Impact of preterm birth on kidney health and development.

Preterm birth, defined as birth before the gestational age of 37 weeks, affects 11% of the newborns worldwide. While extensive research has focused on the immediate complications associated with prematurity, emerging evidence suggests a link between prematurity and the development of kidney disease later in life. It has been demonstrated that the normal course of kidney development is interrupted in infants born prematurely, causing an overall decrease in functional nephrons. Yet, the pathogenesis leading to the alterations in kidney development and the subsequent pathophysiological consequences causing kidney disease on the long-term are incompletely understood. In the present review, we discuss the current knowledge on nephrogenesis and how this process is affected in prematurity. We further discuss the epidemiological evidence and experimental data demonstrating the increased risk of kidney disease in these individuals and highlight important knowledge gaps. Importantly, understanding the intricate interplay between prematurity, abnormal kidney development, and the long-term risk of kidney disease is crucial for implementing effective preventive and therapeutic strategies.

How to Best Protect Kidneys for Transplantation-Mechanistic Target.

The increasing number of patients on the kidney transplant waiting list underlines the need to expand the donor pool and improve kidney graft utilization. By protecting kidney grafts adequately from the initial ischemic and subsequent reperfusion injury occurring during transplantation, both the number and quality of kidney grafts could be improved. The last few years have seen the emergence of many new technologies to abrogate ischemia-reperfusion (I/R) injury, including dynamic organ preservation through machine perfusion and organ reconditioning therapies. Although machine perfusion is gradually making the transition to clinical practice, reconditioning therapies have not yet progressed from the experimental setting, pointing towards a translational gap. In this review, we discuss the current knowledge on the biological processes implicated in I/R injury and explore the strategies and interventions that are being proposed to either prevent I/R injury, treat its deleterious consequences, or support the reparative response of the kidney. Prospects to improve the clinical translation of these therapies are discussed with a particular focus on the need to address multiple aspects of I/R injury to achieve robust and long-lasting protective effects on the kidney graft.

De novo SIX2 activation in human kidneys treated with neonatal kidney stem/progenitor cells.

During development, nephron structures are derived from a SIX2+ stem cell population. After 36 weeks of gestation, these cells are exhausted, and no new nephrons are formed. We have previously described a non-invasive strategy to isolate and expand the native SIX2+ kidney stem cells from the urine of preterm neonates, named neonatal kidney stem/progenitor cells (nKSPC). Here, we investigated the safety and feasibility of administering nKSPC into human kidneys discarded for transplantation during normothermic machine perfusion (NMP) and evaluated the regenerative and immunomodulatory potential of nKSPC treatment. We found that nKSPC administration during NMP is safe and feasible. Interestingly, nKSPC induced the de novo expression of SIX2 in proximal tubular cells of the donor kidneys and upregulated regenerative markers such as SOX9 and VEGF. This is the first time that SIX2 re-expression is observed in adult human kidneys. Moreover, nKSPC administration significantly lowered levels of kidney injury biomarkers and reduced inflammatory cytokine levels via the tryptophan-IDO-kynurenine pathway. In conclusion, nKSPC is a novel cell type to be applied in kidney-targeted cell therapy, with the potential to induce an endogenous regenerative process and immunomodulation.

Tigecycline-induced life-threatening coagulopathy in a patient with a Mycobacterium abscess: a case report and step-by-step diagnostic approach.

Tigecycline is a broad-spectrum antibiotic that is indicated in the treatment of complicated intra-abdominal infections and complicated skin and skin and soft-tissue infections. We report the case of a 53-year old kidney transplant patient with a severe Mycobacterium abscess who developed life-threatening coagulopathy after initiation of tigecycline therapy. Further analysis revealed a severe hypofibrinogenemia. A few case reports previously described an association between tigecycline and prolongation of clotting time. Our case confirms an uncommon yet possibly life-threatening side-effect of tigecycline. Medical practitioners should be aware of this potential coagulopathy and we recommend routine monitoring of coagulation parameters in patients receiving tigecycline.