Nature Reviews Disease Primers最新文献

Chronic kidney disease (CKD) is defined by persistent abnormalities of kidney function or structure that have consequences for the health. A progressive decline of excretory kidney function has effects on body homeostasis. CKD is tightly associated with accelerated cardiovascular disease and severe infections, and with premature death. Kidney failure without access to kidney replacement therapy is fatal - a reality in many regions of the world. CKD can be the consequence of a single cause, but CKD in adults frequently relates rather to sequential injuries accumulating over the life course or to the presence of concomitant risk factors. The shared pathomechanism of CKD progression is the irreversible loss of kidney cells or nephrons together with haemodynamic and metabolic overload of the remaining nephrons, leading to further loss of kidney cells or nephrons. The management of patients with CKD focuses on early detection and on controlling all modifiable risk factors. This approach includes reducing the overload of the remaining nephrons with inhibitors of the renin-angiotensin system and the sodium-glucose transporter 2, as well as disease-specific drug interventions, if available. Hypertension, anaemia, metabolic acidosis and secondary hyperparathyroidism contribute to cardiovascular morbidity and reduced quality of life, and require diagnosis and treatment.

Cushing syndrome (CS) is a constellation of signs and symptoms caused by excessive exposure to exogenous or endogenous glucocorticoid hormones. Endogenous CS is caused by increased cortisol production by one or both adrenal glands (adrenal CS) or by elevated adrenocorticotropic hormone (ACTH) secretion from a pituitary tumour (Cushing disease (CD)) or non-pituitary tumour (ectopic ACTH secretion), which stimulates excessive cortisol production. CS is associated with severe multisystem morbidity, including impaired cardiovascular and metabolic function, infections and neuropsychiatric disorders, which notably reduce quality of life. Mortality is increased owing to pulmonary emboli, infection, myocardial infarction and cerebrovascular accidents. The clinical presentation is variable and because some CS signs and symptoms are common in the general population, the diagnosis might not be considered until many features have accumulated. Guidelines recommend screening patients with suspected CS with 24-h urine cortisol, bedtime salivary cortisol and/or 1 mg dexamethasone suppression test. Subsequently, determining the aetiology of CS is important as it affects management. The first-line therapy for all aetiologies of endogenous CS is surgical resection of the causal tissue, including corticotroph adenoma or ectopic tumour for ACTH-dependent CS or unilateral or bilateral adrenalectomy for adrenal CS. Second-line therapies include steroidogenesis inhibitors for any cause of CS, pituitary radiation (with or without steroidogenesis inhibitors) for CD, and bilateral adrenalectomy for ACTH-dependent causes of CS.

Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia inherited as an autosomal dominant trait and caused by loss-of-function pathogenic variants in genes encoding proteins of the BMP signalling pathway. Up to 90% of disease-causal variants are observed in ENG and ACVRL1, with SMAD4 and GDF2 less frequently responsible for HHT. In adults, the most frequent HHT manifestations relate to iron deficiency and anaemia owing to recurrent epistaxis (nosebleeds) or bleeding from gastrointestinal telangiectases. Arteriovenous malformations (AVMs) in the lungs, liver and the central nervous system cause additional major complications and often complex symptoms, primarily due to vascular shunting, which is right-to-left through pulmonary AVMs (causing ischaemic stroke or cerebral abscess) and left-to-right through systemic AVMs (causing high cardiac output). Children usually experience isolated epistaxis; in rare cases, childhood complications occur from large AVMs in the lungs or central nervous system. Management goals encompass control of epistaxis and intestinal bleeding from telangiectases, screening for and treatment of iron deficiency (with or without anaemia) and AVMs, genetic counselling and evaluation of at-risk family members. Novel therapeutics, such as systemic antiangiogenic therapies, are actively being investigated. Although HHT is associated with increased morbidity, the appropriate screening and treatment of visceral AVMs, and the effective management of bleeding and anaemia, improves quality of life and overall survival.