bluuebunny/crossref_metadata_2025_split huggingface dataset:
#4580 ELEVATED LEVELS OF UREMIC SOLUTES IN THE CEREBROSPINAL FLUID OF HEMODIALYSIS PATIENTS
Authors: Wang Xin , Haq Zahin , Dias Gabriela Ferreira , Debure Ludovic , Wang Lin-Chun , Tao Xia , Thijssen Stephan , Wisniewski Thomas , Kotanko Peter , Grobe Nadja 
Published: June 2023

Abstract

Background and Aims
Uremic solutes are considered as contributing factors to impaired cognitive function in end stage kidney disease (ESKD) [1]. However, the distribution and accumulation of uremic solutes in the central nervous system (CNS) of ESKD patients are not well understood. We measured four uremic solutes in the cerebrospinal fluid (CSF) and plasma of two ESKD patients and investigated the role of routine hemodialysis (HD) in clearing these solutes from their CNS.

Method
We accessed CSF in HD patients with a ventriculo-peritoneal shunt. A review of about 160,000 electronic health records revealed 30 eligible patients, two of whom consented to participate in this IRB-approved one-week study (Western IRB #20172182). On dialysis days, CSF and plasma were collected 2 hours pre- and 2 hours post-HD. Non-dialysis day samples were collected 20 hours post-HD. Samples from healthy subjects were purchased from BioIVT (Westbury, NY). Urea was measured using Horiba C400 Chemical Analyzer. Indoxyl sulfate (IS), p-cresol sulfate (pCS) and trimethylamine N-oxide (TMAO) were analyzed using Agilent Ultivo triple quadrupole mass spectrometer. The dialytic reduction ratio (RR; in %) was calculated as 100 × (pre-HD level – post-HD level) / pre-HD-level.

Results
In both CSF and plasma, levels of all four uremic solutes were elevated in HD patients compared to healthy subjects (Table 1). The ratio of CSF-to-plasma levels was &lt;100% for all solutes. Ratios for HD patients are altered compared to those reported in healthy subjects (Table 1). Longitudinal plasma and CSF solute levels are shown in Figure 1. Plasma RRs for IS, pCS, TMAO and urea were 32%, 23%, 77%, and 67%, respectively. The respective CSF RRs were 29%, 20%, 3%, and 25%.

Conclusion
To the best of our knowledge, this is the first report on CSF levels of IS, pCS, and TMAO in HD patients. Our results indicate that uremic solute levels are elevated in the CSF from HD patients compared to healthy subjects. Moreover, HD only moderately reduces uremic solute levels in CSF. Whether increased CNS levels of uremic solutes are related to cognitive impairment warrants further investigation.
#4590 A PROSPECTIVE STUDY OF EPLERENONE IN THE TREATMENT OF PATIENTS WITH GLOMERULONEPHRITIS
Authors: Papasotiriou Marios , Georgopoulou Georgia Andriana , Bratsiakou Adamantia , Ntrinias Theodoros , Goumenos Dimitrios , Papachristou Evangelos 
Published: June 2023

Abstract

Background and Aims
Clinical evidence suggests that high aldosterone plasma levels contributes to progressive kidney disease. Although administration of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin type 1 receptor blockers (ARB) can delay kidney disease progression, plasma aldosterone levels may increase to a significant extent even after the initiation of such treatment. Thus, administration of mineralocorticoid receptor antagonists such as spironolactone, on top of treatment with ACEi or ARBs has been shown to reduce albuminuria and slow down kidney function deterioration. Nevertheless, there is scanty evidence on the effect of eplerenone in patients with kidney disease due to glomerulonephritis.

Method
In this prospective open-label study, we evaluated the effects of eplerenone in patients with biopsy proven glomerulonephritis already treated with ACEi or ARBs. Patients were divided in the active treatment arm, who received 25 mg of eplerenone daily besides ACEi or ARBs, and a control group that received only standard treatment. Protein excretion in 24 h urine, eGFR, blood pressure and serum K+ levels were measured at 3, 6 and 12 months after study initiation.

