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Background: Direct oral anticoagulants (DOACs) have emerged as the first-line therapy for venous thromboembolism and stroke prophylaxis in atrial fibrillation. As DOACs are partially excreted renally, their safety in patients with chronic kidney disease (CKD) is unclear. Objectives: To synthesize primary evidence on the safety profile of DOACs in patients with CKD. Methods: We searched MEDLINE and Embase from inception to June 2023 for randomized and nonrandomized cohort studies comparing DOACs with vitamin K antagonists (VKAs) in CKD patients. Screening and data collection were conducted in duplicate. The primary safety outcome was major bleeding, defined by International Society on Thrombosis and Haemostasis criteria, stratified by CKD severity. Meta-analysis was done using the Mantel–Haenszel random-effects model, presented as odds ratios (ORs) with corresponding 95% CIs. Results: Of the 2355 articles captured in the literature search, 25 nonrandomized studies (n = 6832) and 6 randomized studies (n = 66,898) were included. DOACs reduced major bleeding compared with VKAs in all subgroups (stage 4: OR, 0.73; 95% CI, 0.58, 0.93; stage 5/renal replacement therapy: OR, 0.70; 95% CI, 0.50, 0.98; stage unspecified: OR, 0.72; 95% CI, 0.63, 0.83). Apixaban and rivaroxaban both reduced major bleeding in stage 5/renal replacement therapy patients (apixaban: OR, 0.66; 95% CI, 0.52, 0.85; rivaroxaban: OR, 0.58; 95% CI, 0.35, 0.94). Conclusion: In this meta-analysis, DOACs reduced major bleeding compared with VKAs in stage 4, stage 5/renal replacement therapy, and CKD stage unspecified patients. Future analysis should evaluate the impact of specific DOACs and dosage on safety and efficacy in this population.

Cone-beam computed tomography (CBCT) is widely used for the technical assessment of standard and complex endovascular aortic interventions. Use of iodinated contrast in CBCT imaging might provide useful additional information; however, this also increases the procedural contrast dose, which may cause renal function deterioration, and the radiation exposure. We describe the technique and feasibility of carbon-dioxide (CO2)-enhanced CBCT for the technical assessment of standard and complex endovascular aortic repair. In our experience CO2-CBCT had no related adverse events and provided satisfactory imaging quality to assess endograft integrity, vessels patency, and was safely performed in case of severe chronic renal insufficiency.

Objectives: There are challenges for the treatment of osteoporosis in patients with kidney failure and monoclonal antibodies (MAb) might be a suitable therapy. However, the efficacy and safety of MAb among patients with osteoporosis and renal insufficiency remains unclear. Methods: We systematically searched PubMed, Embase, and Cochrane Central for studies evaluating the efficacy and safety of the use of MAb in patients with osteoporosis and renal insufficiency. We pooled risk ratios (RR) and 95% confidence intervals (CI) for binary outcomes. Mean difference (MD) was used for continuous outcomes. Results: We included 5 studies with 33,550 patients. MAb therapy decreased the risk of vertebral fractures (RR 0.32; 95% CI 0.26–0.40; P

Objective: At present, there remains controversy regarding the clinical efficacy of Corbrin (Bailing) capsules in the treatment of renal insufficiency (RI). A meta-analytic approach was adopted in this study to assess the clinical efficacy of Corbrin capsules for treating RI, aiming to provide a certain level of clinical evidence to guide the selection of RI therapeutic interventions. Methods: The meta-analysis was conducted on databases containing PubMed, CNKI, Weipu Database, Cochrane Library and Wanfang until January 2023. The search for relevant studies was conducted without language restrictions. The study encompassed a randomized controlled trial that examined the efficacy of Corbrin capsules in treating RI. Blood urea nitrogen (BUN), serum creatinine (Scr), 24-h urine protein quantity (24 h UPQ), and estimated creatinine clearance (ECC) were amalgamated using standardized mean difference (SMD) and its corresponding 95 % confidence interval (CI). Meanwhile, the treatment effect (TE) outcome was aggregated using odds ratio (OR) and its corresponding 95 % CI. To evaluate heterogeneity, the Q test and I2 statistics were employed within a random-effects model framework. Results: A total of 11 eligible articles were included, involving 1100 patients (594 in the Corbrin capsule group and 516 in the control group). Compared with control subjects, the SMD was-1.3532 for Ser (95 % CI: 2.0617 to −0.6448), −1.7868 for UPQ (95 % CI: 2.8901 to −0.6836), −1.3302 for BUN (95 % CI: 2.2428 to −0.4176), and 1.7842 for ECC (95 % CI: 0.6774–2.8910). TE had an OR of 1.9786 (95 % CI: 0.7153–5.4734), and publications were not found to be biased (t = 0.5627, P = 0.6738). Conclusion: In RI patients, Corbrin capsule has a relatively good therapeutic effect.

ABSTRACT: Ustekinumab is a first-line drug for Crohn's disease. However, little is known about its potential adverse effects on renal function. We present the case of a 42-year-old man with Crohn's disease who developed chronic renal dysfunction during ustekinumab treatment, which resolved after discontinuing ustekinumab. The findings underscore the importance of close monitoring of renal function in patients receiving ustekinumab, particularly those with preexisting kidney disease or risk factors for renal dysfunction.

Background: Familial Mediterranean fever (FMF) is a hereditary periodic fever syndrome inherited as an autosomal recessive pattern; nonetheless, patients with symptomatic heterozygous variants exist. This study aimed to review children with genetically-proven FMF, to describe their mutation maps and clinical characteristics, and to explore the genotype–phenotype correlation. Methods: Medical charts of pediatric FMF patients who were diagnosed by both genetic mutation and clinical criteria and followed up at our hospital were reviewed. Demographic and clinical data, results of MEFV genetic testing, procedures, concomitant medical conditions, disease severity, and treatment response were recorded and analyzed. Results: A total of 132 patients (71 females [54%]) were included in the final analysis. The average ages at presentation and diagnosis were 6.2 ± 3.1 and 7.6 ± 4.4 years, respectively. The most common clinical features were abdominal pain (n = 120, 91%), fever (n = 97, 73.5%), and arthritis (n = 75, 56.2%). Gastrointestinal endoscopy was the most frequently reported procedure (n = 27, 20.45%). The most common mutation was R202Q (n = 71, 53.8%), followed by E148Q (n = 36, 27.3%), M694V (n = 30, 22.7%), and V726A (n = 22, 16.7%). Two rare variants with potential pathogenicity were identified—namely, c.-15 and c.-330. A novel MEFV mutation (p. Lys629 Met) was noted. Abdominal pain, arthritis, arthralgia, and skin rashes were more common with the R202Q mutation. Patients with compound heterozygous mutations showed a higher rate of abdominal pain (94.1%) and exhibited the best response to colchicine (67.6%). Patients with complex alleles had the highest rate of fever (80%) and arthritis/arthralgia (70%). Conclusion: FMF is endemic in Jordan. Genetic testing is important in FMF evaluation; however, the genotype–phenotype correlation needs further study. The R202Q mutation is possibly pathogenic and is associated with the manifestation of the full spectrum of FMF features; hence, it needs to be considered in the diagnosis of FMF patients in Jordan.

