Unveiling drug induced nephrotoxicity using novel biomarkers and cutting-edge preventive strategies.

Drug-induced nephrotoxicity is still a significant obstacle in pharmacotherapy of various diseases and it accounts for around 25 % of serious side-effects reported after drug administration. Furthermore, some groups of drugs such as nonsteroidal anti-inflammatory drugs, antibiotics, antiviral drugs, antifungal drugs, immunosuppressants, and chemotherapeutic drugs have the "preference" for damaging the kidney and are often referred to as the kidney's "silent killer". Clinically, the onset of acute kidney injury associated with drug administration is registered in approximately 20 % of patients and many of them develop chronic kidney disease vulnerability. However, current knowledge about the mechanisms underlying this dangerous phenomenon is still insufficient with many unknowns. Hence, the valuable use of these drugs in clinical practice is significantly limited. The main aim of this study is to draw attention to commonly prescribed nephrotoxic drugs by clinicians or drugs bought over the counter. In addition, the complex relationship between immunological, vascular and inflammatory events that promote kidney damage is discussed. The practical use of this knowledge could be implemented in the engineering of novel biomarkers for early detection of drug-associated kidney damage such as Kidney Injury Molecule (KIM-1), lipocalin associated with neutrophil gelatinase (NGAL) and various microRNAs. In addition, the utilization of artificial intelligence (AI) for the development of computer algorithms that could detect kidney damage at an early stage should be further explored. Therefore, this comprehensive review provides a new outlook on drug nephrotoxicity that opens the door for further clinical research of novel potential drugs or natural products for the prevention of drug-induced nephrotoxicity and accessible education.

Current state and novel outlook on prevention and treatment of rising antibiotic resistance in urinary tract infections.

Antibiotic-resistant bacteria are currently an important public health concern posing a serious threat due to their resistance to the current arsenal of antibiotics. Uropathogens Escherichia coli (UPEC), Proteus mirabilis, Klebsiella pneumoniae and Enterococcus faecalis, antibiotic-resistant gram-negative bacteria, cause serious cases of prolonged UTIs, increasing healthcare costs and potentially even leading to the death of an affected patient. This review discusses current knowledge about the increasing resistance to currently recommended antibiotics for UTI therapy, as well as novel therapeutic options. Traditional antibiotics are still a part of the therapy guidelines for UTIs, although they are often not effective and have serious side effects. Hence, novel drugs are being developed, such as combinations of ß-lactam antibiotics with cephalosporins and carbapenems. Siderophoric cephalosporins, such as cefiderocol, have shown potential in the treatment of individuals with significant gram-negative bacterial infections, as well as aminoglycosides, fluoroquinolones and tetracyclines that are also undergoing clinical trials. The use of cranberry and probiotics is another potential curative and preventive method that has shown antimicrobial and anti-inflammatory effects. However, further studies are needed to assess the efficacy and safety of probiotics containing cranberry extract for UTI prevention and treatment. An emerging novel approach for UTI treatment is the use of immuno-prophylactic vaccines, as well as different nanotechnology solutions such as nanoparticles (NP). NP have the potential to be used as delivery systems for drugs to specific targets. Furthermore, nanotechnology could enable the development of nano antibiotics with improved features by the application of different NPs in their structure, such as gold and copper NPs. However, further high-quality research is required for the synthesis and testing of these novel molecules, such as safety evaluation and pharmacovigilance.