Results
Out of 83 patients who were screened, 62 patients were included in the final analysis. Twenty-six received eplerenone and 36 were treated with ACEi (25) or ARBs (9) alone (controls). After 1 year of treatment with eplerenone, proteinuria decreased from 1597 to 1145 mg/24 h while it did not alter in controls. Eplerenone reduced proteinuria especially in those with baseline proteinuria of &gt;1000 mg/24 h. Kidney function remained stable in patients treated with eplerenone (from eGFR: 82.51±22.6 to 84.68±31.7 ml/min/1.73 m2, p = 0.8) and showed a non significant deterioration in controls (from eGFR: 68.39±26.2 to 66.63±29.8 ml/min/1.73 m2, p = 0.08). Systolic blood pressure was significantly reduced in the active treatment arm (from 128.1±17.5 to 126.3±10.93 mmHg, p = 0.03), whereas eplerenone did not increase serum K+ levels or had any other significant adverse effect.

Conclusion
Administration of eplerenone at a dose of 25 mg/day, on top of treatment with ACEi or ARBs, can further reduce proteinuria and systolic blood pressure in patients with chronic glomerulonephritis.
#4621 TREATMENT PREFERENCES TO SERIOUS ILLNESS IN PATIENTS RECEIVING PERITONEAL DIALYSIS
Authors: Cheng Ching-I , Chuang Pei-Ni , Peng Jen-Kuei , Chueh Shu-Neng , Lai Chun-Fu , Tasi Hung-Bin , Chiang Chih-Kang , Tsai Jaw-Shiun 
Published: June 2023

Abstract

Background and Aims
People with end-stage kidney disease receiving maintenance dialysis are more likely to receive intensive pattern of end-of-life care than those with other severe illness. It's important to understand the preferences to cardiopulmonary resuscitation (CPR) and other end-of-life care. However, no prior studies have investigated patients receiving peritoneal dialysis. This study aimed to explore the preference to CPR and patterns of end-of-life care in patient receiving peritoneal dialysis (PD), which had not been specifically investigated in the literature.

Method
This cross-sectional study of patients receiving PD was conducted in the National Taiwan University Hospital between Dec. 2021, and Mar. 2022. Patients were enrolled if they were 20 years or older, sufficiently fluent to complete surveys and cognitively able to provide written informed consent and had received maintenance peritoneal dialysis for at least 3 months. Enrollee were asked to the Chinese version of Physician Orders for Life-Sustaining Treatment questionnaire.

Results
Among 400 eligible patients, 364 (91%) responded to the questionnaire. The average age was 55.5 years; 50.3% were men. Among the 364 responders, 73.6% selected do not attempt resuscitation (DNR) and 26.4% preferred CPR. Multivariate logistic analysis revealed that age (OR = 0.96, 95% CI 0.94-0.98), male (OR = 2.44, 95% CI 1.45-4.1) and residual kidney Kt/V (OR = 2.45 95% CI 1.24-4.82) were associated with CPR. If they are facing on serious illness, 47.5% of participants prefer to “Focus on comfort”, 28.6% choose “try treatments, but do not suffer” and 23.9% request “live as long as possible”. Furthermore, 51.4% of participants selected “No artificial nutrient support” in the end of life and 87.1% select “comfort care” as their first priority. Paradoxically, only 13.5% of the patients who preferred CPR took “staying alive” as their first priority, while 71.9% focused on “comfort care”.