Background: The frontier of onco-nephrology, particularly renal complications of cancer and treatment, remains unexplored. We revisit the fundamental tool of diagnosing kidney disease, renal biopsy, in cancer patients with renal manifestation. Methods: Patients who received renal biopsy from July 2015 to July 2019 were analyzed. Primary outcomes included end-stage renal disease (ESRD), mortality, and catastrophic outcome defined as either ESRD or mortality. A Cox proportional hazards model and Kaplan–Meier technique were used to assess the association with outcome measurements and survival analyses. Immunosuppression after renal biopsy and response to the treatment were evaluated. Results: Among the 77 patients, the median age was 66 years (interquartile range [IQR] 59–73 years) and 46 (59.7%) were male. At the time of renal biopsy, 57 patients (74%) had various degrees of renal insufficiency. Tubulointerstitial damage score, quantified by renal pathology, were associated with higher hazards of ESRD (hazard ratio [HR], 1.77; 95% confidence interval [95% CI], 1.20 to 2.61; P = 0.004) and catastrophic outcome (HR, 1.30; 95% CI, 0.99 to 1.70; P = 0.058). The response rate to immunosuppression was lower in those diagnosed with tubulointerstitial nephritis (1 of 4 patients, 25%) than those with glomerulopathy (10 of 20 patients, 50%). Conclusion: Renal biopsy may improve diagnostic accuracy and assist in treatment guidance of cancer patients with renal manifestation. Renal biopsy should be encouraged with clinical indication. Collaboration between oncologists and nephrologists is of paramount importance to provide more comprehensive care for caner patients.

Summary: Background: While low sodium intake (40 years with stable blood pressure (BP), without heart failure or postural hypotension were randomised to intensive dietary counselling (target sodium intake

Objective: To evaluate the effects of intradialytic exercise (IDE) (exercise performed during dialysis) on sarcopenia and quality of life (QoL) in patients with end-stage renal disease (ESRD). Data Sources: A comprehensive search of 7 electronic databases was performed to identify randomized controlled trials measuring the effects of IDE in adults with ESRD. Searches were limited to the English language. Study Selection: Included studies were randomized controlled trials that measured the effects of IDE in adults with ESRD. Comparator groups received usual care or low-intensity sham interventions. Outcomes of interest were muscle mass, strength, physical function, and QoL. Papers were independently screened for eligibility by 2 authors, and any discrepancies resolved by a third author. Data Extraction: One author extracted the data from the included studies. Data were compared and discussed across the team members. Two authors independently assessed risk of bias using the Cochrane Risk of Bias 2 tool. Quality was assessed using the van Tulder scale and a narrative synthesis was conducted. Best evidence synthesis was used to structure the reviews findings. Data Synthesis: Fourteen studies were included in this review (n=837). While risk of bias was found high in 11 studies, demonstrating mainly selection, performance, and detection bias, the best evidence synthesis indicated strong evidence of resistance training improving muscle mass (16%-4.2%) and strength (45%-18%), and moderate evidence of combined exercise improving strength (37%), and various physical function scores. Conclusions: Overall, there is strong evidence of resistance exercise, with moderate evidence of combined exercise, improving sarcopenia-related muscle and strength loss, and QoL in end-stage kidney disease. Adequately powered, good quality studies are required to determine the optimal exercise prescription to maximize outcomes.

Background: In this study, we reported the real-life results of data from impaired renal patients with urothelial carcinoma who were treated with ICTs., Methods: The patients were categorized into 3 different groups GFR ≥60mL/min (normal), 60mL/min-30mL/min (low), and less than 30 mL/min (very low) based on GFR. The primary endpoints were the overall response rate (ORR), overall survival (OS), duration of response with ICT, and safety. Median follow-up and OS were estimated by using the Kaplan-Meier method., Results: One hundred-five (60.3%) of patients were GFR normal, 26.4% were GFR low with 30mL/min-60mL/min, and 13.2% were very low group. ORR for GFR normal, low and very low groups were 36% (n = 38), 26% (n = 12) and %31 (7); P = .2, respectively. The median duration of response for GFR normal, low and very low groups were 47.2 months (95% CI, 24.5-51.4), 33.1 months (95% CI, 26.9-47), and 23.5 months (95% CI, 12.2-43.7); P = .01, respectively. The Median OS rate for GFR normal, low and very low groups were 11.9 (7.2-16.5) months, 4.7 (1.8-7.7) and 6.8 (1.1-13.6) months, P = .015, respectively. In addition, GFR <60 ml/min HR = 1.6; 95% CI 1.12-1.80; P = .02, maintained a significant association with OS in multivariate analysis., Conclusions: Long-term follow-up of real-world data confirms that the overall survival rate and durable response rate with ICT were higher in patients with GFR >60mL/min. On the other hand, we demonstrated that ICT was effective and a durable response seen in a group of patients with renal inpairement who did not have an effective systemic treatment option., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Piflufolastat F-18, a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, is predominantly eliminated via urinary excretion, and the kidneys have one of the highest absorbed doses. Therefore, this subgroup analysis aimed to investigate the impact of piflufolastat F-18 on renal function and its diagnostic performance in patients stratified by baseline renal function., Patients and Methods: The OSPREY clinical trial enrolled 2 cohorts: A-high-risk patients undergoing radical prostatectomy with pelvic lymphadenectomy, and B-patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Baseline estimated glomerular filtration rates were calculated, and patients were stratified by baseline chronic kidney disease (CKD) stage. Changes in serum creatinine within 28 days postdose and diagnostic performance of piflufolastat F-18 were assessed for each CKD stage group in both cohorts., Results: 385 patients (cohort A, n = 268; cohort B, n = 117) underwent piflufolastat F-18-PET/CT. Baseline and postpiflufolastat F-18 median creatinine levels (mg/dL) were similar for patients in cohort A (0.95 [n = 264] vs. 0.95 [n = 252], respectively) and cohort B (0.93 [n = 116] vs. 0.96 [n = 84], respectively). Among 332 men (cohort A, n = 249; cohort B, n = 83) with baseline and postpiflufolastat creatinine measurements, there were minimal changes in creatinine across all baseline CKD stage groups (median change ranged from -0.02 to 0.023 in groups with >1 patient). The diagnostic performance of piflufolastat F-18 showed no meaningful differences when stratified by baseline CKD stage., Conclusion: Piflufolastat F-18 appears to be safe and effective for imaging prostate cancer, including men with mild/moderate renal insufficiency., Competing Interests: Disclosure Research funding was provided by Lantheus. Saradha Baskaran, Nancy Stambler, Vincent A. DiPippo, and Bela S. Denes are full-time employees of Lantheus, and the latter 3 own Lantheus stock., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Direct oral anticoagulants (DOACs) have emerged as the first-line therapy for venous thromboembolism and stroke prophylaxis in atrial fibrillation. As DOACs are partially excreted renally, their safety in patients with chronic kidney disease (CKD) is unclear., Objectives: To synthesize primary evidence on the safety profile of DOACs in patients with CKD., Methods: We searched MEDLINE and Embase from inception to June 2023 for randomized and nonrandomized cohort studies comparing DOACs with vitamin K antagonists (VKAs) in CKD patients. Screening and data collection were conducted in duplicate. The primary safety outcome was major bleeding, defined by International Society on Thrombosis and Haemostasis criteria, stratified by CKD severity. Meta-analysis was done using the Mantel-Haenszel random-effects model, presented as odds ratios (ORs) with corresponding 95% CIs., Results: Of the 2355 articles captured in the literature search, 25 nonrandomized studies ( n  = 6832) and 6 randomized studies ( n  = 66,898) were included. DOACs reduced major bleeding compared with VKAs in all subgroups (stage 4: OR, 0.73; 95% CI, 0.58, 0.93; stage 5/renal replacement therapy: OR, 0.70; 95% CI, 0.50, 0.98; stage unspecified: OR, 0.72; 95% CI, 0.63, 0.83). Apixaban and rivaroxaban both reduced major bleeding in stage 5/renal replacement therapy patients (apixaban: OR, 0.66; 95% CI, 0.52, 0.85; rivaroxaban: OR, 0.58; 95% CI, 0.35, 0.94)., Conclusion: In this meta-analysis, DOACs reduced major bleeding compared with VKAs in stage 4, stage 5/renal replacement therapy, and CKD stage unspecified patients. Future analysis should evaluate the impact of specific DOACs and dosage on safety and efficacy in this population., (© 2024 The Authors.)

