bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0094KLOTHO DECLINE IS ASSOCIATED WITH PRO-HYPERTROPHIC SIGNALING IN MYOCARDIUM OF NEPHRECTOMIZED SPONTANEOUSELY HYPERTENSIVE RATS (PILOT SYUDY)
Authors: Bogdanova Evdokia , Dobronravov Vladimir , Semenova Natalia , Zubina Irina , Galkina Olga , Beresneva Olga , Ivanova Galina , Parastaeva Marina , Kayukov, Ivan , Smirnov Alexei 
Published: June 2020

Abstract

Background and Aims
Klotho deficiency is suggested to be involved in cardiac complications in chronic kidney disease (CKD) through modulation of intracellular pro-hypertrophic signaling pathways.
The aim of this study was to investigate the molecular mechanisms of myocardial remodeling in the settings of Klotho decline in experimental CKD.

Method
Systolic blood pressure (BP), myocardial mass index (MMI), serum and urinary creatinine (Cr), serum urea (Ur), inorganic phosphate (Pi), 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), Klotho, myocardial Klotho, calcineurin/ NFAT and beta-catenin expression (IHC), quantitative morphometry of cardiomyocite (CM) thickness and nuclei area (hematoxylin and eosin), myocardial perivascular (PF) and interstitial fibrosis (IF), renal fibrosis (RF) (Masson’s trichrome) and Klotho expression (rKl, IHC) were analyzed in spontaneously hypertensive rats with 3/4 or 5/6 nephrectomy (Nx) and duration of experimental exposure 1 and 2 mo (Nx1, n = 9; Nx2, n = 8). Controls were sham operated (SO) animals (SO1, n = 9; SO2, n = 9).

Results
The experimental model was corresponded to the initial stages of CKD (Ur level was between 6.64 and 13.36 mmol/L, serum Cr increased less than 50% vs SO, RF did not exceed 22 % FOV). Serum concentration of Klotho and rKl expression decreased, while MMI, CM thickness increased in both Nx1 and Nx2 (Table). There were no differences in serum Pi, FGF23 and PTH levels in Nx1 vs SO (Table). In Nx2 Klotho decline was accompanied by the development of IF and PF, serum 25OHD decrease, Pi and FGF23 increase vs SO2 (Table). In multiple regression analyzes including SO and Nx animals rKl was independently associated with MMI (β = -0.38 ± 0.16, p = 0.026), and CM thickness (β = -0.64 ± 0.14, p &lt;0.001). Myocardial fibrosis was associated with rKl level (IF: β = -0.87 ± 0.19, p = 0.001) and serum 25OHD (PF: β =-0.34 ± 0.15, p=0.032). According to pilot data of IHC, in Nx rat myocardium Klotho protein expression decreased, cytoplasmic calcineurin and nuclear NFAT in CM were observed (Figure), suggesting an increase in the activity of the calcineurin / NFAT signaling pathway. An intracellular redistribution of β-catenin from the cytoskeleton to the cytoplasm and nuclei were observed in CM of Nx rats (Figure), likely corresponding to increase in the activity of Wnt signaling.

Conclusion
Associations of CM hypertrophy, myocardial fibrosis and Klotho decline in CKD may be mediated by calcineurin / NFAT and Wnt signaling in myocardium.
P0098CHANGES OF PERICYTE IN AGING KIDNEY
Authors: Kim Hyung Duk , Kim Eun Nim , JIN YONGJIE , Lim Ji Hee , Kim Yaeni , Ban Tae Hyun , Park Cheol Whee , Choi Bum Soon 
Published: June 2020

Abstract

Background and Aims
In aging kidney, oxidative stress and inflammation lead to a decrease in renal function. Recent studies related to the aging process of the kidneys have shown that pericyte is a progenitor cell of myofibroblast, and the relationship between renal fibrosis and pericyte has been reported. In this study, we investigated the pericytes changes in aging kidneys and mechanism of aging-related pericyte changes.

Method
In vivo study, 2, 24-months-old mice and 18-month-old mice treated with pentoxifylline for 6 months were analyzed with western blot. And renal biopsy from KT donors were analyzed. Donors under age 25 were assigned to young group and donors over age 60 to old group.

Results
Changes of pericytes in mice and human renal tissues were consistent with those in the aging model. In the old age group, pericytes were decreased and interstitial fibrosis was increased. Western blot analysis in mice kidney revealed that IL-1β, IL-6 and TNF-α were significantly increased in old age and significantly decreased in pentoxifylline group. Angiopoietin 2 was increased in old age group and decreased in pentoxifylline group.

