bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO079SOY PROTEINS PREVENT HEART REMODELING IN WISTAR RATS ON HIGH SODIUM CHLORIDE DIET
Authors: Beresneva Olga , Parastaeva Marina , Ivanova Galina , Kulikov Aleksander , Kucher Anatoly , Smirnov Kirill , Khasun Mokhamad , Kayukov, Ivan 
Published: May 2021

Abstract

Background and Aims
Increased salt intake has been linked to a number of poor effects, such as myocardial remodeling [1], independently of blood pressure level. Yet, many aspects of this remodeling are not well understood. The aim of the study was to find echocardiographic myocardial changes in Wistar rats on high sodium chloride (NaCl) diet, as well as to prove protective effects of diet, containing soy proteins.

Method
28 male Wistar rats (age of 2.5-3.0 months) were enrolled in the observational prospective study (4 month) and subdivided into several groups. 1) Standard diet-Control group (C, n = 8, 20.16% protein of animal origin and 0.34% NaCl); 2) High salt diet (n = 10, 8% NaCl); 3) Low-protein diet (n=10, 10% soy protein (SUPRO 760) and 8% NaCl).
Tail systolic blood pressure (BP) measurement, as well as echocardiographic examination were performed in anesthetized rats. Statistical analysis was performed with STATISTICA 10 software package. Fisher's LSD test was used. The significance level was &lt;0.05. All data are presented as mean ± SEM.

Results
Keeping rats on a diet with 8% NaCl did not lead to significant changes in blood pressure (group 2 - 138.0 + 5.0, group 3 - 134.0 + 5.0 mm Hg), compared to C (135.0 + 5.0 mm Hg). On the contrary, left ventricle back wall width in rats of group 2 was significantly higher (1.83 ± 0.09 mm, p &lt;0.02), than in C (1.49 ± 0.10 mm) or animals from group 3 (1, 47 ± 0.09mm).
The values of end systolic left ventricle size, interventricular septum width, mitral valve systolic movement and tricuspid valve systolic movement in group 3 were significantly lower (1.67 ± 0.08 mm, 2.18 ± 0.13 mm, 2.70 ± 0.23 mm), than in group 2 (3.26 ± 0.33mm, p &lt;0.037; 2.00 ± 0.12mm, p &lt;0.043; 2.67mm ± 0.15, p &lt;0.0124; 3.56 ± 0.34mm , p &lt;0.0148, respectively). At the same time, left ventricular chamber size and thickness of interventricular septum did not differ significantly. In C animals, mitral valve movement (1.96 ± 0.09 mm; p &lt;0.0008) and tricuspid valve movement (2.35 ± 0.07 mm; p&lt;0.0012) were significantly lower than in rats of group 2 but not differed much from the values found in group 3.

Conclusion
High sodium containing diet does not necessarily lead to the development of arterial hypertension in Wistar rats, but may cause heart remodeling, while soy proteins counteracts the development of left ventricle hypertrophy, even in case of high sodium consumption.
MO081THE INFLUENCE OF VITAMIN D3 ON PODOCYTE DIFFERENTIATION IN SITU AND IN VITRO
Authors: Lange Tim , Kuhn Laura , Böttcher Marie-Christin , Simm Stefan , Hammer Elke , Kaderali Lars , Völker Uwe , Weber Claudia , Endlich Karlhans , Endlich Nicole 
Published: May 2021

Abstract

Background and Aims
Dedifferentiation of podocytes affects their complex 3 D morphology and is the main initiator for the development of chronic kidney disease (CKD). Unfortunately, there is no causal therapy for CKD until today. Thus, inadequate and late treatment lead to end-stage renal disease which subsequently makes renal replacement therapy inevitable. To address this, new treatment options are of high significance for CKD patients. Recently, vitamin D3 (VitD) became a promising candidate, but it is controversially discussed. In the present study, we investigated the influence of VitD on podocyte differentiation and the related pathways in situ and in vitro.

