bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO041: Impaired ACE2 glycosylation and protease activity lowers susceptibility to SARS-COV-2 infection in Gitelman/Bartter syndromes
Authors: Bertoldi Giovanni , Ravarotto Verdiana , Sgarabotto Luca , Gobbi Laura , Federica Stefanelli Lucia , Calò Lorenzo 
Published: May 2022

Abstract

BACKGROUND AND AIMS
ACE2, part of the counter-regulatory arm of the renin–angiotensin system, serves both as protective toward oxidative stress and cardiovascular remodeling and as a key entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 has two isoforms, non-glycosylated and glycosylated, the latter being accountable for the binding with SARS-CoV-2. After the binding, viruses use proteases as cathepsin-L (Cat-L) to entry the cells. Both ACE2 glycosylation and Cat-L activity are pH-dependent. Gitelman and Bartter syndromes (GS/BS), rare genetic tubulopathies, are characterized by electrolytic alterations, activation of the renin–angiotensin system, yet normo-hypotension, increased levels of ACE2 and metabolic alkalosis with likely increased intracellular pH. We reported that during the first wave of COVID-19 in early 2020 none of our cohort of 128 GS/BS patients from the major hotspots in Northern Italy had been infected or suffered any major COVID-19 symptoms and in a second survey on the same cohort in 2021, we reported only eight positives, four asymptomatic and four with very light symptoms This study aims to investigate potential mechanisms as ACE2 glycosylation and Cat-L activity related to patients’ metabolic alkalosis and viral entry/infection.

METHOD
Mononuclear cells ACE2 glycosylation (Western blot) and blood Cat-L activity (ELISA) from 20 GS/BS patients have been compared with those from 15 healthy subjects.

RESULTS
Non-glycosylated ACE2 was higher in GS/BS (0.82 ± 0.19 d.u. versus 0.67 ± 0.13, P = 0.01); glycosylated ACE2 was not different (0.85 ± 0.28 in GS/BS versus 0.73 ± 0.23, P = 0.19). Cat-L activity was lower in GS/BS (3.90 ± 1.13 r.f.u. versus 5.31 ± 0.8, P &lt;0 0.001) and inversely correlated with blood bicarbonate (HCO3−), while a negative correlation between glycosylated ACE2 and HCO3− approaches statistical significance (P = 0.08).

CONCLUSION
GS/BS's metabolic alkalosis, likely by increasing intracellular pH, influences the glycosylation of ACE2 and the activity of Cat-L, providing a mechanistic explanation for the near-complete absence of COVID-19 or its symptoms reported in our cohort. These findings provide a rationale for pursuing the identification and/or synthesis of new drugs that specifically target ACE2 glycosylation and/or proteases involved in SARS-CoV-2 infection.
MO065: The Association of Glomerular Neural Cell Adhesion Molecule-1 Expression with Membranous Lupus Nephritis and the Injury of Central Nervous System
Authors: Liu Yang , Zhang Mingchao , Luo Song , Xu Feng , Yang Fan , Chen Dacheng , Xia Wen , Miao Yiqi , Jiao Chenfeng , Chen Xin , Liu Xia , Hu Winxin 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Neural cell adhesion molecule-1 (NCAM-1) has been found to be associated with central nervous system (CNS) injury in patients with lupus nephritis in small case series. This study aimed to explore the relationship between glomerular NCAM-1 expression and CNS injury in patients with membranous lupus nephritis (MLN) and the influence of NCAM-1 expression on the prognosis of MLN.

METHOD
238 patients(47 class V, 132 mixed class V + III/IV, 46 class III/IV, 7 class II, 6 lupus podocytopathy) with SLE-associated CNS injury were screened from the LN cohort between 2009 and 2019. CNS injury was assessed by clinical and brain MRI. Patients without CNS injury were served as the control. The degree of electron-dense subepithelial deposits and proportion of podocyte foot process effacement (FPE) was assessed semi-quantitatively by electron microscopy. Kidney NCAM-1 was stained by immunohistochemistry. The NCAM-1 expression in patients with different classes of LN and its relationship with CNS injury was analyzed.