Conclusion
In aging kidney, pericytes have been shown to exhibit numerical reduction and loss of perivascular location as in the aging mice model. These changes in pericytes are thought to be induced by angiopoietin 2 excretion.
P0101INHIBITION OF TUMOR NECROSIS FACTOR ALPHA ENHANCED ANTIFIBROTIC EFFECT OF EMPAGLIFLOZIN IN AN ANIMAL MODEL WITH RENAL INSULIN RESISTANCE
Authors: Keshawy Mohammed , Mohammed Hoda 
Published: June 2020

Abstract

Background and Aims
Insulin resistance (IR) has emerged as one of the main risk factors for renal fibrosis (RF) that represents a common stage in almost all chronic kidney disease. The present study aims to investigate the inhibitory effect of empagliflozin (EMPA “a sodium-glucose co-transporter 2 inhibitor”) and infliximab [IFX “a tumor necrosis factor-α (TNF-α) antibody”] on RF in rats with induced IR.

Method
IR was induced by adding 10% fructose in drinking water for 20 weeks. Thereafter, fructose-induced IR rats were concurrently treated with EMPA (30 mg/kg), IFX (1 dose 5 mg/kg), or EMPA + IFX for 4 weeks, in addition to IR control group (received 10% fructose in water) and normal control (NC) group.

Results
Rats with IR displayed hyperglycemia, deterioration in kidney functions, glomerulosclerosis, and collagen fiber deposition in renal tissues as compared to NC. This was associated with downregulation of the renal sirtuin 1 (Sirt 1) expression along with higher renal tissue TNF-α and transforming growth factor-β1 (TGF-β1) levels. Both EMPA and IFX significantly modulated the aforementioned fibrotic cytokines, upregulated the renal Sirt 1 expression, and attenuated RF compared to IR control group. Of note, IFX effect was superior to that of EMPA. However, the combination of EMPA and IFX alleviated RF to a greater extent surpassing the monotherapy. This may be attributed to the further upregulation of renal Sirt 1 in addition to the downregulation of fibrotic cytokines.

Conclusion
These findings suggest that the combination of EMPA and IFX offers additional benefits and may represent a promising therapeutic option for RF.
P0102A REVIEW OF RENAL BIOPSIES IN A LARGE UK RENAL CENTRE- A 20 YEAR EXPERIENCE
Authors: Hudson Amy , Sinha Smeeta 
Published: June 2020

Abstract

Background and Aims
Percutaneous renal biopsy is the mainstay of renal pathological diagnosis. Not only does it secure an accurate diagnosis, but also lends itself to guiding the prognosis of a myriad of renal disorders. An important diagnostic modality for nephrologists, they have contributed greatly to the field of nephrology, both in terms of the classification of diseases and assisting in understanding their pathogenesis. Adequacy of the tissue samples of at least ten to fifteen glomeruli is generally preferred. The aim of our retrospective study was to review the renal biopsies done in one large UK renal centre, namely Salford Royal Foundation Trust, over the last twenty years. This Trust covers a catchment area that serves approximately 1.5 million people.

Method
A list of all renal biopsies performed at Salford Royal Foundation Trust between January 2000 to January 2020 was generated by our pathology department. Following this, each individual biopsy report was reviewed. In addition to this, certain information was collated from individual patient records; namely patient demographics, the indication for biopsy, tissue type (native or transplant), histological diagnosis and outcomes. Our centre has an excellent electronic patient record (EPR). This enabled us to analyse full clinical data retrospectively for each case.

Results
Between January 2000 and January 2020 a total of 3555 renal biopsies were performed at Salford Royal Foundation Trust. These biopsies were performed solely by nephrology specialists and supervised trainees, under ultrasound guidance. 177.5 biopsies were performed on average, per year, ranging between 140 – 203.
90% of biopsies were performed on native kidneys, with 10% being performed on transplanted kidneys.
10% of biopsies had normal histology morphologically when reviewed by light microscopy. There diagnoses of these included entities minimal change disease and thin basement membrane disease most commonly.
IgA nephropathy was the most common glomerular pathology identified, in keeping with the wealth of published literature. There were over 525 biopsies done confirming IgAN as the primary pathology.
7% of biopsies had a crescentic glomerular pathology when examined histologically. The main causes included crescentic IgA nephropathy and anca-associated vasculitis.

