bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO769COMPARISON OF HEMODIALYSIS CONNECTORS CAPS VS ANTIMICROIAL BARRIER CAPS IN CENTERAL LINE-ASSOICATED BLOOSTREAM INFECTION RATES FOR HEMODIALYSIS PATIENTS
Authors: Hemeyer Connie , Moreland Marshall , Olson Elsa , Fitzpatrick Peter , Hickson Latonya 
Published: May 2021

Abstract

Background and Aims
Central line-associated bloodstream infections (CLABSI) lead to increased morbidity and mortality in hemodialysis-dependent patients and are costly to treat. Devices such as hemodialysis connector caps (Tego) and antimicrobial barrier caps (ClearGuardHD) represent promising interventions to reduce CLABSIs. The aim of this study was to assess the efficacy of these devices in reducing CLABSIs in hemodialysis patients who use tunneled dialysis catheters at outpatient dialysis units in a healthcare system.

Method
In a retrospective review of a quality improvement project, we compared cumulative 6-month CLABSI infection rates before and after transition from Tego connectors to ClearGuardHD caps. CLABSI events, reported to National Healthcare Safety Network (NHSN), were expressed as CLABSI events per 100 patient-months. All adult patients (age &gt;18 years) receiving hemodialysis via a tunneled central catheter were included in the study from February 2018-August 2020. The study cohort was comprised of 13 outpatient dialysis units in a healthcare system with locations throughout the Northern Midwest and Southeastern United States. The date of change from Tego to ClearGuardHD was phased throughout the different units over the study period with events recorded 6 months pre- and post-intervention. Patients receiving home dialysis therapies were excluded from the study.

Results
The cumulative 6-month CLABSI event rate decreased by 75.7%; Tego (0.465/100 patient-months) vs. ClearGuardHD caps (0.113/100 patient-months). A total of 17 CLABSI occurrences were reported within 3,654 patient-months with Tego use. However, only 4 CLABSI occurrences were reported within 3,527 patient-months during ClearGuardHD use.

Conclusion
ClearGuardHD caps reduced the rate of CLABSI among hemodialysis patients and are superior to Tego connectors. These findings support prior studies. Implementation of ClearGuardHD caps may help eliminate CLABSI-associated morbidity among individuals requiring maintenance hemodialysis therapy.
MO243STUDY ON THE EFFECT AND MECHANISM OF NOVEL REGULATORY T CELL (CD4+CD126LOWFOXP3+ TREG) IMMUNOTHERAPY IN LUPUS NEPHRITIS*
Authors: Xu Zhenjian , Chen Junzhe , Xu Anping 
Published: May 2021

Abstract

Background and Aims
Our previous study found a new regulatory T cell subpopulation, CD4+CD126lowFoxp3+ regulatory T cells (CD4+CD126lowFoxp3+ Treg). This cell can maintain a stable immune regulatory function in the inflammatory state. Through in vivo and in vitro experiments, we have confirmed that CD4+CD126lowFoxp3+ Treg has an immunotherapeutic effect on T cell-mediated mouse models of autoimmune diseases such as colitis and collagen-induced arthritis (CIA). Further experimental studies showed that CD4+CD126lowFoxp3+ Treg could reduce the kidney injury caused by autoantibodies and prolong the survival time of lupus mice. However, the mechanism of CD4+CD126lowFoxp3+ Treg immunotherapy in lupus nephritis is not clear. The purpose of this study was to explore the mechanism of CD4+CD126lowFoxp3+ Treg immunotherapy in mice with lupus nephritis.

Method

In vitro experiments
CD4+CD126lowFoxp3+ Treg or CD4+CD126lowFoxp3+ Treg pretreated with PD-1 inhibitor were co-cultured with T or B lymphocytes of lupus mice under different in vitro culture condition. The expression levels of Akt and mTOR of Treg in each group were measured under immunoinflammatory conditions. To observe the effects and differences of Treg groups on the activation, proliferation and differentiation of T or B cells and other immunomodulatory effects.