Background: Tinzaparin could be easier to manage than unfractionated heparin in patients with severe renal impairment. However, clinical and pharmacologic data regarding its use in such patients are lacking., Objectives: The aims of this study were to determine, in patients with estimated glomerular filtration rate (eGFR) of <30 mL.min⁻ 1 , tinzaparin pharmacokinetics (PK) parameters using a population PK approach and bleeding and thrombotic complications., Methods: We performed a retrospective observational single-center study, including in-patients with eGFR of <30 mL.min⁻ 1 receiving prophylactic (4500 IU.d⁻ 1 ) or therapeutic (175 IU.kg⁻ 1 .d⁻ 1 ) tinzaparin. Measured anti-Xa levels were analyzed using a nonlinear mixed-effects modeling approach. Individual predicted tinzaparin exposure markers at steady state were calculated for each patient and dosing regimen. The PK was also evaluated through Monte Carlo simulations based on the final covariate model parameter estimates., Results: Over a 22-month period, 802 tinzaparin treatment periods in 623 patients were analyzed: two-thirds received a prophylactic dose, 66% had an eGFR of <20 mL.min⁻ 1 , and 25% were on renal replacement therapy. In patients for whom anti-Xa measurements were performed (n = 199; 746 values), PK parameters, profiles, and maximum plasma concentrations were comparable with those in patients without renal impairment or in healthy volunteers. In the whole population, major bleeding occurred in 2.4% and 3.5% of patients receiving prophylactic and therapeutic doses over a median 9- and 7-day treatment period, respectively. No patients had thrombotic complications., Conclusion: Tinzaparin PK parameters and profiles were not affected by renal impairment. This suggests that tinzaparin, at therapeutic or prophylactic dose, could be an alternative to unfractionated heparin in hospitalized patients with severe renal impairment., Competing Interests: Declaration of competing interests I.G.T. has received honoraria from Aguettant, Bayer, BMS-Pfizer, Leo-Pharma, Sanofi, Stago, and Viatris. G.M. has received honoraria from Bayer Healthcare, BMS-Pfizer, Leo-Pharma, and Sanofi. P.M. has received honoraria from Bayer Healthcare, BMS-Pfizer, Leo-Pharma, and Sanofi. P.G. has received honoraria from Sanofi. All other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Lower limb complications are major adverse events in patients with peripheral artery disease (PAD) and chronic kidney disease (CKD). These complications can lead to morbidity, disability, reduced quality of life, and higher health care costs. We sought to determine how interim lower limb complications modify the subsequent risk of progression to kidney failure, all-cause mortality before kidney failure, and cardiovascular (CV) events in a cohort of patients with CKD stages G3 to G5. Methods: We performed a retrospective cohort study using patient-level data obtained by linking several administrative databases from Manitoba, Canada. We used Fine and Gray regression models for the primary outcomes of (1) kidney failure adjusted for the competing risk of all-cause mortality, (2) death before kidney failure, and (3) cardiovascular-related hospitalization with the competing risk of non-CV death. Results: A total of 92,618 patients were included in the final cohort, with a median follow-up time of 2.56 years. Compared with patients who did not experience an interim lower limb complication, there was a higher risk of kidney failure (adjusted hazard ratio [HR] 2.51, 95% confidence interval [CI] 2.10–3.00), all-cause mortality before kidney failure (adjusted HR 2.73, 95% CI 2.55–2.92), and CV events (adjusted HR 2.12, 95% CI 1.90–2.38). Conclusions: Interim lower limb complications are associated with an increased risk of kidney failure, all-cause mortality before kidney failure, and cardiovascular-related hospitalization. Clinical trials of screening and treatment strategies for patients with CKD at risk for lower limb complications may help determine optimal strategies to manage this risk.

Background: Thrombocytopenia (TP) is the major event associated with linezolid (LZD) therapy. We investigated the incidence and risk factors for thrombocytopenia in hospitalized adults who received LZD (1200 mg/day) between 2015 and 2017. HIV-positive, death during follow-up and those with a baseline platelet count ≤100 × 103/mm3 were excluded. Method: TP was defined as a decrease in platelet count of ≥20% from the baseline level at the initiation of linezolid therapy and a final count of 20 mg/kg/day were not risk factors. Conclusion: The results showed that the incidence of linezolid-induced thrombocytopenia was lower in patients with normal renal function and higher in those with platelet counts ≤200 × 103/mm3 or serum creatinine >1.5 mg/dL at the start of the treatment.