Conclusion
Kidney biopsies have long been regarded as safe, minimally invasive procedures are of paramount importance to our diagnostic armamentarium. Our data echoes that of already published pathology series, IgAN being the most common glomerular pathology in our series. We further plan to analyse the various conditions and their outcomes in further detail.
P0105THE ROLE OF PROTEOGLYCANS IN GLOMERULAR PHYSIOLOGY AND PATHOPHYSIOLOGY
Authors: Khramova Alina , Ebefors Kerstin , Nyström Jenny 
Published: June 2020

Abstract

Background and Aims
Damage to the filtration barrier in the kidney may result in proteinuria, a hallmark of kidney disease. The glomerular filtration barrier consist of 3 layers: the endothelial cells with their endothelial surface layer (ESL), the glomerular basement membrane and podocytes. The ESL is rich in negatively charged molecules, such as proteoglycans (PGs). The negatively charged molecules restrain the flow of charged molecules, as albumin, over the barrier. Loss of ESL has been shown to lead to proteinuria without damage to the other structures of the filtration barrier. In order to gain further knowledge about the function and composition of the glomerular ESL we eluted the glomerular ESL from rats and analyzed the PG content as well as the effect of loss of the ESL on the function of the glomerular filtration.

Method
The basic principles of ion exchange chromatography were applied in this study. In order to elute highly negatively charged proteoglycans of the ESL, we used 1 M NaCl solution (HS). 1 M mannitol (HO) was included to evaluate osmotic effects. A control fraction was eluted with normal saline solution (0,15 M NaCl) (NS). Solutions were introduced intraarterially to rat kidneys under anesthesia in vivo. Venous effluent was collected and analyzed using proteomics and mass spectrometry. Fractional clearance of albumin was measured as well as GFR. Electron microscopy (EM) was used to investigate changes to the filtration barrier and the thickness of the glomerular ESL. Immunohistochemistry was used to confirm the presence of identified PGs in human tissue.

Results
We identified 15 PGs and PG candidates in ESL as well as hyaluronan. The most abundant PGs were lumican, glypican-1, syndecan-4, perlecan, podocan, decorin, serglycan, agrin and biglycan. In general, PGs were found in in all HS, NS and HO fractions, but in higher yields in the HS samples. EM demonstrated that the glomerular ESL thickness was significantly reduced in HS perfused rats – 28% (p&lt;0.05) compared to rats perfused with NS. Rats perfused with HS also had increased fractional clearance of albumin compared to NS and HO, and a large reduction of GFR 10 minutes after perfusion.

Conclusion
The ESL itself represents a dynamic structure with significant molecular turnover and is formed by PGs, glycosaminoglycans, glycoproteins and soluble proteins. In our study, we identified several PGs in the glomerular endothelial ESL. We show that loss of ESL leads to increased albumin fractional clearance and reduction in GFR after perfusion, strongly suggesting that the ESL is important for preventing proteinuria. Characterizing the composition of the glomerular ESL is therefore of great importance, and can give new possible targets for treatment of proteinuria.
P0106URINE COMPLEMENT FRAGMENTS ARE ASSOCIATED WITH KIDNEY FUNCTION AND DISEASE ETIOLOGY
Authors: He Tianlin , Beige Joachim , Siwy Justyna , Golovko Igor , Pejchinovski Martin , Metzger Jochen , Mullen William , Vlahou Antonia , Mischak Harald 
Published: June 2020

Abstract

Background and Aims
Changes in complement factors have been associated with chronic kidney disease, most prominently in the context of C3 glomerulopathy. Based on these reports, the hypothesis was generated that specific urine complement fragments are associated with kidney disease etiologies, and progression of the disease may be reflected by changes in these proteins or peptides. In this study, we aimed at investigating the occurrence of complement fragments in urine, and their association with kidney function in general and disease etiology in particular.

Methods
Urine samples from patients with kidney disease of different etiologies and control subjects with normal kidney function were investigated using tandem mass spectrometry coupled with capillary electrophoresis and liquid chromatography to identify complement derived peptides based on their amino acid sequence. Subsequently, distribution of these peptides in the different kidney disease etiologies and normal kidney function was investigated via analysis of datasets recorded in the human proteome/peptidome database. All datasets, where eGFR was available and at least one of the complement peptides detected, were included.