In vivo experiments
CD4+CD126lowFoxp3+ Treg (2 × 106/mouse) and CD4+CD126lowFoxp3+ Treg (2 × 106/mouse) pretreated with PD-1 inhibitor and PBS were injected into NZM2328 lupus mice, respectively. After cell injection, urine protein was measured weekly. Autoantibody expression in lupus mice was measured every two weeks. The effects of Treg on the proliferation and differentiation of T/B cells in lupus mice were observed. The therapeutic effects of Treg on lupus mice were observed.

Results
Compared with CD4+CD126lowFoxp3+ Treg, the expression of Akt and mTOR increases in PD-1 inhibitors pretreatment cells. The activation, proliferation and differentiation functions of T or B lymphocytes of lupus mice were significantly weakened by immunosuppression of PD-1 inhibitors pretreated Treg in vitro, indicating that CD4+CD126lowFoxp3+ Treg may inhibit Akt-mTOR signaling pathway through PD-1 in in vitro.
Compared with CD4+CD126lowFoxp3+ Treg, the activation, proliferation and differentiation functions of T or B lymphocytes of lupus mice were significantly weakened by immunosuppression of PD-1 inhibitors pretreated Treg in vivo. And its therapeutic effect on lupus mice was ineffective, indicating that CD4+CD126lowFoxp3+ Treg may inhibit Akt-MTOR signaling pathway through PD-1 in vivo.

Conclusion
CD4+CD126lowFoxp3+ Treg may inhibit the Akt-mTOR signaling pathway by expressing PD-1, and maintain stable immunomodulatory function in the inflammatory state, thus producing immunotherapeutic effect on lupus nephritis mice.
MO252PLA2R -VE MEMBRANOUS GLOMERULONEPHRITIS PATIENTS SHOWS MORE EFFECTIVE RESPONSE THAN PLA2R +VE ON TACROLIMUS PLUS LOW DOSE PREDNISOLONE THERAPY*
Authors: Jaiswal Akhilesh Kumar , Prasad Narayan , Agarwal Vikas , Behera Manas Ranjan 
Published: May 2021

Abstract

Background and Aims
PLA2R is an autoantigen present in glomerular podocytes of Membranous Nephropathy (MN) patients. Several drugs have been tried which included nonspecific anti-proteinuric agents; corticosteroids, alone or with alkylating agents; cyclosporine; intravenous Ig; mycophenolate mofetil; and rituximab. There is no standard therapy for patients with frequent relapsing or steroid-dependent MN. We propose the efficacy of low dose Tacrolimus (TAC) plus prednisolone and associated changes in anti-PLA2R in adult IMN.

Method
Total 101 membranous nephropathy patients were treated with combination of prednisolone 1mg/kg alt-day) and Tac 0.1mg/kg/day (trough 6-10 ng/ml first 6M and 4-6 ng/ml for next 3M) then both taper by 1/3 every month up to 12M. Out of 101 patients; 15 diabetic; 7 lupus; 1HBV and 1 ankylosing spondylitis patients were excluded. Finally; 77 Patients were followed and evaluated for the anti-PLA2R level at baseline; 3M; 6M; 12M and end of follow-up (17-61 ; median 38 months). CR; PR; relapse; and side-effects were recorded.Of the 77 patients; at 3M 60(77.92%; CR-37; PR-23); at 6M 61(79.22%; CR-53; PR-8); at 12M 53(68.86%; CR-47; PR-6) achieved remission. Eight (10.38%) relapsed and 16(20.77%) showed no response at 12M. At end of follow-up; out of 54 responsive patients 37(68.51%; CR-36; PR-1) remained in remission and 17(31.48%) patients relapsed.

Results
Out of 77 patients; 51 (66.3%) were anti-PLA2R positive. Remission rate was significantly low in PLA2R+ve than PLA2R-ve (36/51 vs 24/26; p=0.03) at 3M; (36/51 vs 25/26; p=0.009) at 6M and (31/51 vs 22/26; p=0.03) at 12M. PLA2R level was decreased by 60.38% and 77.56% at 3M and 6M respectively (1A & 1B). There were significant correlations between PLA2R level and 24h proteinuria at baseline; 3M and at 6M (1C). During therapy 4 patients develop cutaneous tenia; 1 osteonecrosis of the femur head; 1 corpus tunnel syndrome; 4 onset diabetes; 3 tremor; and 14 patients experienced GI symptoms. The eGFR was decreased significantly (p=0.003) by 26.5% at the end of therapy and was normalized after stopping Tac; and 5 non-responsive patients had doubling of serum creatinine and progressively deteriorated eGFR. To note; 4 females had pregnancy and successful delivery in our cohort of patients.