Method
We combined a podocyte dedifferentiation model (GlomAssay) with an automated imaging procedure (Aquifer Imaging Machine). We analyzed cultured glomeruli from transgenic mice expressing cyan-fluorescent protein (CFP) under the control of the nephrin promoter which were treated with VitD and its` analogue (calcipotriol). In this model, the decreasing CFP fluorescence is as a read out for podocyte (de)differentiation. Additionally, VitD-, calcipotriol- and VitD receptor (VDR) inhibitor (PS121912)-treated glomeruli were investigated by RNA-Seq and LC-MS/MS to reveal the molecular effects of VitD on podocyte differentiation. Furthermore, we treated cultured murine podocytes with VitD, calcipotriol and PS121912 to elucidate the morphological and molecular changes by immunofluorescence staining, RT-qPCR and Western blot.

Results
VitD- and calcipotriol-treated glomeruli showed a significantly higher intensity of CFP fluorescence after 9 days, indicating higher level of nephrin compared to the control. This was verified by RT-qPCR and Western blot for nephrin and CFP. Additionally, we found an upregulation of VDR in VitD- and calcipotriol-treated glomeruli compared to controls. By transcriptomic and proteomic analysis, we identified molecular patterns that are specific for the different treated groups. Thus, we observed differential gene expression in VitD- and Wnt-signaling pathway as well as regulated genes that are essential for the actin cytoskeleton, focal adhesion formation and the slit membrane. Beside this, cultured podocytes showed a significant upregulation of the slit membrane protein nephrin, VDR and CYP24A1 by VitD. This is accompanied by an altered morphology of the podocytes due to a reorganization of the actin cytoskeleton.

Conclusion
Our results show that VitD influences podocyte differentiation in situ and in vitro by the regulation of specific signaling pathways.
MO083SYSTEMATIC HISTOLOGICAL SCORING OF TUBULOINTERSTITIAL LESIONS CORRELATE WITH CLINICAL PARAMETERS IN ANCA-ASSOCIATED GLOMERULONEPHRITIS
Authors: Tampe Björn , Hakroush Samy 
Published: May 2021

Abstract

Background and Aims
Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We have previously reported that severe deterioration of kidney function is associated with necrotizing and crescentic ANCA glomerulonephritis (GN), classified into Berden’s crescentic class or ANCA renal risk score (ARRS) high risk. However, tubulointerstitial inflammation associated with either histopathological subgrouping or ARRS remains elusive. Furthermore, clinical and laboratory markers of AAV disease severity or deterioration of kidney function in association with inflammatory findings in the kidney have not been described yet. Since aggressive immunosuppressive therapy is recommended for remission induction especially in severe cases of AAV, we here aimed to expand our current knowledge with regard to histopathological classification of tubulointerstitial injury and inflammatory findings analogous to the Banff classification.

Method
A total number of 50 renal biopsies with confirmed renal involvement of AAV were retrospectively included between 2015 till 2020 in a single-center observational study. Renal biopsies were evaluated for either focal, crescentic, mixed or sclerotic class (according to Berden et al.) and ARRS low, intermediate or high risk (according to Brix et al.). Inflammatory and fibrotic tubulointerstital alterations were evaluated analogous to Banff scoring system for allograft pathology.

Results
We here show that distinct inflammatory lesions are associated with glomerular findings classified into either histopathological subgrouping or ARRS. Furthermore, interstitial inflammation and tubulitis correlate with disease severity and decline of kidney function in AAV. Finally, we provide data that tubulointerstitial injury and inflammatory findings correlate with short-term outcome in response to aggressive immunosuppression and remission induction therapy.

