Search Results (1,541)

Background/Objectives: The treatment landscape of relapsed/refractory multiple myeloma (RRMM) has significantly evolved with the introduction of novel classes of agents and, more recently, of T-cell-redirecting therapies, including bispecific antibodies (BsAbs). It is essential to enhance and harmonize the therapeutic management of BsAbs within clinical practice. Methods: We performed a modified Delphi expert consensus study on the use of BsAbs targeting the B-Cell Maturation Antigen (BCMA) in patients with triple-class-exposed (TCE) RRMM. The study was conducted in April–November 2025 following established guidelines and best practices for defining consensus. The key phases in the use of anti-BCMA BsAbs were identified and explored. Results: Fifteen Italian hematologists with expertise in the care of TCE RRMM completed two Delphi rounds. Agreement (defined as ≥67% of panelists) was achieved on most of the topics evaluated. In particular, all panelists considered the step-up dosing phase feasible in an outpatient setting, under specific circumstances, and dosing de-escalation in responding patients to reduce the risk of adverse events. For most of them, anti-BCMA BsAb treatment is also feasible in several challenging subgroups, including frail patients (93% agreement) and those with high-risk cytogenetics (93%), extramedullary disease (93%), end-stage renal disease (86%), active plasma cell leukemia (79%), and central nervous system involvement (67%). In addition, agreement (93%) was reached on the possible sequential use of BCMA-targeting therapies, preferentially BsAbs following CAR-T, though a switch in the target antigen should primarily be considered. Conclusions: In this article, we address the main challenges related to the real-world use of anti-BCMA BsAbs in patients with TCE RRMM, offering expert recommendations to complement existing guidelines and support clinical practice. Full article

Chronic kidney disease (CKD), one of the major global public health burdens, continues to exhibit a rising prevalence worldwide. The growing population of patients with end-stage renal disease (ESRD) has led to an increasing demand for renal replacement therapy (RRT). Although dialysis effectively prolongs survival, it fails to fully replicate kidney function. In addition, the persistent shortage of donor kidneys results in prolonged waiting periods for kidney transplantation. Emerging renal replacement strategies, such as kidney organoids, have demonstrated considerable potential. However, multiple technical limitations continue to hinder their near-term clinical translation. Bioartificial kidneys (BAKs), which integrate engineering and biological technologies, generally consist of artificial filtration membranes and living-cell bioreactors designed to mimic native kidney function. Advances in nanotechnology, biomaterials, and tissue engineering have accelerated the development of implantable bioartificial kidneys (iBAKs), making them an important research direction in renal replacement therapy. These innovations have improved membrane performance, biocompatibility, and cellular integration; however, substantial challenges remain regarding long-term stability, immune compatibility, and clinical validation before translation into human applications. Specifically, limited cell sources and uncertain long-term biocompatibility remain major barriers to iBAK development. In the future, biosensors and artificial intelligence (AI) technologies may be incorporated into bioartificial kidneys to enable personalized precision therapy. This review focuses on the developmental and major challenges of bioartificial kidneys, with detailed discussion of recent progress in implantable artificial kidneys. Full article

Hemodialysis (HD) remains the most widely adopted renal replacement therapy for patients with end-stage kidney disease; however, its delivery entails a substantial environmental burden due to high water and energy consumption and extensive reliance on single-use synthetic polymeric membranes. As the global prevalence of chronic kidney disease increases, the ecological footprint of dialysis systems has become a critical challenge for sustainable healthcare. Conventional HD membranes, based on petroleum-derived polymers, provide controlled permeability but are inherently non-renewable, non-biodegradable, and susceptible to fouling and bio-incompatibility, underscoring the need for alternative, more sustainable materials. Chitosan has emerged as a promising biopolymer owing to its biodegradability, intrinsic antimicrobial activity, chemical versatility, and favorable hemocompatibility. This review presents a comprehensive analysis of chitosan-based hybrid membranes for HD, with emphasis on sustainability-driven material innovation. The structural chemistry and functional properties of chitosan are discussed in relation to molecular weight, degree of deacetylation, and supramolecular organization, followed by a comparative assessment of chitosan derived from crustacean, insect, fungal, and cephalopod sources. Attention is given to fungal chitosan as a naturally deacetylated, high-purity, and reproducible biomaterial aligned with circular bioeconomy principles. Eco-innovative extraction and purification strategies, including enzymatic and low-energy processes, are critically examined alongside membrane fabrication approaches such as polymer blending, electrospinning of hollow fibers, and functionalization strategies aimed at improving hemocompatibility, antimicrobial performance, and fouling resistance. Key challenges related to membrane reuse, scale-up, regulatory compliance, and clinical translation are also addressed. Overall, this review highlights fungal-derived chitosan as a sustainable platform for next-generation HD membranes. Full article