Conclusion
PLA2R+ve patients showed poor response compare to PLA2R-ve patients. Remission with Tacrolimus and prednisolone therapy is comparable to historical Ponticelli (Pred plus CYP) regimen. Successful pregnency was ovserved on Tac based regimen.
MO259LYMPHOPENIA AT ANCA-GLOMERULONEPHRITIS DIAGNOSIS IS CORRELATED WITH SEVERITY AND RENAL PROGNOSIS
Authors: Wacrenier Samuel , Riou Jeremie , Jourdain Pierre , Guibert Fanny , HENRY NICOLAS , Assia DJEMA , Coindre Jean Philippe , Crochette Romain , Cousin Maud , Croue Anne , Jean François SUBRA , Piccoli Giorgina , Jean François AUGUSTO , Brilland Benoit 
Published: May 2021

Abstract

Background and Aims
Lymphopenia is commonly observed in various autoimmune diseases, such as systemic lupus erythematosus, where it has been associated with disease activity or prognosis. However, in ANCA-associated vasculitis (AAV) only few, small-scale studies have been targeted to this issue. Research has not yet focused on ANCA-glomerulonephritis (ANCA-GN) patients. Thus, the aim of this study was to analyze the association between lymphocyte counts and outcomes in a large cohort of ANCA-GN patients.

Method
We used the Maine-Anjou AAV registry that retrospectively gathers data on consecutive patients affected by AAV in four French Nephrology Centers, recorded since January 2000. We analyzed clinical, biological, and histological data at diagnosis of ANCA-GN. Biological data, including lymphocyte counts, were collected before the administration of any immunosuppressive treatment. Risk factors for end-stage kidney disease (ESKD) were analyzed. Event-free survival was also assessed.

Results
Among the 145 patients included in the study, 53 (37%) patients presented with lymphopenia at ANCA-GN diagnosis. Lymphopenic patients were older (72 [63–79] vs 66 [56–73] years old, p = 0.010), had a lower renal function at baseline (eGFR 13 mL/min vs 26 mL/min, p = 0.002), and a higher proteinuria (1.86 [1.21–3.52] g/g vs 1.30 [0.75–2.65] g/g, p = 0.042). There was a trend for a higher BVAS (18 [14–22] vs 15 [12–20], p = 0.076) in lymphopenic patients. Therapeutic management between the two groups was similar. There was no difference in relapse rate between the two groups but lymphopenic patients were more likely to require kidney replacement therapy (51% vs 25%, p = 0.003) and were more likely to die (34% vs 17%, p = 0.039). Lymphopenia was correlated with histological lesions and especially with the percentage of sclerotic glomeruli (p = 0.0027). ESKD-free survival and overall survival were lower in lymphopenic patients (p &lt; 0.0001 and 0.0051 respectively). In multivariate Cox analysis, lymphopenia, but not death, was an independent risk factor for ESKD (HR 4.47 (95% confidence interval: [2.06–9.72], p &lt; 0.001).

Conclusion
Lymphopenia correlates with severity of ANCA-GN at diagnosis and predicts poor renal outcome. In this view, lymphopenia could be used as a simple and cost-effective biomarker to assess renal prognosis at ANCA-GN diagnosis.
MO262THE SINGLE-CELL TRANSCRIPTOMICS OF HUMAN IGA NEPHROPATHY
Authors: Zhong Yong , Xiao Xiangcheng 
Published: May 2021

Abstract

Background and Aims
The exact molecular mechanisms underlying IgA nephropathy (IgAN) remains incompletely defined. Therefore, it is necessary to further elucidate the mechanism of IgA nephropathy and find novel therapeutic targets.

Method
Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from 4 IgAN and 1 control subjects to define the transcriptomic landscape at the single-cell resolution. Unsupervised clustering analysis of kidney specimens was used to identify distinct cell clusters. Differentially expressed genes and potential signaling pathways involved in IgAN were also identified.