Background: The use of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal impairment has been approved; however, limited clinical data exist. Accordingly, we aimed to compare outcomes and adverse events associated with remdesivir in hospitalized patients with COVID-19, with and without severe renal impairment., Methods: Hospitalized patients with COVID-19 undergoing a 5-day remdesivir course at Taipei Veterans General Hospital from April 1 to July 31, 2022, were enrolled. Comparative analysis of outcomes and safety between patients with or without severe renal impairment (estimated glomerular filtration rate of < 30 mL/min per 1.73 m 2 ) were conducted. Prognostic factors associated with 28-day mortality in patients with severe renal impairment were investigated using logistic regression analysis., Results: A total of 671 hospitalized patients, including 132 patients with severe renal impairment, who received a 5-day course of remdesivir were analyzed. The 28-day mortality was higher in patients with severe renal impairment than in patients without severe renal impairment (15.2% vs. 7.8%). The proportion of patients with acute kidney injury (AKI) and deteriorated liver function after completing remdesivir therapy was similar between the patients with and without severe renal impairment, and the recovery rate of AKI was similar in both groups. The sequential organ failure assessment score was an independent factor associated with 28-day mortality in patients with severe renal impairment., Conclusions: Remdesivir was well-tolerated in hospitalized patients with COVID-19, regardless of renal function. Our findings support the recent recommendation to administer remdesivir in patients with severe renal impairment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The number of cancer patients receiving long-term hemodialysis (HD) is increasing, and HD could jeopardize treatments' safety and efficacy. Therefore, managing anticancer drugs is critical in this frail population. In addition, evidence of HD safety or risk is regularly released both for cytotoxic chemotherapy (CT) or hormone therapy (HT) as well as new therapies with molecularly targeted therapies (MTT), immune checkpoint inhibitors (ICI), and a summary of current knowledge is needed., Methods: We aimed to synthesize available data on cancer treatments in HD patients using PubMed database, FDA labels, summary of product characteristics (SmPC), FDA and EMA approval documents, guidelines and finally case reports for which relevant pharmacokinetic (PK) data is available., Results: For CT, recently proposed guidelines were balanced by the publication of particular toxic reports following them. SmPC was helpful in some cases, but no data was found for most CTs. MTT, both oral and monoclonal antibodies, were rarely modified by HD. However, HD patients have particular frailty that could require dose adaptation despite no substantial PK modification. Similarly, exposure to ICIs is unlikely to be modified by HD since immunoglobulins are not dialyzable. For HT, PK characteristics and HD impact were more heterogeneous and were reviewed molecule by molecule., Conclusions: We summarized current knowledge on HD and cancer treatments. Data remains scarce, and the latest guidelines rely on few clinical data. There is a need to collect both retrospective and prospective data to better characterize the safety and relevant dose and schedule adaptations whenever needed in this situation to reinforce future guidelines., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: The accuracy of urine dipsticks to detect increased albuminuria is uncertain. We aimed to assess the diagnostic accuracy of urine dipsticks for detecting albuminuria. Methods: A systematic review of studies that assessed the diagnostic accuracy of urine dipstick testing for detecting albuminuria has been conducted (using as reference standard the albuminuria in a 24-hour sample or the albumin-to-creatinine ratio) in Scopus, PubMed, and Google Scholar. The risk of bias of the included studies has been assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Whenever possible, we performed meta-analyses for sensitivity and specificity. The certainty of the evidence has also been assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Results: A total of 14 studies have been included in this review, having assessed all albumin-to-creatinine ratio (ACR) as assessed standard. Each study used different dipstick types. The resulting pooled sensitivity and specificity for each cutoff point were as follows: for ACR >30 mg/g (13 studies): 0.82 (95% confidence interval: 0.76–0.87) and 0.88 (0.83–0.91); for ACR 30–300 mg/g (7 studies): 0.72 (0.68–0.77) and 0.82 (0.76–0.89); and for ACR >300 mg/g (7 studies): 0.84 (0.71–0.90) and 0.97 (0.95–0.99), respectively. An overall high risk of bias, an important heterogeneity in all pooled analysis, and a very low certainty of the evidence have been found. Conclusions: Pooled sensitivity and specificity of urine dipsticks have been calculated for different ACR cutoff points. However, the dipstick types differed across studies, and the certainty of the evidence was very low. Thus, further well-designed studies are needed to reach more confident estimates and to assess accuracy differences across dipstick types. Registration: PROSPERO (CRD42019124637).

Introduction: With the rise in complementary medicine usage, mind-body interventions (MBI), encompassing therapies like yoga and music therapy, have been gaining interest. The use of MBI in non-chronic kidney disease (CKD) patients have demonstrated efficacy for ameliorating pain, stress and anxiety symptoms. As CKD patients often suffer from these symptoms, MBI may serve as potential adjunctive therapies. This review aimed to summarize the studied indications of MBI among CKD patients. Methods: A systematic review was performed in Medline®, Embase®, Scopus®, CINAHL®, CENTRAL® and PsycInfo® in accordance to the PRISMA and SWiM checklists. Randomised controlled trials (RCTs) which evaluated the use of MBI among adult CKD patients were included. The efficacy of each MBI was determined by reduction in symptoms severity scores. All adverse reactions were documented. Results: Of the 7,417 articles screened, 32 RCTs were included. Music therapy (n = 11), relaxation therapy (n = 9) and spiritual therapy (n = 6) were the most well studied MBIs. Frequently studied indications for MBIs were anxiety symptoms (n = 12), pain (n = 7) and depressive symptoms (n = 5). Music and spiritual therapies were shown to reduce 8.06–43.5 % and 36.1–41.1 % of anxiety symptoms respectively. For pain relief, music (41.8 %–61.5 %) and yoga therapies (36.7 %) were shown to be effective for reduction of pain. Lastly, spiritual therapy was shown to reduce depressive symptoms by 56.8 %. No adverse effects were reported for any MBI. Conclusion: Music therapy, relaxation and spiritual therapies are more well-studied MBIs which were shown to reduce anxiety, depressive symptoms and pain in CKD patients. Larger RCTs are required to confirm the efficacy and safety of promising MBIs.

Introduction: Uremic pruritus (UP) is one of the most bothersome symptoms among chronic kidney disease (CKD) patients. The pathophysiology of UP remains elusive, resulting in limited treatment options. The inability of standard medical treatments to provide effective relief has piqued interest in complementary and alternative medicine (CAM). Methodology: A systematic review of randomized controlled trials (RCTs) summarizing the efficacy and safety profile of CAM used for UP in CKD patients was performed. CAM interventions were classified using categories proposed by the National Center for Complementary and Integrative Health. The efficacy of each CAM was determined from changes in UP severity and all reported adverse effects were extracted. Results: Of 5242 articles screened, 34 RCTs were included, with 15 (44.1 %) studies having a sample size greater than 50. The studies considered 21 treatments including omega-3 fatty acid supplementation (n=5), acupuncture (n=5), topical capsaicin (n=4) and acupressure (n=3). Acupuncture, acupressure and topical capsaicin were shown to be effective in improving uremic pruritus. Interventions which include oral omega-3 fatty acid and zinc supplementation demonstrated mixed efficacy. Other therapies such as evening primrose oil, turmeric, vitamin B3, vitamin D and thermal therapy were not effective for treatment of UP. Common adverse effects reported with topical capsaicin included mild burning sensations (50.0–88.2 %) or erythema (6.7–22.7%) while that of acupuncture included soreness (7.5 %), bleeding (6.0–7.5%) and hematoma (1.9 %). Conclusions: Acupuncture, acupressure and topical capsaicin have the largest body of evidence for efficacy in the treatment of UP. Larger and higher quality RCTs are required to examine the efficacy and safety of promising CAM.