Objective: The prevalence and clinical impact of iron deficiency (ID) in patients with heart failure (HF) in Oman remain insufficiently characterized. This study aimed to evaluate the prevalence of ID and its association with clinical outcomes, as well as to assess the impact of iron supplementation on hospitalization and mortality among HF patients. Methods: A retrospective observational cohort study included adult patients (≥18 years) with HF who had ≥2 iron profiles; patients with end-stage renal disease were excluded. ID was defined using American Heart Association (AHA) and European Society of Cardiology (ESC) criteria. Results: Of 2246 patients screened, 211 met inclusion criteria (57.8% female; mean age 70 ± 12.7 years). ID prevalence was 68.3% (AHA) and 71.1% (ESC), with ESC criteria detecting more biochemical deficiencies. ID was associated with higher all-cause and HF-related readmissions (p < 0.01), longer length of stay (p = 0.045), and more atrial fibrillation (AF) (p < 0.01). All-cause mortality was similar, although the composite of mortality and readmission was slightly higher with ID (p = 0.052). Iron supplementation significantly increased ferritin (+32 ng/mL) and transferrin saturation (+2.8%) (p < 0.01) and was linked to fewer strokes (p = 0.049), with no major differences in other outcomes. Conclusions: The study found that ID was highly prevalent; however, systematic screening was not routinely practiced, which largely led to delayed initiation of appropriate management. Routine ESC-guided ID screening and management are recommended. However, given the retrospective, non-randomized study design, these findings should not be interpreted as evidence of a causal treatment effect and are likely influenced by confounding by indication. Prospective randomized studies are needed to confirm these observations. Full article

Background/Objectives: Sarcopenia is highly prevalent in patients with end-stage renal disease and is associated with adverse outcomes. We evaluated the diagnostic accuracy of rectus femoris ultrasound, compared with bioimpedance spectroscopy (BIS), for identifying sarcopenia defined by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) in haemodialysis patients, and derived overall and sex-specific ultrasound cut-off values. Methods: In this single-centre cross-sectional study, haemodialysis patients were assessed for sarcopenia according to EWGSOP2 criteria. Rectus femoris thickness (RFT) and cross-sectional area (CSA) were measured by ultrasound, while BIS was used to estimate body composition. Receiver operating characteristic (ROC) curves were constructed, and areas under the curve (AUC) with 95% confidence intervals were estimated to assess the ability of ultrasound and BIS-derived parameters to discriminate confirmed sarcopenia. Optimal overall and sex-specific cut-off values were determined using the Youden index. Results: A total of 115 patients were included. Median age was 73.0 years [IQR: 63.0–82.0], 67.0% were men. Sarcopenia was diagnosed in 50 patients (43.5%; 95%CI: 34.3–53.0). RFT and CSA showed moderate diagnostic accuracy for confirmed sarcopenia, with AUCs of 0.73 (95%CI: 0.63–0.82) and 0.72 (95%CI: 0.63–0.81), respectively. Ultrasound cut-offs of 11.9 mm for RFT and 4.4 cm² for CSA yielded high sensitivity and moderate specificity. Conclusions: Rectus femoris ultrasound represents a feasible bedside approach for identifying EWGSOP2-defined sarcopenia in haemodialysis patients. Its diagnostic performance was comparable to that of BIS-derived measures, supporting its potential use in routine clinical practice. Further studies are warranted to validate the proposed cut-off values. Full article

