Chronic kidney disease (CKD) is a common complication of diabetes. As the diabetes population grows many more people will experience kidney disease. It has been estimated that 40 percent of patients with diabetes will develop chronic kidney disease, with a significant proportion of these patients requiring kidney replacement therapy. CKD is more aggressive in people with diabetes and they progress from moderate to severe CKD more quickly compared to people without diabetes. While previous studies have identified some of the factors that explain the relatively rapid progression of CKD in patient with diabetes, there are several potentially modifiable factors that require further exploration. Establishing the association between these factors and progression would inform more targeted approaches to preventing CKD progression in this population. Thereby, reducing the number of people with diabetes who develop end stage kidney disease and require renal replacement therapy.
Using the CPRD data, this study aims to examine the association between depression, glycaemic variability; and progression from moderate kidney function to end stage kidney disease in people with diabetes. As part of the work we aim to study exposures to glucose lowering therapies in diabetes patients with CKD stage 3 &below and risk for hospital admissions and A&E attendances due to diabetes. We hope that the insights provided by the study will highlight potentially important considerations that need to be made in the care provided to people with diabetes to prevent CKD progression and potential treatment hazards following deterioration in kidney function.
Background: Diabetes is the leading cause of chronic kidney disease (CKD). Diabetes patients with co-morbid CKD are a high-risk population, with an accelerated rate of progression to end-stage-kidney-disease (ESKD) and higher mortality compared to people without diabetes. People with diabetes are three and half times more likely to need renal replacement therapy (RRT) than the general population. Treating advanced kidney disease in people with diabetes is very costly and is consuming a growing proportion of NHS resources. Therefore, identifying strategies to improve the management of CKD is of high importance. Kidney function decline in people with diabetes is associated with multiple factors. While glucose exposure and hypertension are the most established risk factors, we have identified some less well studied and potentially modifiable factors that may indicate some additional therapeutic targets. These factors include glycaemic variability and depression.
Aim: The aim of this study is to estimate the risk contribution of glycaemic variability and depression to progression of CKD from stage 3 onwards in patients with diabetes. A secondary aim will be to model the risk hazards (hospitalisation and emergency-department attendance) associated with different hypoglycaemic agents in the advanced CKD population.
Method: A retrospective observational study using the Clinical Practice Research Datalink (CPRD) to model the identified risk factors using cumulative incident function analysis. The proposed risk modelling of hypoglycaemic agents will require linkage to HES (Admitted-Patientcare and A&E).
Outcome to be measured: The primary observation of interest will the development of ESKD (CKD stage 5) requiring dialysis or transplantation or a sustained eGFR <15ml/min/1.73m2 for >90 days according to last available eGFR result. Diabetes related hospitalisation and accident and emergency attendance in CKD patients with comorbid diabetes. Secondary outcomes will include changes in eGFR from baseline to final follow up point.
The outcomes identified below related to the two study aims (as identified in section E,)
Aim 1- Primary Outcome: The development of end stage kidney disease (ESKD, CKD stage 5) requiring dialysis or transplantation or a sustained estimated GFR <15ml per minute per 1.73 m2 for at least 90 days according to last available eGFR result.
Secondary Outcome: Changes in estimated glomerular filtration rate (eGFR) from baseline to final follow up point.
Aim 2- Primary Outcome: Diabetes related hospitalisation and accident and emergency attendance in CKD patients with comorbid diabetes.
Angus Forbes - Chief Investigator - King's College London (KCL)
Hellena Habte-Asres - Corresponding Applicant - King's College London (KCL)
David Wheeler - Collaborator - University College London ( UCL )
Dorothea Nitsch - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Trevor Murrells - Collaborator - King's College London (KCL)
HES Accident and Emergency;HES Admitted Patient Care;Practice Level Index of Multiple Deprivation