Results
Our analysis identified 14 cell subsets in kidney biopsies from IgAN patients, and analyzed changing gene expression in distinct renal cell types. We found increased mesangial expression of several novel genes including MALAT1, GADD45B, SOX4 and EDIL3, which were related to proliferation and matrix accumulation and have not been reported in IgAN previously. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling and NOD-like receptor signaling. Moreover, the receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. Specifically, IgAN with overt proteinuria displayed elevated genes participating in several signaling pathways which may be involved in pathogenesis of progression of IgAN.

Conclusion
The comprehensive analysis of kidney biopsy specimen demonstrated different gene expression profile, potential pathologic ligand-receptor crosstalk, signaling pathways in human IgAN. These results offer new insight into pathogenesis and identify new therapeutic targets for patients with IgA nephropathy.
MO265LONGITUDINAL CHANGE IN PROTEINURIA AND KIDNEY OUTCOMES IN C3 GLOMERULOPATHY
Authors: Caravaca-Fontán Fernando , Goicoechea de Jorge Elena , Praga Manuel 
Published: May 2021

Abstract

Background and Aims
The association between a change in proteinuria over time and its impact in kidney prognosis has not been analyzed in C3 glomerulopathy. This study aims to investigate the association between the longitudinal change in proteinuria and the risk of kidney failure.

Method
Retrospective, multicenter observational cohort study in 35 nephrology departments belonging to the GLOSEN group. Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. A joint modeling of linear mixed-effects models was applied to assess the underlying trajectory of a repeatedly measured proteinuria, and a Cox model to evaluate the association of this trajectory with the risk of kidney failure.

Results
The study group consisted of 85 patients, 70 C3 glomerulonephritis and 15 dense deposit disease, with a median age of 26 years (range 13–41). During a median follow-up of 42 months, 25 patients reached kidney failure. The longitudinal change in proteinuria showed a strong association with the risk of this outcome, with a doubling of proteinuria levels resulting in a 2.5-fold increase of the risk. A second model showed that a ≥50% proteinuria reduction over time was significantly associated with a lower risk of kidney failure (HR: 0.79; 95%CI:0.56–0.97; p&lt;0.001). This association was also found when the ≥50% proteinuria reduction was observed within the first 6 and 12 months of follow-up.

Conclusion
The longitudinal change in proteinuria is strongly associated with the risk of kidney failure. The change in proteinuria over time can provide clinicians a dynamic prediction of kidney outcomes.
MO277THE RATIO OF NEUTROPHIL TO LYMPHOCYTE AS A POTENTIAL MARKER OF CLINICOPATHOLOGICAL ACTIVITY FOR SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Han Qianqian , Liang Peifen , Li Jiajia , Liu Bo , Hu‘an’g Rong , Yang Qiongqiong 
Published: May 2021

Abstract

Background and Aims
The ratio of neutrophils to lymphocytes (NLR) is a novel inflammatory factor that is elevated in systemic lupus erythematosus (SLE) and related to disease activity. However, the relationship between NLR and renal pathological manifestations in patients with lupus nephritis (LN) has not been studied.

Method
In this retrospective study, 240 SLE patients were recruited. 186 patients with renal involvement and 124 LN patients underwent renal biopsy. In the meanwhile, control groups included 125 chronic kidney disease (CKD) patients and 125 healthy volunteers. Patients with SLE disease activity 2000 (SLEDAI-2K) &gt;9 and ≤ 9 were defined as severely active and mildly active, respectively. Clinical parameters and pathological data were collected. The correlations between NLR and clinicopathological features were analyzed.

