatory skin diseases and kidney disease, but the size and nature of this association remain unclear. We plan to investigate and quantify the association between chronic kidney disease and inflammatory skin diseases in the general population. To understand the timing of events, we will also examine the association of chronic kidney disease with atopic eczema and psoriasis, specifically among people with diabetes. Patients with diabetes undergo periodic blood testing for kidney function, so the occurrence of new kidney disease can be reliably detected. Exploring and highlighting the potential role of skin diseases as possible risk-factors or markers for kidney disease could be important for defining at-risk populations who might benefit from regular kidney function monitoring, guiding judicial use of drugs that could cause kidney problems among patients with skin conditions, and help us understand why kidney disease occurs.
Technical Summary: 
We aim to explore the association between CKD and common non-communicable inflammatory skin diseases (i.e. atopic eczema, psoriasis, rosacea, hidradenitis suppurativa). The diagnosis of CKD requires evidence of an abnormally low estimated glomerular filtration rate (eGFR), but creatinine tests are not routinely offered or performed for everybody. However, we have shown that prevalent cases of CKD can be reliably ascertained through pooling accumulated test results over several years. Incident CKD can be accurately detected in at-risk populations, like those with diabetes, who undergo regular routine kidney function monitoring. We, therefore, plan to address our research question through two complementary study designs (1. prevalent case-control; 2. cohort) allowing us to assess both the magnitude and the temporal direction of the association between inflammatory skin diseases and CKD. We will define our main outcome, CKD, based on two consecutive reduced eGFR measurements, and we will apply previously validated algorithms where available to detect inflammatory skin diseases (i.e. the exposures). Initially, we will include all CPRD patients with prevalent CKD in March 2018 (each matched on GP practice, age and sex with up to 5 individuals without CKD) in a case-control analysis. We will fit conditional logistic regression models to compare the prevalence CKD among individuals with and without inflammatory skin diseases, and multinomial regression models to assess the association by CKD stage. Subsequently, we will conduct a cohort analysis, including all individuals in CPRD with diabetes (2004-2018). We will fit Poisson regression models to compare the rate of incident CKD among patients with and without atopic eczema and psoriasis. We will consider various lifestyle variables, medications, and recognised risk factors of CKD as potential confounders and/or mediators, and will employ a purposeful hierarchical approach to model building for a-priori covariate selection.
Health Outcomes to be Measured: 
Primary: Chronic kidney disease (CKD) Secondary: CKD stage and renal replacement therapy (RRT) Overall we aim to explore the link between skin disease (exposure: atopic eczema, psoriasis, rosacea, and hidradenitis suppurativa) and kidney disease (outcome). However in practice, in Study A (case-control study) the exposure/outcome will be reversed, with CKD as exposure, and outcome as skin disease, while in Study B (cohort study) the exposure will be skin disease and the outcome(s) kidney disease.
Collaborators: 

Dr Dorothea Nitsch - Chief Investigator - London School Of Hygiene & Tropical Medicine (LSHTM)
Kate (Kathryn) Mansfield - Collaborator - London School Of Hygiene & Tropical Medicine (LSHTM)
Professor Liam Smeeth - Collaborator - London School Of Hygiene & Tropical Medicine (LSHTM)
Sinead Langan - Collaborator - London School Of Hygiene & Tropical Medicine (LSHTM)
Dr Yochai Schonmann - Corresponding Applicant - London School Of Hygiene & Tropical Medicine (LSHTM)

Linkages: 
Patient IMD;Practice IMD (Standard)