Conclusion
Around 75% of PD patients selected DNR when cardiopulmonary arrest. Age, gender, residual Kt/V were important factors associated with CPR preference. Most patients preferred supportive pattern of end-of-life care. Integrating patients' treatment preference to serious illness and values and goals of end-of-life care in shared decision making is important for patients receiving dialysis.
#4659 PREVALENCE OF LIVER STEATOSIS MEASURED BY MULTIFREQUENCY BIOIMPEDANCE IN PATIENTS WITH CKD
Authors: Barril Guillermina , Nogueira Ángel , Josa Esmeralda , Alvarez Graciela , Cortinas Alejandra , Núñez Almudena , Giorgi Avión , Sanchez Carmen , Ruperto Mar 
Published: June 2023

Abstract

Background and Aims
The increase in visceral fat is one of the factors that contribute to the increased cardiovascular risk associated with CKD. There are few data on the prevalence of hepatic steatosis in patients with CKD. The Maltron multifrequency BIA offers us the possibility of evaluating it. The purpose of this study was to determine the prevalence of hepatic steatosis by means of multifrequency bioimpedance and to correlate it with its presence by ultrasound or CT in patients with CKD on Advanced CKD(ACKD) and HD.

Methods
We carried out a study of body composition with BIA in 315 patients, analyzing with the Maltron monitor Bioscan i-touch8 the determination of hepatic steatosis and its classification into 4 stages of involvement (normal, mild, moderate, moderately-severe and severe steatosis. We also correlated with ultrasound studies that had In order to see coincidence, we also obtained data from 9 patients without CKD.We established global steatosis prevalence and in CKD and HD and correlated with GOT,GPT,GGT,MIS, waist/height ratio, mass-fat and BMI.

Results
315 patients evaluated for CKD 151 (48%) and HD 163 (52%), 67.9% men aged 70.79 ± 12.87 years (sig difference between CKD and HD (72.4 ± 2.7) vs 69.2 ±14.3) p0.023. Globally we found healthy liver in 37.9% and steatosis in 61.3% appearing mild-13.4%, moderate 11.8%, light-high 11.4% and high 24.5%. We observed healthy liver in 35.1% in ACKD vs 40.5% in HD. We did not find significant differences between liver enzyme values between healthy liver and steatosis at a global level. We established correlation/coincidence between ultrasound/CT and BIA in 72 patients. We found a healthy liver BIA-ECHO correlation in 43 cases (93.4%), steatosis by BIA coincides with ECHO in 41.6%. If we combine healthy liver + mild steatosis by BIA, the BIA-Echo healthy liver coincides in 92.7% and steatosis in 50%. Establishing cut-off points for BMI, % fat mass and waist/height index using COR curves, we obtain areas-under-the-curve 0.828, 0.738 and 0.853 respectively, being Waist-height index (WC 0.6) with better sensitivity 80% and specificity 71, 3%. If we determine the area of fat mass with another tool, we see AUC 0.838 with 72.3% specificity and 91.3% sensitivity to detect normal liver.

Conclusion
1) A high prevalence of hepatic steatosis due to IAB appears in patients with CKD greater in CKD than in HD. 2) There is a good correlation with ECO for a healthy liver and there are parameters that correlate well in a healthy liver diagnosis. 3) Specific studies of Ultrasound-BIA are needed to validate the diagnosis of steatosis.
#4661 KIDNEY TRANSPLANTATION IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS IS ASSOCIATED WITH A HIGH INCIDENCE OF POST-TRANSPLANT CANCER
Authors: Perna Alessandro , Campise Maria Rosaria , Alfieri Carlo Maria , Regalia Anna , Cresseri Donata , Verdesca Simona , Castellano Giuseppe 
Published: June 2023

Abstract

Background and Aims
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are challenging systemic diseases. Kidney transplantation is the treatment of choice for patients with AAV and end stage kidney disease.[1] AAV relapses after transplantation are rare and data regarding AAV recurrences in this setting are lacking.[2]

Method
In this single-centre retrospective cohort study, we analyzed the data from medical records of adult patients transplanted at our transplant Center between February 2006 and January 2022 and followed at the Nephrology Unit of the same Hospital: Fondazione IRCCS Cà Granda Ospedale Policlinico in Milan.

