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Article Citation - WoS: 2Citation - Scopus: 2Potential Role of SGLT-2 Inhibitors in Improving Allograft Function and Reducing Rejection in Kidney Transplantation(Wiley, 2025) Demir, Mehmet Emin; Helvaci, Ozant; Yildirim, Tolga; Merhametsiz, Ozgur; Sezer, SirenSodium-glucose cotransporter-2 inhibitors (SGLT-2i) have demonstrated renoprotective and cardioprotective benefits beyond their antiglycemic effects. Their potential utility in kidney transplant recipients (KTRs) for preserving graft function and reducing rejection risk is currently under active investigation. Preliminary studies indicate that SGLT-2i therapy stabilizes estimated glomerular filtration rate (eGFR), decreases glomerular hyperfiltration, and improves metabolic outcomes in KTRs. Emerging clinical evidence also suggests that SGLT-2i may be associated with reduced rates of acute rejection, although direct immunosuppressive actions remain unclear. Experimental findings further suggest that SGLT-2i modulates gene regulation pathways involved in inflammation, oxidative stress, and fibrosis, contributing to improved allograft outcomes. Current safety data in KTRs are reassuring, without significant increases in urinary tract infections or adverse graft events. Nevertheless, long-term prospective studies specific to transplant populations are lacking. This review summarizes available evidence regarding the mechanisms of action, clinical efficacy, and safety profile of SGLT-2i in kidney transplantation, emphasizing their metabolic, hemodynamic, inflammatory, and immunomodulatory effects.Article Citation - WoS: 14Citation - Scopus: 15The Results of Sglt-2 Inhibitors Use in Kidney Transplantation: 1-Year Experiences From Two Centers(Springer, 2023) Demir, Mehmet Emin; Ozler, Tuba Elif; Merhametsiz, Ozgur; Sozener, Ulas; Uyar, Murathan; Ercan, Zafer; Turkmen Sariyildiz, GulcinPurposeSodium-glucose co-transporter-2 inhibitor (SGLT-2i) administration is associated with some concerns in regard to the increased risk of genital and urinary tract infections (UTI) in kidney transplant recipients (KTR). In this study, we present the results of SGLT-2i use in KTR, including the early post-transplant period.MethodsParticipants were divided into two groups: SGLT-2i-free diabetic KTR (Group 1, n = 21) and diabetic KTR using SGLT-2i (Group 2, n = 36). Group 2 was further divided into two subgroups according to the posttransplant prescription day of SGLT-2i; < 3 months (Group 2a) and >= 3 months (Group 2b). Groups were compared for development of genital and urinary tract infections, glycated hemoglobin a1c (HgbA1c), estimated glomerular filtration rate (eGFR), proteinuria, weight change, and acute rejection rate during 12-month follow-up.ResultsUrinary tract infections prevalence was 21.1% and UTI-related hospitalization rate was 10.5% in our cohort. Prevalence of UTI and UTI-related hospitalization, eGFR, HgbA1c levels, and weight gain were similar between the SGLT-2i group and SGLT-2i-free group, at the 12-month follow-up. UTI prevalence was similar between groups 2a and 2b (p = 0.871). No case of genital infection was recorded. Significant proteinuria reduction was observed in Group 2 (p = 0.008). Acute rejection rate was higher in the SGLT-2i-free group (p = 0.040) and had an impact on 12-month follow-up eGFR (p = 0.003).ConclusionSGLT-2i in KTR is not associated with an increased risk of genital infection and UTI in diabetic KTR, even in the early posttransplant period. The use of SGLT-2i reduces proteinuria in KTR and has no adverse effects on allograft function at the 12-month follow-up.Article Complex Multisource Sound Induces Greater Neurodegeneration in Neonatal Rat Brain than Single-Source Sound(Frontiers Media SA, 2026) Daltaban, Iskender Samet; Aydin, Mehmet Dumlu; Eyupoglu, Eylem Eren; Demirci, Elif; Okuyan, Aybike Aydin; Demir, Mehmet EminBackground: Excessive noise exposure is a known environmental health hazard linked to neurological injury and cognitive deficits. Whether complex sound waveforms from multiple sources exacerbate brain damage compared to a single-source noise of equal intensity