Results
Twenty one different urinary peptides derived from complement could be identified. These peptide fragments originated from the complement factors C3, C4A and C4B, and CFB. Further investigation of 4557 datasets recorded in the urine proteome/peptidome database meeting the aforementioned inclusion requirements (eg available eGFR values and with at least one of the complement peptides detected), revealed, for most C3-derived peptides, an inverse, while for the majority of peptides derived from CFB, a positive association with eGFR.
The table lists the detected complement derived peptides, the parental protein (Complement X), rho and p-value of the association with eGFR, and the number of samples (n) where the peptide was detected.
When investigating the urine complement fragments, as a result of disease etiology, disease-specific distribution was detected, indicating a distinct association of complement factors and associated proteases, depending on disease etiology. As an example, the peptide distribution in AKI, IgA-Nephropathy (IgA-N) and vasculitis is shown in the Figure.

Conclusion
Multiple complement-derived peptides are significantly associated with kidney function, and with certain kidney disease etiologies, such as AKI, IgA-N or vasculitis. Proteomic screening of these complement factors may provide a basis, not only for non-invasively assessing kidney disease, but also for an opportunity to develop novel drugs; the latter, via targeting the associated proteases responsible for the release of these complement-derived peptides, in a specific kidney disease manner, in urine.
P0114BENEFITS AND CHALLENGES OF A RENAL BIOPSY REGISTRY AND NETWORK - FCGG EXPERIENCE
Authors: Laurens Wim , De Meester Johan , Sprangers Ben , Van Laecke Steven , Amélie Dendooven , Evelyne Lerut , Vande Walle Johan , An De Vriese , Pipeleers Lissa , Bart Maes , Mark Helbert , Hellemans Rachel , Tom Dejagere 
Published: June 2020

Abstract

Background and Aims
End December 2016, a renal biopsy network in the Flemish region (Belgium) was founded as a collaboration between the renal pathologists and nephrologists. This FCGG network introduced a uniform renal biopsy request form, a well-structured report form of the renal pathology examination and a comprehensive list of renal pathology diagnoses.

Method
Following informed consent [99.5%] and in compliance with GDPR, the registration of the renal biopsies consists of basic categorical renal data, structured renal pathology information and the final clinical renal disease.

Results
In 2017 and 2018, 1385 renal biopsies were registered – 10.5 per million inhabitants per year; in addition, 28 patients had a repeat biopsy in the same time frame (2%). Of the pediatric patients ( age &lt; 18 years; N=92; 6.6%), 23 had IgA nephropathy, 20 a minimal change disease and 15 another type of glomerulonephritis. The biopsy was reported as normal or non-diagnostic in 15 patients (16%) – the majority was clinically considered as glomerulonephritis. The spectrum of the adult population was quite similar across gender and age groups: 56% glomerulonephritis [= IgA nephropathy [19%] + FSGS [8%] + pauci-immune glomerulonephritis [7%] + other GN [22%] ), 10% tubulo-interstitial nephritis, 7% acute tubular necrosis [ATN], 7% diabetes mellitus, and 7% nephroangiosclerosis. Exceptions are pauci-immune glomerulonephritis as the most important renal disease in women aged 65 years and older, and lupus nephritis as the second most important glomerulonephritis in women aged 18-44 years. Only a small percentage of adult renal biopsies yielded no result (7%), clinically interpreted as glomerulonephritis in 50% of the cases.

Conclusion
The FCGG network has provided a more intense collaboration between renal pathologists and nephrologists mainly by standardizing the renal biopsy reading and reporting across all centers. More precise estimates of the prevalent renal diseases were provided for the first time; however, in order to get full information, renal diseases diagnosed by other techniques ( serology, genetic analysis ) should also be collected in the future. Efforts will be done to coordinate the clinical care of renal diseases, particularly the more rare renal diseases, and to offer access to new therapeutic molecules or new schemes, through this super-regional network.
P0126RENAL TRANSPLANT PATIENTS UNDER CALCINEURIN INHIBITOR THERAPY RAPIDLY ACQUIRE AN ABERRANT LYSOSOMAL LESION IN PROXIMAL TUBULAR CELLS
Authors: Vervaet Benjamin , Kojc Nika , Nast Cynthia , Schreurs Gerd , D'Haese Patrick , De Broe Marc 
Published: June 2020

