bluuebunny/crossref_metadata_2025_split huggingface dataset:
#2292 Incremental peritoneal dialysis: an individualized therapy with better clinical outcomes and reduced environmental and economic impact
Authors: Domingos Diogo , Ávila Gonçalo , Carnevale Andreia , Francisco Diogo , Fernandes Adriana , Calça Rita , Branco Patrícia , Matias Patrícia 
Published: May 2024

Abstract

Background and Aims
Incremental peritoneal dialysis (IPD) is based on the prescription of a dose lower than the standard “full dose” (SPD). The achievement of individualized clearance goals is based on the combination of peritoneal and renal clearance. IPD as the initial PD strategy seems to be a convenient and resource-sparing technique, but its impact in long term outcomes and in the environment lacks evidence.
The aim of this study is to evaluate IPD outcomes and to analyze the potential impact of this initial approach on costs, total and plastic waste, and water consumption.

Method
Single-center observational retrospective study that included a cohort of 87 prevalent PD adults. Patients were assigned in two groups according to their initial PD prescription—IPD group [continuous ambulatory PD (CAPD): less than 4 dwells daily, less than 2L dwell volume, and/or PD less than 7 days/week; automated PD (APD): without a long dwell, less than 10 L delivered, and/or PD for less than 7 days/week] and SPD group. Primary outcomes were residual kidney function preservation, technique survival and mortality. Secondary outcomes were peritonitis rate and hospitalizations. The reductions related to costs, total and plastic waste, and water usage were also compared between groups.

Results
In 57 (65%) of the patients IPD was the initial therapy, while 30 (35%) patients were prescribed SPD. The median follow-up was 23 months and the median transition time from 2 to 3 and from 3 to 4 exchanges were 6 and 14 months in CAPD, respectively. APD patients transitioned to SPD after a median of 9 months.
Patients in IPD group had a higher glomerular filtration rate (7 vs. 3.7, mL/min/1.73 m2, p &lt; 0.001) in the first 6 months, and after 24 months (4.8 vs. 1.9, mL/min/1.73 m2, p = 0.002. IPD was also associated with a longer technique survival (p = 0.026), lower hospital admissions per year (0.23 vs. 0.5, p = 0.001), and lower mortality (1.8% vs. 13.3%, p = 0.027).
Compared to SPD, 2 and 3 exchanges per day led to a reduction in costs of approximately 8500 or 4100 euros/patient-year, total waste of 266 or 143 kg/year/patient, in plastic waste of 159 or 69 kg/year/patient, and water savings of 28,620 or 12,420 L/year/patient, respectively.
In APD, IPD led to a reduction of 4400 euros/ patient-year in cost, 211 kg/year/patient in total and of 139 kg/year/patient in plastic waste, and water savings of 25,020 L/year/patient.

Conclusion
Prescription of initial individualized IPD is associated with better clinical outcomes in patients with substantial RKF. This approach was a significant economic and environmental impact, with a reduction in total and plastic waste, and water consumption.
#2307 Serum NGAL, MMP-9 and suPAR in the assessment of kidney impairment and cardiovascular risk in children and adolescents with type 1 diabetes or obesity
Authors: Kostopoulou Eirini , Kalavrizioti Dimitra , Davoulou Panagiota , Vamvakas Sotirios , Papachristou Evangelos , Spiliotis Bessie , Goumenos Dimitrios , Papasotiriou Marios 
Published: May 2024

Abstract

Background and Aims
Type 1 diabetes mellitus (DM1) and obesity represent two chronic paediatric diseases with worryingly rising incidence, characterized by chronic inflammation, endothelial dysfunction and increased risk for kidney impairment and cardiovascular disease. The aim of this cross-sectional study was to explore the potential usefulness of serum Neutrophil Gelatinase-Associated Lipocalin (NGAL), Matrix Metalloproteinase-9 (MMP-9) and Soluble Urokinase Plasminogen Activator Receptor (suPAR) for predicting early kidney injury or increased cardiovascular risk in children and adolescents with DM1 or obesity.