RESULTS
In total, positive NCAM-1 staining was found in 59 of 238 (24.8%) LN patients with CNS injury. NCAM-1 positive rates were significant higher in the cases with class V (22/47, 46.8%) and mixed class (35/132, 26.5%) than those with proliferative class (2/46, 4.3%), class II (0/7) and lupus podocytopathy (0/6). NCAM-1 positive rate was significantly higher in class V (46.8% versus 13.3%, P &lt; 0.001) and mixed class (26.5% versus 7.3%, P &lt; 0.001) patients with CNS injury than those patients without CNS injury. Compared with NCAM-1 negative MLN (included class V and mixed class) patients with CNS injury, NCAM-1 positive MLN patients had much higher proportion of nephrotic syndrome (54.4% versus 37.2%, P = 0.03), hypoalbuminemia (66.7% versus 49.2%, P = 0.029), extensive subepithelial immune deposits (56% versus 25.5%, P = 0.009) and proportion of FPE (75.4 ± 10.2% versus 68.1 ± 16.6%, P = 0.038), and significantly lower duration of SLE (12.0 (3.0, 48.0) months versus 26.0 (4.5, 84.0) months, P = 0.046) and renal CI score (2.0 (1.0, 3.0) versus 3.0 (2.0, 4.0), P &lt; 0.001). No significant differences were found between the NCAM-1 positive and NCAM-1 negative MLN patients in the baseline SCr level, imaging features of brain MRI, extrarenal organ involvement and long-term patient and renal outcomes.

CONCLUSION
NCAM-1 is associated with MLN (including class V and mixed class) and CNS injury, and NCAM-1 positive MLN shows special clinicopathological features of renal injury, indicating that NCAM-1 positive MLN could be a subtype of MLN.
MO074: SGLT2 Inhibition Promotes Intrinsic Kidney Regeneration by Cells of the Renin Lineage
Authors: van der Pluijm Loïs , Koudijs Angela , Stam Wendy , Rotmans Joris , Gross Kenneth W , Paul Pieper Michael , Jan van Zonneveld Anton , Bijkerk Roel 
Published: May 2022

Abstract

BACKGROUND AND AIMS
With chronic kidney disease (CKD) prevalence rapidly increasing, the need for novel therapies is rising. Sodium glucose co-transporter-2 (SGLT2) inhibitors were originally developed to treat hyperglycemia in patients with type 2 diabetes mellitus. Clinical trials with the SGLT2 inhibitor empagliflozin revealed a marked attenuation of the slope of kidney function decline, also in patients with non-diabetic CKD. The exact mechanism of this kidney sparing effect still remains to be clarified. Interestingly, cells of renin lineage (CoRL), residing in the juxtaglomerular apparatus to regulate blood pressure and fluid balance, have been demonstrated to harbor a stem cell like potential. CoRL have the ability to replenish glomerular cell number by dedifferentiating, migrating and subsequently replacing various glomerular cell types in different kidney injury mouse models. Considering that empagliflozin treatment affects renin plasma levels and electrolyte balance in patients, we hypothesized that empagliflozin could have an effect on CoRL-induced glomerular regeneration.

METHOD
Experiments were performed in a Ren1cre; tdTomato lineage-trace mouse strain that expresses a tomato fluorescent label in all cells derived from renin lineage. Two kidney injury mouse models were applied; bilateral ischemia reperfusion injury (bIRI) and 5/6 nephrectomy (5/6NTx). Empagliflozin (10 mg/kg) was administered daily via oral gavage for 14 days. Subsequently, mice were sacrificed and kidneys were harvested for histological analysis.

RESULTS
In both the bIRI and 5/6NTx model, empagliflozin intake led to an increase (&gt;2-fold) of CoRL found in the intraglomerular regions compared with vehicle control littermates. These CoRL seemed to selectively differentiate towards different glomerular cell types per model: bIRI combined with empagliflozin administration resulted in an increase of claudin- (10-fold) and integrin-α8- (1.5-fold) tomato double positive cells, suggesting favored differentiation from CoRL to respectively a parietal epithelial or mesangial cell type. In contrast, in the empagliflozin treated 5/6NTx model, an increase (1.5-fold) in tomato-podocyn double positive cells was observed, implying more restocking of glomerular podocytes by CoRL in this model.

