# Progression of albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) over 24 years in people with type 2 diabetes. Drivers, potential protectors and associated mortality

## TL;DR

This study tracks kidney health decline in people with type 2 diabetes over 24 years, identifying factors like blood pressure and smoking that accelerate chronic kidney disease progression and increase mortality.

## Contribution

The study provides long-term insights into CKD progression in T2D patients, identifying sex and smoking as novel predictors of eGFR decline and mortality.

## Key findings

- Female sex and smoking were significant predictors of eGFR decline in patients without baseline CKD.
- Systolic and diastolic blood pressure were key drivers of ACR progression in patients with increased ACR and preserved eGFR.
- Mortality rates increased with CKD severity, with the highest 10-year mortality in patients with increased ACR and reduced eGFR.

## Abstract

The pathophysiology of chronic kidney disease (CKD) and type 2 diabetes (T2D) is multifactorial and associated with a plethora of underlying conditions and complications. Their link is reciprocal and understanding its nature, particularly over time, could improve the health of many.

A prospective study was conducted to examine the development of the two main components of CKD (urine albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR)) over 24 years (2001–2024) in a sample of 718 individuals with a diagnosis of T2D. Longitudinal modelling was conducted to examine the rate of change of ACR and eGFR over the 24 years, as well as whether sex, smoking status, glycated haemoglobin (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) influenced that rate of change in both our total sample and three sub‐groups (no CKD, CKD with increased ACR and preserved eGFR, and CKD with increased ACR and reduced eGFR).

At baseline, 428 (59.6%) patients were male while 290 (40.4%) were female. Mean age at baseline was 56.6 ± 12.4 years. Mean follow‐up period was 16.4 ± 2.1 years. 451 (62.8%) patients had a normal ACR and eGFR ≥60 mL/min/1.73 m2, no CKD. At 24‐year follow‐up, 196 (43%) of these patients had progressed to an ACR >3 mg/mmol and/or eGFR<60 mL/min/1.73 m2, developing CKD. At final follow‐up, 282 patients were still alive. In the whole cohort, 10 (1.4%) patients progressed to end‐stage kidney disease eGFR<15 mL/min/1.73 m2.

For the whole cohort ACR increased exponentially, while eGFR decreased linearly by 1.02 mL/min/1.73 m2 per year.

For ACR: SBP (β = 0.36, 95% CI [0.24, 0.48]) and DBP (β = 0.40, 95% CI [0.16, 0.64]) were the only significant independent predictors of ACR progression particularly in the sub‐group with increased ACR and preserved eGFR.

For eGFR: Female sex (β = −3.79, 95% CI [1.96, 5.63]), SBP (β = −0.12, 95% CI [−0.17, −0.06]), DBP (β = −0.19, 95% CI [−0.08, −0.31]), HbA1c (β = −1.17, 95% CI [−0.63, −1.71]), baseline cholesterol (β = 0.86, 95% CI [0.29, 1.43]) and smoking (β = −2.05, 95% CI [−3.80, −1.30]) were significant independent predictors of eGFR progression, but only in the non‐CKD at baseline sub‐group.

At the end of follow‐up 436 (60%) of people had died including 219 (48.6%) of the patients with no CKD at baseline, compared to 158 (76.7%) of people with increased urine ACR/preserved eGFR and 59 (96.7%) of those with increased urine ACR and reduced eGFR, with 10 year mortality rates of 6.6%, 14.5% and 26.6%, respectively. In the whole cohort only 10 (1.4%) patients progressed to end‐stage kidney disease (eGFR<15 mL/min/1.73 m2).

This study revealed several factors that are associated with accelerated progression of CKD over 20 + years, including female sex and current/previous smoking. At baseline, the group with ACR >3 mg/mmol exhibited the highest rate of ACR increase. Multiple factors influenced eGFR decrease in those with baseline eGFR ≥60 mL/min/1.73 m2. Mortality rate was profoundly influenced by historical CKD status.