Because of the global shortage of donor kidneys, xenotransplantation emerges as a potential solution for individuals with kidney failure who face challenges in securing a suitable donor kidney. A study featured in this month's issue of Kidney International assesses the kidney physiology of a porcine kidney transplanted into a brain-dead human with kidney failure, demonstrating life-sustaining physiological function for 7 days. Together with preclinical nonhuman primate studies, decedent models provide complementary data for development of clinical kidney xenotransplantation., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Demand for kidney grafts outpaces supply, limiting kidney transplantation as a treatment for kidney failure. Xenotransplantation has the potential to make kidney transplantation available to many more patients with kidney failure, but the ability of xenografts to support human physiologic homeostasis has not been established. A brain-dead adult decedent underwent bilateral native nephrectomies followed by 10 gene-edited (four gene knockouts, six human transgenes) pig-to-human xenotransplantation. Physiologic parameters and laboratory values were measured for seven days in a critical care setting. Data collection aimed to assess homeostasis by measuring components of the renin-angiotensin-aldosterone system, parathyroid hormone signaling, glomerular filtration rate, and markers of salt and water balance. Mean arterial blood pressure was maintained above 60 mmHg throughout. Pig kidneys secreted renin (post-operative day three to seven mean and standard deviation: 47.3 ± 9 pg/mL). Aldosterone and angiotensin II levels were present (post-operative day three to seven, 57.0 ± 8 pg/mL and 5.4 ± 4.3 pg/mL, respectively) despite plasma renin activity under 0.6 ng/mL/hr. Parathyroid hormone levels followed ionized calcium. Urine output down trended from 37 L to 6 L per day with 4.5 L of electrolyte free water loss on post-operative day six. Aquaporin 2 channels were detected in the apical surface of principal cells, supporting pig kidney response to human vasopressin. Serum creatinine down trended to 0.9 mg/dL by day seven. Glomerular filtration rate ranged 90-240 mL/min by creatinine clearance and single-dose inulin clearance. Thus, in a human decedent model, xenotransplantation of 10 gene-edited pig kidneys provided physiologic balance for seven days. Hence, our in-human study paves the way for future clinical study of pig-to-human kidney xenotransplantation in living persons., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Toxin- and drug-induced tubulointerstitial nephritis (TIN), characterized by interstitial infiltration of immune cells, frequently necessitates dialysis for patients due to irreversible fibrosis. However, agents modulating interstitial immune cells are lacking. Here, we addressed whether the housekeeping enzyme glutamyl-prolyl-transfer RNA synthetase 1 (EPRS1), responsible for attaching glutamic acid and proline to transfer RNA, modulates immune cell activity during TIN and whether its pharmacological inhibition abrogates fibrotic transformation. The immunological feature following TIN induction by means of an adenine-mixed diet was infiltration of EPRS1 high T cells, particularly proliferating T and γδ T cells. The proliferation capacity of both CD4 + and CD8 + T cells, along with interleukin-17 production of γδ T cells, was higher in the kidneys of TIN-induced Eprs1 +/+ mice than in the kidneys of TIN-induced Eprs1 +/- mice. This discrepancy contributed to the fibrotic amelioration observed in kidneys of Eprs1 +/- mice. TIN-induced fibrosis was also reduced in Rag1 -/- mice adoptively transferred with Eprs1 +/- T cells compared to the Rag1 -/- mice transferred with Eprs1 +/+ T cells. The use of an EPRS1-targeting small molecule inhibitor (bersiporocin) under clinical trials to evaluate its therapeutic potential against idiopathic pulmonary fibrosis alleviated immunofibrotic aggravation in TIN. EPRS1 expression was also observed in human kidney tissues and blood-derived T cells, and high expression was associated with worse patient outcomes. Thus, EPRS1 may emerge as a therapeutic target in toxin- and drug-induced TIN, modulating the proliferation and activity of infiltrated T cells., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Though remdesivir benefits COVID-19 patients, its use in those with renal dysfunction is currently limited due to concerns about possible toxic effects of accumulated sulfobutylether-β-cyclodextrin (SBECD) on liver and kidney. We examined renal and hepatic function for a month in renally-impaired COVID-19 patients who were treated or not treated with remdesivir to assess the safety of the drug. A retrospective study was performed in adult COVID-19 patients with glomerular filtration rates of <30 ml/min/1.73 m 2  at admission to a tertiary care hospital between November 2020 and March 2022. Data on serum creatinine and liver chemistry were collected serially. A total of 101 patients with impaired renal function were analyzed, comprising 64 remdesivir-treated patients and 37 who did not receive any antiviral agent. Although remdesivir-treated patients were more likely to be infected with the Omicron variant (79.7% vs. 48.6%), baseline characteristics did not differ significantly between the two groups. Among patients who initially did not require dialysis, 18.4% (7/38) of remdesivir-treated patients developed acute kidney injury (AKI) at days 4-6, compared with 51.7% (15/29) of non-remdesivir-treated patients. Liver injury severity worsened in 3.1% (2/64) of remdesivir-treated patients and 5.4% (2/37) of non-remdesivir-treated patients at days 4-6. In addition, there was no significant increase in AKI and liver injury over time in remdesivir-treated patients, and there were no cases of discontinuation of remdesivir due to adverse reactions. Concerns regarding the safety of SBECD should not lead to hasty withholding of remdesivir treatment in renally-impaired COVID-19 patients., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: The clinical importance of adhering to the regimen in tuberculosis patients has been widely investigated, but most studies were conducted in controlled settings and in limited populations. We aimed to measure the level of real-world adherence during intensive phase and investigate the predictors and the risk of mortality and health outcomes of intensive phase non-adherence in tuberculosis patients., Study Design: We conducted a nationwide cohort study by linking the Korean National Tuberculosis Surveillance System and the National Health Information Database., Methods: We included all incident drug-susceptible tuberculosis patients who initiated the regimens recommended by the World Health Organization from 2013 to 2018. Adherence was measured using the proportion of days covered (poor [<50%], moderate [50%-79%], and high [≥80%]). We used logistic regression model to assess predictors and the Cox proportional hazard model to evaluate the risk of mortality and health outcomes with intensive phase non-adherence., Results: Of 46,818 patients, there were 8% and 11% with poor and moderate adherent groups, respectively. Age ≥45 years, insulin use, and history of renal failure were predictors of non-adherence. Compared with high adherent group, poor and moderate adherent groups were associated with a substantial risk of mortality (poor: hazard ratio, 2.14 [95% confidence interval, 1.95-2.34]; moderate: 1.76 [1.62-1.92]). Similar trends were observed for health outcomes. Stratified analyses showed a higher risk of mortality in patients with medical aid, low income, and history of renal failure, systematic corticosteroids, and immunomodulators., Conclusions: Non-adherence during intensive phase increased mortality risk by twofold, underscoring targeted intervention for high-risk population, including advanced diabetes, and immunocompromised patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The mechanisms of tissue damage in kidney amyloidosis are not well described. To investigate this further, we used laser microdissection-mass spectrometry to identify proteins deposited in amyloid plaques (expanded proteome) and proteins overexpressed in plaques compared to controls (plaque-specific proteome). This study encompassed 2650 cases of amyloidosis due to light chain (AL), heavy chain (AH), leukocyte chemotactic factor-2-type (ALECT2), secondary (AA), fibrinogen (AFib), apo AIV (AApoAIV), apo CII (AApoCII) and 14 normal/disease controls. We found that AFib, AA, and AApoCII have the most distinct proteomes predominantly driven by increased complement pathway proteins. Clustering of cases based on the expanded proteome identified two ALECT2 and seven AL subtypes. The main differences within the AL and ALECT2 subtypes were driven by complement proteins and, for AL only, 14-3-3 family proteins (a family of structurally similar phospho-binding proteins that regulate major cellular functions) widely implicated in kidney tissue dysfunction. The kidney AL plaque-specific proteome consisted of 24 proteins, including those implicated in kidney damage (α1 antitrypsin and heat shock protein β1). Hierarchical clustering of AL cases based on their plaque-specific proteome identified four clusters, of which one was associated with improved kidney survival and was characterized by higher overall proteomic content and 14-3-3 proteins but lower levels of light chains and most signature proteins. Thus, our results suggest that there is significant heterogeneity across and within amyloid types, driven predominantly by complement proteins, and that the plaque protein burden does not correlate with amyloid toxicity., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Integrated kidney care requires synergistic linkage between preventative care for people at risk for chronic kidney disease and health services providing care for people with kidney disease, ensuring holistic and coordinated care as people transition between acute and chronic kidney disease and the 3 modalities of kidney failure management: conservative kidney management, transplantation, and dialysis. People with kidney failure have many supportive care needs throughout their illness, regardless of treatment modality. Kidney supportive care is therefore a vital part of this integrated framework, but is nonexistent, poorly developed, and/or poorly integrated with kidney care in many settings, especially in low- and middle-income countries. To address this, the International Society of Nephrology has (i) coordinated the development of consensus definitions of conservative kidney management and kidney supportive care to promote international understanding and awareness of these active treatments; and (ii) identified key considerations for the development and expansion of conservative kidney management and kidney supportive care programs, especially in low resource settings, where access to kidney replacement therapy is restricted or not available. This article presents the definitions for conservative kidney management and kidney supportive care; describes their core components with some illustrative examples to highlight key points; and describes some of the additional considerations for delivering conservative kidney management and kidney supportive care in low resource settings., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this review is to appraise and assimilate evidence from studies that have reported on the cost-effectiveness of screening programs for chronic kidney disease (CKD)., Methods: The study protocol was registered on International Prospective Register of Systematic Reviews (PROSPERO). The final search was conducted on 18 January 2023 using 7 databases. Screening of articles, data extraction, and quality assessment was performed by 2 independent reviewers. The ISPOR-AMCP-NPC checklist was used to assess the credibility of the included studies., Results: From 4948 retrieved studies, a final total of 20 studies were included in the qualitative synthesis. Studies found that screening in diabetic populations was cost-effective (n = 8, 57%) or even cost-saving (n = 6, 43%). Four studies (67%) found that screening in hypertensive populations was also cost-effective. For the general population, findings were inconsistent across studies in which many found screening to be cost-effective (n = 11, 69%), some cost-saving (n = 2, 12%), and others not cost-effective (n = 3, 19%). The most influential parameters identified were prevalence of CKD and cost of screening., Conclusions: Screening for CKD in patients with diabetes or hypertension is recommended from a cost-effectiveness point of view. For the general population, despite some inconsistent findings, the majority of studies demonstrated that screening in this population is cost-effective, depending mainly on the prevalence and the costs of screening. Healthcare decision makers need to consider the prevalence, stratification strategies, and advocate for lower screening costs to reduce the burden on healthcare budgets and to make screening even more favorable from the health-economic perspective., Competing Interests: Author Disclosures Prof Dr Postma reports grants and personal fees from Pharmacoeconomics Advice Groningen (PAG) B.V., grants and personal fees from Health-Ecore, outside the submitted work; Prof Dr Postma holds stocks in Health-Ecore and PAG B.V., all pharmacoeconomic consultancy companies. Prof Dr Boersma received grants and honoraria from various other medical and pharmaceutical companies and he holds stocks in Health-Ecore B.V. No other disclosures were reported., (Copyright © 2023. Published by Elsevier Inc.)

