bluuebunny/crossref_metadata_2025_split huggingface dataset:
#4210 ZETOMIPZOMIB DEMONSTRATES CLINICALLY MEANINGFUL IMPROVEMENT IN UPCR IN NEPHROTIC RANGE PROTEINURIA PATIENTS: RESULTS FROM THE OPEN-LABEL MISSION STUDY
Authors: Parikh Samir , Saxena Amit , Leff Richard , Hua Steven , Park Eunmi , Henig Noreen 
Published: June 2023

Abstract

Background and Aims
Prospective cohorts have shown that patients with LN and nephrotic range proteinuria at baseline have a lower probability of achieving renal response [1]. These patients may require more time due to slower proteinuria recovery. Results previously reported on the Phase 2, open-label MISSION study evaluating the safety and tolerability of zetomipzomib in active proliferative LN including patients with nephrotic range proteinuria, demonstrated clinically meaningful renal responses [2]. A post-hoc analysis of MISSION patients with nephrotic range proteinuria is presented here.

Method
In the MISSON Phase 2 study, patients with active proliferative LN (Class III or IV ± V) with 24-hour urine protein to creatinine ratios (UPCR) ≥1.0 mg/mg despite stable background therapy received 60 mg of zetomipzomib subcutaneously once weekly (first dose: 30 mg) in addition to stable background therapy for 24 weeks. End of treatment (EOT) was at Week (W) 25, and end of study (EOS) occurred at W37. The primary endpoint was the number of patients with ≥50% reduction in UPCR from baseline after 24 weeks of treatment. Nephrotic range proteinuria was defined as UPCR ≥3.0 mg/mg at baseline as per KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases.

Results
Of 17 evaluable patients who reached EOT, 4 patients had nephrotic range proteinuria, with 3 having hypoalbuminemia (serum albumin ≤3.5 g/dL) at baseline. Patients with nephrotic range proteinuria had mean LN duration of 4.14 years with mean 24-hour UPCR of 5.78 mg/mg, mean serum albumin of 3.0 g/dL, mean blood pressure of 124/81 mmHg and mean eGFR of 122.5 mL/min/1.73 m2. All 4 patients were on concomitant corticosteroids (mean dose: 19.81 mg/d), mycophenolate mofetil, hydroxychloroquine and antihypertensives. After 24 weeks of zetomipzomib treatment, 3/4 patients with nephrotic range proteinuria achieved ≥50% reduction in UPCR at W25 (EOT) and W37 (EOS, 12 weeks post-treatment) (Table 1). Serum albumin levels also improved and normalized by EOS in all 3 patients with hypoalbuminemia at baseline (Table 1). eGFR levels generally remained stable throughout the study. Reduction of daily steroid dose to 10 mg/day was observed in all 4 patients as early as W13 and at EOT/EOS while other background therapy doses remained stable throughout the study. Improvement and/or normalization in key serologic biomarkers, including anti-dsDNA and C3/C4, were also observed in patients with abnormal levels at baseline.

Conclusion
In this post-hoc subgroup analysis of MISSION Phase 2 study, zetomipzomib treatment demonstrated clinically meaningful improvement in UPCR and normalization of albumin levels in patients with nephrotic range proteinuria and hypoalbuminemia. These results further support the potential activity of zetomipzomib in hard-to-treat LN patients.
#4234 ADAM17 MODULATES IFN-MEDIATED INFLAMMATION IN RENAL TUBULAR CELLS
Authors: Riera Marta , Riveira-Muñoz Eva , Galdon Eric , Garcia-Vidal Edurne , García Eva Rodríguez , Crespo Marta , Ballana Ester , Barrios-Barrera Clara 
Published: June 2023

Abstract

Background and Aims
In diabetic patients, hyperglycemia has been associated with a hypoxic state that contributes to an increased rate of morbidity due to Acute Kidney Failure (AKI). For this reason, we are interested in studying the molecular mechanisms involved in the development of AKI to contribute to the search for effective therapies that can help prevent these episodes. We focused on ADAM17, a disintegrin and metalloproteinase that sheds the ectodomains of cell surface proteins, among which inflammatory cytokines stand out. In an animal model, we showed that the absence of ADAM17 in the renal tubule reduces protein expression related to fibrosis and inflammation induced by diabetes. In this context, we aimed to study the role of ADAM17 in modifying the expression of inflammatory molecules regulated by interferon (IFN) in renal proximal tubule cells subjected to hyperglycemic stress. In this study, we analyzed the effect of ADAM17 deletion in human renal tubular cells (HKC-8) incubated in high-glucose medium and subjected to hypoxia.

