Current Opinion in Nephrology and Hypertension最新文献

Purpose of review: Cardiorenal disease is commonly complicated by iron deficiency, which worsens clinical outcomes regardless of haemoglobin levels. This review evaluates recent evidence on intravenous iron therapy in this setting.

Recent findings: Recent randomized trials demonstrate the important role of intravenous iron in improving functional status and quality of life as well as reducing hospitalizations in patients with heart failure and iron deficiency. In chronic kidney disease, intravenous iron showed potential cardiovascular benefits beyond anaemia correction and is now recommended in updated guidelines. Although historically there were concerns regarding adverse reactions, recent trial data using modern high-dose intravenous irons have demonstrated an acceptable safety profile.

Summary: Intravenous iron offers clinical benefits in cardiorenal disease, supporting its expanded use even in the absence of anaemia. Broader adoption in clinical practice remains limited despite updated guidelines. Whilst safety data are generally reassuring, further studies will help define long-term safety and optimal use in non-dialysis, non-anaemic populations.

Purpose of review: The spectrum of kidney diseases caused by variation in the apolipoprotein L1 ( APOL1 ) gene was identified in 2010 among patients with recent African ancestry. In the United States, inheriting two APOL1 risk variants (high-risk genotypes) markedly increases risk for solidified glomerulosclerosis, focal segmental glomerulosclerosis, collapsing glomerulopathy, lupus nephritis, and sickle cell nephropathy. Kidneys from African American deceased donors with APOL1 high-risk genotypes also fail more rapidly after transplant. One risk variant increases nephropathy risk in Africa. This review focuses on novel therapies targeting APOL1 and the changing landscape of APOL1 genotyping in patients at risk for APOL1 -mediated kidney disease (AMKD).

Recent findings: Renin-angiotensin-aldosterone system blockade and sodium-glucose cotransporter 2 inhibitors slow nephropathy progression but are not curative. Medications directly targeting APOL1 mRNA and blocking APOL1 protein effects are undergoing clinical trials in AMKD, including APOL1 small molecule inhibitors, an APOL1 antisense oligonucleotide, and a Janus kinase (JAK) signaling inhibitor to reduce APOL1 expression. Early results are promising and provide hope for well tolerated and effective therapies. If successful, more patients will need to be considered for APOL1 genotyping, and our approach to diagnosing and treating chronic kidney disease in populations with recent African ancestry will change dramatically.

Summary: Mechanisms of APOL1 risk variant nephrotoxicity remain unclear; nonetheless, specific therapies for AMKD show great promise and may improve understanding of disease processes. With ongoing clinical trials and the potential for effective AMKD treatments, more widespread APOL1 genotyping will likely be needed.

Purpose of review: Renin-angiotensin-aldosterone system inhibitors (RAASi), including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), are fundamental in chronic kidney disease (CKD) management, particularly in proteinuric conditions. However, their use in advanced CKD (eGFR <30 ml/min/1.73 m 2 ) remains debated because of risks of hyperkalaemia, acute kidney injury (AKI), and hypotension. This review evaluates the latest evidence, including the STOP-ACEi trial, to inform the risks and benefits of RAASi in advanced CKD.

Recent findings: The STOP-ACEi trial, a multicentre randomized controlled trial (RCT), investigated RAASi discontinuation in 411 patients with advanced CKD. After 3 years, discontinuation did not slow eGFR decline or reduce mortality, while continuation was associated with a numerical trend towards lower end-stage kidney disease (ESKD) rates. Meta-analyses also indicate that ACEi may offer superior kidney protection compared to ARBs, though both lower cardiovascular risk and this difference may not be clinically significant. Combination ACEi/ARB therapy provides no additional benefits and increases adverse events, such as hyperkalaemia and hypotension. Adjunct therapies like potassium binders and sodium-glucose cotransporter-2 (SGLT2) inhibitors may enable safer RAASi use in high-risk patients.

Summary: Current evidence supports RAASi continuation in most CKD patients, including those with advanced disease, unless contraindicated. Future studies should refine patient selection criteria and optimize adjunctive strategies to mitigate adverse effects.

Purpose of review: Patients with kidney disease, especially patients with kidney failure, are disproportionately affected in settings of active conflict, as they rely on near constant medical care for survival. Recent increases in violent conflicts are endangering increasing numbers of patients, requiring immediate attention, a revision of current knowledge and constructive actions.

Recent findings: Recent violent conflicts have revealed the profound vulnerability of patients with chronic kidney disease (CKD). In war-torn regions such as Ethiopia, Sudan, Gaza, and Ukraine, availability of essential services has been disrupted. Patients with CKD often lose access to antihypertensive and antidiabetic medications. Dialysis-dependent patients face high mortality when centres are damaged, or supply chains are cut. In Sudan, over 65% of patients on haemodialysis developed complications due to missed treatments. Sources from the wars in Bosnia, Ethiopia, and Gaza have reported mortality rates of patients with kidney failure reaching close to 50% or even exceeding it. In contrast, reports from Ukraine have shown that with intact infrastructure and sustained international support, dialysis services can be maintained and even expanded. These experiences underline the critical role of logistics, preparation, and humanitarian coordination in sustaining kidney care during conflict.

Summary: Conflicts severely compromise kidney care by disrupting continuity of treatment, dialysis infrastructure, and supply chains. Outcomes vary widely depending on external support and blockade status. Preventable deaths among dialysis patients are common in besieged regions. Preparedness, coordination, and open supply lines are essential to mitigate humanitarian catastrophe among vulnerable kidney patients.