remains unclear. We investigated the effects of identical music played either through one or four loudspeakers on the developing brain of newborn rats. Methods: Forty-one newborn Sprague-Dawley rat pups (both sexes), along with their dams, were randomly assigned to three groups: control (no noise, n = 6), single-speaker exposure (n = 15), and multi-speaker exposure (n = 20). From postnatal day 0 to 30, the exposure groups were subjected to an 8-min music track (similar to 85 dB SPL) either via one loudspeaker (simple waveform) or simultaneously via four loudspeakers (complex interfering waveform), six times daily at 4-h intervals. Sound intensity was calibrated at the cages with a sound-level meter. All procedures followed ARRIVE guidelines and the EU Directive 2010/63/EU for animal research, with institutional ethical approval. After 1 month, rat brains were examined histologically. Unbiased stereology was used to estimate neuronal densities in the temporal lobe (including amygdala and hippocampal dentate gyrus). Immunohistochemistry for neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) and TUNEL assay (terminal deoxynucleotidyl transferase dUTP nick-end labeling) was performed to identify neuronal integrity, astroglial response, and apoptosis, respectively. Outcome measures were degenerated (TUNEL-positive) neuron densities and histopathological lesions. Statistical comparisons were made using Student's t-tests or ANOVA and chi-square tests (with p < 0.05 considered significant). Results: Eight of 20 pups (40%) in the multi-speaker group died during the exposure period, compared to 5/15 (33%) in the single-speaker group and 3/6 (50%) in controls (differences not statistically significant). Maternal rats exhibited agitation, stress behaviors, and weight loss under noise; some eventually ceased escape attempts (habituation/helplessness behavior) in both noise-exposed groups. Histologically, the multi-speaker exposure caused more severe brain injury than the single-speaker exposure. Pups in the multi-speaker group showed frequent subarachnoid hemorrhages and cortical microvascular bleeding in the temporal lobes, whereas these lesions were mild or infrequent in the single-speaker group and absent in controls. Neurons in noise-exposed brains displayed morphological signs of degeneration (shrunken, angulated cell bodies with pyknotic nuclei and condensed cytoplasm), which were markedly pronounced in the multi-speaker group. Stereological cell counting revealed a significant increase in apoptotic neuron density in both sound-exposed groups, with the multi-speaker group highest. For example, in the hippocampal dentate gyrus, the mean density of TUNEL-positive (degenerating) neurons was 13,450 +/- 1,560 per mm(3) in the multi-speaker group vs. 7,600 +/- 980 per mm(3) in the single-speaker group and only 200 +/- 34 per mm(3) in unexposed controls (p < 0.05). In the amygdala, apoptotic neuron density averaged 3,460 +/- 863 per mm(3) (multi-speaker) vs. 1,470 +/- 285 (single-speaker) and 1,321 +/- 234 (control), with the multi-speaker group showing a significantly higher burden of neuronal cell death (p < 0.005 for complex vs. simple waveforms). Correspondingly, multi-speaker exposed brains showed intense immunostaining for NSE and GFAP fragmentation, indicating widespread neuronal loss and reactive astroglial injury, whereas single-speaker exposure caused only moderate changes. Conclusion: Identical musical noise caused substantially more neurodegeneration in the developing brain when delivered as complex wave interference from multiple speakers rather than as a single-source sound of the same intensity. Complex multisource waveforms appear to amplify the harmful effects of noise on neonatal brain tissue, likely through interference-driven pressure fluctuations. These findings have clinical and public health implications, suggesting that current noise exposure guidelines should consider not only sound intensity and duration but also the acoustic complexity and source configuration, especially to protect vulnerable populations such as infants and children from high-intensity multisource noise environments.