Copper is essential for mitochondrial respiration, antioxidant defense, extracellular matrix maturation, and cellular signaling, yet disturbances in its abundance or intracellular distribution can damage the kidney through mechanistically distinct pathways. Cuproptosis is a specific copper-dependent form of regulated cell death in which copper binds lipoylated mitochondrial proteins, promotes aggregation of tricarboxylic acid cycle components, destabilizes iron–sulfur cluster proteins, and elicits FDX1- and protein lipoylation-dependent proteotoxic stress. This mechanism should be distinguished from broader copper-associated injury, including redox imbalance, glutathione depletion, respiratory-chain inhibition, senescence, apoptosis, and lysyl oxidase-mediated matrix remodeling. This narrative review examines how renal copper uptake, trafficking, and compartmentalization interact with cell-specific metabolism to shape copper-related cell fates across acute kidney injury, nephrotoxicity, renal ischemia–reperfusion injury, crystal- and lipid-related tubular injury, diabetic kidney disease, podocyte injury, chronic kidney disease and renal fibrosis, end-stage renal disease, renal cell carcinoma, and hereditary copper disorders. Mechanistic evidence is strongest in selected acute tubular, crystal-injury, and renal cancer models, in which transporter manipulation, DLAT oligomerization, iron–sulfur perturbation, or functional rescue has been demonstrated. In chronic kidney disease and fibrosis, copper-DLAT interactions, complex IV inhibition, COMMD1-SOD1 dysfunction, and ATP7A-FBLN4-LOX signaling establish pathogenic copper dependence but do not yet demonstrate a complete canonical cuproptosis pathway. By integrating disease-specific evidence with the molecular determinants of copper handling and protein lipoylation, this review identifies current therapeutic opportunities, candidate biomarkers, and key research priorities while preserving the distinction between cuproptosis and other forms of copper-associated kidney injury. Full article

Background/Objectives: Tuberculous constrictive pericarditis (TCP) is characterized by “backward failure” and systemic venous congestion, leading to secondary multi-organ dysfunction. The Model for End-Stage Liver Disease (MELD) 3.0 score assesses liver, renal, and nutritional status, yet its prognostic utility in TCP remains undefined. This study aimed to evaluate the preoperative MELD 3.0 score as a predictor of time to discharge in patients undergoing pericardiectomy for TCP. Methods: We analyzed 190 patients undergoing pericardiectomy for TCP between 2018 and 2024. The association between preoperative MELD 3.0 scores and time to discharge (ICU, postoperative, and total) was assessed using Fine–Gray competing risks regression to account for in-hospital mortality. Models were adjusted for age, albumin, and anti-tuberculosis therapy. Results: Each unit increase in MELD 3.0 was associated with higher operative mortality (OR 1.21, p = 0.013). In multivariable analysis, a high MELD 3.0 score (>median 9.6) was independently associated with a lower probability of discharge (i.e., delayed discharge) for total hospital stay (subdistribution hazard ratio [sHR] 0.606, 95% CI 0.453–0.811), postoperative stay (sHR 0.665), and ICU stay (sHR 0.658). Preoperative albumin was also a strong predictor of faster discharge. Conclusions: The preoperative MELD 3.0 score independently predicts delayed hospital discharge after pericardiectomy for TCP, even when accounting for mortality risk. It serves as a pragmatic tool for quantifying the systemic burden of congestion and stratifying perioperative risk. Full article

Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus and remains a major cause of chronic kidney damage and progression to end-stage renal disease. Although kidney biopsy is considered the diagnostic gold standard, its invasive nature, risk of complications, sampling limitations, and limited suitability for repeated monitoring highlight the need for reliable non-invasive biomarkers. Urinary exosomes have emerged as a promising source of renal molecular information because they are easily accessible and contain stable bioactive molecules, including microRNAs, transfer RNA-derived fragments, messenger RNAs, long non-coding RNAs, and proteins. This review summarizes available evidence on urinary exosomal biomarkers in lupus nephritis, with particular emphasis on their potential utility in diagnosis, assessment of disease activity, monitoring of treatment response, and prognosis. The literature search was conducted in PubMed and Embase using the keywords “lupus nephritis” and “urinary exosomes”. Studies were included if they investigated urinary exosomes in lupus nephritis and evaluated their relevance to disease diagnosis, activity, therapeutic response, histopathological findings, or renal outcomes. Among the analyzed biomarkers, urinary exosomal miR-146a appears to be the most consistently reported diagnostic marker, showing increased expression in active lupus nephritis and the ability to distinguish patients with renal involvement from those without nephritis. Other molecules, including selected miRNAs, tsRNAs, long RNAs, and proteins, have also shown potential clinical relevance, although their validation remains limited. Current evidence suggests that urinary exosomes may provide a non-invasive platform for improving the clinical assessment of lupus nephritis. However, most available studies are limited by small sample sizes, single-center designs, heterogeneous methodologies, and insufficient external validation. Further large-scale prospective studies are required to standardize exosome isolation and biomarker quantification and to determine whether urinary exosomal biomarker panels can complement kidney biopsy in clinical practice. Full article

Background: Simultaneous pancreas–kidney transplantation (SPKT) restores both renal function and endogenous insulin secretion in selected patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease (ESRD). Whether SPKT provides superior patient survival, kidney graft outcomes and cardiovascular benefit compared with kidney transplantation alone (KTA) remains debated, particularly when KTA is performed from a living donor. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed/MEDLINE was searched using a predefined strategy including terms related to pancreas transplantation, kidney transplantation alone, T1DM, and ESRD/chronic kidney disease. Eligible studies included adult T1DM/ESRD populations comparing SPKT with KTA, including living-donor kidney transplantation (LDKT) and deceased-donor kidney transplantation (DDKT) and reporting clinically relevant outcomes. Full texts were reviewed and categorized as core comparative evidence, secondary/supportive evidence or excluded records. A quantitative synthesis was additionally performed for studies reporting directly comparable adjusted hazard ratios for patient mortality and kidney graft failure in the SPKT versus LDKT comparison. Results: Nineteen observational studies met the inclusion criteria and were included in the qualitative synthesis. SPKT consistently provided superior metabolic control and insulin independence when pancreas graft function was maintained. Compared with deceased-donor or mixed KTA cohorts, SPKT was frequently associated with more favorable long-term patient survival and cardiovascular outcomes in selected recipients. However, comparisons with LDKT yielded less consistent results, with several registry-based analyses reporting equivalent or superior kidney graft and survival outcomes after living-donor transplantation. Quantitative synthesis of the two studies providing directly comparable adjusted hazard ratios demonstrated a higher risk of patient mortality (HR 1.30, 95% CI 1.10–1.54) and kidney graft failure (HR 1.43, 95% CI 1.24–1.66) following SPKT compared with LDKT. Formal meta-analysis of SPKT versus DDKT was not feasible because of substantial heterogeneity in outcome definitions, statistical reporting methods and follow-up duration across studies. Conclusions: In adults with T1DM and ESRD, successful SPKT provides a durable metabolic advantage and may improve long-term outcomes compared with deceased-donor KTA in selected patients. Across analyses that included all transplanted recipients from the time of surgery (intent-to-treat), early perioperative risk is higher after SPKT but may be offset over time when pancreas graft function is maintained. Evidence does not support a universal survival superiority of SPKT over living-donor kidney transplantation. Our quantitative synthesis of intent-to-treat, transplant-date analyses indicates that LDKT is associated with lower risks of patient mortality and kidney graft failure compared with SPKT when a suitable living donor is available. Treatment decisions should be individualized, considering living-donor availability, anticipated waiting time and dialysis exposure, cardiovascular and surgical risk, and the likelihood of durable pancreas graft function, with greater weight given to contemporary cohorts. Full article

