ABSTRACT
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors in nephrotic patients on immunosuppression are underexplored. We evaluated dapagliflozin's impact in non-diabetic primary nephrotic syndrome. METHODS: Randomized controlled clinical trial was conducted on 60 non-diabetic primary nephrotic syndrome patients, equally assigned to dapagliflozin and control groups. All patients received the standard of care medication and the Dapagliflozin group received 10 mg dapagliflozin in addition. Demographic data, nephrotic syndrome etiology, proteinuria levels, eGFR, and immunosuppression doses, were well-matched. After 6 months of follow up primary outcomes included changes in and eGFR. RESULTS: Both groups exhibited significant reductions in proteinuria after 6 months, with the dapagliflozin group achieving a mean UPCR reduction of - 94.7%, and the control group - 86.7% (p < 0.001). However, the comparative change in proteinuria between both groups did not reach statistical significance (p = 0.158). Dapagliflozin initially led to a transient eGFR decline. Dapagliflozin also resulted in a significant mean body weight reduction (p < 0.001) and notable improvements in triglyceride levels compared to the control group (p = 0.045). CONCLUSION: In primary nephrotic syndrome patients, adjunct dapagliflozin may enhance the standard of care. While notable, the reduction in proteinuria was comparable to that of the control group by the study's end. Furthermore, after 6 months, eGFR remained stable in both groups. However, significant weight loss and serum triglyceride reduction were particularly pronounced in the dapagliflozin group. Further long-term investigations are necessary to address potential immunosuppression-related confounding effects in patients with primary glomerular disease.
ABSTRACT
Folic acid (FA), with its anti-inflammatory and antioxidant properties, may offer protection against ischemia-reperfusion (IR) injury. This study investigated whether FA safeguards rat kidneys from IR by targeting high mobility group box-1 (HMGB1), a key inflammatory mediator. Fifty adult male Wistar rats were randomly allocated into four groups: control, IR, IR + FA pretreatment, and FA alone. Compared to controls, IR significantly impaired renal function and elevated levels of malondialdehyde, HMGB1, NF-κB, and caspase 3. FA pretreatment effectively reversed these detrimental changes, protecting renal function and minimizing tissue damage. The FA-alone group showed no significant differences compared to the control group, indicating no adverse effects of FA treatment. Mechanistically, FA inhibited HMGB1 expression and its downstream activation of NF-κB and caspase 3, thereby quelling inflammation and cell death. FA shields rat kidneys from IR-induced injury by suppressing HMGB1-mediated inflammation and apoptosis, suggesting a potential therapeutic avenue for IR-associated kidney damage.