Conclusion
In summary, we here provide evidence that a systematic scoring of inflammatory and degenerative tubulointerstitial lesions correlate with severe renal impairment and short-term response to remission induction therapy. Since aggressive immunosuppressive therapy is recommended for remission induction especially in severe cases of AAV, systematic histopathological scoring of tubuloinsterstital lesions could further improve our current knowledge of ANCA GN progression.
MO084THE INFLUENCE OF INTRAVENOUS CORTICOSTEROIDS ON PLASMA SIRTUIN-1 AND SCLEROSTIN LEVELS IN PATIENTS WITH PRIMARY GLOMERULAR DISEASE
Authors: Peczek Katarzyna , Nowicki Michal 
Published: May 2021

Abstract

Background and Aims
SIRT-1 is member of seven protein family that are involved in the cellular response to inflammatory, metabolic, and oxidative stress. The sirtuin family is a group of class III histone deacetylases. The best known of the family is SIRT-1. It may induce organ protection through inactivation of apoptosis and anti-inflammatory action.
Sclerostin is a glycoprotein produced by the osteocytes and an inhibitor of Wnt signaling. Increased activity of sclerostin increases the resorption of bone tissue and inhibits osteogenesis. It has been hypothesized that by deacetylating histones SIRT-1 could negatively regulate sclerostin gene. That mechanism requires a confirmation in clinical setting.
This exploratory study was designed to assess the influence of high doses of intravenous methylprednisolone on plasma SIRT-1 and sclerostin levels in patients with primary glomerular disease.

Method
The study included 40 patients (25 M, 15 F; mean age 53.1±14 years, mean eGFR 58.9±31.3 ml/min) in different stages of chronic kidney disease. 20 patients had eGFR below the median value of 46 ml/min. The main inclusion criterion was the clinical and histopathological diagnosis of primary glomerular disease and urine protein excretion &gt;2.0 g/24h. The main biopsy-proven diagnoses were IgA nephropathy (13 patients) and focal segmental glomerulonephritis (FSGS) (13 patients). The patients were hospitalized to receive scheduled intravenous pulses of methylprednisolone 20-30 mg/kg/day for three consecutive days followed by oral prednisone 0.8-1.0 mg/kg/day.
The blood was taken before the administration of methylprednisolone to assess SIRT-1, sclerostin, calcium, phosphate and PTH and urine for was taken for the measurement of calcium, phosphate and albumin to creatinine ratio. The same laboratory tests were repeated after 4, 7 and 30 days of steroid therapy.

Results
Plasma SIRT-1 during increased significantly during steroid administration (Fig.1). Plasma sclerostin did not change significantly during the study however a statistically significant correlation between the changes of SIRT-1 levels and sclerostin was found. In a multiple regression model the changes of plasma sclerotin induced by steroid therapy explained the largest part of the variance of the respective changes of plasma SIRT-1.

Conclusion
Plasma SIRT-1 increases during high-dose corticosteroids therapy. The negative relation between the changes of plasma SIRT-1 and plasma sclerostin may suggest a protective role of SIRT-1 against the rapid bone loss induced by corticosteroids.
MO085MONOCLONAL GAMMOPATHY OF UNKNOWN SIGNIFICANCE AMONG MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS PATIENTS
Authors: Kovala Marja , Seppala Minna , Kaartinen Kati , Meri Seppo , Honkanen Eero Olavi , Räisänen-Sokolowski Anne 
Published: May 2021

Abstract

Background and Aims
Monoclonal gammopathy is an entity where a B-cell or plasma cell clone produces monoclonal immunoglobulin. When paraproteinemia and a kidney disease is discovered without criteria for treatment of haematological malignangy, the entity is called monoclonal gammopathy of unknown significance (MGUS) or of renal significance (MGRS). It can cause variable histology, among which membranoproliferative glomerulonephritis (MPGN) has been described. Direct entrapment of paraprotein in glomeruli/tubules can be observed by immunofluorescence (IF), but IF can also be negative as paraprotein can cause complement-associated disease by acting as an activator of the classical pathway or as a dysregulator of the alternative pathway. Electron microscopy (EM) is needed to differentiate possible organized deposits.

