The scarcity of donor kidneys often turns anatomically variant grafts into an allocation problem, and kidneys with duplicated ureters may be declined in some centers because of concerns about ischemic vulnerability and subsequent urological complications. This systematic review and meta-analysis aimed to estimate pooled rates of urological complications in such grafts to inform acceptance and operative planning. Scopus, PubMed, Europe PMC, Epistemonikos, and Web of Science were searched through to 6 June 2026. Eligible case series and cohort studies included at least five patients, and reported urological outcomes after kidney transplantation using donor kidneys with duplicated or multiple ureters. Pooled proportions were estimated using a generalized linear mixed model with binomial likelihood, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. A total of 11 retrospective studies comprising 226 transplant recipients were included. The pooled proportion of overall structural urological complications was 5.35
Abstract The annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) was conducted with 4529 dialysis facilities at the end of 2023, of which 4470 facilities (98.7%) responded to the facility survey and 4284 facilities (94.6%) responded to the patient survey. The increase in the number of patients on dialysis in Japan has slowed in recent years. The number of patients on dialysis at the end of 2023 was 343,508, which less than the previous year. The prevalence of patients on dialysis was 2762.4 per million population. The prevalent patients on dialysis in the patient survey had a mean age of 70.09 years. Among these patients, diabetic nephropathy was the most common primary disease (39.5%), followed by chronic glomerulonephritis (23.4%) and nephrosclerosis (14.0%). The number of incident patients on dialysis during 2023 was 38,764, which decreased by 919 from 2022. Among incident patients on dialysis, the mean age was 71.59 years, and diabetic nephropathy (38.3%) was the most common cause of end-stage kidney disease. The second most common cause was nephrosclerosis (19.3%), which surpassed chronic glomerulonephritis in 2019 and has continued to increase. The crude annual mortality rate was 11.0%, with 38,073 patients dying during 2023; this rate was the same as last year’s. The three major causes of death were infectious disease (22.7%), which surpassed heart failure in 2022, heart failure (20.4%), and malignancy (7.6%). The number of patients treated by hemodiafiltration (HDF) has been rising since 2012, reaching 203,113 by the end of 2023 and accounting for 59.1% of all patients on dialysis. The number of peritoneal dialysis (PD) patients was 10,585 in 2023, which has slightly increased since 2017. Combination or hybrid therapy with hemodialysis (HD) or HDF was given to 21.0% of patients on PD. Home HD therapy was conducted in 799 patients as of the end of 2023; it decreased by 28 from 2022. In 2023, the use of ultrasound in vascular access management and the disinfection status of probe heads were investigated in the facility survey for the first time. In addition, exercise therapy, nutritional guidance, and activities of daily living levels, as well as the occurrence of the following events in 2023 were investigated at the patient survey: malignancies, deep vein thrombosis, pulmonary embolism, vascular access occlusion, and fundal hemorrhage. Hospitalization status and reasons for hospitalization were also surveyed for each patient in 2023. Clinical data about COVID-19 was also investigated in 2023 as 2022. Results obtained for each condition provide a framework to develop more clinically effective practice patterns for these conditions. Trial registration The Japanese Society for Dialysis Therapy (JSDT) Renal Data Registry (JRDR) was approved by the Japanese Society for Dialysis Therapy ethics committee. It was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry on 10 September 2020 and in the UMIN clinical trials registration system (UMIN000018641).
