Renal ischemia is a common cause of acute kidney injury (AKI), particularly in critical care settings, and remains a major challenge in nephrology due to the lack of effective therapeutic options. In AKI, there is an overstimulation of NAD⁺-consuming enzymes leading to NAD⁺ depletion. To help replenish cellular NAD⁺ stores, this study explores for the first time the therapeutic potential of activating nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in the NAD⁺ salvage pathway, in a rat model of unilateral renal ischemia-reperfusion injury (IRI). Our findings demonstrate that SBI797812 (SBI)-induced NAMPT activation significantly improves renal function post-IRI, primarily through the NAD⁺/SIRT1/PGC-1α signaling pathway. NAMPT activation resulted in significant improvement in kidney function, including restored urine flow rate, reduced creatinine and blood urea nitrogen (BUN) levels, and decreased kidney injury biomarkers such as KIM-1 and NGAL. Additionally, SBI led to a reduction in inflammatory markers (NFκB, TNF-α and IL-6), oxidative stress markers, and caspase-3, indicating enhanced renal protection. Western blot analysis further revealed upregulation of key mitochondrial biogenesis markers, including SIRT1, PGC-1α, and TFAM, highlighting the link between NAD⁺ restoration and improved mitochondrial function. In contrast, the inhibition of NAMPT with FK866 exacerbates injury, as indicated by worsened histological features, increased inflammation, and tubular necrosis, confirming the crucial role of NAMPT in mitigating ischemic damage. Considering the importance of NAD metabolism in mitochondrial function and cellular resiliency to tissue injury, these results underscore NAMPT activation as a promising therapeutic strategy for renal IRI, offering new insights for the management of ischemic AKI.

Objectives: This study aimed to evaluate adherence to therapy in hypoparathyroidism and related endocrine–metabolic disorders and to assess its association with biochemical outcomes, hypocalcemia episodes, and health-related quality of life (HRQoL). Methods: In accordance with PRISMA 2020 guidelines, PubMed, Scopus, Google Scholar, and the Cochrane Library were searched until September 2025. The eligible studies were randomized controlled trials, cohort, case–control studies, cross-sectional, and observational studies that reported adherence to calcium/vitamin D or recombinant parathyroid hormone therapy. Results: twenty-three studies were included in the qualitative synthesis, and 11 studies were included in the quantitative meta-analysis. Pooled medication adherence compliance was 70–82% and improved with simplified regimens and the use of recombinant PTH. Additionally, this was also associated with an improvement in HRQoL (p < 0.0001) and a lower risk of hypocalcemia (p < 0.0001). Conversely, multifactorial regulation was observed as the level of adherence had no significant effect on serum calcium levels (p = 0.7116). Sensitivity analyses demonstrate the strength of findings and indicate no significant publication bias. Conclusions: Medication adherence is a key factor in determining patient-centered outcomes in hypoparathyroidism. Better adherence is linked to a higher quality of life and fewer episodes of hypocalcemia, while its effect on biochemical parameters seems minimal. Educational programs, simple treatment regimens, and wider access to rhPTH therapy can be used to improve patient management of the disease over time.