Background/Objectives: To identify independent predictors of major amputation using adjusted effect estimates. Methods: PubMed, Scopus, Web of Science, and Cochrane Library were searched from inception to 1 March 2024, alongside grey literature. Studies reporting adjusted predictors of major amputation (at or proximal to the wrist or ankle) were eligible. Adjusted odds ratios (aORs) reported by ≥2 studies were pooled using random-effects models. Results: Forty-two studies were pooled. Markers of clinical severity showed the strongest associations: critical limb ischemia (aOR = 4.60, 95% CI 4.20–5.00), leukocytosis (aOR = 3.42, 1.72–5.13), end-stage renal disease (aOR = 3.19, 2.94–3.44), and Rutherford class ≥ IIb (aOR = 3.16, 1.87–4.45). Moderate associations included chronic kidney disease (aOR = 2.22, 1.68–2.76), current smoking (aOR = 2.21, 2.13–2.28), and several comorbidities (prior bypass surgery, chronic obstructive pulmonary disease, peripheral vascular disease; aORs 1.82–1.92). Sociodemographic factors and diabetes mellitus showed smaller but consistent effects (aORs 1.19–1.64). Lower serum albumin (aOR = 0.58, 0.45–0.70) and statin use (aOR = 0.71, 0.66–0.75) reduced odds. Hemoglobin, modelled per unit increase rather than dichotomised, was unexpectedly associated with increased odds (aOR = 1.59, 1.55–1.63), most plausibly reflecting residual confounding. Heterogeneity was substantial for most predictors (I² frequently > 80%). Conclusions: To our knowledge, this is the first meta-analysis of major amputation restricted to adjusted estimates across diverse populations and both amputation levels. Ischemic burden and systemic disease severity dominate the risk profile, whereas diabetic foot ulcer, wound depth, wound infection, coronary artery disease, and neuropathy did not retain independent significance after adjustment. Given the observational evidence base and substantial heterogeneity, these findings should inform risk stratification rather than causal inference. Full article

Background: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease worldwide. Despite robust evidence-based guidelines, real-world adherence to recommended preventive care remains inadequate. Most prior evaluations have focused on individual care components rather than comprehensive composite care delivery. Methods: A retrospective cross-sectional study of 1010 adult patients with diabetes attending outpatient clinics at King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Jeddah, Saudi Arabia. Full guideline-concordant care (GCC) was defined as composite completion of HbA1c monitoring, albuminuria screening using the urine albumin-to-creatinine ratio (ACR), and renin–angiotensin–aldosterone system inhibitor (RAASi) use among patients with detected albuminuria. Multivariable logistic regression (n = 1007) identified independent predictors of full GCC. Results: Only 22.7% (95% CI: 20.1–25.3%) of patients achieved full GCC. Partial care was the most common pattern (46.2%), followed by no care (20.7%) and near-complete care (10.4%). HbA1c testing was performed in 55.0% and albuminuria screening in 49.3% of patients. Among those with detected albuminuria, RAASi therapy was prescribed in 78.9%. Primary care management (OR 4.79, 95% CI 3.45–6.66; p < 0.001) and hypertension (OR 2.00, 95% CI 1.33–3.00; p = 0.001) were independently associated with full GCC. Age, gender, kidney function, and cardiac disease were not significant predictors. Conclusions: Substantial gaps exist in guideline-recommended DKD care, driven primarily by screening deficiencies rather than treatment failures. Care delivery is influenced more by healthcare setting than by patient characteristics, highlighting the need for system-level interventions targeting detection infrastructure across all care settings. Full article