Abstract Background The (pro)renin receptor [(P)RR] is a multifunctional protein, and its soluble form [s(P)RR], generated by proteolytic cleavage, has been proposed as a biomarker reflecting tissue renin–angiotensin system activity. Patients on maintenance hemodialysis (HD) have a high burden of cardiovascular disease driven by accelerated atherosclerosis. Serum s(P)RR levels are associated with atherosclerosis progression independently of conventional risk factors, suggesting its potential as a novel cardiovascular biomarker in this population. Herein, we investigated the association between s(P)RR and lower limb amputation in patients undergoing HD. Methods Serum s(P)RR levels were measured before and after amputation in 11 patients. (P)RR immunostaining was performed on amputated tissues to assess the local expression. Furthermore, serum s(P)RR levels were compared between 27 patients on HD who underwent lower limb amputation (amputation group) and 250 patients on HD without a history of amputation (control group). Results Although elevated s(P)RR levels were observed in patients on HD who underwent lower limb amputation, no evident (P)RR expression was detected in the amputated tissues, and serum s(P)RR levels showed no significant changes before and after amputation. Moreover, the association between serum s(P)RR levels and limb amputation remained significant after adjusting for atherosclerotic progression factors other than C-reactive protein (CRP) but disappeared when adjusted for CRP. Conclusions These findings suggest that chronic inflammation plays a role in the relationship between lower limb amputation and elevated serum s(P)RR levels.
Abstract Background Septic acute kidney injury (AKI) is a life-threatening complication with high morbidity and mortality. Despite decades of research, therapeutic options remain limited to supportive care, underscoring the urgent need to decipher the molecular drivers that govern septic AKI. Methods We used a murine LPS-induced septic AKI model and cultured BUMPT cells. miR-378c expression was assessed by qPCR and fluorescence in situ hybridization. Gain- and loss-of-function studies were performed using miR-378c mimics or locked nucleic acid (LNA) inhibitors in vivo and immune-responsive gene 1 (IRG1) overexpression in vitro. Molecular mechanisms were investigated via chromatin immunoprecipitation (ChIP), luciferase reporter assays, western blotting, and immunofluorescence. Results miR-378c was significantly upregulated in renal proximal tubules after LPS challenge. NF-κB p65 directly bound to the miR-378c host gene promoter and drove its transcription, confirmed by ChIP and NF-κB inhibition with TPCA-1. Overexpression of miR-378c exacerbated kidney dysfunction, tubular apoptosis, and inflammation, while its inhibition conferred protection. IRG1, encoding the immunomodulatory enzyme that produces itaconate, was identified as a direct target of miR-378c. miR-378c suppressed IRG1 expression, and IRG1 overexpression alone reduced LPS-induced apoptosis and proinflammatory cytokine production (IL-1β, IL-6, TNF-α). Conclusions We define a maladaptive NF-κB/miR-378c/IRG1 axis in septic AKI, where inflammation-induced miR-378c silences a key metabolic protector in tubular cells. Targeting this pathway represents a promising therapeutic strategy to preserve renal function during sepsis.
Abstract Background Renal dysfunction is a common complication in patients supported with left ventricular assist devices (LVADs), and a subset requires long-term renal replacement therapy (RRT). The coexistence of right heart failure (RHF), venous congestion, and hemodynamic instability complicates dialysis management. However, evidence guiding dialysis modality and vascular access selection in this population remains limited, leaving key clinical decisions unsupported. Methods We conducted a scoping review in accordance with the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. PubMed, Scopus, and the Cochrane Library were searched for studies published between January 2015 and October 2025. We included studies involving adult LVAD recipients requiring maintenance dialysis after LVAD implantation, focusing on dialysis modality, vascular access, clinical outcomes, and RHF. Two reviewers independently screened studies and extracted data. A structured descriptive analysis was performed across predefined domains. Results A total of 31 studies were included, comprising 17 cohort studies, 8 case reports or case series (20 patients), and 6 narrative reviews. All reported LVADs were continuous-flow devices. Hemodialysis was the predominant modality, whereas peritoneal dialysis was suggested as a potential alternative in patients with hemodynamic instability or RHF. Cohort studies rarely reported dialysis modality or vascular access in detail, and no comparative analyses were identified. Vascular access strategies and the impact of RHF on dialysis outcomes were also insufficiently evaluated. Most studies originated from the USA, indicating limited geographic diversity. Conclusions Current evidence does not adequately support clinical decision-making regarding dialysis modality or vascular access in LVAD-supported patients. Despite increasing clinical complexity, key determinants, such as RHF, are not systematically evaluated. Prospective and comparative studies are urgently needed to establish evidence-based dialysis strategies in this population.