Method
Serum samples were obtained from children and adolescents aged &lt;18 years old with DM1 (n=35) or obesity (n=38) and normal renal function with no history of albuminuria, as well as from healthy controls (n=23). Serum NGAL, MMP-9 and suPAR concentrations were measured using commercially available sandwich ELISA kits (NGAL: (DY1757-05), MMP-9: (DMP900); suPAR: (DUP00); R&D systems). All patients were evaluated for anthropometric indices (weight, height, BMI) while for different degrees of weight status we used the body mass index (BMI) z-score adjusted for age and sex. Estimated glomerular filtration rate (eGFR) was calculated according to the revised bedside Schwartz formula.

Results
Serum NGAL values were found significantly higher in patients with obesity but not in those with DM1. A positive correlation was found in patients with T1DM with diabetes duration (Spearman rho 0.364, p=0.044), and in all study participants with BMI z-score (Spearman rho 0.401, p=0.004). Furthermore, serum MMP-9 levels were significantly increased in patients with T1DM and in patients with obesity compared to controls. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls (Table 1). Finally, serum suPAR levels showed a negative correlation with age (Spearman rho −0.359, p&lt;0.001) and creatinine levels (Spearman rho −0.334, p=0.005), and a positive correlation with BMI z-score (Spearman rho 0.354, p=0.009).

Conclusion
Circulating NGAL, MMP-9 levels may prove useful as surrogate biomarkers to creatinine, GFR and albumin excretion rate for early detection of kidney injury, inflammation or endothelial dysfunction and cardiovascular complications in children and adolescents with T1DM or obesity. Children with obesity may have impaired inflammation status, kidney and endothelial function to a higher degree compared to children with T1DM, which may suggest that obesity may impose a greater health burden than T1DM, at least during childhood or the first years after T1DM diagnosis.
#694 Effects of nonsteroidal mineralocorticoid receptor antagonists on kidney of cirrhotic rats
Authors: Huang Hui-Chun , Chuang Chiao-Lin 
Published: May 2024

Abstract

Background and Aims
Aldosterone binds to renal mineralocorticoid receptors (MRs) to regulate fluid and electrolytes homeostasis. In addition, aldosterone can be deleterious as a driver of inflammation and tissue fibrosis in several organs. Thus, blockade of aldosterone represents an important option to mitigate the target-organ damage. Mineralocorticoid receptor antagonists (MRAs) have been widely used as diuretic drugs for the management of hypertension, cirrhosis, and heart failure. However, the use of MRAs is limited by adverse events such as hyperkalemia. More recently, novel nonsteroidal selective MRAs with improved safety profiles have been developed. This nonsteroidal MRA (finerenone) has higher selectivity and stronger affinity for the MR, leading to lower risk of hyperkalemia. Recent evidences showed that finerenone reduces albuminuria, risk of CKD progression, and cardiovascular events in patients with chronic kidney disease and type 2 diabetes with a low incidence of hyperkalemia related treatment discontinuation.
The pathophysiology of cirrhosis is very similar to that of cardiac failure. Decompensated cirrhosis is frequently treated with the MRAs. In addition to fluid management, MRAs showed hepatoprotective actions via reducing oxidative stress and inflammatory responses in CCl4-induced and common bile duct ligation (CBDL)-induced liver injury models. The potential beneficial effects of nonsteroidal MRA on cirrhosis had never been studied. This study aims to explore the renal protective role of nonsteroidal selective MRA and associated mechanisms in common bile duct ligation-related liver injury in rat model.