Abstract

Background and Aims
Calcineurin inhibitor therapy has changed the field of (renal) transplantation by considerably prolonging graft survival. Yet, all immunosuppressive calcineurin inhibitors are nephrotoxic that eventually contribute to complete scarring of the renal allograft. In renal biopsy analysis many histopathological features have been considered indicative of CNI nephrotoxicity, i.e. striped fibrosis, vascular hyalinosis, isometric tubular vacuolization, glomerulosclerosis, cellular infiltration and tubular atrophy, however, all are rather aspecific and can be secondary to many other causes. During the course of evaluating the specificity of a recently discovered proximal epithelial lysosomal lesion (i.e. multiple enlarged (&gt;1,2µm) dysmorphic lysosomes containing dispersed electron dense non-membrane bound aggregates) in patients with Chronic Interstitial Nephropathy in Agricultural Communities (CINAC), we observed it to be present in renal transplant patients treated with cyclosporine or tacrolimus. Here, we test the hypothesis whether this lysosomal lesion is acquired during CNI therapy.

Method
A retrospective transmission electron microscopic analysis was performed to evaluate the presence of the typical lysosomal lesion on the following biopsies from renal transplant patients: 20 deceased donor implantation biopsies; 5 living donor implantation biopsies. For another 10 additional deceased donor renal allograft recipients, we evaluated implantation as well as protocol biopsies taken after 6 and 12 months of CNI treatment that started immediately after transplantation. Also included were 24 indication biopsies of CNI treated renal transplants.

Results
Of the total set of implantation biopsies (n=35), 2 (6%) were positive for the aberrant lysosomal phenotype on EM, whereas in the protocol and indication biopsies prevalence of the lesion was considerably higher ranging between 56% (protocol) and 80% (indication) of cases.

Conclusion
CNI therapy is associated with the fairly rapid appearance of a particular proximal tubular lysosomal phenotype observable on EM, that was not (or rarely) present at implantation. Whether this lesion is related to CNI toxicity and indicative for the outcome for the graft and/or patient survival after renal transplantation has to be investigated in a prospective trial.
P0136COMPARISON OF SECONDARY IGA NEPHROPATHY OF ANKYLOSING SPONDYLITIS AND PRIMARY IGA NEPHROPATHY IN CLINICAL AND PATHOLOGICAL FEATURES
Authors: Xue Qin , Zhang Guang Li , Tian Zebo 
Published: June 2020

Abstract

Background and Aims
Renal involvement is one of the most common extra-articular complications caused by ankylosing spondylitis (AS). The main pathological manifestation is secondary IgA nephropathy(SIgAN) in Chinese AS patients. The difference between SIgAN and primary IgAN (PIgAN) remains unclear due to the lack of cases. Therefore, the aim of this retrospective study was to compare the clinical and pathological features of SIgAN of AS (SIgAN-AS) and PIgAN, to detect the pathogenesis of SIgAN

Method
Clinical characteristics and pathological data were collected in patients who were diagnosed with IgAN by renal biopsy in our hospital from Jan 2008 to Oct 2018. Patients with SIgAN-AS were recruited by the ratio 1:5 of patients with primary IgAN as the control group in the study. Fifteen patients with SIgAN-AS and Seventy-five patients with PIgAN were enrolled in this retrospective study.

Results
There were 15 cases in AS group, including 13 male and 2 female. The cohort of 75 patients with PIgAN included 34 male and 41 female. There were more males in AS group 13/15 (86.7%) vs 37/75(49.3%) ,P &lt; 0.05. Compared with PIgAN patients, SIgAN-AS patients had higher incidences of hematuria( 13/15(86.7%)vs 44/75 (58.7%) , P &lt; 0.05), lower levels of 24-hour urinary protein(0.85±0.68 vs 1.57±1.54g, P &lt; 0.05), but higher levels of eGFR (CKD-MDRD formula) (117.60±37.33 vs 85.35±31.36, P &lt; 0.05),eGFR (CKD-EPI formula) (128.01±41.58 vs 92.75±36.09, P &lt; 0.05), Albumin (44.67±3.48 vs 41.09±7.07 g/L, P &lt; 0.05) ESR (43.20 ±33.94 vs 18.79±16.26mm/h, P &lt; 0.001) , and CRP (21.19±30.61 vs 2.11±4.58mg/L, P &lt; 0.001) . From the perspective of renal pathology of PIgAN, SIgA-AS patients had fewer incidences of renal tubular atrophy / interstitial fibrosis of nephropathy (P &lt;0.05). The immunohistostaining analysis showed higher incidences of dominant deposits of single IgA in mesangial cell area (P &lt; 0.05).

Conclusion
Patients with SIgAN-AS is more common in male and display a milder progression than those with primary IgAN. Majority of the SIgAN-AS can be improved with early intervention.