Renal Effects of Empagliflozin Alone or in Combination with Semaglutide in Albuminuric Type 2 Diabetes: A Randomized, Placebo-Controlled Trial
Abstract
. Background: Kidney gene expression has been shown to be associated with kidney function in diabetic kidney disease (DKD) patients by cross-sectional transcriptomics studies. However, how the renal transcriptome correlates to disease progression has not been established due to the paucity of longitudinal studies. We hypothesized that certain intra-kidney transcriptomic patterns associated with progressive DKD may elucidate disease drivers and predictive factors. Methods: RNA-seq data from micro-dissected kidney biopsies and post-biopsy clinical data were available for 19 DKD patients. Patients were stratified into rapid and non-rapid progressors based on the following: eGFR decline more than ≤ -5 ml/min/year, CKD stage advancement, ≥ 30% UACR increase, nephrotic range albuminuria, and a composite outcome of kidney failure/ ≥ 40% eGFR loss. Gene signatures associated with rapid DKD progression were identified by differential expression (DEA), weighted gene co-expression network (WGCNA) and pathway enrichment analyses. Results: We identified 265 statistically significant ( Padj < 0.05) rapid progression-associated genes in the glomerular and tubulointerstitial compartments across all disease progression definitions through DEA. With WGCNA, 1 module in the glomeruli and 7 in the tubulointerstitium were found to be significantly correlated to eGFR slope ( P < 0.05). The rapid progression-associated genes in the glomeruli were enriched for pathways linked to cell adhesion by…
How strong is the evidence?
Evidence Hub reads this as a randomized trial. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 19 participants or records.
Read the paper
Related studies
- Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol
- Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
- SGLT2 Inhibitors in Heart Failure: Targeted Metabolomics and Energetic Metabolism
- Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Sodium-glucose cotransporter inhibitors: beyond glycaemic control
- Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.