Anyanwagu U, Donnelly R, Idris I: Individual and Combined Relationship between Reduced eGFR and/or Increased Urinary Albumin Excretion Rate with Mortality Risk among Insulin-Treated Patients with Type 2 Diabetes in Routine Practice. Kidney Dis 2019;5:91–99
A decrease in glomerular filtration rate (GFR), and an increase in albuminuria are both recognized potential risk factors for cardiovascular disease (CVD) and all-cause mortality (ACM) in both diabetic and non-diabetic subjects. The extent to which these parameters are independent of traditional risk factors (like obesity, hypertension, hyper-lipidemia, smoking, and age) remains controversial. The risks associated with these parameters are not well understood in subjects with type 2 diabetes (T2DM) receiving insulin for management of hyperglycemia.
Anyanwagu and co-workers examined this issue by an observational cohort study enabled by a probe of a large administrative database involving UK primary care practices. Patients with T2DM receiving insulin at baseline (n=18, 227). Four non-overlapping groups were assembled based on entry criteria: group 1- eGFR <60ml/min/1.73m2, and urinary albumin:creatinine ratio (uACR) of >300mg/gm; group 2- eGFR <60ml/min/1.73m2 and uACR <300mg/gm; group 3- eGFR > 60ml/min/1.73m2 and uACR >300mg/gm; group 4- eGFR >60ml/min/1.73m2 and uACR <300mg/gm. The primary end-point examined was ACM with secondary end-points of CVD mortality and morbidity. Using group 1 as the comparator, group 2 had a hazard ratio (HR) for ACM of 0.94 (CI=0.79–1.12); group 3 had a HR for ACM of 0.80 (CI=0.68–0.96; group 4 had a HR for ACM of 0.72 (CI=0.59–0.87). The impact of the intensity of blood pressure control and statin use could not be evaluated. Sodium-glucose transport protein 2 (SGLT2) inhibitors were used in only 0.5% of the subjects studied and the means glycated haemoglobin (HbA1c) at entry was 8.7%, 63% were obese, and 14% were smokers. High uACR was the major driver of adverse outcomes. The combination of low eGFR and high uACR was independently associated with an increased risk for CVD events, even after adjustment for all measured other risk factors. Very clearly, subjects with T2DM treated with insulin and having lower GFR and higher uACR are at the greatest risk for morbidity and mortality. These are the patients who should receive aggressive treatment directed at blood pressure, glycemia, lipidemia, obesity, and smoking. It is possible that newer non-insulin agents, like SGLT2 inhibitors, may alter the landscape for prevention of CVD and CKD in this group of vulnerable patients.