Acute kidney injury is very common in critically ill patients requiring renal replacement therapy. Despite the advancement in medicine, the mortality rate from septic shock can be as high as 60%. This manuscript describes drug-dosing considerations and challenges for clinicians. For instance, drugs’ pharmacokinetic changes (e.g., decreased protein binding and increased volume of distribution) and drug property changes in critical illness affecting solute or drug clearance during renal replacement therapy. Moreover, different types of renal replacement therapy (intermittent hemodialysis, prolonged intermittent renal replacement therapy or sustained low-efficiency dialysis, and continuous renal replacement therapy) are discussed to describe how to optimize the drug administration strategies. With updated literature, pharmacodynamic targets and empirical dosing recommendations for commonly used antibiotics in critically ill patients receiving continuous renal replacement therapy are outlined. It is vital to utilize local epidemiology and resistance patterns to select appropriate antibiotics to optimize clinical outcomes. Therapeutic drug monitoring should be used, when possible. This review should be used as a guide to develop a patient-specific antibiotic therapy plan.

Acute lung injury (ALI) afflicts approximately 200,000 patients annually and has a 40% mortality rate. The COVID-19 pandemic has massively increased the rate of ALI incidence. The pathogenesis of ALI involves tissue damage from invading microbes and, in severe cases, the overexpression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). This study aimed to develop a therapy to normalize the excess production of inflammatory cytokines and promote tissue repair in the lipopolysaccharide (LPS)-induced ALI. Based on our previous studies, we tested the insulin-like growth factor I (IGF-I) and BTP-2 therapies. IGF-I was selected, because we and others have shown that elevated inflammatory cytokines suppress the expression of growth hormone receptors in the liver, leading to a decrease in the circulating IGF-I. IGF-I is a growth factor that increases vascular protection, enhances tissue repair, and decreases pro-inflammatory cytokines. It is also required to produce anti-inflammatory 1,25-dihydroxyvitamin D. BTP-2, an inhibitor of cytosolic calcium, was used to suppress the LPS-induced increase in cytosolic calcium, which otherwise leads to an increase in proinflammatory cytokines. We showed that LPS increased the expression of the primary inflammatory mediators such as toll like receptor-4 (TLR-4), IL-1β, interleukin-17 (IL-17), TNF-α, and interferon-γ (IFN-γ), which were normalized by the IGF-I + BTP-2 dual therapy in the lungs, along with improved vascular gene expression markers. The histologic lung injury score was markedly elevated by LPS and reduced to normal by the combination therapy. In conclusion, the LPS-induced increases in inflammatory cytokines, vascular injuries, and lung injuries were all improved by IGF-I + BTP-2 combination therapy.

This study was undertaken to test two therapies for acute kidney injury (AKI) prevention, IGF-1, which is renal protective, and BTP-2, which is a calcium entry (SOCE) inhibitor. We utilized lipopolysaccharide (LPS) IP, as a systemic model of AKI and studied in five groups of animals. Three experiments showed that at 7 days: (1) LPS significantly reduced serum IGF-1 and intramuscular IGF-I in vivo gene therapy rescued this deficiency. (2) Next, at the 7-day time point, our combination therapy, compared to the untreated group, caused a significant increase in survival, which was noteworthy because all of the untreated animals died in 72 h. (3) The four pathways associated with inflammation, including (A) increase in cytosolic calcium, (B) elaboration of proinflammatory cytokines, (C) impairment of vascular integrity, and (D) cell injury, were adversely affected in renal tissue by LPS, using a sublethal dose of LPS. The expression of several genes was measured in each of the above pathways. The combined therapy of IGF-1 and BTP-2 caused a favorable gene expression response in all four pathways. Our current study was an AKI study, but these pathways are also involved in other types of severe inflammation, including sepsis, acute respiratory distress syndrome, and probably severe coronavirus infection.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder marked by the development of cysts in the kidneys and other organs, leading to diverse clinical manifestations, including kidney failure. The psychological burden of ADPKD is substantial, with significant contributors including pain, daily life disruptions, depression, anxiety, and the guilt associated with transmitting ADPKD to offspring. This review details the psychological impacts of ADPKD on patients, addressing how they navigate physical and emotional challenges, including pain management, genetic guilt, mood disorders, and disease acceptance. This review also underscores the need for comprehensive research into the psychological aspects of ADPKD, focusing on the prevalence and contributing factors of emotional distress and identifying effective strategies for managing anxiety and depression. Furthermore, it highlights the importance of understanding the diverse factors that influence patients' quality of life and advocates for holistic interventions to address these psychological challenges.

The increasing prevalence of kidney failure highlights the crucial need for effective patient-physician communication to improve health-related quality of life and ensure adherence to treatment plans. This narrative review evaluates communication practices in the context of advanced kidney disease, focusing on the frameworks of shared decision-making, advanced care planning, and communication skills training among nephrologists. The findings highlight the significant gaps in patient-physician communication, particularly in the domains of advanced care planning, shared decision-making, and dialysis withdrawal. When communication in such situations falls short, it affects patient satisfaction and outcomes. Effective communication is essential for managing advanced kidney disease, requiring a patient-centered approach that includes patients, families, and healthcare providers in care planning. This review advocates for a more integrated, empathic approach to healthcare interactions, emphasizing the importance of including patients, their families, and healthcare providers in a collaborative model based on goals of care. Moreover, it highlights the role of patient-reported outcome measures and patient experience of care in assessing the quality of care in dialysis settings. Here, we call for enhanced training programs regarding communication skills for physicians and emphasize the need for systemic changes to foster patient-centered communication. Graphical abstract