CONCLUSION
SGLT2 inhibition by empagliflozin treatment leads to increased CoRL-mediated intrinsic regeneration potential and provides the kidney with different replenished cell types in different kidney disease models. Our findings demonstrate a novel mechanism via which SGLT2 inhibition might protect against kidney injury.
MO077: Systemic Therapy with a Single-Dose Kidney-Targeted Bioengineered VEGF Construct Improves Stenotic Kidney Hemodynamics in Experimental Renovascular Disease
Authors: Chade Alejandro , Bidwell Gene 
Published: May 2022

Abstract

BACKGROUND AND AIMS
We recently developed a construct of an elastin-like polypeptide fused to VEGF (ELP-VEGF) and showed its efficacy to target and protect the kidney after single systemic administration in a swine model of unilateral renovascular disease (RVD) via therapeutic angiogenesis. Despite a demonstrated renal efficacy, the possibility of off-target binding of VEGF to other organs and undesired effects exists. Thus, we augmented renal specificity by adding a kidney-targeting peptide (KTP) and showed that KTP-ELP accumulates in the kidney to a greater extent than ELP (rodents and swine). Furthermore, addition of KTP redirected ELP-VEGF, which was found at high levels in the liver, to the kidney (rodents). The current proof-of-concept study aims to define the renal therapeutic efficacy of the KTP-ELP-VEGF construct after systemic administration in RVD.

METHOD
RVD was induced in 12 pigs by unilateral renal artery stenosis and observed for 10 weeks. After 6 weeks, pigs were treated with a single IV dose of untargeted ELP-VEGF, KTP-ELP-VEGF (1 mg/kg, through ear vein) or placebo (n = 4 each). RBF, GFR and cortical perfusion were quantified in vivo using multi-detector CT before and 4 weeks after treatment/placebo. An additional four animals were used as normal controls.

RESULTS
Stenotic-kidney hemodynamics were similarly reduced in all RVD pigs 6 weeks after induction of renal artery stenosis. Administration of ELP-VEGF or KTP-ELP-VEGF led to significant improvements in RBF, GFR and cortical perfusion compared with pretreatment values, suggesting no interference with VEGF's biological activity. Notably, KTP-ELP-VEGF showed a slightly greater improvement in stenotic kidney hemodynamics than untargeted ELP-VEGF.

CONCLUSION
This study builds on our recent work and shows for the first time the biological activity and therapeutic efficacy of KTP-ELP-VEGF, expanding the potential of strategies using targeted renal treatments and offering the possibility of intra-renal and systemic routes of administration. The traits of KTP-ELP carriers strengthened drug-delivery strategies by minimizing off-target effects of VEGF or any other therapeutic cargo, which may help to extend applications to other forms of renal disease.
MO103: ANCA Vasculitis with Renal Impairment in the Elderly
Authors: Chemli Imen , Hammouda Mouna , Ben Salem Meriem , Ben Salah Manel , Handous Insaf , Letaief Ahmed , Aloui Sabra , Skhiri Habib 
Published: May 2022

Abstract

BACKGROUND AND AIMS
ANCA vasculitis is a serious pathology and life threatening. Kidney damage is common. Few studies have focused on ANCA vasculitis in the elderly. The geriatric population is particular by its polypathology and its polypharmacy. Our objective was to detail the clinical-biological, immunological and histological characteristics of patients aged 65 years or over with ANCA vasculitis with renal impairment as well as the therapeutic and evolutionary modalities.

METHOD
This is a retrospective, monocentric and descriptive study, carried out in the nephrology department of the CHU Fattouma Bourguiba in Monastir during a period of 12 years extending between January 2008 and January 2021. We collected 21 elderly patients aged 65 years and over with ANCA vasculitis with renal impairment diagnosed in the nephrology department, according to the criteria of ACR 1990 and Chapel Hill 1994.

RESULTS
The mean age of our patients was 69.52 ± 5.53 years with a predominance of women (sex ratio: 1.1). Essential hypertension was the most common medical history, observed in 19% of cases followed by diabetes and a history of asthma. The circumstance of discovery was renal signs in 80.9% of cases and haemoptysis in 9.5%. The median time between the onset of symptoms and the diagnosis was 15 days. General signs dominated the clinical picture: a deterioration in general condition was observed in 61.9% of cases, fever in 33.3% of cases and headache in 19% of cases. Proteinuria and haematuria were found in all cases, oliguria in 68.42% of cases, oedema in 36.68% and arterial hypertension in 26.31%. Extrarenal signs were dominated by respiratory involvement observed in 71.42% of cases. Microscopic polyangiitis was the most common type observed in 81% of cases, followed by granulomatosis with polyangiitis in 9.5% and eosinophilic granulomatosis with polyangiitis in 9.5%. All patients had received corticosteroid therapy with a median duration of 6 months. Intravenous cyclophosphamide was prescribed for 57% of patients. Seven patients had received corticosteroid therapy alone. In 57% of cases, maintenance treatment with azathioprine (Imurel) was administered during 17.25 ± 10.10 months. Plasmapheresis was performed only in a patient who presented with intra-alveolar haemorrhage. Complete remission was noted in four cases (19%) and partial remission in six cases (28.57%). At the third month of follow-up, 81% of patients were alive, 76.2% of cases at 1 year and 62% of cases at 5 years. Mortality was 19%. Infectious complications secondary to treatment were noted in 38.1% of cases.

