bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO055: Multi-Class Segmentation of Kidney Tissues using Convolutional Neuronal Networks (CNNS)
Authors: Schmitz Jessica , Christensen David , Müller Lena , Neugebohren Lina , Zachrau Tim , Philine Brandt Hannah , Größler Frederik , Johannes Tilman , Gwinner Wilfried , Hinrich Bräsen Jan 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Routine pathological diagnostics in kidneys are mainly based on semi-quantitative eyeballing. In own former studies, we showed predictive value of precise immune cell quantification in allografts using digital semi-automated techniques. We now aim to achieve fully automated segmentation workflow with CNNs.

METHOD
Standard routine stains (immuno/histochemistry, immunofluorescence) were digitized (20×) with Metafer, a commercial scanning/imaging platform. Diagnostically relevant anatomical compartments (cortex, medulla, glomeruli, tubuli [proximal/distal/collecting duct], glomerular/peritubular capillaries and nuclei) were manually annotated by use of immunomarkers to generate large data sets on human renal biopsies and nephrectomies. Data were used to train multi-class semantic segmentation CNNs with broad data augmentation to achieve a robustness against staining variances.

RESULTS
Using Jones-HE stains for multi-class segmentation, a cortex-medulla-extrarenal CNN revealed pixel based hit rates above 97.9%, detection of glomeruli had a pixel based hit rate above 99%, a multi-class CNN for tubules, tubular membranes and peritubular capillaries resulted in a hit rate of 91.5%, and nuclear-based cell detection shows pixel based hit rates above 98%. Identification of cell location in interstitium, tubuli, glomeruli, peritubular and glomerular capillaries reached very high hit rates: Glomerular endothelial cells actually result in 83% true positives, 13% false negatives and 4% false positives. Additionally, a tubulus classifier (proximal tubulus, distal tubulus, collecting duct and atrophic tubulus) with an accuracy &gt;90% was developed.

CONCLUSION
Automated structure segmentation by CNNs can complement and specify classical nephropathological diagnostics, especially for spatial risk marker evaluation in early transplant biopsies.
MO056: Alteration of Glycocalyx on Endothelium of Peritubular Capillaries in CKD
Authors: Ermert Katja , Mara Klinkhammer Barbara , Miriam Buhl Eva , Floege Jürgen , Boor Peter 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The glycocalyx is a carbohydrate-rich gel-like mesh, which covers the luminal surface of cells, including the endothelium. The glycocalyx is involved in many regulatory functions of the endothelium, including vascular permeability. In chronic kidney disease (CKD), peritubular capillaries undergo anatomical, structural and functional alterations such as rarefaction, increased tortuosity and increased permeability. Here, we hypothesized that the glycocalyx of peritubular capillaries might be affected in CKD and investigated morphological and ultrastructural pathological alterations of the glycocalyx in different murine CKD models and human kidney tissue.

METHOD
We stained the glycocalyx of peritubular capillaries in kidney tissue of murine and human CKD specimen using different fluorescently labeled plant-derived lectins. Next, we established the Lanthanum Dysprosium Glycosamino Glycan adhesion (LaDy GAGa) staining technique to visualize the ultrastructure of the glycocalyx using transmission electron microscopy and to perform quantitative analyses. Finally, we analyzed the expression and regulation of glycocalyx components in primary murine endothelial cells.

RESULTS
Fluorescence stainings using different lectins with high affinity to components of the renal glycocalyx revealed a reduced binding to the endothelium in CKD. We found a similar change in a human kidney tissue. The LaDy GAGa staining technique visualized the ultrastructure of the glycocalyx and enabled quantitive analyses. We found a significant reduction of the glycocalyx thickness and density in two different models of renal fibrosis and CKD, i.e. unilateral ureteral obstruction and ischemia–reperfusion injury. Additionally, mRNA expression of proteins involved in glycocalyx biology, synthesis and turnover, i.e. syndecan 1 and glypican 1, which are main components of the glycocalyx, and exostosin 2, involved in the synthesis of the glycocalyx, were significantly upregulated in endothelial cells isolated from murine CKD models.

