Current Opinion in Nephrology and Hypertension最新文献

Purpose of review: Continuous renal replacement therapy (CRRT) is a vital medical intervention used in critically ill patients with acute kidney injury (AKI). One of the key components of adequate clearance with CRRT is the use of anticoagulants to prevent clotting of the extracorporeal circuit. Regional citrate anticoagulation is the most often recommended modality. The term 'citrate toxicity' is used to describe potential adverse effects of accumulation of citrate and subsequent hypocalcemia. However, citrate is itself not inherently toxic. The term and diagnosis of citrate toxicity are questioned in this review.

Recent findings: Citrate is being increasingly used for regional anticoagulation of the CRRT circuit. Citrate accumulation is infrequent and can cause hypocalcemia and metabolic alkalosis, which are potential adverse effects. Citrate itself, however, is not a toxic molecule. The term 'citrate toxicity' has been used to denote hypocalcemia and metabolic acidosis. However, citrate administration is well known to cause systemic and urinary alkalinization and under certain circumstances, metabolic alkalosis, but is not associated itself with any 'toxic' effects.We review the existing literature and debunk the perceived toxicity of citrate. We delve into the metabolism and clearance of citrate and question current data suggesting metabolic acidosis occurs as the result of citrate accumulation.

Summary: In conclusion, this article calls into question prevailing concerns about 'citrate toxicity'. We emphasize the need for a more nuanced understanding of its safety profile. We recommend discarding the term 'citrate toxicity' in favor of another frequently used, but more meaningful term: 'citrate accumulation'.

Purpose of review: Kidney function declines with normal aging. But it also declines with the progression of some diseases. This review calls for a more nuanced interpretation of kidney function in the geriatric population, who may have frailty and comorbidities.

Recent findings: GFR declines with healthy aging kidneys. Aging kidney changes include decreased cortical volume, senescent global glomerulosclerosis, and reduced nephron numbers. Yet normal aging is not associated with increased glomerular volume or single-nephron GFR. The prevalence of GFR less than 60 ml/min/1.73 m 2 in the geriatric population is high. However, the decline in GFR with normal aging may not reflect true CKD without albuminuria. Although the risk of ESKD and mortality increases in all age groups when eGFR less than 45 ml/min/m 2 , there is no significant increased relative risk of ESKD and mortality in the geriatric population when eGFR 45-59 ml/min/m 2 in the absence of albuminuria. Innovative approaches are needed to better estimate GFR and define CKD in the geriatric population.

Summary: The expected GFR decline in the geriatric population is consistent with normal aging kidney changes. To avoid CKD overdiagnosis and unnecessary referrals to nephrology for possible CKD, age-adapted definitions of CKD in the absence of albuminuria are needed.

Purpose of review: Although most of the current medical education literature has focused on teaching strategies, little attention has been devoted to selecting appropriate course content. Despite elegant descriptions of physiologic mechanisms in recent decades, medical school curricula and students continue to rely on outdated textbooks and certification examination study aids composed to fit an antiquated exam blueprint.

Recent findings: Advances in our understanding of potassium physiology offer multiple examples of key concepts that deserve to be included in the modern-day renal physiology curriculum, including the relationship of potassium to blood pressure and the potassium 'switch', the aldosterone paradox, and novel pharmacologic agents that target dietary potassium absorption and potassium handling in the kidney.

Summary: Key advances in our understanding and application of renal physiology to patient care have not been readily integrated into the nephrology curriculum of medical students. Difficult questions remain regarding when new concepts are sufficiently established to be introduced to medical students in the preclinical years.

Purpose of review: The transmembrane protein 16A (TMEM16A) Ca 2+ -activated Cl - channel constitutes a key depolarising mechanism in vascular smooth muscle and contractile pericytes, while in endothelial cells the channel is implicated in angiogenesis and in the response to vasoactive stimuli. Here, we offer a critical analysis of recent physiological investigations and consider the potential for targeting TMEM16A channels in vascular disease.

