Simona Kerezieva

Background/Objectives: Sodium–glucose cotransporter 2 (SGLT2) inhibitors are established in the treatment of chronic kidney disease (CKD), but evidence in CKD caused by glomerular disease is limited, and patients on intensified immunosuppression have been excluded from the randomised trials. We examined the effect of dapagliflozin on proteinuria and kidney function over two years in such a population. Methods: In this single-centre retrospective cohort study, we compared 147 patients treated with dapagliflozin 10 mg daily between 2021 and 2025 with 170 historical controls followed between 2014 and 2021; most had biopsy-proven glomerular diseases. Proteinuria and estimated glomerular filtration rate (eGFR) were assessed at months 0, 12 and 24, and comparisons used analysis of covariance adjusted for baseline. Subgroups on intensified immunosuppression at entry were prespecified. Results: Proteinuria fell by 51.9% under dapagliflozin and by 22.2% in the historical cohort; the adjusted geometric mean ratio (GMR) was 0.684 (95% CI 0.534–0.878; p = 0.003). During the second year, eGFR declined more slowly with dapagliflozin (a difference of 4.61 mL/min/1.73 m² per year; 95% CI 1.82–7.41; p = 0.001), although eGFR at month 24 did not differ significantly after adjustment for baseline (p = 0.15). An eGFR below 15 mL/min/1.73 m² was reached by 0.7% of treated patients and by 11.8% of controls. Among patients on intensified immunosuppression, proteinuria fell by 67.5% when dapagliflozin was added, compared with 4.6% on the same treatment alone (adjusted GMR 0.371; 95% CI 0.234–0.586; p < 0.001). Conclusions: Dapagliflozin was associated with a progressive antiproteinuric effect, most marked in patients on intensified immunosuppression, and with a slower decline in kidney function during the second year. Because this study was observational, the true effects are likely to be smaller than those observed.

Background/Objectives: Sodium–glucose cotransporter 2 (SGLT2) inhibitors are established in chronic kidney disease, but evidence in glomerular disease is limited and patients on intensified immunosuppression have been excluded from the randomised trials. We examined the effect of dapagliflozin on proteinuria and kidney function over two years in such a population. Methods: Single-centre retrospective cohort study with historical controls. 147 patients treated with dapagliflozin between 2021 and 2025 were compared with 170 patients seen between 2014 and 2021, most with biopsy-proven glomerular diseases. Proteinuria and estimated glomerular filtration rate (eGFR) were assessed at months 0, 12 and 24, and comparisons used analysis of covariance adjusted for baseline. Subgroups on intensified immunosuppression at entry were prespecified. Results: Proteinuria fell by 51.9% under dapagliflozin and by 22.2% in the historical cohort; the adjusted geometric mean ratio (GMR) was 0.684 (95% CI 0.534–0.877; p = 0.003). During the second year the decline in eGFR was 4.61 mL/min/1.73 m² per year slower under dapagliflozin (95% CI 1.83–7.40; p = 0.001), and an eGFR below 15 mL/min/1.73 m² was reached by 0.7% of treated patients against 11.8% of controls. Among patients on intensified immunosuppression, proteinuria fell by 67.5% when dapagliflozin was added, against 4.6% on the same treatment without it (adjusted GMR 0.371; 95% CI 0.236–0.583; p < 0.001). Conclusions: Dapagliflozin was associated with a progressive antiproteinuric effect, most marked in patients on intensified immunosuppression, and with stabilisation of kidney function. Given the observational design, these magnitudes should be read as an upper bound.

Background: N^ε-(carboxymethyl)-lysine (CML) is formed in the human body by non-enzymatically driven reactions including glycation, oxidation, and lipoxidation. CML is a ubiquitous product of normal physiology, but its levels are increased under disease conditions like chronic kidney disease (CKD) and diabetes mellitus (DM). Free CML is eliminated from the human body mainly through kidney excretion, and its accumulation in the kidney tissue is linked to CKD pathogenesis. Aim: The main goal of this study was to evaluate the relative contribution of CKD and Type 2 DM (T2DM) to the accumulation of CML in patients’ sera. Methods: The study included 22 patients with CKD without DM, 55 with CKD and comorbid T2DM, and 21 with T2DM without CKD. Serum CML levels were measured by ELISA. The Kruskal-Wallis test was used to detect differences among groups. Spearman correlation analysis was performed, and the one-tailed Dunn test was considered to indicate statistical significance at p < 0.05. Results: The median serum CML levels (CKD, 658.4 ± 434.3 ng/mL; CKD + T2DM, 431.3 ± 327.9 ng/mL; T2DM, 273.9 ± 134.2 ng/mL) differed significantly (p < 0.05) among the three patient groups. A positive correlation was observed between serum CML and microalbuminuria (p = 0.004; r = 0.58), proteinuria (p = 0.002; r = 0.6), and age (p = 0.007; r = 0.52) only in the CKD patients. In all T2DM patients, independent of CKD status, serum CML correlated negatively (p < 0.05) with postprandial glucose and duration of diabetes, while its correlation with fasting glucose and HbA1c was negative only in the T2DM cohort without CKD. Conclusions: In patients with CKD, higher levels of CML were observed compared to those with T2DM. Serum CML correlated positively with proteinuria, albuminuria, and patient age in non-diabetic CKD patients, and negatively with blood glucose, HbA1c, and DM duration of T2DM in patients without CKD.

Diabetes mellitus (DM) is a metabolic disease of chronic insulin deficiency or resistance. The progression of DM is associated with long-term damage to macro- and micro-vascular body systems and causes serious health complications. Up to 40% of DM patients develop chronic kidney disease (CKD), mainly as a consequence of diabetic nephropathy (DN). Hence, strict glycemic control is recommended to slow down CKD progression. Hyperglycemia causes complications in diabetic patients through the glycation of various proteins. The interaction of glucose with the free NH2 groups of proteins results in the formation of the early glycation product fructosamine (FA). FA has a short half-life (1 to 2 weeks) and hence it has the potential of an early marker for glycemic control. Although long used in the clinical practice, the FA diagnostic and prognostic significance remains questionable. In this study, we tested the FA potential to serve as a glycemic marker in DM patients with DN. We found that DM patients have significantly higher serum FA levels than non-diabetics. Further, the serum FA level in diabetics correlates positively with the blood glucose concentration. Finally, the mean serum FA level was higher in DM patients with DN, compared to those without DN. These results establish FA as a promising marker for glycemic control in DN patients.