CONCLUSION
Visualization of glycocalyx using specific ultrastructural analyses allows qualitative and quantitative analyses, revealing significant pathological alterations in the glycocalyx of peritubular capillaries in CKD.
MO068: Paraoxonase 2 Protects the Kidney Tissue from Aldosterone-Promoted Oxidative Stress in Milan Normotensive Rats Strain
Authors: Suzumoto Yoko , Manco Giuseppe , Capasso Giovambattista , Trepiccione Francesco 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Kidney plays a pivotal role on the maintenance of blood pressure by the regulation of sodium reabsorption. Aldosterone sensitive distal nephron finely tunes salt reabsorption through several transporters, including the epithelial sodium channel (ENaC). Alteration in ENaC function leads to clinical relevant conditions associated with high or low blood pressure when gain or loss of function mutations occur, respectively.
Recently, accumulating evidence suggests the putative role of renal Paraoxonase 2 (PON2) as regulator of ENaC function. PON2 is a membrane-associated enzyme showing hydrolytic activity against 3-oxo-C12 homoserine lactone, a signaling molecule produced by bacteria and mainly Pseudomonas aeruginosa. PON2 also exhibits antioxidant property. In the distal nephron, PON2 is expressed in principal cells, and in vitro it physically interacts with ENaC subunits and inhibits ENaC channel activity in Xenopus oocytes likely by modulating channel assembly in the endoplasmic reticulum. However, the role of PON2 in the kidney is still not known.
In the present study, we investigate whether PON2 is regulated by changes in aldosterone state and its role in aldosterone-induced oxidative stress in the kidneys.

METHOD
We addressed these issues utilizing both in vivo and in vitro approaches, such as

RESULTS
We first demonstrated that in Milan normotensive rats strain, PON2 is upregulated by low-salt state according with α-ENaC activation. This regulation is aldosterone sensitive since pretreatment with mineralocorticoid receptor antagonist spironolactone prevented the stimulatory effects of sodium restricted diet. Furthermore, low-sodium diet inducing PON2 upregulation was associated with reduced ROS levels, more specifically superoxide levels, but treatment with spironolactone prevented this beneficial effect, by increasing ROS level in kidney cortex.
Since antihypertensive drugs spironolactone and canrenone contain a lactone residue in their molecular structure, we tested whether they could directly interact with PON2. We demonstrated in vitro that spironolactone and canrenone were able to inhibit PON2 lactonase activity and so to directly interfere with PON2 function. Finally, Milan hypertensive rats, carrying a mutation of α-adducin as determinant of their hypertensive phenotype, presented with higher level of ROS while PON2 was upregulated.

CONCLUSION
These results demonstrate PON2 as a novel target of steroid hormone aldosterone. PON2 may serve as a potential ROS scavenger mechanism protecting the kidneys from aldosterone-promoted oxidative stress.
MO078: Dietary Supplementation with Cysteine During Pregnancy Rescues Maternal Chronic Kidney Disease-Induced Hypertension in Male Rat Offspring: The Impact of Hydrogen Sulphide and Microbiota-Derived Tryptophan Metabolites
Authors: Tain You-Lin , Hsu Chien-Ning 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Maternal chronic kidney disease (CKD) is linked to offspring hypertension. Gut microbiome and its tryptophan metabolites, nitric oxide (NO) and renin–angiotensin system (RAS) are closely related to the development of hypertension. Hydrogen sulphide (H2S) has shown antihypertensive effect. Our objective was to test whether L- or D-cysteine supplementation in pregnancy can prevent hypertension programmed by maternal CKD in adult offspring and explored the protective mechanisms.

METHOD
CKD was induced in pregnant Sprague-Dawley rats by a 0.5% adenine diet for 3 weeks. L- or D-cysteine was supplemented at 8 mmol/kg body weight/day during pregnancy. Male offspring were sacrificed at the age of 12 weeks (n = 8/group).

