Current Opinion in Nephrology and Hypertension最新文献

Purpose of review: In this review, we highlight the importance of understanding the inherent biological variability in normal kidney, or healthy reference tissue, to establish an accurate reference point for biomedical research. We explore this and the advantages and limitations of various sources of healthy reference tissue suitable for structural and omics-level studies.

Recent findings: Several large consortia are employing omic technologies for diseased and normal kidney tissue, underscoring the importance of utilizing healthy reference tissue in these studies. Emerging approaches, such as artificial intelligence and multiomic analyses, are expanding our understanding of structural and molecular heterogeneity in healthy reference kidney tissue and uncovering new insights.

Summary: Biological variability in healthy reference tissue at the functional, structural, and molecular level is complex and remains an active area of study. Thoughtful selection of healthy reference tissue sources is critical, providing the greatest potential for producing high-quality research outcomes.

Purpose of review: Metabolic dysfunction associated steatotic liver disease (MASLD) is increasing throughout the world, affecting nearly one in three individuals. Kidney stone disease, which is also increasing, is associated with MASLD. Common risk factors for both, including obesity, diabetes, dyslipidemia, hypertension, and metabolic syndrome, are likely drivers of this association. We present here a review of the associations and possible interconnections between these two common disease processes.

Recent findings: Epidemiological studies are discordant regarding the impact of sex on this association and on the impact of MASLD on incident stone risk. The nature of kidney stones is rarely taken into account.A favorable milieu for uric acid kidney stone formation may be created by a lower urine pH resulting from defective ammonium production associated with insulin resistance, common in MASLD.Endogenous oxalate synthesis, a major risk factor for calcium oxalate kidney stones, may be increased in MASLD via decline in the activity of enzymes involved in the detoxification of glyoxylate, the immediate precursor of oxalate.

Summary: The nature of kidney stones associated with MASLD and factors driving this association remain to be elucidated. Potential mechanisms identified underlying this include an increase in the risk factors for both uric acid and calcium oxalate kidney stones.

Purpose of review: Aldosterone dysregulation plays a major role in the pathogenesis of hypertension, cardiovascular disease, and kidney disease. Traditionally, steroidal mineralocorticoid receptor (MR) antagonists, namely spironolactone and eplerenone, have been the only available options to target aldosterone. Over recent years, a host of promising novel aldosterone-targeted pharmacologic agents have been developed thereby providing new options to mitigate aldosterone-mediated cardiovascular and kidney disease.

Recent findings: Recently, a number of nonsteroidal MR antagonists (finerenone, esaxerenone, and ocedurenone) and highly specific aldosterone synthase inhibitors (baxdrostat, lorundrostat, dexfadrostat, and vicadrostat) have been developed. The early clinical data for these novel medications looks promising regarding their efficacy in improving blood pressure control, preventing adverse cardiovascular outcomes, and slowing chronic kidney disease progression. Moreover, they appear to be generally safe and well tolerated.

Summary: In the coming years, nonsteroidal MR antagonists and aldosterone synthase inhibitors are likely to play an increasingly large role in routine medical practice to help improve cardiovascular and kidney outcomes.

Purpose of review: Apolipoprotein-L1 (APOL1) G1 and G2 risk variants, found in people of recent west sub-Saharan African ancestry, dramatically increase the likelihood of kidney disease, yet the incomplete penetrance an diverse clinical manifestations underscore the need to understand the molecular and environmental factors that modulate APOL1-mediated toxicity.

Recent findings: Recent studies confirm that risk variants exert a toxic gain-of-function effect, exacerbated by inflammatory triggers such as HIV infection and COVID-19. Epigenetic mechanisms and microRNA pathways further modulate APOL1 expression, influencing disease penetrance. Multiple models have clarified how subcellular localization, signal peptide processing, and interactions with the endoplasmic reticulum may contribute to pathogenesis. Therapeutic advances include inhibitors targeting APOL1 ion channel activity and strategies that block key inflammatory signaling pathways.

Summary: These findings highlight a multifaceted disease process driven by both the intrinsic toxic potential of APOL1 variants and numerous extrinsic triggers. Understanding this complex interplay will be pivotal for risk stratification and the development of precision therapies, potentially improving outcomes for populations disproportionately affected by APOL1-associated kidney disease.