Method
CBDL was used to create liver injury in the Male Sprague-Dawley Drats. Finerenone (10 mg/kg/day) or vehicle was administered since the 1st day after CBDL. The effects of nonsteroidal selective MRA on kidneys were surveyed in two paralleled series on the 7th day (inflammation) and the 28th day (cirrhosis), respectively. The following parameters were evaluated: (a) hemodynamic parameters; (b) serum potassium, liver and renal function; (c) in-situ kidney perfusion; (d) western analyses of renal cortex and medulla.

Results
Compared with the vehicle-treated group, there was significantly lower renal vascular responsiveness to ET-1 in CBDL rats receiving 28 days of MRA (p&lt;0.05) (Fig. 1B), but not in those receiving 7 days of MRA (Fig. 1A). MRA treatment led to no significant change in mean arterial pressure, portal pressure, serum potassium, liver, and renal function in CBDL rats (Table 1). The expressions of vasoactive mediators, such as iNOS, eNOS, ETA, and ETB in both renal cortex and medulla showed no significant change in CBDL rats following 28 days of MRA treatment (Fig. 2).

Conclusion
MRA treatment led to no significant effects on hemodynamics, liver, and renal function, but lower renal vascular responsiveness to ET-1 in CBDL rats receiving 28 days of MRA. The exact mechanisms remained to be further studied.
#348 Neutrophil membrane-derived nanovesicles deliver IL-37 to repair renal endothelial cells in ischemia‒reperfusion injury
Authors: MA Wenjie , Zhou Changcheng , Wu D I , Long Chengcheng , Liu Jingyu , Jia Ruipeng 
Published: May 2024

Abstract

Background and Aims
Renal ischemia‒reperfusion injury (IRI) is one of the most important causes of acute kidney injury (AKI). Interleukin (IL)-37 is a novel anti-inflammatory factor, but its application is still limited by its low stability and delivery efficiency. In recent years, engineered extracellular vesicles (EVs) have attracted substantial attention as an emerging drug delivery system. The aim of this study was to investigate the reparative effect of neutrophil membranes-derived nanovesicle (N-MV)-delivered IL-37 on renal IRI and its mechanism of action.

Method
The density gradient centrifugation method was used to extract peripheral blood neutrophils from rats, and the differential centrifugation method was used to extract neutrophil membranes. Cell membranes and IL-37 were then extruded with polycarbonate porous membranes with different pore sizes using a mini extruder to prepare IL-37 that was coated with neutrophil membrane (N-MV@IL-37). Subsequently, the physical and chemical properties and in vitro biological functions were identified. The in vivo distribution of N-MV@IL-37 as well as the renal function and inflammatory response in rats were further evaluated in a rat renal IRI model, and the targeting and anti-inflammatory mechanisms of N-MV@IL-37 were further explored.

Results
N-MV@IL-37 not only enhanced the stability of IL-37 but also targeted endothelial cells via P-selectin glycoprotein ligand-1 (PSGL-1) on neutrophil membrane surfaces. In vitro experiments showed that N-MV@IL-37 inhibited endothelial cell apoptosis and inflammatory factor production and promoted endothelial cell viability and angiogenesis. In the rat renal IRI model, N-MV@IL-37 inhibited renal cell apoptosis and alleviated inflammatory responses, thereby improving renal function in IRI rats.

Conclusion
N-MVs provide an effective method of delivering IL-37, thereby alleviating the inflammatory response due to renal IRI and repairing renal endothelial cells; these vesicles could be a potential system for the treatment of renal IRI. Meanwhile, N-MVs also provided a drug delivery platform to provide a new strategy for the treatment of other IRI-like diseases.
#2468 2-Step-Scores with optional histopathology for the prediction of delayed graft function and 1-year transplant loss in Eurotransplant
Authors: Becker Jan Ulrich , Ernst Angela 
Published: May 2024

Abstract

Background and Aims
The decision for acceptance or discard of the increasingly rare and marginal deceased donor kidneys in Eurotransplant (ET) countries has to be made without solid evidence. Thus, we developed and validated flexible clinicopathological scores we call 2-Step Scores for the prognosis of delayed graft function (DGF) as 2-Step-DGF and one-year death-censored transplant loss (1y-tl) as 2-Step-1y, reflecting current practice of six ET countries including Croatia and Belgium.