RESULTS
Maternal CKD-induced hypertension was similarly prevented by L- or D-cysteine supplementation. The protective effects of L- and D-cysteine are related to reducing oxidative stress, rebalancing the RAS and reshaping the gut microbiome. L-cysteine therapy protected adult offspring against hypertension and was associated with enhanced H2S production, restoration of NO bioavailability, enhancement of beneficial genera Oscillibacter and Butyricicoccus, depletion of indole-producing genera Alistipes and Akkermansia and reduction of indole metabolites. D-cysteine treatment increased tryptophan metabolites in the kynurenine pathway, decreased those in the serotonin pathway and enriched the genera Bacteroides and Odoribacter abundance.

CONCLUSION
In summary, these results suggest that L- and D-cysteine protect against maternal CKD-induced offspring hypertension, likely by enhancing H2S production, modulating gut microbiota and its derived metabolites and restorating NO and RAS.
MO097: Idiopathic Hypercalciuria: Calciuria and Citraturia Evolution. A 20-year Longitudinal Study
Authors: Maria Barrera Herrera Aidana , Pérez Suárez Germán , Isabel Luis Yanez Maria , Lopez Martel Debora , Monge Zamorano Margarita , García Cantón César , Manuel Garcia-Nieto Victor 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Reduction and normalization of calciuria in children with idiopathic hypercalciuria (IH) was published by Aladjem et al. (1996). The association between IH and hypocitraturia was described in two Brazilian studies; however, further studies are needed to determinate the caracteristics of its relation.
We studied calcium and citrate urinary excretion in children diagnosed with IH and followed up until adulthood.
METHOD: A total of 34 patients (12 M and 22 F) were studied. IH diagnosis was performed at the age of 7.9 ± 3 years (range: 1–14). Hypercalciuria was defined as urinary calcium excretion of &gt;4 mg/kg/day in two successive samples. Calciuria and citraturia were collected in the first urine sample of the day at the same time as bone densitometry was performed.
Three determinations were made: the first (D1) at age 10.5 ± 2.7 years (range: 6.5–16.8), the second (D2) at age 14.5 ± 2.7 years (range: 9.9–19.5) and the third (D3) at age 28.2 ± 2.8 years (range: 24.1–35.9).
RESULTS: Calcium/creatinine ratio (P = 0.005) and citrate/creatinine ratio (P &lt; 0.001) reduction during follow up was observed. In addition, we observed an increase in the calcium/citrate ratio (P = 0.008). Patients with a calcium/creatinine ratio higher than 0.20 mg/mg decreased from 100% at diagnosis to 52.9% (18/34) on D1 and to 26.5% (9/34) on D2 and 23.5% (8/34) in adulthood (D3). Lithogenetic risk decreased from diagnosis (15/28; 53.6%) to D1 (13/32; 40.6%) and D2 (8/28; 28.6%) but increased in adulthood (21/30; 70%).

CONCLUSION
It is difficult to explain why some IH patients present a decrease in both calcium and citrate excretion in adolescence and early adulthood, which has an impact on lithogenic risk. The interpretation of these results is complex. Bone is the largest reservoir of alkaline salts in the body. Our hypothesis is that late hypocitraturia observed in patients with IH would be an indirect sign of high functional osteoblastic activity. Increased proximal tubular citrate reabsorption would denote an increased bicarbonate production, which is necessary as osteoblastic activity increases, thus requiring increased inputs of alkali, calcium (normalized calciuria) and phosphate. Another option could be the development of incomplete distal renal tubular acidosis.
MO099: Elastography in the Assessment of Chronic Kidney Disease: A Meta-Analysis
Authors: Maralescu Felix-Mihai , Chiodan Milena , Sircuta Alexandru , Schiller Adalbert , Petrica Ligia , Bob Flaviu 
Published: May 2022

Abstract

BACKGROUND AND AIMS
We require an imagistic quantitative technique for the diagnosis and assessment of chronic kidney disease (CKD). Renal elastography has been widely used in the last years in different studies; however, the results across them are not consistent and, as a result, we conducted a meta-analysis of the published literature on this topic.

