DETERMINANTS OF KIDNEY FUNCTION DECLINE AND RAPID PROGRESSION IN DIABETIC KIDNEY DISEASE

Introduction:

Diabetic kidney disease (DKD) is heterogenous in the speed of progression to end stage kidney disease (ESKD). A significant proportion of patients with DKD progress rapidly to ESKD, notwithstanding optimal treatment. We aimed to assess the determinants of kidney function decline and rapid progression in DKD.

Methods:

In this single centre retrospective longitudinal study, we measured the progression of DKD as eGFR slope. Rapid progression was defined as eGFR slope < -5 ml/min/year. We measured eGFR slope using linear mixed effects regression. Predictors of eGFR slope and rapid progression were then identified by multivariate linear and logistic regression respectively.

Results:

Mean eGFR slope in the cohort was -6.43 (95% CI: -7.02 to -5.84) ml/min/year. Out of 274 patients, 159 (58%) had rapid progression. Patients with non-proteinuric DKD had the least tendency for progression (eGFR slope -3.72 ml/min/year), while those with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) had the greatest propensity for progression (eGFR slope -10.84 ml/min/year). After multivariate analysis, rural residence, baseline eGFR, HFmrEF/HFpEF, resistant hypertension, treatment with intravitreal anti-vascular endothelial growth factor agents and intercurrent acute kidney injury (AKI), non-proteinuric DKD and sodium glucose cotransporter-2 (SGLT2) inhibitor exposure significantly predicted eGFR slope. Of these, SGLT2 inhibitor exposure and non-proteinuric DKD were associated with slower decline in eGFR, while the others were associated with faster eGFR decline. The kidney function preserving effect of SGLT2 inhibitors and renin angiotensin system inhibitors was evident in proteinuric DKD.

Rapid progression in DKD was predicted by age at initial diagnosis (odds ratio [OR] 1.03 for each year, 95% CI 1.00 to 1.06, p = 0.04), baseline eGFR (OR 1.03 per ml of baseline eGFR, 95% CI 1.01 to 1.05, p = 0.001) HFmrEF/HFpEF (OR 3.41, 95% CI 1.16 to 9.94, p = 0.02) and intercurrent AKI (OR 2.19, 95% CI 1.13 to 4.47, p = 0.02). Resistant hypertension (OR 1.95, 95% CI 0.97 to 3.93, p = 0.06) and chronic foot ulcer (OR 2.29, 95% CI 0.96 to 5.44, p = 0.06) increased the odds of rapid progression, though the effects did not reach statistical significance. Non-proteinuric DKD (OR 0.19 95% CI 0.10 to 0.37, p = 0.001) significantly lowered the odds of rapid progression. SGLT2 inhibitor exposure (OR 0.55, 95% CI 0.29 to 1.02, p = 0.06) lowered the odds of rapid progression; however, this effect fell short of statistical significance.

Conclusions:

This study has identified novel predictors of kidney function decline in DKD like HFmrEF/HFpEF, resistant hypertension and intercurrent AKI calling for a holistic approach to retardation of DKD progression, taking cognizance of a multitude of predictors

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.