Method
We investigated the prevalence, clinical parameters, histology, and the type of monoclonal gammopathy in biopsy-proven MPGN between 2006-2017. A total of 15 adult patients with a detected urine and/or serum paraprotein with concurrent biopsy-proven diagnosis were discovered among 60 patients (Figure 1). Two diagnostic biopsies were from transplants.

Results
MGUS was diagnosed in 15/60 (25%) of patients. Clinical variables are summarized in Table 1. The mean age at presentation was 59 years (37-79), 47-% were males. Smoldering myeloma was diagnosed in 2 (13%) patients and overt malignancy in 3 (20%) patients.
Histological features are summarized in Table 2. There were 7 (47%) with dominant staining for C3 (6 with C3 glomerulonephritis, 1 Dense Deposition Disease) and 8 (53%) with dominant staining for Ig, of which 4 (31%) had mesangioproliferative, 4 (31%) membranoproliferative, 3 (23%) minimal change, 2 (15%) crescentic and 1 (8%) exudative pattern in light microscopy (LM). Seven (47%) biopsies, which did not stain for kappa or lambda light chains. The most common EM deposit location was subendothelial (69%).

Conclusion
MPGN was associated with a significant risk of underlying monoclonal gammopathy, as many (25%) patients were diagnosed with concurrent MGUS. When MPGN is observed, it should prompt investigations of the possible underlying monoclonal gammopathy and possibly, hematological neoplasm.
MO086THE EFFECT OF HIGH SODIUM CHLORIDE INTAKE ON CARDIOVASCULAR SYSTEM AND KIDNEYS IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Kayukov, Ivan , Beresneva Olga , Parastaeva Marina , Ivanova Galina , Zaraiski Mikhail , Kucher Anatoly , Smirnov Kirill , Khasun Mokhamad , Smirnov Alexei 
Published: May 2021

Abstract

Background and Aims
It is believed that high consumption of sodium chloride (NaCl) leads to the development of arterial hypertension, which result in heart remodeling, however, NaCl can probably cause direct heart damage. We aimed to evaluate the effects of high and normal NaCl containing diets on blood pressure (BP), myocardial remodeling, as well as on the level of nuclear transcription factor κB (NFκB) expression in myocardium and kidneys.

Method
49 spontaneously hypertensive rats (SHR) were enrolled and subdivided into 2 groups: Group 1 (n=24) received standard diet (NaCl=0,34%); Group 2 (n=25) was on high sodium diet (NaCl=8%). In 2 months, systolic BP, myocardial and renal mass indices, morphological changes, as well as NFκB expression in heart and kidneys were assessed. Results are presented as mean ± SD.

Results
BP in group 2 did not change significantly (190 ± 10 mm Hg, p&gt; 0.05) compared to group 1, yet left ventricle muscle mass indices as well as, right and left kidney mass indices were higher. Hypertrophy of cardiomyocytes (CMC) was found in group2: (area of the nucleus- 43.55 ± 17.39 μm2 (p &lt;0.001); area of CMC-21799.31 ± 579.89 μm2 (p &lt;0.001), compared to group 1: (area of the nucleus- 36.14 ± 4.67 μm2 (p &lt;0.001); area of CMC-19011.13 ± 571.8 μm2 (p &lt;0.001). Also, perivascular fibrosis was found in group2 (area of perivascular connective tissue(APCT)- 4038.96 ± 28.58 μm2 (p &lt;0.001), compared to group1 (APCT-3718.36 ± 91.8 μm2, p &lt;0.001). An increase in arterial wall thickness was noted in group 2 (15.71 ± 6.28 μm, p&lt;0,001), compared to group 1 (13.51 ± 8 ,68 μm, p&lt;0,001). The expression level of NFκB in myocardial tissue (n = 7) in group 2 was 33 times higher, and in kidney tissue (n = 5) 12 times higher than in group 1 (n = 8).