METHOD
The databases of PubMed, Medscape and Medline were searched for all studies published in English from 2010 until November 2021 that evaluated kidney shear wave speed (KSWS) by elastography in patients with CKD. Trial design, methodological information, patient characteristics, interventions, results and outcome data were all collected from each study according to a set protocol.

RESULTS
We found 33 publications, yet only 18 studies that utilized point shear wave elastography (Virtual Touch Quantification—VTQ system) were compared because the values achieved using different types of elastography are not evaluable. Finally, 1995 attendees (1241 patients with CKD versus 781 healthy subjects as the control group) were included. When comparing mean values of KSWS between studies, we found increased heterogeneity Q = 513.133; DF = 10; P &lt; .001, I2 (inconsistency) = 98.12% (95% CI for I2 97.52–98.57%). With a standardized mean difference of –0.216, patients with CKD have a lower KSWS than healthy controls. A positive association between KSWS and eGFR was also discovered across the presented studies, with a pooled correlation coefficient of 0.38 (Z = 10.3, P &lt; .001), Q = 73.3, DF = 5, P &lt; .001, I2 = 93.18% (95% CI for I2 87.86–96.18). The pooled area under the ROC curve for KSWS to predict mild renal disease was 0.831 (95% CI, P &lt; .001), Q = 28.32, DF = 6, P = .0001, I2 = 78.8% (95% CI for I2 56.37–89.72).
In the four articles that used the Elast-PQ method, the data presented were insufficient for statistical analysis: area under the curve values are used to compare distinct characteristics (differentiating KSWS between mildly and moderately impaired kidneys, between non-diabetic, prediabetic and diabetic patients, or KSWS between CKD and control group), therefore not being suitable for further evaluation.

CONCLUSION
The results show that patients with CKD have a lower KSWS than healthy controls. It remains a viable method for monitoring the progression of CKD but because the number of studies involving renal elastography that have been published is limited and show an increased heterogeneity more research is needed to determine which factors actually influence KSWS in CKD patients and, as a result, to specify the role and indication of renal elastography in clinical practice.
MO100: Alectinib-Induced Reversible Acute Kidney Injury
Authors: Conceição Suse , Moreira Fonseca Nuno , Navarro David , Ribeiro Francisco , Nolasco Fernando 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Alectinib is a second generation anaplastic lymphoma kinase (ALK) tyrosine inhibitor approved for ALK-positive lung adenocarcinoma. This drug may be associated with acute kidney injury, mainly causing acute tubular necrosis. Usually inducing a reversible chronic increase of serum creatinine that improves after dose reduction or suspension. Severe renal impairment is a very rare adverse effect.

METHOD
We report a case of 85-year-old male patient diagnosed with ALK-positive lung adenocarcinoma for which alectinib was started with a good neoplasm response. He was admitted to our hospital due to acute kidney injury, presenting with anasarca, anuria, hyperkalemia and metabolic acidosis which required emergency dialysis support.

RESULTS
Alectinib was discontinued, and the patient recovered from kidney function. However, subsequent re-administration of alectinib (1 month thereafter) caused a new episode of acute kidney injury, requiring new transitory dialysis therapy with new recovering kidney function after drug suspension.

CONCLUSION
This case is unusual due to its severe renal presentation. Thus far, there have only been two similar cases reported. Our case report shows an uncommon and severe adverse effect of alectinib, where it is found that there exists a temporal relation between alectinib exposure and acute kidney injury. Furthermore, the patient recovered from kidney function after drug discontinuation. Frequent monitoring of renal functions is important, as it allows for drug dosage adjustment, which can prevent severe AKI and reduce the morbidity of these frail patients.
MO120: Kidney Biopsy—Safety at Neprology Gold Standard
Authors: Marques Filipe , Silva Onassis , Outerelo Cristina , Lopez Noélia , Fernandes Paulo , Nogueira Estela , Jorge Sofia , Gameiro Joana , António Lopes José 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Percutaneous renal biopsy is a fundamental technique for the diagnosis of numerous renal pathologies. However, it is an invasive technique that requires operator experience and is associated with adverse outcomes. Bleeding complications such as haematuria or perirenal hematoma are frequent, but generally self-limiting, and may rarely be severe to the point of culminating in hypovolemic shock or death. The objectives of this study are to identify the rate of adverse outcomes and potential predictors of adverse outcomes related to the procedure.