Background: Coral reef aorta (CRA) is defined by the presence of heavily calcified exophytic plaques that protrude into the aortic lumen. However, the exact causes and development of this condition are still not fully understood. When the aortic branches are affected, it can result in various symptoms. Despite ongoing research, there is currently no established consensus on the best treatment for CRA. This review aims to examine the latest findings regarding the clinical presentation and approach to treating patients with CRA., Methods: We conducted a systematic electronic search of the literature using the PubMed and Embase databases. Throughout the search, we adhered to the guidelines outlined in the PRISMA framework. From the identified publications, we extracted information pertaining to patients' characteristics, symptoms, and types of treatment from a total of 124 cases reported over the past 20 years. The primary focus of our analysis was to assess the improvement of signs and symptoms, as well as to evaluate any postoperative complications. To achieve this, we performed both descriptive and inferential analyses on the collected data. Additionally, we conducted subgroup analyses based on treatment types and symptoms observed at presentation, presenting the findings in the form of odds ratios (ORs)., Results: After removing duplicate articles, we carefully screened the titles of 67 retrieved articles and excluded those that did not align with the purpose of our study. Subsequently, we thoroughly analyzed the remaining 41 articles along with their references, ultimately including 29 studies that were deemed most relevant for our systematic review. We examined a total of 124 cases of patients diagnosed with CRA, comprising 77 (62.1%) females and 48 (38.7%) males, with a mean age of 59 years (range: 37-84). The predominant signs and symptoms observed were intermittent claudication, reported in 57 (46.0%) patients, followed by refractory hypertension in 45 (36.3%) patients, intestinal angina in 28 (22.6%) patients, and renal insufficiency in 15 (12.1%) patients. Among the treated patients, 110 (88.7%) underwent open surgery repair (OSR), 11 (8.9%) received endovascular treatment, and 3 (2.4%) underwent laparoscopy. Postoperatively, a significant number of patients experienced substantial relief or complete resolution of their symptoms, as well as improved control of hypertension and renal function. In the group of patients treated with OSR, the inhospital stay mortality rate was 10.9%, the morbidity rate was 28.2%, and the reintervention rate was 15.5%. The high mortality rate during hospital stays in this group may be associated with such invasive procedures performed on patients who have substantial cardiovascular burden and multiple comorbidities. Conversely, no postoperative complications were reported in the group of patients treated with endovascular procedures or laparoscopic surgery., Conclusions: While coral reef aorta (CRA) is considered a rare condition, it is crucial for the medical community to remain vigilant about its diagnosis, particularly in patients presenting with symptoms such as intermittent claudication, refractory hypertension, renal impairment, or intestinal angina. Based on the findings of this review, both OSR and endovascular treatment have shown promise as viable therapeutic options. Although endovascular therapies may not always be feasible or may have reduced durability in these calcified bulky lesions, they should be considered in patients with multiple comorbidities, due to the high postoperative mortality rates associated with more invasive approaches. Additionally, these endoluminal procedures have demonstrated good patency rates during the 18-month follow-up period. It is essential to emphasize that the treatment strategy should be determined on a case-by-case basis, involving a multidisciplinary team to tailor it to the specific needs of each individual patient., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: With the prolonged life expectancy in solid organ transplant recipients, their quality of life and fertility desire become of particular concern. Pregnancy in pancreas-alone transplantation, although rare and complicated to manage, is not impossible anymore. We here report such a case with literature review to address this issue. Case report: A 29-year-old, primigravida patient with underlying stage 4 chronic renal insufficiency and type 1 diabetes mellitus post pancreas-alone transplantation 5 years prior to her initial visit consulted our service. Antepartum care with intensive monitoring of blood pressure, renal function, and tacrolimus serum concentration were given. Successful maternal and fetal outcomes are presented here. Conclusion: Child-bearing in solid organ transplantation recipients has become more promising nowadays, even for a difficult case of pancreas-alone transplant recipient complicated with chronic renal insufficiency and superimposed pre-eclampsia. Thorough antepartum counseling and cautious monitoring of maternal, fetal and graft conditions by multidisciplinary specialties are key to favorable pregnancy outcomes.