Recent findings: Genetic deletion or pharmacological inhibition of TMEM16A channels in vascular smooth muscle decreases artery tone and lowers systemic blood pressure in rodent models. Inhibition of TMEM16A channels in cerebral cortical pericytes protects against ischemia-induced tissue damage and improves microvascular blood flow in rodent stroke models. In endothelial cells, the TMEM16A channel plays varied roles including modulation of cell division and control of vessel tone through spread of hyperpolarisation to the smooth muscle cells. Genetic studies implicate TMEM16A channels in human disease including systemic and pulmonary hypertension, stroke and Moyamoya disease.

Summary: The TMEM16A channel regulates vascular function by controlling artery tone and capillary diameter as well as vessel formation and histology. Preclinical and clinical investigations are highlighting the potential for therapeutic exploitation of the channel in a range of maladaptive states of the (micro)circulation.

Purpose of review: Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular disease. Epithelial sodium channel (ENaC) plays a critical role in renal electrolyte and volume regulation and has been implicated in the pathogenesis of SSBP. This review describes recent advances regarding the role of ENaC-dependent inflammation in the development of SSBP.

Recent findings: We recently found that sodium enters dendritic cells via ENaC, a process regulated by serum/glucocorticoid-regulated kinase 1 and epoxyeicosatrienoic acid 14,15. Sodium entry activates NADPH oxidase, leading to the production of isolevuglandins (IsoLGs). IsoLGs adduct self-proteins to form neoantigens in dendritic cells that activate T cells and result in the release of cytokines promoting sodium retention, kidney damage, and endothelial dysfunction in SSBP. Additionally, we described a novel mechanistic pathway involving ENaC and IsoLG-dependent NLRP3 inflammasome activation. These findings hold promise for the development of novel diagnostic biomarkers and therapeutic options for SSBP.

Summary: The exact mechanisms underlying SSBP remain elusive. Recent advances in understanding the extrarenal role of ENaC have opened a new perspective, and further research efforts should focus on understanding the link between ENaC, inflammation, and SSBP.

Purpose of review: The purpose of this review is to describe an approach that emphasizes shared decision-making for patients with decompensated cirrhosis and acute kidney injury when liver transplantation is either not an option, or unlikely to be an option.

Recent findings: When acute kidney injury occurs on a background of decompensated cirrhosis, outcomes are generally poor. Providers can also be faced with prognostic uncertainty. A lack of guidance from nephrology and hepatology professional societies means that providers rely on expert opinion or institutional practice patterns.

Summary: For patients who are unlikely to receive liver transplantation, the occurrence of acute kidney injury represents an opportunity for a goals of care conversation. In this article, we share strategies through which providers can incorporate more shared decision-making when caring for these patients. The approach involves creating prognostic consensus amongst multidisciplinary teams and then relying on skilled communicators to share the prognosis. Palliative care consultation can be useful when teams need assistance in the conversations.

Purpose of review: Cardiomyopathy in chronic kidney disease (CKD) is a complex condition with multiple triggers and poor prognosis. This review provides an overview of recent advances in CKD-associated cardiomyopathy, with a focus on pathophysiology, newly discovered biomarkers and potential therapeutic targets.

Recent findings: CKD is associated with a specific pattern of myocardial hypertrophy and fibrosis, resulting in diastolic and systolic dysfunction, and often triggered by nonatherosclerotic processes. Novel biomarkers, including amino-terminal type III procollagen peptide (PIIINP), carboxy-terminal type I procollagen peptide (PICP), FGF23, marinobufagenin, and several miRNAs, show promise for early detection and risk stratification. Treatment options for CKD-associated cardiomyopathy are limited. Sodium glucose cotransporter-2 inhibitors have been shown to reduce left ventricle hypertrophy and improve ejection fraction in individuals with diabetes and mild CKD, and are currently under investigation for more advanced stages of CKD. In hemodialysis patients calcimimetic etelcalcetide resulted in a significant reduction in left ventricular mass.

