# Association of Albuminuria Within the Normoalbuminuric Range With All‐Cause Mortality in People With Type 2 Diabetes

## TL;DR

Higher albuminuria within normal levels is linked to increased mortality in people with type 2 diabetes, suggesting potential benefits of early intervention.

## Contribution

The study reveals that even mild albuminuria within the normoalbuminuric range is independently associated with higher mortality in type 2 diabetes patients.

## Key findings

- Mortality risk increased with higher albumin excretion rate (AER) within the normoalbuminuric range.
- The association remained significant in individuals with and without chronic kidney disease (CKD).
- A non-linear relationship was found between AER and mortality after adjusting for kidney function.

## Abstract

To investigate the independent association of albuminuria within the normoalbuminuric range with all‐cause mortality in normoalbuminuric people with type 2 diabetes with and without chronic kidney disease (CKD).

This observational, prospective, multicentre, cohort study enroled 15,773 individuals with type 2 diabetes in 2006–2008. At baseline, albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) were assessed together with cardiometabolic risk profile, treatments, complications, and comorbidities. All‐cause mortality was verified on 31 October 2015.

Of the 15,656 participants (99.3%) with valid information on vital status, 11,460 (71.2%) were normoalbuminuric, 9984 (87.1%) without and 1476 (12.9%) with CKD. Normoalbuminuric individuals were stratified into three (< 5, 5–15, and > 15 mg·day−1) or two (< 10 and 10–29 mg·day−1) AER subcategories. When adjusting for age, sex, eGFR, prior cardiovascular disease, cardiovascular risk factors, and treatments, mortality risk was higher in participants with AER 10–29 versus < 10 mg·day−1 (hazard ratio, 1.120 [95% confidence interval, 1.028–1.221], p = 0.009) and 15–29 versus < 5 mg·day−1 (1.243 [1.099–1.406], p < 0.0001). When stratifying by CKD status, the adjusted risk remained significantly increased only for AER 15–29 versus  < 5 mg/24 h in individuals with (1.404 [1.111–1.774], p = 0.005) and, to a lesser extent, without (1.167 [1.009–1.350], p = 0.038) CKD. A non‐linear association was observed between AER as Log2 transformed continuous variable and mortality.

For the same level of kidney function, higher AER within the normoalbuminuric range was independently associated with all‐cause mortality, thus supporting to the use of albuminuria‐lowering drugs in people with type 2 diabetes and mildly elevated albuminuria.

ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.