Seminars in Nephrology

Acute kidney injury (AKI) is estimated to occur in approximately 13.3 million patients per year with an estimated mortality of 1.7 million. Approximately 85% of cases occur in low-resource settings where access to kidney replacement therapy (KRT) may be limited or nonexistent. The true extent of AKI, including access to KRT in developing countries, is largely unknown because appropriate systems are not in place to detect AKI or report it. Barriers to provision of KRT in low-resource settings revolve around systems management and funding, however, there also are region-specific issues...

Although medicinal plants are beneficial, they also can be important risk factors for the development of acute and chronic kidney injury, as well toxicity of other solid organs. There are a lack of reports of adverse kidney events and drug interactions resulting from medicinal plants owing to a lack of professional surveillance and specific data on kidney toxicity, especially in low-resource settings. Within the context of increased medicinal plant use and lack of effective regulatory control, safety is a key priority issue...

Advances in kidney genomics in the past 20 years has opened the door for more precise diagnosis of kidney disease and identification of new and specific therapeutic agents. Despite these advances, an imbalance exists between low-resource and affluent regions of the world. Individuals of European ancestry from the United States, United Kingdom, and Iceland account for 16% of the world's population, but represent more than 80% of all genome-wide association studies. South Asia, Southeast Asia, Latin America, and Africa together account for 57% of the world population but less than 5% of genome-wide association studies...

Glomerular diseases account for a significant proportion of chronic kidney disease in low-income and middle-income countries (LMICs). The epidemiology of glomerulonephritis is characterized inadequately in LMICs, largely owing to unavailable nephropathology services or uncertainty of the safety of the kidney biopsy procedure. In contrast to high-income countries where IgA nephropathy is the dominant primary glomerular disease, focal segmental glomerulosclerosis is common in large populations across Latin America, Africa, Middle East, and South East Asia, while IgA nephropathy is common in Chinese populations...

The acute coronavirus disease-2019 (COVID-19) pandemic has had a significant impact on the incidence and prevalence of acute kidney injury and chronic kidney disease globally and in low-income settings. Chronic kidney disease increases the risk of developing COVID-19 and COVID-19 causes acute kidney injury directly or indirectly and is associated with high mortality in severe cases. Outcomes of COVID-19-associated kidney disease were not equitable globally owing to a lack of health infrastructure, challenges in diagnostic testing, and management of COVID-19 in low-income settings...

Xenotransplantation has seen recent global interest peak as a result of several clinical xenotransplants being performed in decedents and a live cardiac recipient. However, underpinning these latest transplants have been decades of invested scientific research programs that have been developing the ideal donor source animals to avoid the overwhelming hyperacute xenograft rejection seen using nongenetically modified animal organs, tissues, and cells. However, this also needs to be undertaken along with the development of safe and efficacious xenotransplantation technologies, immunosuppression, monitoring, disease screening, patient selection, societal education, and acceptance...

Transplant professionals strive to improve domestic kidney transplantation rates safely, cost efficiently, and ethically, but to increase rates further may wish to allow their recipients and donors to traverse international boundaries. Travel for transplantation presents significant challenges to the practice of transplantation medicine and donor medicine, but can be enhanced if sustainable international registries develop to include low- and low-middle income countries. Robust data collection and sharing across registries, linking pretransplant information to post-transplant information, linking donor to recipient information, increasing living donor transplant activity through paired exchange, and ongoing reporting of results to permit flexibility and adaptability to changing clinical environments, will all serve to enhance kidney transplantation across international boundaries...

The most precious gift that can be given is, arguably, a living organ to a person in need of replacement because of failure of that organ. Kidney transplantation remains the best modality of renal replacement therapy and there is an ever-increasing demand for organ donation. The inability of cadaveric organ donation to meet the needs of the increasing numbers of patients on global waiting lists highlights the important needs for alternate sources for kidneys such as those from living kidney donation. However, living donor kidney transplantation has been a focus of intense debate, with ethical concerns and controversies emanating from operating on an individual who does not need, and is put at a small but quantifiable risk from, the surgical intervention...

With the continuing disparity between organ supply to match the increasing demand for kidney transplants in patients with renal failure, donation after the circulatory determination of death (DCDD) has become an important and increasing global source of kidneys for clinical use. The concern that the outcomes of controlled DCDD donor kidney transplants were inferior to those obtained from donors declared dead by neurologic criteria has largely diminished because large-scale registry and single-center reports consistently have reported favorable outcomes...

Migrants represent a large and diverse population globally that includes international refugees, stateless persons, expatriate workers, and more. Many migrants face significant barriers in accessing health care, especially scarce and costly resources such as dialysis and kidney transplantation. Improving equity of access to these kidney replacement therapies for migrant populations may present a range of complex ethical dilemmas, particularly in the setting of crises and when considering the use of residency status and citizenship as eligibility criteria for access to treatment...