Method
ADAM17 was depleted using CRISPR/Cas9 (ADAM17-KO). Cells were incubated for 6 h or 24 h with high (35 mM HG) or normal (5.5 mM NG) glucose concentrations and were subjected to hypoxia plus 2h re-oxygenation (HIPX). Gene expression of several IFN-regulated inflammatory markers (IL6, IL8, CXCL10, ISG15, IL1a, IL1b, IL12A, CCL5, and CCL2) was determined in wild-type (WT) and ADAM17-KO cells.

Results
The absence of ADAM17 in HKC-8 cells induced changes in the mRNA expression of genes controlled by IFN, which is accentuated by the hyperglycemic stimulus. Under hypoxic and re-oxygenation conditions, these changes were in the same line, with more discrete values compared to control cells. TNFa, CXCL10 and LNC2 were the most relevant genes reduced in injury conditions in the ADAM17-KO cell line.

Conclusion
ADAM17 deletion modulates the expression of most IFN-regulated genes that could undergo post-transcriptional changes and subsequently act as an acute mechanism of protection from injury. The results show that ADAM17 plays a major role in the underlying inflammatory response to acute kidney injury, indicating its potential as a therapeutic target. The analysis of circulating proteins will provide information about this process to better understand the mechanism of action of ADAM17 in the protection of renal tubular damage.
#4240 SUCCESSFUL PROPHYLAXIS WITH STROVAC VACCINE AGAINST URINARY TRACT INFECTION AFTER KIDNEY TRANSPLANTATION
Authors: Haziyev Elgun 
Published: June 2023

Abstract

Background and Aims
Urinary tract infections (UTI) are the most common of infections after renal transplantation with an estimated incidence between 10 and 98%. Recurrent urinary tract infections (rUTIs) increase mortality and reduce graft survival after renal transplantation. The present case describes an immunization strategy against bacterial strains after kidney transplantation.

Method
We administered urinary tract vaccine for prophylaxis for rUTIs after kidney transplantation. A kidney transplant recipient with 3 or more UTI episodes/year underwent immunization with 3 subcutaneous injections (once a week) of inactivated bacteria-StroVac (follow-up 12 months before to 12 months after immunization). StroVac contains 10 strains of inactivated bacteria (6 types of Escherichia coli, Proteus mirabilis, Morganella morganii, Enterococcus feacalis, Klebsiella pneumoniae). A year later the StroVac Booster was administered once. Urine culture analysis was given every 3 months for a year. Clinical and laboratory comparisons were made. The results were evaluated statistically.

Results
Before initiation of prophylaxis, patient had a UTI incidence of 5. The patient had symptoms such as fever, dysuria, or urgency and were positive in urine dipstick examination for pyuria or nitrituria. Vaccination with StroVac significantly reduced the incidence of UTI yielding a mean annual incidence of 1 (p&lt;0.05).

Conclusion
StroVac is an effective and lasting non-antibiotic prophylaxis for rUTI, easy to administer with low rates of adverse events and should be offered to patients with rUTI after kidney transplantation.
#4261 RELATIONSHIP BETWEEN FLUID OVERLOAD AND AVERAGE PLASMA REFILL RATE IN HEMODIALYSIS PATIENTS
Authors: Wang Lin-Chun , Mermelstein Ariella , Raimann Jochen , Moissl Ulrich , Zhang Hanjie , Thijssen Stephan , Kotanko Peter 
Published: June 2023

Abstract

Background and Aims
Attaining the optimal balance between achieving adequate volume removal while preserving organ perfusion remains challenging in patients on maintenance hemodialysis (HD). Quantification of fluid status using bioimpedance spectroscopy (BIS) has become routine in many countries. Inadequate vascular space refill from the interstitial tissue (plasma refill rate, PRR) is the main contributing factor of hemodynamic instability during HD. We aimed to explore the association between fluid overload (FO) and plasma refill rate (PRR) in chronic HD patients.