Purpose of review: Hypertension has long been recognized as a modifiable risk factor for cardiovascular events. However, the role of intensive blood pressure (BP) control in preventing kidney disease progression continues to be debated. This review will provide a brief update on the evidence in support of or against the intensive control of BP on kidney outcomes in patient with chronic kidney disease (CKD), focusing particularly on trial-grade evidence.

Recent findings: Recently, three large trials conducted in China compared the effects of intensive BP control in adults with cardiovascular risk factors. All three trials demonstrated that intensive BP control confers cardiovascular benefits, but mixed results were noted in terms of the risk of adverse kidney outcomes. In individual-level meta-analyses of six trials of different BP control strategies in patients with CKD, intensive BP control appeared to reduce the risk of kidney replacement therapy in those with CKD stage 4-5, but not in patients with CKD stage 3.

Summary: Most guidelines continue to recommend a systolic BP target of 120-130 mmHg for patients with CKD given the cardiovascular benefits observed in trials of intensive BP control, though there are some signals of potential risks to the kidney with this BP treatment strategy.

Purpose of review: Glucagon-like peptide-1 receptor agonists (GLP1RA), initially approved for glycemic control in type 2 diabetes mellitus (T2DM), have emerged as agents for weight loss, cardiovascular and kidney protection. This review summarizes the evidence supporting the benefits of these therapies on cardiorenal outcomes.

Recent findings: Clinical trials have consistently demonstrated reductions in major adverse cardiovascular events with GLP1RA treatments. Recently, the FLOW trial revealed that semaglutide reduced the composite outcome of kidney failure, at least 50% decline in estimated glomerular filtration rate, kidney or cardiovascular mortality by 24% in patients with T2DM, thereby establishing GLP1RA as a pillar of therapy in this population. New evidence suggests favorable effects on kidney endpoints in nondiabetic individuals with overweight or obesity. Dedicated trials have also provided evidence for reduction in the risk for heart failure hospitalization and improvement in symptoms in individuals with heart failure with preserved ejection fraction. Subgroup analyses have suggested that GLP1RAs confer additive cardiorenal benefits irrespective of background medication use.

Summary: There is increasing evidence that GLP1RA reduces the risk for cardiovascular events, chronic kidney disease progression, and heart failure hospitalizations. Further data on the effect of dual and triple GLP1-based therapies on cardiorenal outcomes is required.

Purpose of review: Essential (primary or idiopathic) hypertension is presented as the most prevalent 'cause' of arterial hypertension, which is a paradoxical statement for a condition whose causes are unknown. The consequence of this description is that secondary hypertension is held to be exceptional and, therefore, very rarely sought for in current clinical practice. Labelling a hypertensive patient as 'essential' means that no further investigations will be undertaken to discover the cause of hypertension, therefore neglecting the possibility of long-term cure of hypertension and sentencing the patient to a life-long drug treatment.

Recent findings: We will describe how the notion of essential hypertension has developed and whether scientific evidence from the most recent studies still support the conclusion that it is highly prevalent. The concept of secondary hypertension along with the criteria to be used to define it as such are also being examined.

Summary: The evidence that secondary hypertension is highly prevalent, when systematically sought for, should increase the awareness of this condition and lead to a broader search for it, which are fundamental steps to achieve cure or a better control of high blood pressure, thus improving patients' outcome and quality of life.

Purpose of review: This review examines the effects of occupational heat stress on kidney health. It focuses on the role of hyperthermia in the development of acute kidney injury (AKI) and its potential progression to chronic kidney disease of nontraditional etiology (CKDnt). We highlight the physiological mechanisms by which hyperthermia affects kidney function and discuss emerging preventive strategies.

Recent findings: Hyperthermia places the kidneys in a vulnerable state. As body temperature increases, blood flow is directed toward the skin to aid in cooling, diverting it away from internal organs like the kidneys to support blood pressure regulation. At the same time, hyperthermia and dehydration increases energetic demand to promote fluid and electrolyte conservation. Collectively, this can create a localized supply-demand mismatch, resulting in tissue hypoxia that can damage kidney tissues. These findings highlight that heat hyperthermia can lead to subclinical kidney damage, with potential long-term implications for kidney health.

Summary: Heat-induced AKI is a growing public health concern. Individuals engaged in manual labor with prolonged exposure are at risk of CKDnt. Interventions aimed to prevent hyperthermia show promise in mitigating the risk of AKI. Further research is necessary to refine these strategies and establish evidence-based guidelines for reducing heat-related kidney injuries.