Conclusion
High consumption of NaCl induces NFκB activation in kidneys and myocardium, and may cause myocardial remodeling, probably via NFκB - associated signaling pathways.
MO088CLINICOPATHOLOGICAL FEATURES OF THROMBOTIC MICROANGIOPATHY
Authors: Menezes Maria Do Mar , Soares Elsa , Viana Helena , Góis Mário , Nolasco Fernando 
Published: May 2021

Abstract

Background and Aims
TMA is a rare and severe endothelial lesion with thrombus formation and vascular occlusion with organ damage. It can be a complication of several clinical conditions. The aim of this study was to characterize clinical and pathological findings of patients with confirmed kidney TMA.

Method
We performed a retrospective observational descriptive study that analyzed all patients with TMA diagnosed by kidney biopsy, in two hospital centers, from January 2015 until December 2020. Clinical, laboratorial, pathologic characteristics were analyzed as also therapeutic performed and kidney and patient outcomes.

Results
Our sample had 14 patients, the majority female (n=11, 78%) with a mean age of 45±10 years-old and 12 (80%) were Caucasian. Six (40%) had past medical history of HTA, 2 (13%) had Multiple Myeloma, 4 (26%) transplant (3 kidney, 1 lung) and none had positive viral serology’s. Prodromal symptoms included diarrhea in 2 (13%) patients, neurological in 3 (20%) and previous infection in 3 (20%).
Mean laboratorial values were: Hemoglobin 7.8 g/dL, platelets 161.000/uL; LDH 586 UL; bilirubin 1.38 mg/dL, haptoglobin 1,55 g/L. Only 5 had schistocytes. ADAMTS13 activity was &gt;10% in all performed and in all, Coombs test were negative.
C3 was consumed in 3 (20%) patients and C4 in 2 (13%) but complement phenotypic study was normal in all performed patients. Auto-immune study revealed: 1 positive ANA, dsDNA negative in all but one with positive c1q antibody. One had positive antiphospholipid syndrome (AFS) antibodies and one scleroderma antibodies.
Main kidney presentation was acute kidney injury in 8 (53%) patients, with mean eGFR 14ml/min/1,73m2. Mean proteinuria was 2,5 g/24h and half (50%) had hematuria.
Kidney biopsies had a mean of 11,85 glomerulus, of which 14% sclerotic, mean interstitial fibrosis and tubular atrophy score 1,7. Acute tubular necrosis was present in 7 (46%) and inflammatory infiltrate in all, endotheliosis in 13 (86%), mesangiolysis in 3 (20%), arteriolar thrombus in 10 (66%), glomerular thrombus in 6 (40%), ischemic glomerulus in 12 (80%) and double-contour appearance in 7 (46%).
TMA etiologies were the following: 2 malignant hypertension, 2 proteasome inhibitor (PI), 1 scleroderma, 1 lupus, 1 AFS, 2 calcineurin and mammalian target of rapamycin inhibitors, 2 antibody mediated rejection (AMR), 1 methylmalonic acidemia and 2 undetermined.
Treatment performed encompassed: hypertension management, withdrawal od PI, changing immunosuppression, AMR treatment, cyanocobalamin, lupus induction treatment and eculizumab.
Kidney recovery was observed in 8 patients (53%). Patient survival at 6 months was 73%.