Results
The NLR of SLE group was significantly higher than that of the sex-age matched control groups. Patients with nephritis had higher NLR levels than those without nephritis [2.88(1.81,4.32) vs. 2.43(1.55,3.90), P=0.044; Figure 1]. Increased NLR was observed in severely active group compared to mildly active group [3.00(1.84,4.28) vs.2.36(1.61,3.51), P=0.020; Figure 1]. NLR was significantly positively related with SLEDAI score (r=0.131, P=0.043), Renal SLEDAI score (r=0.173, P=0.023), C-reactive protein (CRP; r=0.213, P=0.002), 24-hour urine protein (r=0.274, P&lt;0.001; Figure 2A), renal activity index (AI; r=0.192, P=0.033), cellular crescents (r=0.274, P=0.006) and tubular atrophy (r=0.226, P=0.011), and negatively correlated with serum albumin (r=-0.187, P=0.004; Figure 2A). Based on the receiver operating characteristic (ROC) curve, the best NLR cut-off value to predict severe activity and cellular crescents was 2.19 and 3.16, respectively. The ability of NLR to differentiate severely active from mildly active SLE was stronger than CRP and weaker than C3 (Figure 3A). The ability of NLR to predict cellular crescents was better than C3, but not superior to SLEDAI and RSLEDAI. Interestingly, the ROC fitted by NLR and RSLEDAI had a higher AUC and sensitivity [AUC=0.75(0.66,0.84), sensitivity=82.6%, specificity=63.6%; Figure 3B].

Conclusion
NLR was a non-invasive and potential inflammatory factor to evaluate clinical and renal pathological activity in patients with SLE.
MO278IMMUNOSUPPRESSIVE THERAPY VERSUS SUPPORTIVE CARE IN IGA NEPHROPATHY PATIENTS WITH STAGE 3 AND 4 CHRONIC KIDNEY DISEASE
Authors: Stefan Gabriel , Stancu Simona , Zugravu Adrian Dorin , Petre Nicoleta , Mircescu Gabriel 
Published: May 2021

Abstract

Background and Aims
The use of immunosuppressive therapy for IgA nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease (CKD) is controversial.

Method
We performed a monocentric retrospective study on 83 consecutive IgAN patients (age 41 [33-56] years, 72% male, eGFR 36.1 [25.4-47.5] mL/min) with stage 3 or 4 CKD and proteinuria ≥ 0.75g/day who received uncontrolled supportive care (Supp) (n=36), corticosteroids (CS) (n=14) or CS combined with monthly pulses of cyclophosphamide (CS+CFM) (n=33) between 2010-2017. Patients were followed until composite endpoint (doubling of serum creatinine, ESKD (dialysis or renal transplant) or death, whichever came first) or end of study (May 2018).

Results
Patients were followed for a median of 29 (95%CI 25.2, 32.7) months, and 12 (15%) patients experienced the composite endpoint.
There were no differences between the three studied groups regarding age (Supp 46 [33.5-61.0] vs CS 40 [33-47] vs CS+CFM 41 [34-48] years), eGFR (Supp 37.7 [27.5-49.2] vs CS 40.3 [32.5-54.6] vs CS+CFM 31.5 [22.7-44.3] mL/min), proteinuria (Supp 1.9 [1.4-3.5] vs CS 1.3 [1.0-1.7] vs CS+CFM 1.7 [1.1-2.9] g/g creatinine), MESTC score (Supp 2.5 [1.5-4.0] vs CS 2 [0-2] vs CS+CFM 3 [2-3]), hypertension (Supp 94% vs CS 86% vs CS+CFM 94%) and therapy with renal angiotensin system inhibitors (Supp 83% vs CS 64% vs CS+CFM 67%).
Mean renal survival time for the entire cohort was 81.0 (95%CI 73.1, 89.0) months; we found similar renal survival time between the three groups (Supp 79.0 (95%CI 66.5, 91.6) vs CS 69.3 (95%CI 47.7, 91.0) vs CS+CFM 73.7 (95%CI 66.0, 81.4) months, p=0.4).
In univariate and multivariate Cox regression analysis adjusted for IgAN progression factors, immunosuppressive therapy was not associated with better renal survival when compared to supportive therapy (Table 1).

Conclusion
Within the limitation of a retrospective study, we found no benefit from immunosuppressive therapy in patients with IgAN with stage 3 and 4 CKD as compared to supportive care.
MO287REAL WORLD COMPARISON OF THE PREDICTIVE UTILITY OF INTERNATIONAL IGA RISK PREDICTION SCORE AND KIDNEY FAILURE RISK EQUATION IN IGA NEPHROPATHY PATIENTS
Authors: Mohammed Sophia , Chinnadurai Rajkumar , Ponnusamy Arvind 
Published: May 2021

Abstract

Background and Aims
IgA nephropathy is the most prevalent cause of glomerular disease worldwide. The international IgA risk prediction (IgAN) score is a well validated tool to predict the risk of 50% decline in eGFR or end stage renal disease (ESRD) at five years after biopsy in patients with IgA nephropathy. Also, the four variable kidney failure risk equation (KFRE) is another validated tool used to predict the two- and five-year risk of progression to ESRD of all cause chronic kidney disease (CKD 3-5).
Our aim is to compare the predictive utility of IgAN score and the KFRE in a real-world cohort of Caucasian patients with long-term follow-up data.

