This case report describes the clinical presentation, diagnostic findings and clinicopathologic features consistent with developmental lung disease (DLD) and pulmonary hypertension (PH) in a 3-month-old Sphynx Munchkin kitten. The kitten was originally referred for episodes of respiratory distress that was unresponsive to medical management, consisting of diuretics, antibiotics and corticosteroids. Echocardiography was consistent with a high probability of PH of a non-cardiac etiology. Baseline blood work, thoracic radiographs, thoracic CT with triphasic angiography and a bronchoalveolar lavage were performed. Thoracic CT revealed diffuse ground-glass opacity with bronchiolectasis and distention of the pulmonary artery and branches. The bronchoalveolar lavage identified an equal distribution of non-degenerative neutrophils and macrophages, with erythrophagocytosis and no overt neoplastic cells or infectious organisms identified. The kitten was humanely euthanized due to the lack of an identifiable treatable etiology and poor prognosis. Histopathological findings were most consistent with DLD with diffuse acinar underdevelopment and vascular changes including pulmonary capillary hemangiomatosis. These findings have not been previously reported in the feline DLD literature.

Phototransformation is an important attenuation process for pharmaceuticals in the aquatic environment. However, there are unknowns regarding the kinetics, products, and mechanisms of the sensitized photolysis of many pharmaceuticals induced by natural sensitizers. In this study, we systematically investigated the photochemical behavior and fate of the diuretic furosemide (FUR) under natural sunlight in the presence of nitrate (NO3[-]) and dissolved organic matter (DOM). Results show that NO3[-] significantly promoted the photodegradation of FUR through photosensitization, with photolysis rate constant in the presence of 1 mM NO3[-] being approximately 1.6-fold higher than that of direct photolysis. The photolysis of FUR predominantly generated hydroxylated product, whose generation and degradation were both facilitated by NO3[-]. DOM exhibited inhibitory effects on NO3[-]-sensitized photolysis of FUR by light screening and radical quenching. The photolysis pathways of FUR in the presence of NO3[-] included decarboxylation, C-N bond cleavage, dechlorination, hydroxylation, ring opening, dehydrogenation, and desulfonamidation. Most photoproducts were predicted to be less ecotoxic, persistent, and bioaccumulative than FUR. Model predictions with APEX indicate that direct photolysis and reaction with carbonate radical were the primary photochemical processes for FUR dissipation in natural waters. The photolysis half-lives of FUR were significantly affected by dissolved organic carbon and water depth. Results of this study fulfill the knowledge gaps in the photochemical behavior and fate of the diuretic drugs in sunlit surface waters.

Kidney dysfunction, characterized by either reduced estimated glomerular filtration rate (eGFR) of <60 ml/min per 1.73 m2 or reduced urinary response to diuretic therapy, is among one of the most powerful risk factors for mortality and adverse cardiovascular events among patients with acute decompensated heart failure (ADHF). Classically postulated hemodynamic mechanisms-including low cardiac output, arterial underfilling and venous congestion-likely interact through complex multi-directional pathways to contribute to kidney dysfunction in ways that remain incompletely understood. However, trials of therapies designed to improve cardiovascular hemodynamics have not consistently translated into improvements in kidney function. Non-hemodynamic contributors such as neurohormonal activation, inflammation, and endothelial dysfunction likely also play important roles in the development of kidney dysfunction in ADHF. A major challenge of the management of ADHF is intense tubular sodium and water avidity, leading to congestion that can be resistant to diuretic therapy. Overcoming diuretic resistance frequently requires escalation of loop diuretics as well as combination diuretic strategies targeting multiple nephron segments, and monitoring of diuretic response to guide titrations of diuretic therapy. Recent studies have also evaluated the safety of initiation of guideline directed medical therapy (GDMT) during hospitalizations for ADHF. Even though GDMT use has been shown to reduce cardiovascular events, rates of use remain low and hospitalizations for ADHF represent opportunities for initiation and/or resumption of GDMT. Many of therapies in ADHF, including decongestion and GDMT initiation, are associated with acute declines in kidney function that remain difficult to interpret and may be misleading if used in isolation without the larger clinical context to guide treatment decisions. Lastly, emerging novel targets for decongestion are being evaluated with the ultimate goal of achieving decongestion without declines in kidney function.

Hypertension guidelines recommend adding antihypertensive therapies until the blood pressure (BP) is below a specific target. If the BP is not below target with 3 medications, including a diuretic, then it is labeled resistant hypertension, and then we investigate for secondary causes, such as primary aldosteronism (PA). PA testing seems complex with 3 results: aldosterone, renin, and the aldosterone-renin ratio. Hence, these tests are ordered infrequently, and the diagnosis of PA is often delayed or never made. Also, heart failure, chronic kidney disease, and other conditions can have elevated aldosterone, which are not PA-related. The traditional treatment with aldosterone receptor blockers/mineralocorticoid receptor antagonists has been helpful, but they block the effects that are mediated through the mineralocorticoid receptor. The non-receptor effects of high aldosterone may continue to cause harm. Therefore, blocking the production of aldosterone with an aldosterone synthase inhibitor (ASI) could be a more complete strategy to address elevated aldosterone levels. In addition, an "ASI Challenge" may help us decide which patients need formal testing for PA. If the systolic blood pressure drops a significant amount (>10 mm Hg), then that suggests aldosterone is a key component of the uncontrolled BP, and those patients should be considered for formal PA testing. For those who drop a modest amount (<10 mm Hg), they would be less likely to need PA testing. Such an approach could use an ASI agent as a diagnostic/screening tool as well as a therapeutic agent, which would be very helpful in the primary care setting.

