Yan Roberth Delmiro Silva

This Current Opinion uses the endothelin receptor antagonist trials in kidney disease to draw lessons for future research. ASCEND, SONAR, PRECISION, and ZENITH-CKD each show something different about dosing, patient enrichment, fluid retention, and the help of SGLT2 inhibitor background therapy. In practice, the class suits a narrow group: confirmed resistant hypertension with chronic kidney disease, no unstable heart failure, and close follow-up of weight, edema, and kidney function. Aprocitentan fits best as a selective add-on for these patients, and new trials should test it against current guideline-based treatment.

Zilebesiran is an investigational RNA interference drug that silences angiotensinogen in the liver and keeps blood pressure down with infrequent doses. This Current Opinion looks at a practical gap: how to manage sepsis, surgery, acute heart failure, volume depletion, or hyperkalemia in a patient whose renin-angiotensin system cannot be switched back on quickly. No harm has been shown, but current reversal approaches seem better suited to planned withdrawal than to emergencies. As phase 3 development moves forward, studies should identify vulnerable patients and decide whether acute care protocols need to change.

Endothelin receptor antagonists reduce albuminuria, but fluid retention and concern about heart failure limit their use in chronic kidney disease. This review asks whether SGLT2 inhibitors given in the background can offset that fluid retention while keeping the kidney benefit. SONAR, ZENITH-CKD, and what is known about the mechanisms on both sides make the combination biologically plausible. The evidence is still short-term and comes mostly from zibotentan with dapagliflozin, so the strategy is presented as a hypothesis to test in trials.

Aprocitentan, a dual endothelin receptor antagonist, is approved as an add-on drug for hypertension that stays uncontrolled despite several medicines. Drawing on the PRECISION trial program, this review weighs its sustained blood pressure lowering and marked fall in albuminuria against the fluid retention it can cause in people with chronic kidney disease. That volume signal is predictable and concentrated in the first weeks, so it can be planned for with sodium and diuretic adjustments. The review also discusses pairing endothelin blockade with SGLT2 inhibitors to improve tolerability.

This systematic review and single-arm meta-analysis pooled observational studies of SGLT2 inhibitors in children and young people with heart failure, looking at ventricular function, functional class, and safety. The pooled data pointed toward better ventricular function and functional class after treatment, with no major safety signal in these cohorts. All included studies were small and uncontrolled, so randomized pediatric trials are still needed.

This literature review searched PubMed and Scopus for recent studies on wearable devices in heart disease. Smartwatches and similar devices helped detect complications such as arrhythmias earlier through real-time alerts, and supervised telerehabilitation with wearables performed about as well as in-person cardiac rehabilitation. Comfort, ease of use, and data privacy were the main barriers to wider adoption.

GLP-1 receptor agonists and dual GLP-1/GIP agonists can help transplant candidates reach the body mass index limits used for listing. This review argues that crossing a body mass index cutoff does not by itself mean a patient is ready for surgery, immunosuppression, and rehabilitation. It separates an access response, which is meeting listing criteria, from a reserve response, which is losing weight while keeping muscle, strength, nutrition, and stable tacrolimus levels, and it proposes a matrix and monitoring domains to tell them apart. Current transplant data are mostly observational and rarely report body composition or frailty.

High blood pressure after kidney transplantation is often driven by calcineurin inhibitors, which make it salt-sensitive through the thiazide-sensitive sodium-chloride cotransporter. This opinion piece reviews aldosterone synthase inhibitors such as baxdrostat, lorundrostat, and vicadrostat, which have shown promise outside transplantation but have never been tested in transplant recipients. Reduced nephron reserve, narrow potassium margins, and interactions with immunosuppressants keep them investigational here. Any transplant trial should compare them with optimized thiazide-type therapy and monitor potassium closely.

Itch from chronic kidney disease is common in people on hemodialysis and disrupts sleep and daily life, yet it is rarely tracked in a consistent way. This review gathers the evidence on judging response to difelikefalin and proposes a short, person-centered assessment: a worst-itch rating scale with questions on sleep and daily burden, adding Skindex-10 and 5-D Itch when needed. Suggested reviews around weeks 4 and 12 follow the trial assessment points. The framework is practical but still needs prospective validation.

Tenapanor lowers phosphate in dialysis by blocking NHE3, an intestinal sodium/hydrogen exchanger, so it also cuts how much sodium the gut absorbs. This perspective proposes that diarrhea and small falls in serum sodium may partly reflect that on-target effect. In some patients it could mean less thirst, lower weight gain between sessions, and less ultrafiltration; in others, fluid losses could worsen low blood volume or instability during dialysis. Future studies should measure these volume effects directly with standardized dialysis endpoints.