Results
We identified 9 patients on 1026 with a pre-transplant diagnosis of AAV; all patients had received previous treatment with cyclophosphamide. Maintenance immunosuppression after transplant was tacrolimus-based in 89% of the patients. At the end of a median follow-up of 132 ± 61.1 months after transplantation, only one case of extra-renal vasculitis relapse was observed (Table 1). The relapse rate was 0.01 per patient per year comparable to what reported in the literature. However, seven patients were diagnosed with cancer after a median follow-up of 81.4 ± 35.8 months after transplantation; six had skin cancer and three a renal cell carcinoma of the native kidneys (cumulative incidence of 78%). One patient died from metastatic spinous cell carcinoma. We therefore decided to make a narrative comparison between this cohort and a previous series published by our group including 19 patients transplanted between December 1987 and January 2006.[3] In the older cohort we reported 7 relapses and a relapse-rate of 0.076 per patient per year (Table 2).

Conclusion
In conclusion, compared with previous data from our group (December 1987-January 2006), we found a consistent decrease in disease relapse (7 relapse in 19 patients previous cohort vs 1 relapse in current cohort) in kidney transplant patients with AAV, followed by the appearance of post-transplant cancer. This result could be attributable to the use of more powerful immunosuppression a deserved particular attention in the follow up of AAV patients after kidney transplantation.
#4688 ATP6V0A4 GENE MUTATION-ASSOCIATED NEPHROPATHY
Authors: Peng Siqi , Wang Bin , Zhang Xiao Liang 
Published: June 2023

Abstract

Background and Aims
The ATP6V0A4 gene is localized to chromosome 7q33∼34 and encodes for vacuolar H+-ATPase (V-ATPase) α4 subunit. Decreased V-ATPase function due to mutations in the ATP6V0A4 genes could cause H+ excretion defect of α-intercalated cells in the renal collecting duct, resulting in hereditary distal renal tubular acidosis (dRTA). However, crucially, no gain-of-function mutations in the ATP6V0A4 gene have been reported previously. This study reports a gain-of-function mutation of ATP6V0A4 gene occurred in a 32-year-old male with metabolic alkalosis, hypokalemia and hearing loss, and further explore potential pathogenic mechanisms of this mutation.

Method
Clinical information was collected from the proband and his family members. Kidney tissue samples were collected for morphological observation and immunohistochemical staining. High-throughput sequencing analyses were done for the proband and his parents. ATP6V0A4 wild-type and mutant plasmids were constructed and used to transfect the 293T cells. After 48 hours of transfection, the expression of ATP6V0A4 was verified using WB analyses and V-ATPase activity was measured by ultraviolet spectrophotometry.

Results
The proband and his father both suffered from severe hypertension and hearing loss. Blood tests showed hypokalemia, metabolic alkalosis and renal insufficiency. Urinalysis indicated acidic urine. Laboratory tests on admission are shown in Table 1. Renal biopsy suggested malignant hypertensive kidney injury. Whole-exome sequencing demonstrated that the proband carried the heterozygous mutation c.1534G&gt;T; p.V512L in exon 15 of the ATP6V0A4 gene. Sanger sequencing confirmed that the variant was inherited from his father. The immunohistochemical results implied the expression of V-ATPase α4 was significantly higher in renal tissues from proband than that of the control who was diagnosed with minimal change disease (Figure 1B).WB analysis showed 293T cells transfected with ATP6V0A4 mutant plasmids with darker protein bands, suggesting higher expression of V-ATPase α4 (Figure 1D). The cells transfected with mutant ATP6V0A4 plasmids showed significantly higher V-ATPase activity compared with wild-type ATP6V0A4 plasmids transfected cells (Figure 1E).