Abstract Background In critically ill adults with acute kidney injury (AKI) and no urgent indications, the optimal timing of kidney replacement therapy (KRT) initiation remains unresolved. Systematic reviews have reached conflicting conclusions, and no trial has prospectively validated a structured deferred strategy. We conducted an umbrella review to map the totality of evidence and appraise the certainty of findings on this question. Methods We searched PubMed, Scopus, Web of Science, and the Cochrane Library (2014 to 1 April 2025) for systematic reviews and meta-analyses (SR/MAs) of randomized controlled trials comparing early versus delayed KRT in ICU adults with AKI. Two reviewers independently performed selection, extraction, AMSTAR 2 quality assessment, and GRADE certainty ratings. Primary study overlap was quantified using the Corrected Covered Area (CCA). Findings were synthesized narratively given the high overlap. The protocol was registered on PROSPERO (CRD42024558822). Results A total of 25 SR/MAs were included. The CCA was 49.75% (very high overlap). AMSTAR 2 quality was high in 2, low in 9, and critically low in 14 reviews. Early KRT was not associated with reduced mortality in any included review. The two reviews rated high on AMSTAR 2 reported risk ratios close to unity: Fayad et al. (Cochrane; RR 0.97, 95% CI 0.87–1.09) and Li et al. (RR 1.00, 95% CI 0.95–1.04). Certainty of evidence was predominantly low or very low. ICU length of stay was modestly reduced in three reviews (MD − 0.69 to −3.24 days); other secondary outcomes were inconsistent. Early KRT consistently increased procedure-related harm: hypotension (6/7 reviews), catheter-related infection (5/6), and hypophosphatemia (5/6). Conclusions Across 25 SR/Mas, early KRT is not associated with a survival benefit and consistently increases procedure-related adverse events in critically ill adults with AKI. The current practice of deferring KRT is supported only by the failure to demonstrate benefit from early initiation, not by prospective evidence of its own safety: neither strategy has been prospectively validated. The marked heterogeneity in how “early” and “delayed” were defined further indicates that a binary timing paradigm inadequately captures the complexity of AKI, and that future research should move toward more individualized initiation strategies.
Abstract Background Static creatinine thresholds after percutaneous coronary intervention may miss early renal dynamics. We examined whether serum creatinine trajectory phenotypes during the first 72 h after intensive care unit admission were associated with mortality and renal outcomes in PCI-treated acute myocardial infarction. Methods We performed a retrospective cohort study using MIMIC-IV version 3.1. Adults with acute myocardial infarction who underwent percutaneous coronary intervention, had an intensive care unit admission, were not receiving chronic dialysis, and had at least two creatinine measurements in the first 72 h were included. Because a precise PCI timestamp was unavailable, trajectories were anchored to intensive care unit admission. Interpolated creatinine fold-change trajectories were clustered with Gaussian mixture models. The primary outcome was 1-year mortality after a 72-h landmark. Secondary outcomes were 28-day mortality, post-landmark renal replacement therapy, and renal nonrecovery. Cox models compared trajectory phenotype with KDIGO stage and a clinically adjusted model. Results After exclusion of 51 patients with apparent death before completion of the 72-h landmark window, the landmark analytic cohort included 1324 patients. Five phenotypes were analyzed: Stable/Recovery ( n = 382), Mild Rise ( n = 433), Moderate Rise ( n = 296), Severe Progressive ( n = 209), and Rapid Progressive ( n = 4). One-year mortality was 13.9%, 6.7%, 12.8%, 32.1%, and 25.0%, respectively. Renal nonrecovery was 8.6%, 3.7%, 8.1%, 33.5%, and 75.0%, and post-landmark renal replacement therapy occurred only in Severe Progressive and Rapid Progressive. Severe Progressive remained associated with higher 1-year mortality than Stable/Recovery after clinical adjustment (hazard ratio 1.56, 95% confidence interval 1.04–2.34) and after additional inclusion of KDIGO stage (hazard ratio 1.54, 95% confidence interval 1.01–2.33). In expanded sensitivity models incorporating measurement frequency, net fluid balance, AMI severity variables, mechanical circulatory support, and LVEF, the Severe/Rapid signal was attenuated, supporting cautious interpretation as exploratory risk enrichment rather than independence from KDIGO staging. Conclusions Early creatinine trajectory phenotypes after ICU admission identified progressive renal-response patterns with concentrated adverse renal events. Their present role is exploratory prognostic enrichment, with substantial overlap with AKI severity, illness severity, cardiac dysfunction, and measurement intensity, pending external validation.