Method
The training set was n = 620 for DGF and n = 711 for 1y-tl, with validation sets n = 158 and n = 162. In step 1, stepwise logistic regression models including only clinical predictors were used to estimate the risks. In step 2, risk estimates were updated for statistically relevant intermediate risk percentiles with nephropathology.

Results
Step 1 revealed an increased risk of DGF with increased cold ischaemia time, donor and recipient BMI, dialysis vintage, number of HLA-DR mismatches or recipient CMV IgG positivity. On the training and validation set, c-statistics were 0.672 and 0.704, respectively. At a range between 18% and 36%, accuracy of DGF-prognostication improved with nephropathology including number of glomeruli and Banff cv (updated overall c statistics of 0.696 and 0.701, respectively).
Risk of 1y-tl increased in recipients with cold ischaemia time, sum of HLA-A. -B, -DR mismatches and donor age. On training and validation sets, c-statistics were 0.700 and 0.769, respectively. Accuracy of 1y-tl prediction improved (c-statistics = 0.706 and 0.765) with Banff ct. Overall, calibration was good on the training, but moderate on the validation set; discrimination was at least as good as established scores when applied to the validation set. Receiver operating characteristics of both 2-Step-DGF and 2-Step-1y compared to established scores are shown in Figs 1 and 2.

Conclusion
Our flexible 2-Step Scores with optional inclusion of time-consuming and often unavailable nephropathology should yield good results for clinical practice in ET, and may be superior to established scores. Our scores are adaptable to donation after cardiac death and perfusion pumps use.
#2139 Non-lupus full house nephropathy: a debatable entity
Authors: Uzzo Martina , Kronbichler Andreas , Alberici Federico , Bajema Ingeborg 
Published: May 2024

Abstract

Background and Aims
The presence of a full house (FH) pattern at immunofluorescence on kidney biopsy in a patient without clinical and laboratory features of systemic lupus erythematosus (SLE) has led to the descriptive term non-lupus full house nephropathy (NLFHN). This systematic review and meta-analysis focus on NLFHN nomenclature, clinical findings and outcomes.

Method
In a reiterative process, all identified terms for NLFHN and other MeSH terms were searched in PubMed. Out of 344 results, 57 records published between 1982 and 2022 were included in the analysis. Clinical data of single patients from different reports were collected and analysed.

Results
Out of the 57 records, 61% were case reports. NLFHN was addressed with 17 different names; the same name used by different authors could refer to different entities. We identified 148 patients: 75 (51%) were males; median age 35 (23-58) years. Serum creatinine and proteinuria at onset were 1.4 (0.8-2.5)mg/dL and 5.7 (2.7-8.8)g/day. Overall, about half of patients achieved complete response.
A causative agent was identified in 51 (44%) patients, predominantly infections(41%). Secondary NLFHN was mostly non-relapsing with worse kidney function at onset compared to idiopathic NLFHN (P = 0.001). Among the 57 (50%) patients with idiopathic NLFHN, complete response was comparable between patients treated with immunosuppression and supportive therapy; however, proteinuria and creatinine at onset were higher in patients treated with immunosuppression (P = 0.089 and P = 0.066). The remaining 7 (6%) patients developed SLE after a median follow-up of 5.0 (1.9-9.0) years.

