Ntatsaki, Eleana; (2022) Aspects of Lupus Nephritis. Doctoral thesis (M.D(Res)), UCL (University College London).

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Abstract

This thesis explores the clinical outcomes of patients with systemic lupus erythematosus (SLE), focussing on Lupus nephritis (LN), specifically on the impact and results of renal replacement therapies on patients and their disease with reference to adherence to treatment. It comprises three separate but related studies. It also reviews the risk factors for renal disease in SLE and their clinical implications as well as the safety of pharmacological treatment options for lupus nephritis. This thesis reviews a combined cohort of adult SLE patients receiving renal transplants (rTp) over a 40-year period (1975-2015) in two tertiary United Kingdom centres, the Royal Free Hospital (RFH) and University College London Hospital (UCLH), and investigates factors influencing mortality, transplant outcome and disease relapses. My research examines the impact of pre-transplant time on dialysis on survival in patients with LN, and investigates the role of non-adherence in graft survival. It also explores further adherence patterns in the LN population of the combined cohort in UCLH and RFH and compares it with one other autoimmune condition, notably vasculitis. Study 1 investigated the time spent on dialysis before rTp and survival following rTp in a cohort of SLE patients. This was a retrospective analysis of 40 adult SLE patients receiving rTp over a 40-year period (1975-2015) and identified that time on dialysis before rTp was the only modifiable survival risk predictor (with a hazard ratio of 1.01 for each additional month spent on dialysis) and suggested that more than 24 months on dialysis adversely affected mortality. No other modifiable predictors associated with mortality, supporting that longer time on dialysis pre-transplantation is an independent modifiable risk factor of mortality in LN. Study 2 examined whether non-adherence is associated with increased rTp graft rejection and/ or failure in patients with LN in the same cohort as Study 1. The role of non-adherence and other potential predictors of graft rejection/ failure were investigated using logistic regression. During a median follow-up of 8.7 years, 17/40 (42.5%) of the patients had evidence of non-adherence. Non-adherent patients had a trend towards increased graft rejection, odds ratio 4.38, (95% confidence interval= 0.73-26.12, p = 0.11.) Interestingly, patients who spent more time on dialysis before rTp were more likely to be subsequently adherent to medication, p=0.01. Study 3 determined self-reported adherence to medication utilising an anonymised questionnaire-based survey and explored influencing factors in LN and renal vasculitis clinics at UCLH and RFH. I compared 114 patients with LN and 80 patients with renal vasculitis to identify emerging patterns, behaviours and differences that could potentially introduce barriers to adherence. Lupus patients were more likely to be female, younger and with longer disease duration (p<0.001). Their adherence decreased with time compared to vasculitis patients (p<0.001). Conversely, the patients with vasculitis had higher attendance at clinic appointments (p=0.02), and were more confident they could manage to take their tablets correctly. "Forgetfulness" regarding medication, and keeping track of hospital appointments were the most common reasons given for non-adherence rather than deliberate non-adherence. Increasing age and taking prednisolone associated with better adherence. In contrast, missing even one outpatient clinic appointment associated with worse adherence. Utilising responses from the survey, a prediction model was proposed to further risk-stratify patients regarding their potential adherence patterns that can identify the "at-risk" patient and alert clinicians to the possibility of poor adherence.

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