Serum ferritin guides iron therapy in hemodialysis patients but also reflects inflammation and systemic illness. We examined the association between baseline serum ferritin and infection-related mortality in maintenance hemodialysis patients. We analyzed 3529 participants in the Japanese Q-Cohort Study. The primary analysis categorized serum ferritin into quartiles. Clinically motivated supplementary analyses used clinical categories, a 300 ng/mL cutoff, and log-transformed ferritin. Infection-related mortality was evaluated using cumulative incidence functions, cause-specific Cox models, Fine–Gray competing-risk models, restricted cubic splines, and sensitivity analyses including C-reactive protein adjustment, adjustment for baseline vitamin D receptor activator use, 3-year restricted follow-up, and a 180-day landmark analysis. During a median follow-up of 3199 days, 1748 deaths occurred, including 451 infection-related deaths. In the primary quartile analysis, Q4 was associated with infection-related mortality in unadjusted and age- and sex-adjusted Cox models, but the association was attenuated after multivariable adjustment (model 3: HR 1.32, 95
Acquired hemophilia A (AHA) is a rare and fatal bleeding disorder. AHA in patients undergoing hemodialysis (HD) often leads to impaired hemostasis, necessitating temporary catheters that increase the risk of catheter-related infection. This complication hinders the use of immunosuppressive therapy, often resulting in treatment failure. We herein report the case of AHA in a patient undergoing HD with life-threatening bleeding and MRSA bacteremia, which was successfully managed with a multimodal approach. A 64-year-old Japanese man had undergone HD owing to diabetic nephropathy and was admitted to our hospital with a massive hematoma in the left iliopsoas muscle and poor hemostasis at the vascular access site. Hemoglobin (Hb) had dropped to 5.0 g/dL despite daily blood transfusions, and activated partial thromboplastin time was alone prolonged around 60.0 s. Transcatheter arterial embolization (TAE) was performed owing to difficulty in hemostasis. After the diagnosis of AHA was made, 60 mg/day of prednisolone and bypassing agents were introduced. Additional plasma exchange (PE) was performed and rituximab was also administered. Factor VIII (FVIII) inhibitor decreased from 91.0 to 32.0 Bethesda Units (B.U)/mL, and hemostasis was achieved temporarily. Despite a decreasing trend, the FVIII inhibitor titer persisted at a high range. Hb decreased to 5.7 g/dL, and blood transfusions were needed again. Thus, a second TAE and a third PE were performed. After that, FVIII inhibitor improved to 7.0 B.U/mL, and hemostasis was fully achieved. Notably, a temporary dialysis catheter led to methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, necessitating careful PSL tapering. At 6 months after discharge, the patient had not experienced any relapse. AHA in patients undergoing HD often leads to difficulty in hemostasis during HD, necessitating temporary catheters that almost induce catheter-related infection. This complication hinders the use of immunosuppressive therapy, sometimes resulting in treatment failure. Given the specific clinical setting of AHA in patients undergoing HD, achieving rapid bleeding control and preparing for impending infections are paramount, which necessitates a well-designed multimodal approach including immunosuppressive therapy and PP (plasmapheresis). This instructive case offers a potential framework for managing similar high-risk patients.