Conclusion
The ATP6V0A4 c.1534G&gt;T; p.V512L mutation is a gain-of-function mutation and this result indicates the possibility that this mutation might enhance the normal physiological function of the V-ATPase, and likely contributes to the increased hydrogen ions excretion and thereby to the development of metabolic alkalosis (Figure 1F).
#4846 ROXADUSTAT-INDUCED HYPOTHYROIDISM: THE EFFECT OF ROXADUSTAT ON SUPPRESSION OF THYROID FUNCTION
Authors: Ohsawa Masato , Kuji Tadashi , Nishihara Masahiro , Ohsawa Rento , Oshikawa Jin 
Published: June 2023

Abstract

Background and Aims
There have been only two case reports of hypothyroidism in patients treated with roxadustat, a HIF-PH inhibitor as new renal anemia drug. However, there has yet been no studies to examine the effect of roxadustat on thyroid function.

Method
In this study, we retrospectively examined the effects of roxadustat on thyroid-stimulating hormone (TSH) in hemodialysis patients by two blood examinations, before and during treatment with roxadustat. We included patients who had TSH levels measured after at least two consecutive weeks of roxadustat treatment and before. We excluded patients with a history of taking other HIF-PH inhibitors before roxadustat. The period was from September 2021 to November 2022 in this interim analysis. A p value of&lt;0.05 was considered statistically significant. Analyses were performed using SPSS.

Results
93 patients were included in this analysis. TSH levels significantly decreased after treatment with roxadustat. A total of 58.1% of patients had decreased TSH levels (2.23 ± 1.18 v.s. 1.81 ± 1.35, μIU/mL, p value = 0.040, Wilcoxon signed-rank test), and 18.3% of patients had a significant decrease below the normal range. Additionally, patients treated with thyroid hormone replacement therapy in primary hypothyroidism had a higher frequency (81.0%) of TSH decrease compared to patients without (p value = 0.013, Pearson's chi-square test).

Conclusion
This is the first study to examine that roxadustat has a suppressive effect on TSH secretion in hemodialysis patients. We also found that roxadustat-induced hypothyroidism is prevalent in the high frequency of TSH suppression, especially in primary hypothyroidism patients treated with thyroid hormone replacement therapy. Thyroid hormone receptor beta (THRβ), which is expressed in the hypothalamus and pituitary gland, plays an important role in regulating thyroid hormone through feedback mechanisms. Yao et al. have reported that roxadustat has a similar structure to T3 and acts as a THRβ-selective ligand, particularly activating THRβ. Therefore, it is possible that roxadustat suppresses TSH secretion through negative feedback via THRβ. It is important to monitor thyroid function in patients receiving roxadustat. Roxadustat should be avoided in patients with primary hypothyroidism, since it is inferred that roxadustat-induced hypothyroidism cannot be improved by enhancement of thyroid hormone replacement therapy.
#4880 SUCCESSFUL LIMB SALVAGE IN A CHALLENGING PATIENT ON DIALYSIS BY IMPLANTATION OF AUTOLOGOUS PERIPHERAL BLOOD MONONUCLEAR CELLS: A CASE REPORT
Authors: Capone Martina , Liberato Lorenzo Di , Ndrecka Olsi , Monaco Maria Pia , Sirolli Vittorio , Vezzani Valeria , Orfeo Chiara Alessia , Giudice Bianca Lo , Bonomini Mario 
Published: June 2023

Abstract

Background and Aims
Peripheral arterial disease (PAD) is an extremely common condition in patients with End-Stage Renal Disease (ESRD) on dialysis. Concomitant comorbidity such as diabetes may be associated with complex vascular dysfunction, and ESRD itself is a recognized risk factor for PAD leading to non healing ulcers and lower limb amputation, which occurs in a high rate of patients [1]. Despite improvement in endovascular techniques for lower extremity revascularization, the incidence of limb salvage among dialysis patients remains poor. Furthermore, lower extremity amputation in these patients is associated with higher mortality rates [2], in addition to important social and economic implications. In this Case Report, an emergent therapy approach was applied aiming to limb salvage in a 74 years old female patient on hemodialysis suffering from lower extremity critical ischemia in diabetic foot infection, otherwise candidate for major amputation, after ineffective angioplasty and Negative Pressure Wound Therapy (NPWT).