Conclusion
These study results highlight the vast context of conditions that TMA can appear. Most of them had only with mild or even absent clinical and laboratory features. Therefore, a high index of suspicion is required to diagnose TMA, allowing targeted treatment to preserve of kidney function.
MO089HISTOMORPHOMETRIC ANALYSIS OF GLOMERULI AND CAPILLARIES DENSITY IN THE INTERSTITIUM IN PREIMPLANTATION NEEDLE BIOPSIES OF PAIRED KIDNEYS HARVESTED FROM ADULT CADAVERIC DONORS
Authors: Adamczak Marcin , Kwiecien Katarzyna , Karkoszka Henryk , Krol Robert , Wiecek Andrzej Jan 
Published: May 2021

Abstract

Background and Aims
Preimplantation needle biopsy of kidney allows more precise interpretation of subsequent kidney biopsies performed after transplantation and potentially also may predict kidney graft survival. It is unknown, whether it is justified to perform the biopsy of one kidney only and then to transmit obtained results also to the second kidney or biopsies of both kidneys are mandatory. The aim of the study was to assess differences regarding glomerular volume, glomerular density and capillary density in the interstitium of both kidneys harvested from the same deceased donor.

Method
The study involved 40 pairs of kidneys (all together 80 kidneys) in which preimplantation kidney biopsies were performed. Kidneys were harvested from 40 deceased donors (17 females and 23 males; mean age 42.3 [37.6-47.0] years old) died because of intracranial haemorrhage (17 donors) or cerebral trauma due to accident (23 donors). Histomorphometric analysis was performed using “Olympus BX51” microscope (Olympus, Tokyo, Japan) coupled with “Olympus BX50” camera and the “cellSens Standard” software (Olympus, Tokyo, Japan). Weibel-Gomez formula was adapted to calculate glomerular volume.

Results
No significant differences were found between mean kidneys length [115.8 (112.4-119.1) vs.115.5 (112.5-118.5) mm], glomerular volume [2.59 (2.24-2.93) vs 2.49 (2.15-2.84) μm3 x106 ], glomerular density [3.43 (3.07-3.80) vs 3.24 (2.87-3.61) n/mm2] and interstitial capillaries density [233.58 (211.26) vs 217.80 (199.45-236.47) n/mm2] of both kidneys harvested from the same deceased donor.

Conclusions
1. Both kidneys harvested from the same deceased donor did not differ significantly in kidney length, glomerular volume, glomerular density and capillary density. 2. Our results justify to preimplantation biopsy of only one kidney and the results from the histomorphometric analysis may be used in the future also for assessment of the second kidney.
MO071PROTEINS LINKED TO ATHEROSCLEROSIS AND CELL PROLIFERATION ARE ASSOCIATED WITH SHRUNKEN PORE SYNDROME IN HEART FAILURE PATIENTS
Authors: Xhakollari Liana , Jujic Amra , Molvin John , Nilsson Peter M , Holm Hannes , Bachus Erasmus , Leosdottir Margret , Grubb Anders , Christensson Anders , Magnusson Martin 
Published: May 2021

Abstract

Background and Aims
The “Shrunken pore syndrome” is characterized by a difference in renal filtration between cystatin C and creatinine resulting in a low eGFRcystatinC/eGFRcreatinine-ratio, and studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with shrunken pore syndrome. In this observational study, we explored associations between shrunken pore syndrome and proteins implicated in cardiovascular disease and inflammation in patients with heart failure.

Method
Plasma samples from 300 individuals HARVEST-Malmö trial hospitalized for the diagnosis of heart failure (mean age 75 years; 30% female), were analyzed with a proximity extension assay consisting of 92 proteins, to identify proteins associated with shrunken pore syndrome. Shrunken pore syndrome was defined as eGFRcystatinC ≤60% of eGFRcreatinine. Proteins associated with shrunken pore syndrome in the initial age and sex-adjusted analyses (Bonferroni-corrected p≤ 5.4x10-4) were further adjusted for relevant covariates.

Results
In multivariate analyses, Shrunken pore syndrome was associated with elevated levels of six proteins; scavenger receptor cysteine-rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor subunit alpha, and tyrosine-protein kinase receptor UFO (p&lt;0.05).

Conclusion
In heart failure patients, shrunken pore syndrome was independently associated with proteins linked to atherosclerosis and cell proliferation.