Therapeutic plasma exchange (TPE) is an established treatment for neuromyelitis optica spectrum disorders (NMOSD) that removes pathogenic aquaporin-4 antibodies (AQP4-IgG). We present the case of a 15-year-old boy with AQP4-IgG–positive NMOSD who underwent six TPE sessions. Quantitative analysis revealed mean removal rates of 84
Abstract Inhibitors of the sodium-glucose cotransporter-2 (SGLT2i) were initially created for managing diabetes mellitus but have suggested significant renoprotective advantages regardless of blood glucose levels. SGLT2-inhibitors have thus emerged as a crucial component in the therapeutic arsenal for managing patients with chronic kidney disease. This narrative review summarizes current mechanistic, preclinical and clinical evidence regarding SGLT2i in ADPKD. Nevertheless, certain patient groups were omitted from the key trials, such as individuals with extremely low estimated glomerular filtration rate (eGFR), those undergoing dialysis, kidney transplant patients, and individuals with autosomal dominant polycystic kidney disease (ADPKD), the most prevalent genetic kidney condition. Given the scarcity of effective treatment options in ADPKD, the application of SGLT2i in this group of patients would be significantly noteworthy. Nonetheless, the blend of inconclusive findings from preclinical models, along with the absence of clinical efficacy data and possible safety issues specific to the disease, presently prevents patients with ADPKD from benefiting from this promising therapeutic option. This creates an immediate demand for properly conducted clinical trials investigating SGLT2i in ADPKD. This narrative review encapsulates the existing understanding of SGLT2i in this particular patient group and highlights ongoing and future clinical trial initiatives across various geographic locations designed to provide SGLT2i to patients with ADPKD.
Oxidative stress is a major contributor to morbidity in patients with end-stage kidney disease. The antioxidant properties of vitamin E-coated hemodialyzers have attracted increasing attention. However, the intrinsic antioxidant capacity of dialysis-related substances themselves remains unclear despite their potential relevance to redox balance during hemodialysis. In this study, we aimed to clarify the antioxidant behavior of several clinically relevant compounds, including uric acid, ascorbic acid, glutathione, glycerin, and recombinant human albumin, by evaluating their ability to suppress chemiluminescence generated by Fenton’s reagent (FeSO4 and H2O2) in aqueous media. To assess the influence of hemoglobin, each antioxidant was dissolved in distilled water or a 3 μM human hemoglobin solution. Additionally, recombinant human albumin was tested in the presence of 1, 2, and 30 μM hemoglobin. A 50 μL sample was mixed with 100 μL of Fenton’s reagent, and luminescence intensity was quantified using a luminometer. The concentrations of FeSO4 and H2O2 were 1 and 10 mM, respectively. The half-maximum inhibitory concentration (IC50) and its negative logarithm (pIC50) were calculated from sigmoidal dose–response curves, and relative activities were compared with those of glycerin, a known hydroxyl radical scavenger. In distilled water, glutathione, ascorbic acid, and uric acid exhibited approximately 100‑, 1000‑, and 20,000‑fold higher antioxidant activities, respectively, than glycerin. Although uric acid substantially suppressed chemiluminescence in distilled water, it showed no antioxidant effect in hemoglobin-containing solution. In contrast, recombinant human albumin increased luminescence intensity when tested alone but markedly suppressed luminescence in the presence of hemoglobin. Based on pIC50 values, antioxidant capacity in distilled water decreased in the order uric acid > ascorbic acid > glutathione > glycerin. Albumin showed clear antioxidant activity under hemoglobin-containing conditions, most likely attributable to its heme-binding ability. Uric acid, ascorbic acid, and glutathione exhibited strong antioxidant activity against Fenton’s reagent in aqueous systems, with uric acid showing the highest potency. Furthermore, recombinant human albumin showed antioxidant activity, most likely through heme sequestration. These findings provide mechanistic insights into the strongly context-dependent antioxidant behavior of dialysis-related solutes. Further validation in ex vivo and clinical studies is required.