Purpose of review: Artificial intelligence is continuously and rapidly evolving. Artificial intelligence has the potential to address several clinical challenges associated with the prevention, detection, and management of acute kidney injury (AKI). This review provides an overview of the state of artificial intelligence for AKI decision-making, highlighting key recent developments, trends, and innovations towards real-world bedside deployment.

Recent findings: External validation of supervised artificial intelligence models for predicting AKI outcomes is now common, with numerous retrospective studies demonstrating strong performance across institutions, patient populations, and international borders. Explainability and transportability of AKI prediction models have become increasingly prioritized, and many recent models use a smaller set of the most widely collected EHR variables with tree-based classifiers. New potential applications focused on supporting bedside AKI decision-making have emerged based on reinforcement learning and causal inference algorithms.

Summary: Although consistency among externally validated AKI models is promising for eventual deployment at the bedside, few have undergone prospective validation, and the real-world clinical impact of artificial intelligence systems for AKI at the bedside remains unclear. Future work should focus on recent advances in artificial intelligence techniques and implementation studies, which assess overall clinical applicability.

Purpose of review: Cognitive impairment (CI) is a frequent and disabling complication in individuals with chronic kidney disease (CKD). With rising CKD prevalence, especially in aging populations, there is a pressing need to understand the complex and multifactorial mechanisms linking kidney dysfunction to cognitive decline.

Recent findings: Emerging evidence highlights the multifactorial pathogenesis of CKD-related CI, involving vascular dysfunction, blood-brain barrier disruption, glymphatic impairment, systemic inflammation, uremic toxin accumulation, hormonal dysregulation, and gut-brain axis alterations. Additionally, mental health comorbidities, sarcopenia, sleep disorders, and renal replacement therapies further modulate cognitive outcomes. Advances in biomarker research and the identification of neuroprotective factors like Klotho may reshape diagnostic and therapeutic strategies.

Summary: CI in CKD results from a convergence of systemic and neural insults, modulated by resilience mechanisms and shaped by aging and comorbidities. Future research should explore interventions targeting modifiable contributors, such as vascular health, inflammation, and uremic toxicity, as well as enhancing neuroresilience to preserve cognitive function in this high-risk population.

Purpose of review: The management of hypertension remains suboptimal despite the widespread use of multiple antihypertensive medication groups. We hereby aim to evaluate the novel therapeutic approaches for the management of hypertension.

Recent findings: As the decline in SBP and/or DBP is associated with a significant decline in major adverse cardiovascular events and all-cause mortality, the optimal management of hypertension is at most importance. The high prevalence of resistant hypertension, approximately 10% of hypertensive population, remains a major concern associated with high morbidity and mortality. Recently, multiple novel pharmacotherapeutic approaches have been implicated in the management of hypertension on various pathophysiological mechanisms, including aldosterone synthetase inhibitors, RNA-based therapies such as antisense oligonucleotides and small-interfering RNA, atrial natriuretic peptide analogs, dual endothelin antagonists, intestinal sodium-hydrogen exchanger-3 inhibitors, compound 17b and nonsteroidal mineralocorticoid receptor antagonists.

Summary: Pharmacotherapeutic management options for hypertension is a growing field of research with potential clinical implications for multiple agents in upcoming years. Such novel approaches have the potential to improve clinical outcomes of hypertension management.

Purpose of review: Chronic kidney disease (CKD) is associated with elevated cardiovascular risk and progression to kidney failure, despite advances in therapy with renin-angiotensin system inhibitors and sodium-glucose-co-transporter-2 inhibitors. Overactivation of the aldosterone pathway contributes to residual cardiorenal risk. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have shown efficacy in reducing cardiorenal outcomes in patients with albuminuric diabetic kidney disease, providing a rationale to explore broader aldosterone pathway inhibition in CKD.

Recent findings: While steroidal MRAs are effective, their use is often limited by hormonal side effects and risk of hyperkalemia. Finerenone, a selective nonsteroidal MRA, showed cardiovascular and renal benefit in CKD patients with diabetes, although with only modest BP-lowering effects. Its role in nondiabetic populations and in those with lower levels of albuminuria remains to be determined. More recently, aldosterone synthase inhibitors (ASIs) have emerged as promising agents that directly suppress aldosterone production. Early-phase studies in patients with CKD, with or without diabetes, have shown reductions in albuminuria and BP, with a favorable safety profile.

Summary: Direct inhibition of aldosterone synthesis may provide a novel and complementary strategy to reduce residual cardiorenal risk in CKD. Ongoing phase 3 trials will be key to defining the clinical utility of ASIs and their integration into future treatment paradigms.

Purpose of review: Chimeric antigen receptor (CAR) T-cell therapy has marked a historic milestone for its remission rates in relapsed/refractory hematological neoplasms. Despite favorable efficacy outcomes, CAR T-cells are associated with potentially severe early and late complications, such as cytokine release syndrome (CRS), neurotoxicity, acute kidney injury (AKI), cytopenias and infections.

Recent findings: AKI is a common complication that normally manifests during the first week following infusion and typically shows recovery within the first month. The risk factors for AKI development include a prior history of chronic kidney disease (CKD), development of CRS or neurotoxicity, antibiotic therapy and the use of intravenous contrast, amongst others.

Summary: AKI a frequent but mild complication, with fast recovery. Future multicentric prospective studies are required to investigate the pathophysiology of AKI following CAR T-cell therapy and the potential preventive treatments. Furthermore, the impact of AKI secondary to CAR T-cell treatment in patients with prior CKD has not been analyzed in long-term follow-up studies.