METHOD
A retrospective analysis of patients undergoing native kidney biopsy at a tertiary centre, between 2015 and 2019 was carried out, based on the demographic and clinical characteristics of the population, analyses (creatinine at admission, pre-procedure and post-procedure blood counts) and control at 24 h after biopsy) and imaging methods (renal ultrasound 24 h after biopsy).

RESULTS
A total of 176 patients were selected, with a mean age of 48.1 ± 17.6 years. They were mostly caucasian (80.1%) and there was a predominance of females (55.7%). Approximately 46.6% had arterial hypertension, although all had their blood pressure controlled at the time of the biopsy. Mean pre-biopsy creatinine value was 2.0 ± 1.7 mg/dL. Mean pre-biopsy haemoglobin value was 12.1 ± 2.0 g/dL and 24 h post-biopsy 11.8 ± 2 .0 g/dL. There was an overall complication rate of 30.1%, corresponding to 5 cases of haematuria, 36 minor hematomas and 8 major hematomas. There were no deaths and there was no need for surgical intervention to control the bleeding. The only predictor of post-biopsy complications was age, with younger patients having fewer complications (43.9 ± 16.2 versus 50.0 ± 17.9, P = .036). There was no correlation between pre-biopsy creatinine or haemoglobin values and the occurrence of complications, nor was there a greater number of complications in hypertensive patients.

CONCLUSION
Although bleeding complications were relatively frequent in this sample, serious events were rare, as this reinforces the safety of this procedure (which provides valuable information about the prognosis and decision of the therapy to be instituted). The presence of arterial hypertension and the pre-biopsy creatininemia value did not increase the risk of complications related to the procedure.
MO126: A ‘Point Prevalence’ Pain Study over 2 Days in Three Dialysis Units in the West of IRELAND
Authors: Gorey David , Lappin David , Murphy David , Reilly Leona , Mannion Eileen , Kennedy Grace , Waldron Dympna 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Point prevalence studies are observational studies, without intervention, and involve collecting data, in patients in multiple care units, at a specific time. It provides no information on outcomes but provides information on how common a problem is, and current management. This type of study can be an ongoing program consisting of multiple research collection days, each performing multiple, independent studies simultaneously. The point prevalence studies are purely observational, and no intervention is required by the study protocol.
The aim of the study is to understand prescribing patterns of analgesia to dialysis patients and incidence of pain among them.

METHOD
This project is a prospective, observational, multicentre, 2-day, point prevalence study of three chronic dialysis units on the prevalence of pain in all patients in receipt of dialysis. Data were gathered regarding analgesia prescribed to patients and whether patients reported pain to the haemodialysis (HD) staff.

RESULTS
A total of 164 patients were audited, with an average age of 67.8 years.
Approximately 19.5% of dialysis patients presenting reported pain. The average age of these patients was 70 years. The most common cause was MSK (34%) then cramps (31%), vascular access pain (16%), ‘other’ (13%) and vascular wounds (6%). Approximately 12.5% of those patients with pain were reviewed by a doctor.
Approximately 50% of the patients are prescribed analgesia. This varied amongst dialysis units with 52% and 26% of patients in the two public units prescribed analgesia and 70% of patients in the private unit. Types of analgesia prescribed to HD patients were paracetamol (75.46%), neuropathic agent (20.12%), codeine (6), tramadol (4), tapentadol (3), pure opioid (4), buphenorphine patch (3) and lidocaine patches (2).

CONCLUSION
This shows a significant impact of pain amongst dialysis patient presenting daily to dialysis units. A prospective research study is planned using a novel Pain App specifically developed for HD patients. This may be structured as a Cluster Clinical trial to compare and contrast outcomes in different centres.