Anyanwagu U, Donnelly R, Idris I: Albuminuria Regression and All-cause Mortality among Insulin-Treated Patients with Type 2 Diabetes: Analysis of a Large UK Primary Care Cohort. Am J Nephrol 2019;49:146–155
Overt albuminuria (Urine Albumin-to-Creatinine Ratio (UACR) > 300 mg/gm) is a well established biomarker for progression of CKD, all-cause mortality and cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Regression of UACR towards normoalbuminuria translates to a lower likelihood of reaching ESRD, but the impact of a regression of albuminuria on mortality is uncertain, especially in insulin-treated subjects with T2DM. Insulin therapy can have proatherogenic activities and promote obesity in T2DM.
Anyanwagu and colleagues studied a large cohort (n = 11,074) of T2DM and overt nephropathy. All treated with insulin in a primary care setting, by employing an administrative database accumulated between 2007 – 2014 in the United Kingdom. The cohort was followed for 5 years and divided into those showing regression of albuminuria (UACR < 300 mg/gm) and those with persistence or worsening albuminuria (> 300 mg/gm; non-regressors). The overall cohort was age 62 years, eGFR of 60 ml/min/1.73m2 at baseline and a HbA1c equal to 8 %.
The 5 years survival was reduced from 95 % to 91 % in the non-regressor population and both all-cause mortality and major atherosclerotic cardiovascular events (mainly strokes) were lower in the regressor population. There was no difference in non-fatal myocardial infarction between the two regression groups. The regression of albuminuria was a result of better glycemic control and / or blood pressure control. Only 14 % of the cohort showed a regression in albuminuria.
This study has numerous weaknesses, including residual confounding, one-time measurement of UACR at baseline, and lack of detail concerning blood pressure (BP) measurements and treatment, a common problem when administrative databases are used in epidemiologic investigations. Nevertheless, the study suggests that regression of albuminuria per se should be regarded as a goal in management of T2DM. The impact of insulin treatment could not be examined as all subjects were treated with insulin. These data also suggest that treatment of subjects with T2DM with agents that aggravate albuminuria might be harmful.