Super high-flux (SHF) dialyzers enhance the clearance of middle-molecule solutes, but their long-term use is often limited by cost and availability. This study evaluated the effects of combined SHF and medium-flux (MF) dialyzers on middle-molecule levels and sleep quality in patients undergoing maintenance hemodialysis (MHD). A prospective longitudinal cohort study was conducted in 60 MHD patients (30 combined SHF–MF and 30 MF alone). The combined SHF–MF group received six SHF (Elisio HX19, Nipro, Japan) and six MF (Elisio 17 M, Nipro, Japan) sessions monthly, whereas the MF-alone group received 12 MF sessions. Predialysis hematological parameters and middle-molecule concentrations were measured quarterly, while sleep quality and pruritus were evaluated at baseline and at study completion using the Pittsburgh Sleep Quality Index (PSQI) and the 5-D Itch Scale. Multivariate linear mixed-effects models were applied to examine longitudinal changes and between-group differences across time points. The overall mean age was 55.0 ± 15.2 years, and 60
Elevated serum concentrations of fibroblast growth factor 23 (FGF-23) are commonly observed in patients with chronic kidney disease on dialysis and appear to be associated with leptin levels and adipose tissue in this population. Therefore, this study aims to explore the association of FGF-23 with body adiposity and leptin in patients undergoing peritoneal dialysis. This cross-sectional study included adult patients on peritoneal dialysis for at least 3 months. Adiposity was assessed by waist circumference and dual-energy X-ray absorptiometry. The adiposity parameters considered were total fat mass, trunk fat mass, body fat percentage, and waist circumference. A total of 50 patients on peritoneal dialysis were included, mean age 55.7 ± 16.2 years, 52
Identifying patients at risk of peritoneal dialysis (PD) discontinuation is important for maintaining long-term PD therapy. However, the risk factors for PD discontinuation remain unclear. We aimed to identify clinical risk factors associated with PD discontinuation, with particular attention to clinical events occurring during the course of PD therapy, in a single-center cohort in Japan. We retrospectively analyzed 65 adult patients who underwent PD between September 2013 and December 2022. Clinical and laboratory data were collected from electronic medical records. The primary endpoint was PD discontinuation, defined as transition to hemodialysis for ≥ 30 days, kidney transplantation, or death from any cause. The risk factors associated with PD discontinuation were evaluated using the Cox proportional hazards model. The median patient age was 64 years (interquartile range [IQR] 53–73 years). During a median follow-up of 41 months (IQR 27–55 months), 46 patients (71
Acquired hemophilia A (AHA) is a rare hemorrhagic disorder caused by autoantibodies against coagulation factor VIII (FVIII). AHA during hemodialysis (HD) initiation is uncommon, but dialysis catheterization and intradialytic anticoagulation may increase bleeding risk. Ocular bleeding is also an uncommon, potentially vision-threatening manifestation. We report a case of AHA unmasked by acute vitreous hemorrhage with marked intraocular pressure elevation during HD initiation. A 61-year-old male with hypertension, diabetes mellitus, and proliferative diabetic retinopathy who had discontinued medical follow-up was transferred to our hospital with ocular pain, visual loss, severe hypertension, and renal failure. Ophthalmologic evaluation showed no light perception in the right eye, markedly elevated intraocular pressure to 78 mmHg, and a flat anterior chamber, findings consistent with vitreous hemorrhage and secondary ocular hypertension in the setting of proliferative diabetic retinopathy and impaired hemostasis. Antihypertensive treatment was initiated, and a temporary dialysis catheter was placed for emergency renal replacement therapy. On day 2, isolated prolongation of activated partial thromboplastin time (APTT) and persistent bleeding from the catheter insertion site were observed. Detailed investigations revealed markedly reduced FVIII activity and the presence of an FVIII inhibitor. APTT cross-mixing tests demonstrated a time-dependent inhibitor pattern, leading to the diagnosis of AHA. HD was initially performed without anticoagulants under bypassing hemostatic therapy. Prednisolone (PSL) was started on day 5, a tunneled cuffed catheter was placed on day 19, and reduced-dose oral cyclophosphamide (CPA) was added on day 28. Subsequently, the bleeding tendency improved, APTT normalized, and the FVIII inhibitor titer decreased. The patient continued maintenance HD while immunosuppression was tapered and was discharged on day 210. This case highlights acute vitreous hemorrhage with marked intraocular pressure elevation as an unusual initial clue to AHA during HD initiation. When ocular hemorrhage is accompanied by unexplained isolated APTT prolongation or persistent catheter-site bleeding, AHA should be promptly considered, even in patients with diabetic retinopathy or uremic bleeding risk. Safe management requires early hemostatic treatment, immunosuppression, and individualized coordination of ophthalmologic care, vascular access, and dialysis anticoagulation.