Objective: to determine the incidence of linezolid-induced haematological toxicity and study the influence of renal clearance on its appearance and the preventive effect of pyridoxine. Methods: a retrospective observational study was conducted. Every patient treated with linezolid in a university hospital during 6 months was included. Haematological toxicity was defined as a decrease of 25% in hemoglobin, of 25% in platelets and/or 50% in neutrophils from baseline. The incidence of haematological toxicity and the percentage decrease in analytical variables were compared in patients with and without renal failure (creatinine clearance lower than 50 mL/min), using the 30 mL/min threshold, and with or without pyridoxine; using Chi -Square and U Mann-Whitney tests, respectively. Results: thirty-eight patients were evaluated. Sixteen (42%) presented haematological toxicity (2 due to a decrease in haemoglobin, 9 in platelets and 8 in neutrophils). Two patients (5%) discontinued treatment due to thrombocytopenia. Toxicity incidence was similar in patients with and without renal failure, 42% vs 42%, p = 0.970, with more or less than 30 ml/min, 67% vs 40%, p = 0.369, or with or without pyridoxine, 47.8% vs 33%, p = 0.376. Patients with renal failure had a significantly greater reduction in platelet count, p = 0.0185. Conclusion: forty-two percent of patients had haematological toxicity, being more frequent platelets and neutrophils reduction. This was not significantly higher in patients with renal failure or in those without pyridoxine. Greater reduction in platelet count was observed in patients with renal failure