Method
Pre-HD FO [l] was assessed once per subject by BIS (Body Composition Monitor; Fresenius Medical Care) in four urban HD dialysis clinics in the U.S. For each treatment within 30 days before and after the BIS measurement, we calculated the respective pre-HD FO by assuming that differences in pre-HD body weight were equivalent to differences in FO. We then used intradialytic hematocrit (measured with the Crit-Line® Monitor, Fresenius Medical Care) and ultrafiltration data to quantify the average PRR, normalized by body weight (Wang et al. Kidney360, 2023): To calculate the starting blood volume (BV), we first calculated the ending BV using the Nadler equation, followed by back-calculating the starting BV based on the cumulative change in relative BV. Plasma refill volume was calculated as the sum of the changes in blood volume and ultrafiltration volume; plasma refill volume was then divided by treatment time and estimated clinical dry weight to calculate the PRR [ml/kg/hr].

Results
We analyzed 746 HD sessions from 79 patients (age 61 ± 15 years; 52 (66%) males; 41 (52%) black and 33 (42%) white). Across all HD sessions, PRR was positively associated with FO [slope estimate 0.92 (95% confidence interval 0.83 to 1.02) ml/kg/hr per 1 l of FO, P value &lt; 0.0001] (Figure 1). This was also the case in subgroup analyses of fluid depleted (r = 0.94, P&lt;0.001), normohydrated (r = 1.03, P&lt;0.0001), and fluid overloaded subjects (r = 0.83, P&lt;0.0001).

Conclusion
Across the entire fluid status spectrum, from fluid depletion to fluid overload, higher FO was associated with higher PRR on average (overall, an increase of 0.92 ml/kg/hr in PRR for each additional liter of FO). While patients with greater FO would be expected to better tolerate higher ultrafiltration rates, there is large inter-individual variability in PRR. Further investigation of the utility of PRR throughout HD may offer novel insights into fluid management and intradialytic symptom mitigation.
#4264 PERITONEAL DIALYSIS AFTER FAILED KIDNEY TRANSPLANT: A SUITABLE OPTION
Authors: Francisco Diogo , Carnevale Andreia , Ávila Gonçalo , Calça Ana Rita , Matias Patrícia , Branco Patrícia 
Published: June 2023

Abstract

Background and Aims
Despite great advances in graft survival, kidney transplant (KT) recipients frequently return to dialysis. The aim of this study was to perform an analysis of peritoneal dialysis (PD) outcomes of patients with a failed KT.

Method
Single-center retrospective cohort study with end-stage renal disease (ESRD) patients who started PD from 1st January 2010 to 31st December 2017. Two groups were analyzed - patients who started PD with no previous renal replacement therapy (RRT) - PD first -, and patients who transitioned directly from a failed kidney transplant.

Results
Among 152 patients who started PD, 115 were PD first and 15 transitioned from KT. The population included 63,1% of male gender, with a mean age of 52,4 ± 15,5 years and had PD median vintage of 30 months (IQR 20,6). Patients who transitioned from KT were significantly younger (mean age 42,8 ± 14,3 vs. 53,7 ± 15,3, p = 0,015) and had lower prevalence of diabetes mellitus (13,3% vs. 40,0%, p = 0,044). In KT patients, glucocorticoids were continued until there was residual diuresis and non-glucocorticoid immunosuppression was maintained for a median of 180 days (± 176) after PD start. Nearly a third (30,0%) of patients had no hospitalizations and 35,5% had more than 2 hospital admissions. Annual hospitalization rate was higher in prior KT group (1,40 vs. 0,48, p = 0,002). Prior KT associated with higher annual peritonitis rate (0,70 vs. 0,20, p = 0,017). A higher number of MACE was also observed in prior KT group (33,3% vs. 7,9%, p = 0,004). Residual diuresis was significantly lower in the group with previous KT. Neither ultrafiltration failure (6,7% vs. 9,9%, p = 0,974), nor technique survival (death or hemodialysis transfer 53,3% vs. 54,8%, p = 0,917; logrank 0,354) were different between groups.