Method
All available patients with biopsy-proven IgA nephropathy in our centre between January 2001 and December 2013 were included in this observational study. Baseline (biopsy date) data relevant to the scores including demographics, laboratory and the histopathological features were collated at the time of biopsy. Follow up data on renal functions and renal outcome (50% decline in eGFR or reaching ESRD) were collected until an arbitrary end date 31/12/2018.

Results
We had a total of 115 patients recorded over this 13-year period. The median age of our cohort at time of biopsy was 41 years. Men represented 71% of the cohort. At baseline 84% were hypertensive and 11% diabetic. 77% were on a renin-angiotensin blocker, with 53% being on a statin. Out of the 115 patients, 74 were eligible to undergo analysis. The percentage risk of reaching the endpoint (50% decline in eGFR or reaching ESRD) was calculated at 2 years and 5 years for all patients. These results can be seen in table 1 and 2. At 2 years, 7 patients had reached the endpoint: 2 patients had a &gt;50% decline in eGFR, 3 patients received RRT and 2 patients underwent transplantation. At 5 years, 14 patients had reached the endpoint: 3 patients had a &gt;50% decline in eGFR, 6 patients received RRT and 5 underwent transplantation.

Conclusion
Our data suggests that the KRFE tool underpredicts the risk of reaching endpoint, compared to the IgAN. Our study has helped to compare the two tools, but further statistical validation is required using a larger cohort.
MO291RITUXIMAB IS EFFECTIVE AND SAFE IN ADULTS WITH STEROID-DEPENDENT NEPHROTIC SYNDROME: A LONG-TERM, SINGLE-CENTER EXPERIENCE
Authors: Patella Gemma , Comi Alessandro , Coppolino Giuseppe , Comi Nicolino , Fuiano Giorgio , Andreucci Michele , Bolignano Davide 
Published: May 2021

Abstract

Background and Aims
Steroid-dependent nephrotic syndrome (SDNS) may require a prolonged multi-drug therapy with risk of drug toxicity and renal failure. Rituximab (RTX) treatment has been found to be helpful in reducing the steroid dosage and the need for immunosuppressants (ISs), but little data are currently available regarding very long-term outcomes in adults. We herein describe a long-term, single-center experience of RTX use in a large series of adults with SDNS.

Method
We studied 23 adult patients with SDNS (mean age 54.2±17.1 y; 65% male; BMI 28.5±4.7), mostly consequent to membranous (47.8%) or focal glomerulonephritis (30.2 %) who were eligible to start a RTX regimen. Before entering the RTX protocol, proteinuria and eGFR were 7.06±3.87 g/24h and 65.9±28.2 ml/min/1.73 m2, respectively; albumin and CD19/CD20 ratio were 2.9±0.9 g/L and 0.99±0.01 respectively; the mean number of ISs was 2.39±0.89 and the mean annual rate of relapses was 2.2±0.9.

Results
Patients were followed over a mean follow-up of 64 months (range: 12-144). After RTX (mean dose: 1202.1±372.4 mg) the rate of relapses was virtually nullified (p&lt;0.001). eGFR remained roughly stable (62.1±19.8 ml/min/1.73 m2, p=NS), while proteinuria, albumin, CD19/CD20 and BMI all significantly improved (p ranging from 0.01 to 0.001). The mean number of additional ISs was also reduced (0.44±0.12; p&lt;0.001) and RTX enabled discontinuation of steroids in 13/23 (56.5%) patients. No major adverse events related to therapy were recorded.

Conclusion
Findings from this large case-series with a remarkable very long follow-up reinforce the role of RTX as an efficient and safe weapon to improve outcomes in adult patients suffering from SDNS.