Conclusion
The place of NLFHN among glomerular diseases is still uncertain, due to the lack of high-quality evidence and consensus on nomenclature. NLFHN can be evaluated as initial manifestation of SLE, isolated manifestation of SLE or a new disease unrelated to SLE. Data support the classification of SLE and NLFHN as distinct clinical entities, with comparable outcome. However, RCTs are needed to drive strong conclusions on treatments and outcomes.
#2699 Rare glomerular microangiopathy: clinicopathological characteristics and prognosis
Authors: Liu Hanshu , Xia Peng , Wen Yu-Bing , Ye Wei , Ye Wenling , Zhang Lu , Wang Ying , Chen Limeng 
Published: May 2024

Abstract

Background and Aims
Different from the typical histologic changes of thrombotic microangiopathy (TMA), we identified a group of patients whose pathology with glomerular involvement without blood vessel lesions, which was rare and known as glomerular microangiopathy (GMA).

Method
In Peking Union Medical College Hospital, a total of 33 patients were diagnosed as GMA with proliferation and swelling of glomerular endothelial cells, fragmented red blood cells, fibrin or platelet thrombi in the capillary lumen, thickening of the basement membrane, stenosis or occlusion of capillary lumen, but no abnormalities in the endothelium of renal small vessels. The pathology and clinical data were from the medical records and analyzed.

Results
The patients were 66.7% male with a mean of 45 years (14 to 74 years). The primary diseases were Castleman's disease (CD, 30.3%), POEMS syndrome (21.2%), cancer patients receiving agents targeting vascular endothelial growth factor (21.2%), and others. All the patients showed various degrees of proteinuria, with an average 24-hour urinary protein of 2.66 g/d, hematuria (63.6%), and acute kidney injury (AKI, 39.4%). The median serum creatinine (SCr) was 142 (107.5, 169) μmol/L. The AKI patients had lower Alb (P &lt; 0.0001), PLT (P = 0.0192), higher high-sensitivity C-reactive protein (hs-CRP) (P = 0.0199), and reduction of IgA (P = 0.0021). There is no significant difference in SCr and proteinuria among patients with different etiologies. The CD patients exhibited higher hs-CRP and D-Dimer. Treatment included targeting therapy of underlying hematological disorders, glucocorticoid combination with or without immunosuppressant, and supportive treatment. After treatment, we observed proteinuria remission (66.7%), partial improvement (27.3%), or complete recovery (45.5%) of renal function.

Conclusion
In Castleman's disease, POEMS syndrome, and patients receiving agents targeting VEGF, initial attention to GMA might improve the prognosis and shed light on the study of the mechanisms.
#1444 Albuminuria and subsequent risk of kidney events in patients with IgA nephropathy: a nationwide cohort study
Authors: Faucon Anne-Laure , Lundberg Sigrid , Lando Stefania , Wijkström Julia , Segelmark Mårten , Evans Marie , Carrero Juan-Jesus 
Published: May 2024

Abstract

Background and Aims
KDIGO recommends proteinuria &lt;1 g/d as a treatment target in patients with immunoglobulin A nephropathy (IgAN) because of high-risk of progression to kidney failure. However, long-term kidney outcomes in patients with low-grade proteinuria remain poorly studied.

Method
We enrolled patients with biopsy-proven primary IgAN from the Swedish Renal Registry and analyzed associations between first-recorded urinary albumin-to-creatinine ratio (uACR, in categories &lt;0.3, 0.3-0.5, 0.5-1.0, 1.0-1.5, 1.5-2.0 and &gt;2.0 g/g) and the occurrence of major adverse kidney events (MAKE, a composite of kidney replacement therapy [KRT] and &gt;30% decline in eGFR). We also explored the risk of MAKE associated with the fold-change in uACR within a year.