CONCLUSION
ANCA vasculitis in the elderly was characterized by a high clinical polymorphism. Despite the low mortality, disease-related and treatment-related morbidity was significant. Thus, an initial standardized geriatric assessment appears useful in order to better anticipate the occurrence of complications and their management.
MO107: Association of Renal Function with Cardio Metabolic Risk Factors in Elderly Population
Authors: Kibria Golam , Iqbal Masud , Shahnoor Alam Kazi , Chowdhury Maa , Hassan Mz , Chaudhury Sr 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Elderly population is a vulnerable group, and cardiometabolic risk factors are highly prevalent among them. This situation complicates when the renal function becomes impaired. The aim of this study was to evaluate the association of renal function with cardiometabolic risk factors among the elderly subjects.

METHOD
This cross-sectional study was conducted among a group of elderly population (&gt;60 years) living in three different elderly residential complexes. Written informed consent was taken from all. Study population underwent detail history taking, physical examination and relevant investigations. Renal function (eGFR) was estimated by CKD-EPIcr formula. Renal (eGFR, Ur ACR), cardiac (blood pressure, BMI, waist/hip ratio) and metabolic risk factors (lipids, albumin, uric acid, HbA1c) were evaluated. All information was recorded in separate case record form. Collected data were checked for errors and then analysed using the statistical software SPSS 16.

RESULTS
Around 145 subjects were included. About 42% were from 60–65 years of age, 37% from 66–70 years and rest &gt; 70 years. Mean age was 68 ± 5 years with male 52%. Mean eGFR was 71 ± 2 and in male versus female it was 75 ± 22 versus 66 ± 24 mL/min/1.73 m2 (P &lt; .032) . In 20% elderly eGFR was observed &lt; 60 mL/min/1.73 m2. Prevalence of DM, HTN and obesity was 33%, 46% and 9%, respectively. Age (69 ± 5 and 67 ± 5 years, P &lt; .012), waist/hip ratio (1.01 ± 0.16 and 0.97 ± 0.07, P &lt; .04), serum creatinine (1.6 ± 0.4 and 0.9 ± 0.2 mg/dL, P &lt; .001), urinary ACR (320 ± 565 and 82 ± 213 mg/g, P &lt; .001) were significantly altered among patients with impaired renal function (&lt;60 versus &gt;60 mL/min).

CONCLUSION
This study showed that various cardiometabolic risk factors among elderly patients are significantly higher in those with impaired renal function.
MO117: Predictive Factors for Renal Impairment Secondary to Familial Mediterranean Fever in an Algerian Population
Authors: Ghalia Khellaf , Benziane Ali , Benabadji Mohamed 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The aim of this study was to assess predictors of renal involvement and other factors secondary to FMF in renal and overall survival.

METHOD
We prospectively studied 57 Algerian patients admitted to our nephrology department from January 2012 to January 2021. The diagnosis of nephropathy was suspected clinically and biologically and confirmed histologically. The search for mutations in the MEFV gene was carried out in all our patients. The patients were divided into two groups according to their evolution: G1 (patients on dialysis) and G2 (patients not on dialysis).

RESULTS
G1 presents compared to G2 a presence of patients with more men with (P = 1015 × 10−2) but the difference is not significant, consanguinity (P &lt; 4998 × 10−3), later age of onset of FMF (P &lt; 1116 × 10−4), triggers for renal damage (P &lt; 3907 × 10−2), later age of onset of nephropathy (P &lt; 4199 × 10−2), higher C-reactive protein (P &lt; 2561 × 10−2), AA amyloidosis (P &lt; 11.0 × 10−7), higher percentage of sclerosis glomeruli &gt;50% (P &lt; 2052 × 10−4), rapidly progressive glomerulonephritis (P &lt; 1.0 × 10−7), higher proteinuria (P &lt; 1.0 × 10−7), higher serum creatinine (P &lt; 01.15 × 10−5), higher homozygous and/or compound heterozygous at the different gene mutations (P &lt; 3.815 × 10−6) and a higher number of deaths (P &lt; 3.394 × 10−5). The renal and overall survival analysis of the Kaplan–Meier survival analysis curve was significantly different in multivariate analysis (log rank, P &lt; .0001).