Aldosterone dysregulation is a key driver of difficult-to-control and resistant hypertension. Mineralocorticoid receptor antagonists (MRAs) target the aldosterone pathway but their use can be limited by side effects, particularly hyperkalemia and antiandrogenic hormonal effects. Selective aldosterone synthase inhibitors (ASIs) have shown clinically meaningful blood pressure reductions in patients with difficult-to-control and resistant hypertension in recent phase 2b and 3 trials. In this narrative review, we summarize pivotal evidence from phase 2b and phase 3 trials of the second-generation ASIs lorundrostat, baxdrostat, and dexfadrostat, reporting efficacy and core safety signals (hyperkalemia, hyponatremia, and an early functional reduction in estimated glomerular filtration rate (eGFR]). We further discuss the implications of these findings, economic and access considerations, remaining evidence gaps, future research directions, and potential practical treatment algorithms. ASIs offer clinically significant blood pressure lowering with moderate side effects when added on top of current therapies in short-term trials, though long-term outcome data are lacking. In May 2026, the US Food and Drug Administration (FDA) approved the first ASI, baxdrostat, for hypertension treatment in combination with other antihypertensive drugs in inadequately controlled adults. However, gaps remain, most notably the absence of comparative effectiveness trials versus MRAs, the standard fourth-line agent. ASIs target upstream aldosterone production and may offer a distinct, complementary role for patients with intolerance or contraindications for MRA or insufficient response. ASIs may be best reserved for the treatment of uncontrolled or resistant hypertension in combination with other antihypertensives and where MRAs are contraindicated, poorly tolerated, or insufficient.

Hypertension is the leading modifiable risk factor for stroke and a major contributor to cognitive impairment and dementia, with its global burden increasing alongside population aging. Hypertension promotes cerebrovascular damage through endothelial dysfunction, blood-brain barrier disruption, small vessel disease, and accelerated atherosclerosis, all potentially contributing to both ischemic and hemorrhagic stroke risk. These vascular alterations also contribute to neurodegenerative processes, linking hypertension-particularly when present in midlife-to vascular dementia and Alzheimer's disease. Effective blood pressure control (target <130/80 mm Hg) remains central to primary and secondary stroke prevention and is associated with reduced risks of recurrent stroke and cognitive decline. The renin-angiotensin-aldosterone system plays a central role in hypertension-related cerebrovascular injury, with aldosterone excess contributing to vascular inflammation, oxidative stress, and impaired cerebral autoregulation. Resistant hypertension, often driven by aldosterone dysregulation, is associated with increased cardiovascular and neurological risk. Aldosterone synthase inhibitors such as lorundrostat and baxdrostat represent a novel therapeutic approach targeting aldosterone production. Clinical trials demonstrate significant reductions in systolic blood pressure with favorable safety profiles in patients with uncontrolled or resistant hypertension. Although direct evidence for stroke prevention is currently lacking, indirect data suggest that sustained blood pressure reduction and modulation of aldosterone-mediated vascular damage may lower cerebrovascular risk. Aldosterone synthase inhibitors may be particularly relevant in phenotype-driven, personalized treatment strategies for patients with resistant hypertension or suspected aldosterone excess. However, long-term efficacy, safety, and impact on hard outcomes such as stroke and dementia require confirmation in dedicated trials.

Chronic kidney disease (CKD) is highly prevalent globally and affects approximately 1 in 10 adults, with a prevalence of 10% globally and ∼14.4% in North America. High blood pressure (BP) is one of the most common causes for the development of CKD. Conversely, hypertension occurs more frequently in patients with CKD and is found to be uncontrolled in 60%-80% of these patients. The rates of resistant hypertension are amongst the highest for any patient population, with estimates ranging between 40% and 50%. Deteriorating renal function is associated with increasing risk for co-morbid conditions including cardiac disease and stroke. Appropriate management of hypertension is important in patients with CKD but poses frequent challenges in clinical care with the need to balance the desired BP lowering and ideally reno-protective effects against increased risks for nephrotoxicity and medication side effects. Established therapeutic principles in the context of CKD include renin-angiotensin-aldosterone system (RAAS) blockade using either ACE inhibitors or angiotensin receptor blockers (ARBs), sodium-glucose transport 2 (SGLT-2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (nsMRAs), and glucagon-like-peptide-1 (GLP-1) agonists. Aldosterone dysregulation is emerging as another key driver of persistently uncontrolled BP and deteriorating kidney function, not only through the associated sodium and fluid retention but also through BP-independent effects on endothelial function, inflammatory pathways, tissue fibrosis, and hypertrophic responses. The new drug class of aldosterone synthase inhibitors (ASIs), highly selective agents inhibiting CYP11B2 and thereby reducing circulating aldosterone levels, may offer a novel opportunity to effectively lower BP and reduce organ damage mediated by dysregulated aldosterone. Indeed, recently published data from phase 3 randomized controlled hypertension trials with various ASIs have demonstrated substantial office and ambulatory BP lowering efficacy with an acceptable safety profile. A reduction in albuminuria in early phase 2 trials in patients with hypertension and CKD may indicate reno-protective properties of ASIs. Dedicated outcome trials are ongoing to explore these prospects in detail.