Nature Reviews Nephrology最新文献

X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert. Historically, these patients were treated with frequent doses of oral phosphate supplements and active vitamin D, which was of limited efficiency and associated with adverse effects. However, the management of XLH has evolved in the past few years owing to the availability of burosumab, a fully humanized monoclonal antibody that neutralizes circulating FGF23. Here, we provide updated clinical practice recommendations for the diagnosis and management of XLH to improve outcomes and quality of life in these patients.

Diuretic drugs act on electrolyte transporters in the kidney to induce diuresis and are often used in chronic kidney disease (CKD), given that nephron loss creates a deficit in the ability to excrete dietary sodium, which promotes an increase in plasma volume. This rise in plasma volume is exacerbated by CKD-induced systemic and intra-renal activation of the renin–angiotensin–aldosterone-system, which further limits urinary sodium excretion. In the absence of a compensatory decrease in systemic vascular resistance, increases in plasma volume induced by sodium retention can manifest as a rise in systemic arterial blood pressure. Management of sodium and volume overload in patients with CKD is therefore typically based on restriction of dietary sodium intake and the use of diuretic agents to enhance urinary sodium excretion. Thiazide and thiazide-type diuretics are foundational therapies for the management of hypertension, whereas loop diuretics are often needed for volume overload, which might also require combination therapies. Mineralocorticoid receptor antagonists have an important role in the management of diuretic-resistant volume overload or treatment-resistant hypertension. Additionally, diuretics can be used for the diagnosis of kidney diseases and in the management of hyperkalaemia or hypokalaemia, hyponatraemia, hypercalcaemia and hypomagnesaemia.

The kidney proximal tubule reabsorbs and degrades filtered plasma proteins to reclaim valuable nutrients and maintain body homeostasis. Defects in this process result in proteinuria, one of the most frequently used biomarkers of kidney disease. Filtered proteins enter proximal tubules via receptor-mediated endocytosis and are processed within a highly developed apical endo-lysosomal system (ELS). Proteinuria is a strong risk factor for chronic kidney disease progression and genetic disorders of the ELS cause hereditary kidney diseases, so deepening understanding of how the proximal tubule handles proteins is crucial for translational nephrology. Moreover, the ELS is both an entry point for nephrotoxins that induce tubular damage and a target for novel therapies to prevent it. Cutting-edge research techniques, such as functional intravital imaging and computational modelling, are shedding light on spatial and integrative aspects of renal tubular protein processing in vivo, how these are altered under pathological conditions and the consequences for other tubular functions. These insights have potentially important implications for understanding the origins of systemic complications arising in proteinuric states, and might lead to the development of new ways of monitoring and treating kidney diseases.

Olfactory receptors (ORs), taste receptors and opsins are well-known for their pivotal roles in mediating the senses of smell, taste and sight, respectively. However, in the past two decades, research has shown that these sensory receptors also regulate physiological processes in a variety of non-sensory tissues. Although ORs, taste receptors and opsins have all been shown to have physiological roles beyond their traditional locations, most work in the kidney has focused on ORs. To date, renal ORs have been shown to have roles in blood pressure regulation (OLFR78 and OLFR558) and glucose homeostasis (OLFR1393). However, sensory receptors remain drastically understudied outside of traditional sensory systems, in part because of inherent challenges in studying these receptors. Increased knowledge of the physiological and pathophysiological roles of sensory receptors has the potential to substantially improve understanding of the function of numerous organs and systems, including the kidney. In addition, most sensory receptors are G protein-coupled receptors, which are considered to be the most druggable class of proteins, and thus could potentially be exploited as future therapeutic targets.