Diabetic nephropathy (DN) is characterized by abnormal kidney energy metabolism, but its causes and contributions to DN pathogenesis are not clear. To examine this issue, we carried out targeted metabolomics profiling in a mouse model of DN that develops kidney disease resembling the human disorder. We found a distinct profile of increased lactate levels and impaired energy metabolism in kidneys of mice with DN, and treatment with an angiotensin-receptor blocker (ARB) reduced albuminuria, attenuated kidney pathology and corrected many metabolic abnormalities, restoring levels of lactate toward normal while increasing kidney ATP content. We also found enhanced expression of lactate dehydrogenase isoforms in DN. Expression of both the LdhA and LdhB isoforms were significantly increased in kidneys of mice, and treatment with ARB significantly reduced their expression. Single-cell sequencing studies showed specific up-regulation of LdhA in the proximal tubule, along with enhanced expression of oxidative stress pathways. There was a significant correlation between albuminuria and lactate in mice, and also in a Southeast Asian patient cohort consisting of individuals with type 2 diabetes and impaired kidney function. In the individuals with diabetes, this association was independent of ARB and angiotensin-converting enzyme inhibitor use. Furthermore, urinary lactate levels predicted the clinical outcomes of doubling of serum creatinine or development of kidney failure, and there was a significant correlation between urinary lactate levels and biomarkers of tubular injury and epithelial stress. Thus, we suggest that kidney metabolic disruptions leading to enhanced generation of lactate contribute to the pathogenesis of DN and increased urinary lactate levels may be a potential biomarker for risk of kidney disease progression., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The study aimed to determine the influence of induction therapy on the acute cellular rejection (ACR) index in adult heart transplant recipients during the one-year observation. The study population consisted of 256 consecutive adult patients (pts), aged 51.5 (±11.9) years, 199 (77%) men treated with orthotopic heart transplantation (OHT) in the period between 2015 and 2020 in a single high-volume heart transplant center. The endomyocardial biopsies (EMBs) were performed according to the protocol consisting of 7 protocolary EMBs for up to 3 months and 10 EMBs for up to one year after OHT. The rejection index (ACRI) was calculated as the number of scheduled EMBs with the ACR ≥ 2 divided by the total number of protocolary EMBs. The study population was divided into two groups according to the application of basiliximab. The total number of pts. who received basiliximab was 10 (3.9%). The main indications for the usage of the induction therapy were heart retransplantation, mechanical circulatory support (MCS), severe renal insufficiency (eGFR <30 mL/min/1.73 m2), and a panel of reactive antibody (PRA) > 10%. In the group with induction, the mean age was 49 (±14) years; 3 (30%) patients had the MCS prior to OHT, and 3 (30%) patients had heart retransplantation. Four (40%) patients had diabetes mellitus, and 4 (40%) patients had severe renal insufficiency. As maintenance therapy during the observation period, tacrolimus was given to 10 (100%) patients, everolimus to 2 (20%) patients, and MPA to 9 (90%) patients. In the group with no induction, the mean age was 51.8 (±12) years, MCS was used in 56 (23%) patients, 2 (0.8%) patients were retransplanted; 10 (4%) patients had eGFR <30 mL/min/1.73 m2 and 58 (24%) patients had diabetes. Tacrolimus was administered to 243 (99%) patients, cyclosporine to 3 (1%), everolimus to 40 (16%), and mycophenolate to 245 (99.6%) heart recipients. The median one-year ACRI was 0.0, IQR:0.0-0.08 in the group with induction vs. 0.077, IQR: 0.0-0.154 with no induction; p = 0.11. ACRI up to three months was significantly higher in the entire cohort in comparison to up to one year (P < 0.01). The multivariate analysis showed that only everolimus implementation and younger age at the time of transplant influenced patients' mortality rate (P < 0.01). Significant graft rejections (≥ 2R ISHLT) are most common in the first three months after OHT. Patients who are initially at high risk of significant cellular rejection may benefit from induction therapy., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Periprosthetic fractures (PPFs) around the hip joint are increasing in prevalence. In this collaborative study, we aimed to investigate the impact of patient demographics, fracture characteristics, and modes of management on in-hospital mortality of PPFs involving the hip., Methods: Using a multi-centre cohort study design, we retrospectively identified adults presenting with a PPF around the hip over a 10-year period. Univariate and multivariable logistic regression analyses were performed to study the independent correlation between patient, fracture, and treatment factors on mortality., Results: A total of 1,109 patients were included. The in-hospital mortality rate was 5.3%. Multivariable analyses suggested that age, male sex, abbreviated mental test score (AMTS), pneumonia, renal failure, history of peripheral vascular disease (PVD) and deep surgical site infection were each independently associated with mortality. Each yearly increase in age independently correlates with a 7% increase in mortality (OR 1.07, p=0.019). The odds of mortality was 2.99 times higher for patients diagnosed with pneumonia during their hospital stay [OR 2.99 (95% CI 1.07-8.37) p=0.037], and 7.25 times higher for patients that developed renal failure during their stay [OR 7.25 (95% CI 1.85-28.47) p=0.005]. Patients with history of PVD have a six-fold greater mortality risk (OR 6.06, p=0.003). Mode of treatment was not a significant predictor of mortality., Conclusion: The in-hospital mortality rate of PPFs around the hip exceeds 5%. The fracture subtype and mode of management are not independent predictors of mortality, while patient factors such as age, AMTS, history of PVD, pneumonia, and renal failure can independently predict mortality. Peri-operative optimisation of modifiable risk factors such as lung and kidney function in patients with PPFs around the hip during their hospital stay is of utmost importance., Competing Interests: Declaration of Competing Interest A.M is the president of the British Trauma Society. The author(s) received no financial or material support for the research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Angiogenesis and immunosuppression are closely related pathophysiologic processes. Widely prescribed in malignant tumor and proliferative retinal lesions, VEGF signaling pathway inhibitors may cause hypertension and renal injury in some patients, presenting with proteinuria, nephrotic syndrome, renal failure and thrombotic microangiopathy. VEGF signaling pathway inhibitors block the action of both VEGF-A and VEGF-C. However, VEGF-A and VEGF-C produced by podocytes are vital to maintain the physiological function of glomerular endothelial cells and podocytes. There is still no effective treatment for kidney disease associated with VEGF signaling pathway inhibitors and some patients have progressive renal failure even after withdrawal of the drug. Recent studies reveal that blocking of VEGF-A and VEGF-C can activate CD4 + and CD8 + T cells, augment antigen-presenting function of dendritic cells, enhance cytotoxicity of macrophages and initiate complement cascade activation. VEGF and VEGFR are expressed in immune cells, which are involved in the immunosuppression and cross-talk among immune cells. This review summarizes the expression and function of VEGF-A and VEGF-C in the kidney. The current immunoregulation mechanisms of VEGF signaling pathway inhibitors are reviewed. Finally, combinate strategies are summarized to highlight the proposal for VEGF signaling pathway inhibitors., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Renal interstitial fibrosis is the primary pathological basis for the progression and development of various chronic kidney diseases, ultimately leading to renal failure. Obstructive kidney disease caused by conditions such as kidney stones, is a common cause of renal fibrosis. The Hippo pathway is a crucial signaling pathway that senses mechanical forces and is involved in the pathophysiology of fibrosis. In this study, we established a mouse model of obstructive kidney disease induced by unilateral ureteral obstruction (UUO). The UUO procedure significantly upregulated YAP and fibrosis-related gene expression in a time-dependent manner. Morphologically, the renal fibrotic lesions associated with hydronephrosis progressively worsened over time in the UUO group. Atorvastatin, which is widely used to lower blood cholesterol levels, has recently been shown to inhibit Yes1 associated protein (YAP). We treated UUO mice with atorvastatin for 3 and 10 days and observed a decrease in the expression of YAP and fibrosis-related genes at the mRNA and protein levels, along with a reduction in the renal fibrosis analyzed by Masson's staining. These findings suggest that atorvastatin may serve as a preventive agent for fibrosis associated with obstructive kidney disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Predicting long-term kidney allograft failure is an unmet need for clinical care and clinical trial optimization in children. We aimed to validate a kidney allograft failure risk prediction system in a large international cohort of pediatric kidney transplant recipients. Patients from 20 centers in Europe and the United States, transplanted between 2004 and 2017, were included. Allograft assessment included estimated glomerular filtration rate, urine protein-to-creatinine ratio, circulating antihuman leukocyte antigen donor-specific antibody, and kidney allograft histology. Individual predictions of allograft failure were calculated using the integrative box (iBox) system. Prediction performances were assessed using discrimination and calibration. The allograft evaluations were performed in 706 kidney transplant recipients at a median time of 9.1 (interquartile range, 3.3-19.2) months posttransplant; mean estimated glomerular filtration rate was 68.7 ± 28.1 mL/min/1.73 m 2 , and median urine protein-to-creatinine ratio was 0.1 (0.0-0.4) g/g, and 134 (19.0%) patients had antihuman leukocyte antigen donor-specific antibodies. The iBox exhibited accurate calibration and discrimination for predicting the outcomes up to 10 years after evaluation, with a C-index of 0.81 (95% confidence interval, 0.75-0.87). This study confirms the generalizability of the iBox to predict long-term kidney allograft failure in children, with performances similar to those reported in adults. These results support the use of the iBox to improve patient monitoring and facilitate clinical trials in children., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: The study was conducted to investigate the effect of the treatment with imatinib, a c-kit specific inhibitor, on the neointimal hyperplasia (NIH) of aortocaval fistula (ACF) in adenine-induced renal failure rats., Materials and Methods: All rats were randomly assigned to 4 groups: rats were fed on a normal diet (normal group); rats were fed on a 0.75% adenine-rich diet (renal failure group). The remaining rats underwent ACF after receiving a 0.75% adenine-rich diet and received daily saline gavage (model group) or imatinib gavage (imatinib group) for 7 days after surgery. Immunohistochemical method was used to detect c-kit expression, and Elastomeric Verhoeff-Van Gieson (EVG) staining was used to observe morphological changes of the ACF. The Pearson correlation analysis was used to evaluate the correlations of c-kit expression with intimal thickness and the percentage of stenosis, respectively., Results: The renal failure group showed positive c-kit expression on the intima of the inferior vena cava (IVC), whereas the normal group did not. Compared to the model group, intimal thickness (P = 0.001), the percentage of stenosis (P = 0.006) and c-kit expression (P = 0.04) were decreased in the imatinib group at 8 weeks postoperatively. C-kit expression was positively correlated with both intimal thickness and percentage of stenosis (intimal thickness: R = 0.650, P = 0.003; the percentage of stenosis: R = 0.581, P = 0.011) in both the model and imatinib groups., Conclusion: Treatment with imatinib, a c-kit specific inhibitor, was useful to delay the NIH of ACF in adenine-induced renal failure rats., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, author-ship, and/or publication of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: With improvements in care for people with Cystic Fibrosis (pwCF), total survival after Lung Transplantation (LTx) will be longer. Therefore, this population's up-to-date analysis of late-onset post-transplant metabolic and vascular complications will be more relevant in current clinical practice., Methods: We studied 100 pwCF who underwent an LTx between 2001 and 2020 at the University Medical Centre Utrecht, the Netherlands. The median age at transplant was 31 years and 55 percent was male. We assessed survival, the prevalence of metabolic complications (diabetes, renal damage, dyslipidemia, and metabolic syndrome), and vascular complications (hypertension, heart rhythm disease, micro-, and macrovascular disease). In addition, differences in risks for developing complications based on sex and overall survival were analyzed., Results: The prevalence of macrovascular disease raised to 15.9 percent 15 years post-LTx. The prevalence of diabetes increased from 63 percent at LTx to over 90 percent 15 years post-LTx and the prevalence of dyslipidemia increased from 21 percent to over 80 percent. Survival 1-, 2-, 5-, and 10 years post-transplant were 84, 80, 76, and 58 percent respectively. No significant differences were found based on sex., Conclusion: This study shows that the prevalence of cardiovascular risk factors increases after LTx for CF, potentially leading to major complications. These data emphasize the necessity of regular check-ups for metabolic and vascular complications after LTx with specific attention to renal damage. Early recognition of these complications is crucial and will lead to earlier intervention, which could lead to improved prognosis after lung transplantation., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Therapeutic drug monitoring and Model-informed precision dosing allow dose individualization to increase drug effectivity and reduce toxicity., Objectives: To evaluate the available evidence on the clinical efficacy of individualized antimicrobial dosing optimization., Methods: Data sources: PubMed, Embase, Web of Science, and Cochrane Library databases from database inception to 11 November 2022., Study Eligibility Criteria: Published peer-reviewed randomized controlled trials., Participants: Human subjects aged ≥18 years receiving an antibiotic or antifungal drug., Interventions: Patients receiving individualized antimicrobial dose adjustment., Assessment of Risk of Bias: Cochrane risk-of-bias tool for randomized trials., Methods of Data Synthesis: The primary outcome was the risk of mortality. Secondary outcomes included target attainment, treatment failure, clinical and microbiological cure, length of stay, treatment duration, and adverse events. Effect sizes were pooled using a random-effects model. Statistical heterogeneity was assessed by inconsistency testing (I 2 )., Results: Ten randomized controlled trials were included in the meta-analysis (1241 participants; n = 624 in the individualized antimicrobial dosing group and n = 617 in the control group). Individualized antimicrobial dose optimization was associated with a numerical decrease in mortality (risk ratio [RR] = 0.86; 95% CI, 0.71-1.05), without reaching statistical significance. Moreover, it was associated with significantly higher target attainment rates (RR = 1.41; 95% CI, 1.13-1.76) and a significant decrease in treatment failure (RR = 0.70; 95% CI, 0.54-0.92). Individualized antimicrobial dose optimization was associated with improvement, but not significant in clinical cure (RR = 1.33; 95% CI, 0.94-1.33) and microbiological outcome (RR = 1.25; CI, 1.00-1.57), as well as with a significant decrease in the risk of nephrotoxicity (RR = 0.55; 95% CI, 0.31-0.97)., Conclusions: This meta-analysis demonstrated that target attainment, treatment failure, and nephrotoxicity were significantly improved in patients who underwent individualized antimicrobial dose optimization. It showed an improvement in mortality, clinical cure or microbiological outcome, although not significant., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)