Summary: CKD-associated cardiomyopathy is a common and severe complication in CKD. The identification of novel biomarkers may lead to future therapeutic targets. Randomized clinical trials in individuals with more advanced CKD would be well posed to expand treatment options for this debilitating condition.

Purpose of review: Recent advances in the treatment of chronic kidney disease (CKD) have led to the development of several new agents that are kidney protective, particularly in people with diabetes. These agents include sodium/glucose cotransporter-2 inhibitors (SGLT-2 inhibitors), mineralocorticoid receptor antagonists (MRAs), and glucagon-like peptide-1 receptor agonists (GLP-1RAs). This review summarizes the available data regarding the effects of using these therapies in combination.

Recent findings: There is convincing evidence that SGLT-2 inhibitors and MRAs individually improve kidney function and reduce the risk of cardiovascular events in people with CKD, especially diabetic CKD. There is some evidence that GLP-1RAs may be beneficial, but further studies are needed.The available data support an additive kidney and cardiovascular benefit using combination therapy with SGLT-2 inhibitors and MRAs, and possibly with SGLT2 inhibitors and GLP-1RAs, but more long-term data are needed. The currently available data suggest that combining these agents would likely be beneficial and may be an appropriate long-term strategy.

Summary: Several new agents are useful in slowing the progress of CKD. Further research to identify which combinations of agents work best together and which combinations are most effective for people with different characteristics, in order to personalize treatment and improve outcomes for people with CKD, should be a priority.

Purpose of review: There are limited studies on the benefits of low dietary protein intake (DPI) and plant-dominant diets to delay kidney allograft dysfunction. We evaluate evidence regarding the association or effects of the amount and type of DPI on allograft function.

Recent findings: There is conflicting evidence regarding the benefits of low DPI and plant-dominant diet including PLADO and PLAFOND on kidney allograft function. Taking the strength of evidence including study design, sample size, and time to follow-up, the proposed amount of DPI to slow the progression of allograft dysfunction, avoid negative nitrogen balance, and skeletal muscle mass loss is 1.0-1.3 g/kg/day during an immediate posttransplant period or when high protein catabolic rate exists. The DPI may be 0.8-1.0 g/kg/day in patients with stable allograft function. Patients with chronic allograft rejection or estimated glomerular filtration rate <25 ml/min may benefit from the DPI of 0.55-0.60 g/kg/day, while those with failed allograft requiring transition to dialysis including incremental (twice-weekly) hemodialysis should consider increasing DPI to 1.0-1.2 g/kg/day.

Summary: While there is a lack of strong evidence, individualized approaches based on the patient's comorbidities, net state of immunosuppression, and periods posttransplant may guide the appropriate amount and type of DPI to slow allograft dysfunction.

Purpose of review: Kidney disease is associated with major health and economic burdens worldwide, disproportionately carried by people in low and middle socio-demographic index quintile countries and in underprivileged communities. Social determinants such as education, income and living and working conditions strongly influence kidney health outcomes. This review synthesised recent research into multimodal interventions to promote kidney health equity that focus on the social determinants of health.

Recent findings: Inequity in kidney healthcare commonly arises from nationality, race, sex, food insecurity, healthcare access and environmental conditions, and affects kidney health outcomes such as chronic kidney disease progression, dialysis and transplant access, morbidity and mortality. Multimodal approaches to addressing this inequity were identified, targeted to: patients, families and caregivers (nutrition, peer support, financial status, patient education and employment); healthcare teams (workforce, healthcare clinician education); health systems (data coding, technology); communities (community engagement); and health policy (clinical guidelines, policy, environment and research).

Summary: The engagement of diverse patients, families, caregivers and communities in healthcare research and implementation, as well as clinical care delivery, is vital to counteracting the deleterious effects of social determinants of kidney health.