Conclusion
Although higher incidence of diabetes mellitus was observed in PD first group, no differences were identified in ultrafiltration failure rates between groups. Despite significantly lower diuresis in prior KT group, both groups had adequate dialysis efficacy (mean Kt/V&gt;1,7) and similar technique survival. Higher peritonitis rate and MACE incidence was observed in prior KT group, possibly associated with maintenance immunosuppression. Nevertheless, PD is a valid choice for RRT after a failed KT and should be offered to these patients.
#4281 TERTIARY HOSPITAL EXPERIENCE IN AN ESSENTIAL SUBSPECIALTY: ONCONEPHROLOGY
Authors: Garcia Sheila Bermejo , Bolufer Mónica , Viggiano Davide , Callejo Ana , Felip Enriqueta , López Marina , Vergara Ander , Pamplona Irene Agraz , Matamoros Oriol Bestard , Romeo Maria Jose Soler 
Published: June 2023

Abstract

Background and Aims
Kidney complications of cancer patients and cancer in renal patients have increased in recent years. The objective of this study is to evaluate the characteristics of the patients referred to the Onconephrology Unit from January 2021 to December 2021, studying the cognitive and mood status of these patients.

Method
This is a prospective observational study of the Onconephrology consultation at a University Hospital Center during 2021. Clinical and analytical characteristics of the patients and clinical indication for referral were analyzed. In addition, sleep quality, mood and cognitive status were assessed using validated rating scales (Epsworth, Geriatric Depression Scale and Montreal).

Results
Seventy-four patients were evaluated, mean age was 69.6(±11) years, 41(55.4%) men, 47(63.5%) had hypertension, 18(24.3%) diabetics, and 11(14.9%) were affected by heart disease. In addition, creatinine 1.93(±1.1)mg/dl, eGFR 39.97(±20.3)mL/min, proteinuria 187[29-515.9]mg/g, and 4(5.4%) had microhematuria. The most frequent cancers were intestinal, gynecological and mammary with 12.16% (n = 9) each. 58.3% (n = 42) of patients had metastatic disease. 48.7%(n = 36) received chemotherapy and 58.1%(n = 43) targeted therapies. Platinum was the most frequently used chemotherapy and anti-VEGF in terms of targeted therapies, followed by tyrosine kinase inhibitors, anti-PD1 and anti-PDL1. The most frequent clinical indication for referral was acute renal failure (n = 36;48.7%) followed by chronic kidney disease (n = 27;36.49%) and proteinuria (n = 5;6.76%). Rating scales were obtained in 51 patients: 49% (n = 25) were snorers, followed by 17.6% (n = 9) with insomnia and 11.8% (n = 6) with OSAS. 27 patients (36.5%) had cognitive impairment. Mild depression was detected in 13 cases (25.5%) and moderate depression in 11.6% (n = 6). 21 renal biopsies were performed, the most frequent diagnosis was acute interstitial nephritis (71.4%, n = 15) followed by thrombotic microangiopathy (19% n = 4). A total of 15 patients (20.3%) died during the year.

Conclusion
Most patients referred to Onconephrology are affected by advanced oncological disease and consequently had a high mortality. The most frequent indication for referral was acute kidney injury (48.7%). Comprehensive patient care is important, given the prevalence of depressive syndrome. Onconephrology is an example of a comprehensive and multidisciplinary approach to improve the survival and quality of life of patients with advanced cancer and renal disease.
#4285 CAUSES OF PEDIATRIC END STAGE KIDNEY DISEASE IN SUDAN
Authors: Hussein Rasha , Ye Xiaoling (Janice) , Ellidir Rashid , Ali Elitigani , Bakhiet Yassir , Karar Mohamed , Yousif Mohamed , Mustafa Ghassan , Allam Nahla , Yahia Samira , Ahmed Amna , Abdelraheem Mohamed , Kotanko Peter 
Published: June 2023

Abstract

Background and Aims
Sudan is a large Sub-Saharan country with a population of about 48 million people, 41% of them under the age of 15 years and a median age of 18.9 years. To data, no data have been reported on the etiology of end stage kidney disease (ESKD) in children and young adults of less than 18 years of age.

