Diabetes is a health condition where level of sugar in the blood become too high and this can lead to other health problems such as chronic kidney disease (CKD), affecting nearly 40% of people with diabetes. Diabetes can also lead to kidney failure. Diabetic kidney disease gets worse over time as the kidneys stop working properly. In the past, controlling blood pressure and using certain medicines like angiotensin-converting enzyme (ACE) inhibitors were the main ways to slow it down. But now, there are new medicines (called sodium-glucose co-transporter-2 inhibitors (SGLT2) inhibitors and Mineralocorticoid Receptor Antagonists) that can help treat this condition and delay kidney failure.
Most people with CKD get treated by their GP, but not many people getting these new treatments. It's hard to know which patients need these treatments the most, so doctors sometimes don't start them. A simple way to figure out who needs these treatments could help a lot.
The proposed study aims to understand which patients need these medicine and suggest a simple way to manage their treatment based on risk scores. To do this, we will use a big database called the Clinical Practice Research Datalink (CPRD) to look at health information from people in the UK. We will try and understand who is getting these newer treatments and whether there are certain groups of patients not on these treatments who could benefit from them. The results will be shared with doctors, policy makers, and patient charities to improve treatment for people with CKD.
Chronic Kidney Disease (CKD) affects 40% of people with type 2 diabetes (T2D) and is a major cause of End Stage Renal Disease (ESRD). Efforts to slow CKD progression have focused on controlling risk factors and inhibiting the Renin-Angiotensin-Aldosterone System (RAAS). Newer therapies, such as SGLT2 inhibitors and selective non-steroidal MRAs, have shown improved heart and kidney outcomes. However, applying these benefits in everyday practice is challenging. A practical, risk-based management approach could help improve outcomes.
Objectives are to determine:
1. Proportion of patients within each CKD stage achieving the recommended multifactorial targets for individual risk factors (e.g. SBP, Cholesterol, HbA1c) and receiving reno-protective agents (e.g. ACEi/ARB, SGLT2i (including dose)) overall and within each category of Tangri kidney failure risk equation (Tangri-KFRE) score at the following cross-sectional time points:
a. Index
b. 6-months
c. 12 months
d. 18 months
2. What proportion of patients within each CKD stage are at high risk of and experience cardiovascular disease events (e.g. myocardial infarction (MI), stroke, heart failure), all-cause and heart failure specific hospitalization, all-cause mortality and progression to end stage renal disease (e.g. as per NICE definition) overall and within each category of cardiovascular disease (CVD) risk using QRISK®-3 at the following cross-sectional time points:
a. Index
b. 6-months
c. 12 months
d. 18 months
Detailed demographic, anthropometric, medical history and biochemical measures will be assessed in adults with T2D and CKD from 2005 to 2022. CVD and kidney failure risk will be estimated using validated risk equations eg QRISK®-3 and Tangri-KFRE. Data will be analysed to determine cohort characteristics and differences in outcomes between groups (eg sex, age, ethnicity) using multivariable regression in Stata.
This data is key to improving treatment and care for people with T2D and CKD, helping to identify high-risk groups and develop targeted strategies for better outcomes.
The key outcomes for this study include assessing these in patients with T2D and CKD at index, 6-month, 12-months, and 18-months post-index, the:
1. Target for individual risk factors such as HbA1c (52-58 mmol/mol), SBP (10% and >20%
5. CVD (e.g. MI, stroke, heart failure), all-cause and heart failure specific hospitalization, all-cause mortality, and progression to ESRD
6. Patients fulfilling the DAPA-CKD study inclusion criteria (eGFR of 25 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000) and receiving SGLT2i
7. FIDELIO-DKD study inclusion criteria urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300, an eGFR of 25 to less than 60 ml per minute per 1.73 m2 of body-surface area) and receiving selective nsMRA
Francesca Crowe - Chief Investigator - University of Birmingham
Francesca Crowe - Corresponding Applicant - University of Birmingham
Krishnarajah Nirantharakumar - Collaborator - University of Birmingham
Srikanth Bellary - Collaborator - Aston University, Birmingham
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation