Reviews & Analysis

This Review outlines the roles of innate and adaptive immune cells in hypertension. The authors discuss the mechanisms and important properties of immune cells that contribute to hypertension pathogenesis, such as memory and plasticity.

Calcium reabsorption along the nephron is essential for calcium homeostasis and whole-body electrolyte balance. Here, Staruschenko et al. highlight signalling pathways and molecules involved in renal calcium handling in health and disease, and discuss progress in the integration of systems-level and molecular understanding of calcium transport and regulation.

This Review describes parallels in the injury mechanisms that underlie acute kidney injury, chronic kidney disease and allograft injury, and explains how our understanding of the molecular changes that occur in epithelia in the context of kidney disease may contribute to the therapeutic targeting of specific epithelial cell phenotypes for the treatment of transplantation complications.

Despite notable progress in basic, clinical and translational nephrology research in the past 50 years, many challenges remain. In this Review, the authors provide an overview of the current status and future directions in nephrology research and patient care.

Several new drug classes have been demonstrated to improve kidney outcomes in people with diabetes mellitus. Here, the authors examine the evidence for the efficacy and safety of combination treatment to reduce the progression of diabetic kidney disease.

Patients with chronic kidney disease often require complex polypharmacy, require dose adjustments or discontinuation with changes in kidney function, and can be susceptible to the adverse effects of medications. This Review discusses the principles of drug stewardship — that is, the effective, safe and sustainable use of medications — for people with chronic kidney disease.

In this Review, the authors examine the biophysical and biomechanical properties that influence podocyte physiology as they integrate and adapt to stimuli from their dynamic environment within the glomerular capillaries. The authors also discuss how dysregulation and loss of biomechanical resilience in podocytes can contribute to kidney disease.

Renal nanomedicines may hold promise for the detection and treatment of a variety of kidney diseases. This Review describes how our understanding of the physiological principles that regulate the glomerular filtration, tubular secretion, luminal tubular uptake and re-elimination of nanoparticles in the kidneys may facilitate the selective targeting of nanomedicines to specific segments of the nephron.

A number of epidemiological studies have linked markers of underhydration with an increased risk of adverse health outcomes. This Review provides an overview of the mechanisms that regulate body water balance and the adaptive responses to decreased hydration, and describes current understanding of the physiological consequences of underhydration on health outcomes.

This Review summarizes the roles of sirtuins in kidney development, physiological processes and the pathogenesis of acute and chronic kidney diseases. The authors also highlight the potential of sirtuins as therapeutic targets to limit human kidney disease and renal ageing.

Chronic kidney disease is associated with a graded and independent excess risk of sensorineural hearing loss. This Review describes how disruption of shared signalling pathways that are important for the development of both the ear and the kidney and/or the presence of clinical drivers, such as specific medications or treatments, may underlie these associations.

The availability of antiretroviral therapy has led to a transformation in the spectrum of kidney diseases associated with HIV infection. This Review describes the changing pattern of kidney diseases associated with HIV infection, their risk factors, methods of evaluating kidney function in patients with HIV and current therapeutic approaches.

Renal cell carcinoma is a metabolic disease linked to a variety of alterations in genes that regulate cellular metabolism. Here, the authors examine cell-intrinsic metabolic alterations in hereditary and sporadic renal cell carcinoma, and how they can be exploited to develop novel therapeutic interventions.

Here, the authors review traditional and disease-specific risk factors for vascular damage and the cellular and molecular mechanisms that drive vascular injury in systemic lupus erythematosus. They also discuss cardiovascular risk assessment, primary prevention strategies and current and future treatment approaches to cardiovascular disease in systemic lupus erythematosus.

Antibody-mediated rejection is a key mechanism in allograft loss. Here, the authors examine advances in B cell biology and how they can inform the development of new therapies to prevent or mitigate antibody-mediated rejection, with the goal of improving transplantation outcomes.

Sex differences in immune cell function and immune responses affect the development and outcome of diverse diseases. Here, the authors review current understanding of sex differences in immunity. They describe the key mechanisms that mediate sex differences in immune responses and discuss the functional relevance of such differences for immune-related diseases.

Emerging evidence suggests that cells resident within organs — both immune and parenchymal — can facilitate the instigation and propagation of tissue injury. In this Review, the authors discuss findings that suggest that kidney parenchymal cells provide structural immunity to the kidney through the regulation of immune-relevant processes, with consequences for kidney inflammation and injury.

Improved understanding of kidney disease from a sex- and gender-specific perspective is needed to improve patient care. Here, the authors discuss differences in the epidemiology, management and outcomes of acute kidney injury, chronic kidney disease and kidney failure in men and women.

In this Review, Franck Mauvais-Jarvis discusses how adaptive selection during evolution could have shaped sex differences in energy partitioning, adipose tissue function and distribution, and glucose homeostasis. He also discusses the hormonal and genetic mechanisms that underlie these sex differences and their implications for metabolic disease and sex-based precision medicine.

Clonal haematopoiesis of indeterminate potential (CHIP) is associated with increased risk of disease, including cardiovascular and kidney disease. Here, the authors discuss the consequences of CHIP across various organ systems, including direct and indirect effects on kidney health.