Method
We conducted a chart review of all ESKD patients below the age of 18 years treated in a tertiary referral center, the Soba University Hospital (SUH) in Khartoum, the capital of Sudan. The research was approved by the SUH ethical committee. We report descriptive statics, including age, sex, ESKD causes, and kidney biopsy frequency.

Results
We included 885 patients in this analysis, their mean age (SD) was 12 (3.0) years and 57.7% were males. Glomerulonephritis, mostly post-streptococcal glomerulonephritis, was the leading cause of ESKD (36.8%), followed by unknown etiologies (25.3%) and congenital anomalies of kidney and urinary tract (CAKUT; 14.9%). In most patients with glomerulonephritis the diagnosis was based on kidney histology (96.6%). ESKD was attributed to HUS in about 7% of patients. As expected, SLE was more prevalent in females (3:1 ratio) and hereditary nephritis in males (3:1).

Conclusion
Glomerulonephritis and CAKUT account for over 50% of pediatric ESKD patients in this study from a tertiary referral center in Sudan.
#4306 DIALYSIS ADEQUACY AND INCIDENT ATRIAL FIBRILLATION IN HEMODIALYSIS PATIENTS
Authors: Heo Ga Young , Park Jung Tak , Kim Hyo Jeong , Kim Kyung Won , Kwon Youg Uk , Kim Soo Hyun , Kim Gui Ok , Han Seung Hyeok , Yoo Tae-Hyun , Kang Shin-Wook , Kim Hyung Woo 
Published: June 2023

Abstract

Background and Aims
Atrial fibrillation (AF) can lead to stroke, heart failure, and mortality, and has a greater prevalence in dialysis patients than in the general population. Several studies have proposed that uremic toxins might promote AF development. However, the association between dialysis adequacy and incident AF has not been well established.

Method
In this retrospective study, we analyzed 27,475 patients receiving maintenance hemodialysis, included in the Periodic Hemodialysis Quality Assessment by Health Insurance Review & Assessment Service (HIRA). The main exposure was single pooled Kt/V and the primary outcome was the development of AF.

Results
During a median follow-up of 4.8 years, incident AF occurred in a total of 4,229 (15.4%) patients. Participants with higher single pooled Kt/V tended to have lower AF incidence. In survival analysis, there was a graded association between the risk of incident AF and single-pool Kt/V quartiles: subdistribution hazard ratios and 95% confidence intervals (CI) for the second, third, and the highest quartile compared with the lowest quartile were 0.90 (95% CI, 0.83-0.98), 0.85 (95% CI, 0.78-0.93), and 0.80 (95% CI, 0.73-0.89), respectively. When treating single-pool Kt/V as a continuous variable, a similar association was found. In addition, the risk of incident AF in the highest quartile of urea reduction ratio was 0.83-fold (95% CI, 0.76-0.91) lower than in the lowest quartile. Sensitivity analyses showed consistent results. This association was more pronounced in men.

Conclusion
As the part of the Joint Project on Quality Assessment Research by HIRA, this nationwide cohort study showed that lowering uremic toxin burden through increased dialysis clearance could be associated with a lower AF development risk in patients receiving maintenance hemodialysis.
#4372 TYK2-INDUCED STAT ACTIVATION IS ESSENTIAL FOR VASCULAR PRO-CALCIFIC EFFECTS OF LEUKEMIA INHIBITORY FACTOR
Authors: Razazian Mehdi , Voelkl Ioana Alesutan , Pitigala Lakmi , Luong Trang T D , Estepa Misael , Zickler Daniel , Pasch Andreas , Holfeld Johannes , Mueller Mathias , Vlahou Antonia , Eckardt Kai-Uwe , Voelkl Jakob 
Published: June 2023

Abstract

Background and Aims
Hyperphosphatemia in chronic kidney disease (CKD) is closely linked to medial vascular calcification. Phosphate is able to induce pro-inflammatory effects in vascular smooth muscle cells (VSMC), which could actively augment calcification processes. This study investigated the role of the IL-6 family member leukemia inhibitory factor (LIF) during vascular calcification.