Results
We enrolled 1269 patients with primary IgAN (74% men, median 53 years, mean eGFR 33 mL/min/1.73 m², median uACR 0.7 g/g). Compared to patients with uACR &lt;0.3 g/g, those with higher uACR levels were younger, more often men, had a higher prevalence of hypertension, diabetes, acute kidney injury, lower eGFR and serum albumin level, and were less often prescribed RASi. Over median follow-up of 5.5 [2.8;9.2] years, 667 MAKE and 517 KRT events occurred, and 528 patients experienced &gt; 30% eGFR decline. In multivariable analyses, and compared with uACR &lt;0.3 g/g, any higher uACR category strongly and incrementally associated with the risk of MAKE (Figure), with Hazard Ratios (HR) ranging from 1.56 [95% CI 1.14-2.14] in patients with uACR 0.3-0.5 g/g to 4.53 [3.36-6.11] in patients with uACR&gt;2g/g. Similar graded relationships were observed for KRT (HR ranging from 1.39 to 4.65), and for &gt;30% decline in eGFR (HR ranging from 1.76 to 3.47). In the 785 patients who had repeated uACR measurements within a year, and compared with stable uACR, the risk of kidney events was lower if uACR decreased by 2-fold (HR ranging from 0.47 to 0.49), and higher if uACR increased by 2-fold (HR from 1.18 to 2.56), irrespective of baseline uACR.

Conclusion
Our findings show substantial risk of adverse kidney outcomes among patients with IgAN and uACR between 0.3 and 1.0 g/g, a population currently considered at low-risk of CKD progression. Reduction in uACR is associated with better kidney outcomes, irrespective of baseline uACR.
#1342 Updated results from the RUBY-3 study of povetacicept, an enhanced dual BAFF/APRIL antagonist, in autoantibody-associated glomerulonephritis
Authors: Madan Arvind , Park Inwhee , Yalavarthy Rajesh , Mandayam Sreedhar , Kulkarni Hemant , Barratt Jonathan , Davies Rupert , Enstrom Amanda , Thomas Heather , LI Jiahua , Peng Stanford L , Tumlin James 
Published: May 2024

Abstract

Background and Aims
Inhibition of BAFF and/or APRIL has shown promise in IgA nephropathy (IgAN), systemic lupus erythematosus (SLE), lupus nephritis (LN), and primary membranous nephropathy (pMN), and has the potential to exert a disease-modifying effect. Povetacicept (ALPN-303) is an Fc fusion protein of a variant TACI domain engineered for more potent dual BAFF/APRIL inhibition than wild-type TACI or anti-BAFF or anti-APRIL antibodies. In a previous report, povetacicept 80 mg every 4 weeks was initially well tolerated and demonstrated promising, clinically meaningful reductions in urine protein to creatinine ratio (UPCR) and Gd-IgA1 in participants with IgAN (Tumlin J, et al. Poster TH-PO1125 presented at ASN 2023). Updated data are reported here.

Method
RUBY-3 is an open-label, multiple ascending dose, phase 1b/2a study of povetacicept 80 or 240 mg administered subcutaneously once every 4 weeks. Eligible participants are aged ≥18 years with biopsy-confirmed IgAN, LN, or pMN and on maximally tolerated ACE inhibitor/ARB therapy, with well-controlled blood pressure, and disease-specific immunosuppressive therapy where applicable. The primary objective is safety; secondary objectives include pharmacokinetics, pharmacodynamics, immunogenicity, biomarkers, and efficacy.

Results
As of 1 Dec 2023, 12 participants with IgAN have enrolled and received povetacicept 80 mg, with 7 (58%) having received ≥24 weeks of treatment. Povetacicept continues to be well tolerated, with the majority of treatment-emergent adverse events being of low grade. There have been no incidences of severe hypogammaglobulinemia (IgG &lt;3 g/L) or severe infections. Povetacicept 80 mg was associated with a UPCR reduction of 52.6% at 24 weeks (n = 7). Reductions in Gd-IgA1, stable renal function, and pharmacodynamically expected decreases in immunoglobulin levels were also observed. Additional results from the 80 mg cohort with longer duration of follow-up, as well as initial results from the 240 mg dosing cohort, are planned to be presented.

Conclusion
Povetacicept remains well tolerated with multiple dosing and continues to demonstrate very promising activity in IgAN, strongly supporting further study in IgAN as well as other glomerulonephritis and autoantibody-associated diseases.