Background and Objectives: Hyperphosphatemia is a key component of chronic kidney disease-mineral and bone disorder and is associated with higher rates of cardiovascular events and mortality in patients undergoing dialysis. Phosphate binders are essential for phosphorus reduction, and their evaluation relies on several factors, such as chemical composition, binding capacity, and safety profile. Unfortunately, long-term management is hindered by high pill burden and poor adherence. Magnesium phosphate binders have proven effectiveness in reducing phosphate levels. Nevertheless, despite their efficacy, they are not widely used in clinical settings because of concerns related to their use. This study assessed the efficacy of low-dose magnesium carbonate as a phosphate binder in patients undergoing chronic dialysis, focusing on its biochemical control, tolerability, and cost-effectiveness. Materials and Methods: A prospective observational study was conducted on 54 hemodialysis patients with end-stage renal disease at a single dialysis center. Patients were taking either 250 mg magnesium carbonate or 2400 mg sevelamer carbonate for 3 months. Results: Both groups showed decreased phosphorus levels, with a 14.2% significant reduction in the magnesium carbonate group (p < 0.001) and a 5.1% reduction in the sevelamer carbonate group. At the end of the study, no significant differences were observed between the groups (p = 0.682). In the magnesium carbonate group at month 3, compared to baseline, no significant differences were detected in other laboratory parameters reflecting calcium–phosphorus metabolism (Ca—p = 0.681, PTH—p = 0.126). Simultaneously, good compliance without clinically relevant gastrointestinal side effects was observed, including the absence of clinically significant hypermagnesemia. Conclusions: The phosphorus-lowering potential of low-dose magnesium carbonate is non-inferior to that of low-dose sevelamer carbonate. However, its favorable safety profile, low incidence of adverse effects, and cost-effectiveness make it a promising option in clinical practice, further highlighting the need for better recognition by physicians. Full article

Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus, and a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. It is characterized by proteinuria, mesangial expansion, glomerulosclerosis and progressive loss of renal function. Current therapeutic strategies of DN, including renin–angiotensin–aldosterone system (RAAS) blockade, glucagon-like peptide-1 receptor agonists, non-steroidal mineralocorticoid receptor, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, only slow the progression of the disease rather than reversing the pathology. Therefore, there is a growing interest in identifying alternative or complementary therapeutic agents, particularly those derived from natural products with multi-targeted activities. Psoralea corylifolia Linn (PCL) is a medicinal herb commonly used in traditional Asian medicine. It has known pharmacological properties on oxidative stress, inflammation, fibrosis and metabolic disorders. Accumulating recent studies indicated that PCL and its bioactive compounds, such as psoralen, bakuchiol, and corylin, mitigate pathological conditions in various diseases. Here, the current review will provide our current knowledge of major identified and characterized PCL focusing on their biological activity and function, particularly in DN. Full article

Background and Clinical Significance: Gallstone ileus (GI) is a rare but serious complication of gallstone disease. This condition is characterized by migration of gallstones through a cholecystoenteric fistula, resulting in mechanical bowel obstruction. GI primarily affects older patients with multiple comorbidities. Case Presentation: Herein, we describe a case of 68-year-old Saudi woman with a history of end-stage renal disease, pulmonary hypertension, diabetes mellitus, bronchial asthma, and atrial fibrillation. She presented with acute calculous cholecystitis. Due to her condition, she was managed conservatively initially. The patient was recommended laparoscopic cholecystectomy but she declined due to fear of anesthesia-related complications. She re-presented after two months with abdominal pain, vomiting, distension, and constipation. Computed tomography (CT) scan showed a 3.2 cm ectopic gallstone impacted in the distal ileum with proximal bowel dilatation and segmental ischemia, confirming GI. Laparotomy showed bowel ischemia and localized perforation. The patient was managed with enterolithotomy, resection of 25 cm of distal ileum, and primary anastomosis. Post-surgery, the patient had favorable recovery. Conclusions: This case highlights need for early diagnosis and appropriate management of GI in patients with multiple comorbidities. Full article

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Early diagnosis is therefore critical for improving patient outcomes.However, traditional clinical biomarkers are constrained by diagnostic latency and limited sensitivity, particularly in cases of non-albuminuric DKD. To address these limitations, this review systematically explores the technical framework of the pathology-anchored strategy and proposes a two-phase translational approach, consisting of Pathology Anchoring Discovery and Prospective Early Validation. This strategy employs renal biopsy as the pathological gold standard in conjunction with multi-omics technologies to correlate circulating or urinary molecules with specific renal histological lesions, ultimately identifying non-invasive biomarkers with definitive pathological relevance. While numerous biomarkers demonstrate early warning potential in high-risk populations with normal conventional indicators, the pathology-anchored framework serves as a critical bridge linking these clinical biomarkers and distinct pathological changes. This review presents potential insights for early identification, risk stratification, and prognostic assessment of DKD. Full article