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Despite the effectiveness of solid organ transplantation, progress to close the gap between donor organs and demand remains slow. An organ shortage increases the waiting time for transplant and involves significant costs including patient morbidity and mortality. Against the background of a low deceased organ donation rate, this article discusses the option of introducing incentives and removing disincentives to deceased organ donation. Perspectives from ethics, general public opinion, and the health care profession are examined to ensure a comprehensive appraisal and illustrate different facets of opinion on this complex area...

Transplantation is a life-saving medical intervention that unfortunately is constrained by scarcity of available organs. An ideal system for allocating organs should seek to achieve the greatest good for the greatest number of people. It also must be fair and not disadvantage certain populations. However, policies aimed at reducing disparities also must be balanced with considerations of utility (graft outcomes), cost, efficiency, and any adverse effects on organ utilization. Here, we discuss the ethical challenges of creating a fair and equitable organ allocation system, focusing on the principles governing deceased donor kidney transplant waitlists around the world...

Acute kidney injury (AKI) represents a sudden reduction in renal function and is a major clinical problem with a high mortality rate. Despite decades of research, there are currently no direct therapies for AKI. The failure of therapeutic approaches identified in rodents to translate to human beings has led to questions regarding the appropriateness of these models. Our recent data indicate that there are two distinct processes driving tubular injury in the commonly used rat model of warm bilateral renal ischemia reperfusion injury, which often is used to mimic ischemic AKI...

Kidney health and manifestation of disease in transgender men, women, and nonbinary individuals are not well understood. Transgender individuals commonly receive gender-affirming hormone therapy (GAHT) to align their outward appearance with their gender. Recent attention to the differences in fundamental kidney parameters has identified that transgender individuals may manifest levels of these biomarkers differently than their cisgender counterparts. Improving understanding of the differences in biomarkers and in the development of kidney disease is essential to providing appropriate kidney care to this vulnerable population...

Kidney resident macrophages (KRMs) are involved in homeostasis, phagocytosis, defense against infectious agents, response to insults, inflammation, and tissue repair. They also play critical roles in the pathogenesis and recovery from many kidney diseases such as acute kidney injury. KRMs historically have been studied as one homogenous population, but the wide-ranging roles and phenotypes observed suggest that there is greater heterogeneity than previously understood. Advancements in RNA sequencing technologies (single-cell RNA sequencing and spatial transcriptomics) have identified specific subsets of KRMs that are molecularly, functionally, and spatially distinct with dynamic changes after kidney injury...

Acute kidney injury (AKI) is a serious and highly prevalent disease, yet only supportive treatment is available. Nicotinamide adenine dinucleotide (NAD+) is a cofactor necessary for adenosine triphosphate (ATP) production and cell survival. Changes in renal NAD+ biosynthesis and energy utilization are features of AKI. Targeting NAD+ as an AKI therapy shows promising potential. However, the pursuit of NAD+-based treatments requires deeper understanding of the unique drivers and effects of the NAD+ biosynthesis derangements that arise in AKI...

Tamm-Horsfall protein (THP) is produced exclusively by the kidney, where it is released into both the urine and the circulation. Although the primary form of circulating THP is nonpolymerizing, urinary THP exists as a mix of polymerizing and nonpolymerizing forms. Urinary THP has been shown to play roles in such disparate processes as prevention of urinary tract infections and kidney stone formation, along with the regulation of multiple ion channels within the kidney. The generation of THP knockout mouse models has allowed the investigation of these phenomena and shown a prospective role for circulating THP in ischemia-reperfusion acute kidney injury as well as sepsis...

Altered lipid metabolism is a characteristic feature and potential driving factor of acute kidney injury (AKI). Of the lipids that accumulate in injured renal tissues, ceramides are potent regulators of metabolism and cell fate. Up-regulation of ceramide synthesis is a common feature shared across several AKI etiologies in vitro and in vivo. Furthermore, ceramide accumulation is an early event in the natural history of AKI that precedes cell death and organ dysfunction. Emerging evidence suggests that inhibition of ceramide accumulation may improve renal outcomes in several models of AKI...

Although oxygen supplementation is beneficial to support life in the clinic, excessive oxygen therapy also has been linked to damage to organs such as the lung or the eye. However, there is a lack of understanding of whether high oxygen therapy directly affects the kidney, leading to acute kidney injury, and what molecular mechanisms may be involved in this process. In this review, we revise our current understanding of the mechanisms by which hyperoxia leads to organ damage and highlight possible areas of investigation for the scientific community interested in novel mechanisms of kidney disease...