CONCLUSION
There are predictive factors specific to renal injury and FMF that predict renal and overall survival in these patients.
MO118: A Study on Renal Involvement in COVID-19 Patients with or without Preexisting Kidney Disease and Outcome: Acha Single-Centre Retrospective Study
Authors: Sharma Manjuri , Brijesh Singh K , Pegu Gayatri , Kumar Doley Prodip , Gope Manas , Kharbuli Indakiewlin , Dange Shruti 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Chronic kidney disease (CKD) patients and renal allograft recipients (RARs) are at increased risk for severe coronavirus disease 2019 (COVID-19). Acute kidney injury (AKI) can develop in a patient with COVID-19 infection. Data regarding the outcome of COVID-19 patients affected with renal disease are scarce, especially from northeastern part of India.

METHOD
We conducted a single-centre, retrospective, observational study, involving hospitalized COVID-19 affected patients with renal disease in Gauhati Medical College, Guwahati between 1 July 2020 and 30 June 2021. Patients with various forms of kidney disease including AKI, CKD, RAR and glomerulonephritis were included. The main aim of the study was to describe the outcome (in-hospital mortality) in this group of patients.

RESULTS
The study included a total of 384 patients with most patients in the elderly age group (73.7% above 45 years). Most of the patients were male (n = 288, 75%). Those with renal disease were grouped under AKI, CKD, RAR, systemic lupus erythematosus with lupus nephritis (LN) and rapidly progressive GN (RPGN) (20.3%, 75%, 3.4%, 1% and 0.3%, respectively). The mean duration of stay at the hospital was 8.1 days with maximum duration for RAR patients with a mean of 11.2 days. A total of 199 patients (51.8%) died. Mortality data were not available for 19 patients who got transferred to various other departments after recovering from COVID-19. Mortality rates for AKI, CKD, RAR and LN were 37.2%, 55.2%, 53.8% and 75%, respectively. One patient with RPGN also died.

CONCLUSION
COVID-19 affects patients of all age and sex. CKD patients and those on immunosuppressive agents are at higher risk for mortality.
MO131: Prevalence of Pruritus in Spanish Patients with Chronic Kidney Disease and Affectation of Quality of Life
Authors: Areste-Fosalba Nuria , Emilio Sanchez-Alvarez J , Henriquez Fernando , Jesus Lloret Maria , Ulloa Catalina , Buades F Juan M , Mascarós Victoria , Isabel Martínez Puerto Ana , Dolores Arenas María , Yetman Delfina , Furaz Karina 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The prevalence of chronic kidney disease–associated pruritus (CKD-aP) found in different studies ranges from 40% to 90% in patients undergoing haemodialysis, and from 19% to 29% in non-dialysed patients. However, despite pruritus negatively affect the quality of life (QoL) and clinical outcomes as well as increase the risk of mortality, clinicians still tend to underestimate the number of patients with CKD-aP. This study was conducted to estimate the prevalence of pruritus and its impact in different dimensions of QoL in the Spanish population with CKD.

METHOD
A short survey was designed using seven questions included in several validated tools for pruritus assessment. The questionnaire was distributed by the Spanish Society of Nephrology to all their members in the framework of the Pruritus Week. Nephrologists visiting advanced CKD patients asked them to answer the questionnaires voluntarily.

RESULTS
A total of 1605 patients (haemodialysis 92%, peritoneal dialysis 5% and non-dialysis 3%) answered the questionnaire. A prevalence of CKD-aP of 50.5% was reported, 26.7% being moderate-to-severe. As shown in figure 1, the prevalence was higher in non-dialysis advanced CDK patients suggesting a benefit of dialysis in reducing itch. CKD-aP patients reported itching throughout their body and at any part of the day, but more at night. The percentage of patients with mood changes increased as the severity of itch increased, being anguish and lack of rest the parameters that were more highly affected. An increase in depression was also observed. Sexual function and desire impairment increased as severity of CKD-aP increased. Finally, CKD-aP patients reported higher sleeping disturbances than patients with no pruritus (difficulty to sleep, restless sleep and intake of sleep medication), which enhanced with the increase of pruritus severity.

CONCLUSION
CKD-aP is highly prevalent in patients with advanced CKD (non-dialysis and dialysis), which affects patients’ quality of life by inducing mood changes, including depression, impairing sexuality and affecting sleep.