Method
After surgical debridement of the ischemic lesion, an innovative therapeutic approach [3] was performed. It consisted in implantation, in the perilesional area of the affected lower limb, of a concentrate of autologous peripheral blood mononuclear cells (PBMNC) taken from 120 ml of peripheral blood of the patient, by using a selective filtration separation system. This procedure was managed in the operating room and was repeated three times at intervals of 15 days from each other. Since concomitant osteomyelitis occurs in the ischemical diabetic foot under treatment, it was managed with a 2-dose regimen of weekly Dalbavancin, reaching infection control. The patient was followed twice a week for 7 months for regular medications.

Results
After the treatment approach, the granulation tissue improved gradually, obtaining complete surgical wound healing. Since toes gangrene occurs, amputation of the toes was necessary, but limb rescue was successfully reached.

Conclusion
The autologous implantation of PBMNC resulted in limb salvage in this patient on dialysis affected by critical peripheral arterial disease in diabetic foot. This approach has not been described in literature among patients on dialysis, despite the higher mortality rate associated with lower limb amputation in these patients. It seems to be a very promising therapy, with the potential to modify the natural history of no-options critical limb with diabetes complications, in terms of major amputation and overall survival rates. After thorough validation, the reported management could be considered for similar cases.
#4960 TIXAGEVIMAB AND CILGAVIMAB (EVUSHELD) FOR PRE-EXPOSURE PROPHYLAXIS OF COVID-19: A MONOCENTRIC STUDY IN KIDNEY TRANSPLANT RECIPIENTS
Authors: Stefanelli Lucia Federica , Alessi Marianna , Ungaro Claudia , Ciotti Chiara , Calò Lorenzo 
Published: June 2023

Abstract

Background and Aims
Patients, who underwent kidney transplantation, may be at particularly high risk of mortality due to immunosuppressive therapy and underlying comorbidity such as hypertension, cardiovascular disease and diabetes mellitus finally increasing the risk of a severe form of SARS-CoV-2 infection. According to the ERA-EDTA DESCARTES expert opinion, management of immunosuppression in SARS-CoV-2 infection suggests withdrawal of antimetabolite (mycophenolate or azathioprine) in patients with mild upper respiratory and/or gastrointestinal symptoms and discontinuation of all immunosuppressive drugs with maintenance of steroid for severe bilateral pneumonia. Despite SARS-CoV-2 vaccination, kidney transplant patients remain at increased risk for severe COVID-19 infection and mortality and at high priority for additional strategies for preexposure prophylaxis.Tixagevimab and cilgavimab are long-acting monoclonal antibodies against the spike protein of SARS-CoV-2, which block the virus’ attachment and entry into human cells. This combined monoclonal antibody (Evusheld®) has been granted emergency use authorization (EUA) by the U. S food and drug administration (FDA) for individuals 12 years and older who have a moderate to severe immunocompromising condition and may not mount an adequate vaccination response.This single cohort observational study reports the incidence and outcomes of COVID-19 among kidney transplant recipients receiving Evusheld® as preexposure prophylaxis.

Method
Observational monocentric cohort study of 119 kidney transplant patients receiving Evusheld® 150/150 mg intramuscularly as preexposure prophylaxis between July 1, 2022 and December 31, 2022. Inclusion criteria: kidney or combined kidney-pancreas transplantation within 1 year; recent acute allograft rejection; time since COVID-19 infection of 120 days and time since last vaccine dose of 2 weeks.

Results
After a median (range) follow-up of 150 days, COVID-19 was confirmed in 48/119 patients (40.3%), who had only a light form of COVID-19 infection. No one complained side.

Conclusion
Our study reported a low rate of infections with only light symptoms among kidney transplant patients treated with Evusheld®. A long-term study with a larger cohort might better evaluate the efficacy, outcomes and safety of this preexposure prophylaxis.