Trials of hemodialysis catheter lock solutions usually compare formulas as if every lock reached the catheter lumen in the same way. This review argues that tip design, side holes, true luminal volume, fill technique, dwell time, and aspiration also shape how much lock stays where it is needed and how much spills into the bloodstream. It proposes delivered exposure as a framework to explain why infection, patency, and systemic safety results do not always move together. The framework is conceptual and has not been validated at the bedside; its practical message is that future studies should report device and procedure details.

Tolvaptan remains the main disease-modifying drug for autosomal dominant polycystic kidney disease, yet progression varies widely between patients. Experimental and human data suggest that obesity, visceral fat, and altered energy metabolism in cyst cells may speed progression. This review examines whether GLP-1 receptor agonists, including recent semaglutide data in animal models, deserve testing as metabolic add-ons alongside tolvaptan. They are not a treatment for the disease today, and early trials should enrich for patients with high metabolic burden and choose endpoints carefully.

The FDA approval of sparsentan for focal segmental glomerulosclerosis without nephrotic syndrome leaves clinicians to decide which patients should actually receive it. In DUPLEX, sparsentan lowered proteinuria more than irbesartan, but the decline in kidney function over about two years did not differ significantly. This perspective positions it as a non-immunosuppressive option for biopsy-proven disease with persistent proteinuria and no overt nephrotic syndrome, and explains why secondary, genetic, and advanced scarring forms need different reasoning. Its value will depend on choosing patients in whom lowering proteinuria truly matters.

Rituximab can leave residual B cells in lupus nephritis, partly because CD20 is internalized and the drug depends on complement, which is often consumed in active disease. This perspective discusses whether obinutuzumab, a type II anti-CD20 antibody, can reach deeper depletion. Borrowing the idea of minimal residual disease from hematologic oncology, it considers high-sensitivity flow cytometry to measure B cells left in the blood and urinary CD163 to follow inflammation in the kidney. These tools remain investigational and are not validated treatment targets.

Sleep apnea is common in chronic kidney disease and in patients on dialysis. This narrative review asks whether body fluid, including fluid that moves toward the neck when lying down, can change how severe obstructive sleep apnea is at a given time. Small studies, mostly in hemodialysis, link fluid overload with worse apnea, but responses to fluid removal vary and some studies mix obstructive and central events. The idea is plausible in selected patients, yet the evidence does not support changing sleep-study timing or positive airway pressure management.

Chronic hyponatremia is linked to lower bone mineral density, more fragility fractures, falls, and frailty. Cell and animal studies suggest that low sodium can activate bone-resorbing cells and weaken bone formation, which makes a direct effect plausible. Human data are mostly observational and do not yet show that correcting sodium prevents fractures. This review treats chronic hyponatremia as a skeletal risk signal that should prompt assessment of fracture risk, falls, nutrition, and muscle, while it is not yet a treatment target for osteoporosis.

Chronic kidney disease of uncertain cause affects young agricultural workers who often have neither diabetes nor hypertension, and it is now often described as heat stress nephropathy. This review traces how the condition moved from a regional puzzle to a climate and public health concern. It describes a layered model in which repeated heat exposure, dehydration, heavy workload, and recurrent subclinical kidney injury weigh differently from region to region, so the condition should not be treated as a single disease. Water, rest, and shade programs for sugarcane workers, such as the Adelante Initiative, provide the strongest evidence that prevention works.

Cognitive decline in chronic kidney disease is usually explained through separate vascular, uremic, or neurodegenerative pathways. This review proposes a combined kidney-brain framework that adds barrier dysfunction, choroid plexus enlargement, changes in cerebrospinal fluid flow, and glymphatic-related diffusion MRI markers. Lower kidney function also raises blood levels of Alzheimer-related biomarkers such as phosphorylated tau and neurofilament light chain, which can mislead interpretation. Because most human data are cross-sectional, the framework is meant to be tested, and studies should report kidney function and dialysis status alongside imaging and biomarkers.

Drugs that block the vascular endothelial growth factor (VEGF) pathway are central to many cancer treatments but often cause proteinuria, high blood pressure, and changes in kidney function. Most of these effects are expected and manageable, while a minority reflect glomerular injury or thrombotic microangiopathy confined to the kidney, sometimes without the usual blood findings. This review gives oncology teams a practical approach: baseline kidney assessment, serial review of proteinuria and blood pressure, early nephrology input when changes progress, and biopsy when the result would change treatment. The goal is to keep effective cancer therapy while catching serious kidney injury early.