Abstract Background Whether asymptomatic hyperuricemia should trigger pharmacologic intervention in maintenance hemodialysis remains unresolved. This question differs fundamentally from hyperuricemia management in the general population or in nondialysis chronic kidney disease because hemodialysis itself substantially alters urate kinetics, lowers serum urate during each session, and may contract the effective urate burden. In routine dialysis practice, predialysis serum urate values are frequently available and may prompt therapeutic uncertainty even when gout symptoms are absent. We reviewed the recent literature to clarify whether serum urate alone should prompt urate-lowering therapy in hemodialysis patients and to identify which patients may require individualized reassessment because of persistent gout burden. Main body Current evidence does not support a dialysis-specific serum urate threshold that justifies routine pharmacologic treatment of asymptomatic hyperuricemia. Hemodialysis markedly reduces circulating urate, and emerging work suggests that urate burden in hemodialysis may be better interpreted in the context of urate pool and extra-renal urate handling rather than serum urate concentration alone. In parallel, observational studies in hemodialysis have repeatedly shown that lower as well as higher serum urate levels are associated with worse survival, with low urate often linked to malnutrition, frailty, and inflammatory burden. These observations do not prove that low urate itself is harmful, but they caution against assuming that pharmacologic urate lowering is automatically beneficial in patients undergoing hemodialysis. Although cohort studies suggest possible associations between xanthine oxidoreductase inhibitor use and improved mortality or cardiovascular outcomes, these findings remain observational and do not establish a causal benefit in asymptomatic patients. Furthermore, urate-lowering therapy is not harmless: treatment initiation can precipitate gout flares, and flare prophylaxis is particularly challenging in dialysis because colchicine requires conservative use and close toxicity monitoring in severe kidney failure, particularly in the setting of interacting drugs. Drug-specific risks also remain relevant for allopurinol and febuxostat. Conclusions In maintenance hemodialysis, asymptomatic hyperuricemia should not automatically trigger pharmacologic intervention. In the absence of persistent gout burden, a cautious approach is more appropriate than routine serum urate-driven treatment. Treatment decisions should therefore be guided by persistent gout burden rather than by serum urate elevation alone.
Abstract Background Legionella pneumophila is a gram-negative intracellular bacteria that causes pneumonia. In severe cases, combination antimicrobial therapy using azithromycin and ciprofloxacin is recommended and critical care management may be required. Ciprofloxacin requires dose adjustment during kidney replacement therapy; however, dosing guidance during prolonged intermittent kidney replacement therapy (PIKRT) is limited. A population pharmacokinetic (PK) study based on in vitro data suggested high doses would be required to meet pharmacokinetic/pharmacodynamic (PK/PD) targets. Case presentation We describe the PK of intravenous ciprofloxacin in a 71-year-old male with L. pneumophila pneumonia requiring PIKRT. Ciprofloxacin was administered at 400 mg IV every 12 h, in addition to azithromycin. Ciprofloxacin PK modelling described a terminal half-life of 10.7 h and an area under the curve over 24 h (AUC 0-24 ) of 130 mg·h/L. While PK/PD targets specific to L. pneumophila are not established, applying the reported median minimum inhibitory concentration (MIC) for Legionella (0.5 mg/L), and the gram-negative organism PK/PD target AUC 1–24 /MIC > 125, our data supports ciprofloxacin dosing of 400 mg IV every 12 h during PIKRT. Contrary to the prior PK study based on in vitro data, PIKRT did not contribute additional clearance of ciprofloxacin. Conclusions Ciprofloxacin 400 mg IV every 12 h achieved adequate exposure during PIKRT, supporting this dosing regimen for treating L. pneumophila pneumonia. Further studies are needed to establish definitive dosing guidelines in this setting.
