Comment

Graft rejection is traditionally attributed to adaptive immune cells that recognize donor-specific alloantigens, with innate immunity having a secondary role. The finding that recipient natural killer cells are activated by the inability of graft endothelial cells to provide HLA-I-mediated inhibitory signals challenges this dogma and introduces the concept of innate rejection.

Kidneys from older donors might improve the quality of life and survival of patients with kidney failure, yet these organs are often underutilized. Re-framing discussions of organ acceptance from older donors and its benefits over dialysis, especially for older patients and those who cannot tolerate prolonged waiting for transplantation, is urgently needed.

Centenarians — who are a putative model of healthy longevity — often have a low risk of cardiovascular disease, despite an age-associated decline in kidney function. An understanding of the molecular and cellular underpinnings of health kidney ageing in centenarians may provide clues for the prevention or alleviation of the burden of kidney disease in older populations.

American Indian and Alaska Native peoples have low life expectancy and a disproportionate disease burden (including of chronic kidney disease), owing to inadequate education, poverty, discrimination and underfunding in the delivery of health services, and healthcare institutions’ lack of appreciation for cultural differences. These broad quality-of-life issues are rooted in economic adversity and poor social conditions.

The use of cystatin C-inclusive equations will continue to propagate the unnecessary overdiagnosis of chronic kidney disease (CKD) in older people. Cystatin C is less biologically specific for CKD than is serum creatinine, inflates the risks of adverse outcomes compared to measured glomerular filtration rate, and does not establish chronicity at a single time point.

Kidney disease is strongly linked with cardiovascular diseases, hypertension, diabetes, infections and other health conditions, as well as social determinants of health and climate change. Consequently, a holistic approach to promote well-being, protect individual health and improve access to quality primary care will support kidney health.

Chronic kidney disease is a life-changing diagnosis for millions of people worldwide, as the risk of disease progression and kidney failure creates unbearable uncertainty and limits lifestyle. The devastating impact of advanced kidney disease must be acknowledged in the public health agenda to pave way for improved outcomes for patients at all stages of disease.

Clinical algorithms that are used to guide medical decision-making often include sex as a variable. However, binary considerations of sex and/or gender might introduce bias due to potentially inaccurate assumptions about sex and gender-specific physiology, hormones and exposures. An equity-focused approach to sex and gender is essential when using clinical algorithms to ensure health equity across populations.

Clinical trial data suggest that thiazides and thiazide-like drugs could be beneficial for blood-pressure lowering in patients with severe chronic kidney disease. However, prolonged exposure to these photosensitizing drugs could translate into increased risk of squamous cell carcinoma and post-transplant diabetes in the already extremely vulnerable kidney transplant population.

Kidney registries are essential to understanding the burden of kidney disease and facilitating the development of sustainable and effective programs for kidney disease prevention and care. Key barriers to implementation of registries at a global scale include funding and data quality. These issues warrant the attention of the global nephrology community.

Haemodialyser technology has not advanced much in decades, despite its unresolved shortcomings. Sophisticated new computational tools such as high-fidelity surrogate in silico dialyser models could reduce the time and expense of exploring alternative designs, dialysis dose and operating conditions compared with the current gold standard in vitro studies.

Global inequities and inequalities, human and health-care crises, transplantation successes in the face of limited organ availability, and desperate donors and recipients underlie the backstory of organ trafficking, namely the exploitation of the most vulnerable. Despite the framework set out by the Declaration of Istanbul for the ethical donation and transplantation of organs, organ trafficking remains a global challenge.

All patients with kidney disease have the right to have a say in their own clinical care, the provision of health services and research into kidney disease. Patient empowerment and advocacy, especially for those whose views are seldom heard, can be enhanced by working together in communities.

Treatment of chronic kidney disease requires a comprehensive approach including universal access to early diagnosis and to medications that can slow disease progression. Such equitable access is not only an ethical requirement but can also reduce the financial and human costs of advancing kidney and cardiovascular disease.

Overcoming barriers to deliver high-quality care requires an assessment of the contribution of each barrier within a local context. Tools to identify early disease, knowledge of best therapies, access to care providers and medications, and an accountable and integrated health-care system are essential elements of quality care. Education of patients, providers and policy makers in conjunction with advocacy efforts and national policy frameworks are required to deliver high-quality care worldwide.

Many countries worldwide, particularly those with low or lower-middle incomes, do not have enough nephrologists to provide health services for patients with kidney disease. Increasing training opportunities, improving job satisfaction and using new technologies and advances in artificial intelligence could help to increase the nephrology workforce and improve patient outcomes.

The current nomenclature for cardiorenal syndrome is problematic owing to its chronological approach and the systemic nature of some of the subtypes. We suggest adoption of a new concept, chronic cardiovascular–kidney disorder, that better reflects the contributions of common risk factors and shared pathophysiological mechanisms.

First Nations peoples in Australia face systemic inequities in access to kidney transplantation. The National Indigenous Kidney Transplant Taskforce was established to address these. It has provided support to clinicians to implement and evaluate innovative practices and developed strategies to address biases in the structures and models of care that create barriers to wait-listing.

Digital transformation offers unprecedented opportunities for advancing healthcare, but also raises complex ethical and legal challenges. Emerging drivers of health disparity termed ‘digital determinants of health’ call for purposeful, equity-focused strategies to ensure that technological innovation benefits all without exacerbating disparities.

Among global destabilizing events, natural disasters often receive widespread attention whereas protracted conflicts and economic crises fade into the background. Low- and middle-income countries bear the brunt of this indifference, resulting in severely weakened health systems. People who require dialysis are particularly vulnerable, necessitating urgent collaboration to ensure equitable and sustainable care during such crises.