Method
Experiments were performed in primary human aortic VSMCs, ex vivo mouse aortic rings and cholecalciferol treated mice, as well as serum samples from CKD patients and healthy controls.

Results
Phosphate exposure induced LIF release in VSMCs, while supplementation of LIF aggravated calcification and expression of pro-calcific markers in VSMCs. Silencing of LIF or addition of soluble LIF receptor (LIFR) as putative LIF antagonist ameliorated the pro-calcific effects of phosphate. Similarly, effects of phosphate or LIF were blunted by silencing of LIFR or its coreceptor GP130 in VSMCs. Mechanistically, LIF induced phosphorylation of TYK2, which was required for STAT1/3 activation. TYK2 overexpression augmented VSMC calcification, while silencing of either TYK2 or STAT1/3 ameliorated phosphate- and LIF-induced expression of pro-calcific markers. Pharmacological inhibition of TYK2 ameliorated calcification in VSMCs, mouse aortic rings and mice after cholecalciferol treatment. Furthermore, calcification was ameliorated in TYK2-deficient mouse aortic rings and mice after cholecalciferol overload. In a pilot study, LIFR was reduced in serum from patients with CKD and LIFR levels were associated with serum calcification propensity.

Conclusion
Vascular calcification is augmented by LIF, which identifies a crucial role of TYK2 in the pro-calcific reprogramming of VSMCs. Inhibition of this signalling axis might be able to reduce the burden of vascular calcification in CKD.
#4378 GLOMERULAR HYPERFILTRATION AS RISK FACTOR FOR MAJOR ADVERSE CARDIOVASCULAR EVENTS AFTER ACUTE MYOCARDIAL INFARCTION
Authors: Lee Hyo Jin , Jeong Kyunghwan , Hwang Hyeon Seok , Kim Jin Sug , Yoon Soo-Young , Kim Jong Ho , Kim Dae Kyu , Lim So Jin 
Published: June 2023

Abstract

Background and Aims
A reduced glomerular filtration rate (GFR) is a definite risk factor for major adverse cardiovascular event (MACE) in acute myocardial infarction (AMI) patients. While glomerular hyperfiltration (GHF) is associated with early phases of kidney disease, it is unclear whether GHF is associated with higher risk of MACE.

Method
9,561 AMI patients with estimated GFR ≥ 60 mL/min/1.73 m2 were enrolled from prospective population-based national cohort. GHF was defined as GFR &gt; 90th percentile after adjustment for age, sex, lean body mass and history of diabetes and hypertension, systolic blood pressure, left ventricular ejection fraction and use of angiotensin converting enzyme inhibitor or receptor blocker. Patients were divided into two groups (normal filtration group vs. GHF group) and occurrence of 3-year MACEs after AMI were investigated. Sensitivity analyses with different adjusted variables for hyperfiltration or with different patient exclusion criteria, and propensity score matching were conducted to determine consistency of our results.

Results
The GFR in 956 patients with GHF was 113.1±13.1 and it was significantly higher than those in normal filtration patients (87.7±13.1; P&lt;0.001). The incidence rate of MACEs was higher in patients with GHF, and patient with GHF showed significantly higher risk of MACEs even after adjustment for several confounders (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.11-1.63) compared to normal filtration patients. GHF group had significantly higher risk of all-cause mortality (HR 1.65; 95% CI 1.26-2.17) and cardiac death (HR 1.80; 95% CI 1.28-2.54). There was no significant difference in the risk of non-cardiac death between two groups. Sensitivity analyses and propensity score matched analysis also showed similar findings.

Conclusion
GHF was independently associated with increased risk of MACE after AMI and the hazardous effects of GHF was pronounced in all-cause mortality and cardiac death. Our findings suggest that GHF might be a useful marker for predicting MACE after AMI.