Abstract Background Sepsis is defined as a condition in which the host’s response to infection becomes uncontrollable, leading to life-threatening organ damage. It is associated with the cytokine storm phenomenon, caused by excessive cytokine production. Blood purification therapy, which aims to remove cytokines, has attracted attention as a treatment for this problem. We evaluated a new hemoadsorption cartridge, “PF-Large,” fabricated from polymethylmethacrylate fibers, which are known for their cytokine adsorption properties. Methods Using a porcine model of hypercytokinemia induced by lipopolysaccharide infusion, we compared the cytokine adsorption performance of PF-Large with that of the commercially available CytoSorb®. Results PF-Large had a similar cytokine adsorption capacity to CytoSorb®, with particularly high adsorption rates for interleukin (IL)-8 and IL-10, suppressing the peak of cytokine concentrations in vivo. Furthermore, PF-Large maintained higher total protein and albumin concentrations in the blood versus CytoSorb®. PF-Large was also associated with higher blood pH, better acid–base balance, and lower lactate levels during the latter phase of the experiment, suggesting the potential to suppress shock symptoms as well. Conclusion PF-Large achieved cytokine adsorption comparable to the widely used CytoSorb® and mitigated hypercytokinemia-associated organ dysfunction in a porcine model, supporting its potential clinical applicability as a cytokine adsorption therapy.
Abstract Background Hypermagnesemia in a surgical patient potentially causes arrhythmias, whereas it rarely induces devastating outcomes, including cardiac arrest, in the perioperative period. Here, we present a woman who underwent an emergent colostomy owing to impending bowel rupture, immediately after cardiac arrest caused by severe hypermagnesemia due to the magnesium-containing laxative overdose prescribed for chronic constipation and fecal obstruction. Case presentation An 81-year-old woman with chronic constipation developed fecal obstruction despite a large volume of magnesium-containing laxatives to relieve her constipation. She visited our emergency department because she felt severe abdominal pain continuously. Shortly after she arrived at the emergency department, she developed abrupt cardiac arrest, and she was successfully resuscitated by ordinary treatments, including 1 mg of intravenous (IV) adrenaline. Her laboratory test on arrival revealed a serum magnesium level of 18.3 mg/dL. Our surgeons diagnosed her condition as impending bowel rupture, and therefore, they proceeded with an emergent colostomy without preceding renal replacement therapy. We implemented the following procedures to decrease her serum magnesium level: an intravenous 425 mg calcium gluconate, 20 mg of a loop diuretic furosemide, and a large-volume crystalloid infusion, resulting in her serum magnesium level of 12.8 mg/dL during her surgical procedure. The postoperative use of two hemodialysis session led to a normal range of serum magnesium (2.8 mg/dL). The patient’s postoperative course was uneventful, and she was discharged on postoperative day 37. Conclusions The current case report documented that magnesium-containing laxative overdose causes severe hypermagnesemia, resulting in abrupt cardiac arrest, and that a specific emergency surgical procedure is feasible with efforts to decrease the serum magnesium level. However, we argue that implementation of renal replacement therapy, including continuous hemodiafiltration, in addition to surgical intervention, might be one of the best management strategies in a patient with severe hypermagnesemia in combination with an impending surgical problem.
