bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO050: The First Report from the National COVID-19 Autopsy Registry in Germany
Authors: von Stillfried Saskia , David Bülow Roman , Röhrig Rainer , Boor Peter 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Autopsies are an invaluable tool in medicine for studying the pathophysiology of diseases, including kidney diseases and causes of death. To facilitate multicenter autopsy-based studies and to provide a single point of contact for data analysis and reporting, the German COVID-19 Autopsy Registry (DeRegCOVID) was launched in April 2020 to uncover effects on pulmonary (micro)vasculature, systemic viral spread including the kidneys or interaction with the immune system.

METHOD
The electronic registry uses a web-based electronic data collection system. Participation is voluntary and biomaterial remains at each site (decentralized biobanking). As of October 2021, the registry included N = 1129 autopsy cases with 69 271 individual data points containing information on 18 674 available biospecimens, including kidneys as part of the standard sampling protocol, collected at 29 German sites.

RESULTS
In the N = 1095 eligible records, the male-to-female ratio was 1–8:1, with peaks at 65–69 and 80–84 years in men and &gt;85 years in women. Analysis of the chain of events leading directly to death showed that in 86% of autopsy cases, COVID-19 was the actual cause of death, whereas in 14% of cases, COVID-19 was a concomitant disease. The most common immediate cause of death was diffuse alveolar injury/acute respiratory distress syndrome, followed by multiorgan failure, including the kidneys. The registry supports several scientific projects, informs the public and provides reports to federal health authorities, which led to a change in the German Infection Protection Act and facilitated autopsies during pandemics.

CONCLUSION
A national autopsy registry can provide multicenter quantitative information on COVID-19 deaths at the national level to support medical research, policy decisions and public discussions. Previous and ongoing studies also showed the potential of autopsies for nephrology research.
MO053: Are Renal Prognostic Markers Different in Patients with Exostosin 1/2 Positive or Negative Membranous Lupus Nephritis? A Single Center Experience in Turkey
Authors: Ebru Eser Zeynep , Turgutalp Kenan , Karabulut Yasemin , Akcali Esra , Cagatay Kose Emre , Ballı Ebru , Bardak Simge , Demir Serap , Kıykım Ahmet 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Recently, prognostic importance of antibodies in primary membranous nephropathy is well defined. However, knowledge about antibodies related to disease activity in membranous lupus nephritis (MLN) is limited. Exostosin1 and exostosin2 (EXT1/2) are novel antibodies detected in MLN, and further studies are needed for the prognostic significance of them as a marker.
The aim of this study is to determine whether renal prognostic markers differ between EXT1/2 positive and negative MLN patients.

METHOD
This is a single-center, retrospective and observational study. Class 5 MLN patients aged 18 or older were included in the study. Clinical characteristics, results of biochemical analysis and histopathological examination were recorded from 6 to 18 months. The end-point of the study was determined as complete remission, partial remission, need for renal replacement therapy (RRT) and exitus. Group 1: EXT1/2 positive patients. Group 2: EXT1/2 negative patients. Light, immunofluorescent and electron microscopy findings and laboratory parameters were evaluated in EXT1/2 positive and negative patients.

RESULTS
Group 1: n = 11 patients. Group 2: n = 7 patients. The main demographic, biochemical and histopathological characteristics of the groups were shown in Table 1. EXT1/2 negative patients, a higher number of sclerotic glomeruli, interstitial fibrosis and a higher amount of proteinuria were present than positive patients (P &lt; 0.05). EXT1/EXT2 negative patients had significantly lower C3 and C4 levels than positive patients (P &lt; 0.05). EXT1/EXT2 negative patients had a higher RRT or exitus rate within 18 months than positive patients (P &lt; 0.05). In contrast, EXT1/EXT2 positive patients had a higher rate of achieving complete or partial remission within 18 months than negative patients (P &lt; 0.05). The effect of immunosuppressive drug use other than steroids and glomerulosclerosis remission was statistically significant (P = 0.04 and P = 0.011).

CONCLUSION
EXT1/2 negative class 5 LMN patients have more poor renal prognostic indicators than positive patients. RRT or exitus rate is higher in EXT1/EXT2 negative patients than positive patients. However, more randomized controlled studies are needed.
MO057: Serum Irisin and Prediction of Cardiovascular Events in Elderly Patients with CKD Stage 3–5
Authors: Del Mastro Teresa , Arcidiacono Teresa , Bologna Arianna , Edvige Foligno Nadia , Avino Monica , Vezzoli Giuseppe 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Irisin is a circulating myokine released by skeletal muscle after exercise. Its production decreases in chronic kidney disease (CKD) as a potential consequence of sarcopenia and physical inactivity. Irisin produces beneficial effects in glucose and lipid homeostasis: it promotes glucose tolerance and lipid metabolism and improves insulin resistance, stimulates browning of white adipose tissue and upregulates thermogenesis. Irisin may also produce a protective effect on the cardiovascular system as it promoted the proliferation of cardiomyocytes and suppressed myocardial fibrosis and hypertrophy. Low serum irisin was proposed as a predictor of cardiovascular mortality. We studied the relationship of serum irisin with cardiovascular risk in a sample of patients at different stages of CKD not undergoing dialysis and characterized for their artery calcification and mineral metabolism variables.

METHOD
Seventy-nine consecutive patients with stage 3–5 CKD were recruited from the patients of the nephrology outpatient clinic of our institute in Milan from 2010 to 2014. Serum irisin levels were measured at baseline in all recruited patients and in 20 healthy controls. Incident cardiovascular events were recorded during a 3-year follow-up. They included myocardial infarction, angina pectoris, coronary revascularization, congestive heart failure, stroke, TIA and cardiovascular death.

RESULTS
Serum irisin was significantly higher in controls than that in patients with CKD and in patients with CKD stage 3 than that in patients at stage 4 and 5 taken together. Taking controls and patients with CKD together eGFR was positively correlated with serum irisin. Patients with CKD were grouped according to tertiles of serum irisin. Patients in the lowest tertile had lower serum 1,25(OH)2D levels than patients in the middle and the highest tertile. Patients in the highest tertile had lower Kauppila aortic calcification score than patients in the middle and the lowest tertiles. Twenty patients suffered from cardiovascular events during a 3-year follow-up. Cox regression analysis confirmed the association of serum irisin with incident cardiovascular events during the follow-up, as patients in the highest tertile of serum irisin showed a lower cardiovascular risk than patients in the middle or the lowest tertile. Kaplan–Meier survival analysis showed that patients in the highest serum irisin tertile developed less cardiovascular events during the follow-up than patients in the other tertiles taken together (P = 0.049).

CONCLUSION
The present study suggests that irisin is a marker of cardiovascular risk in patients with CKD. It might contribute to the cardiovascular protection that physical exercise and active lifestyle produce in patients with CKD.
MO058: Do Renal Biopsies Assist Understanding of Loin Pain Hematuria Syndrome?
Authors: Sharma Aditi , Prasad Bhanu , Jafari Maryam , Dokouhaki Pouneh 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Loin pain-hematuria syndrome (LPHS) first described in 1967 is a complex and poorly understood rare disease, with a prevalence of 0.012%. It predominantly affects young women in their late 20s and early 30s2. Patients with LPHS experience extreme flank (loin) pain that can be unilateral or bilateral, along with gross or microscopic hematuria. In most cases, the pain is so severe that the patients are forced to quit their jobs, become opiate dependent, need antidepressants, require long term disability and a proportion contemplate committing suicide. Due to inadequate understanding of the pathophysiology of LPHS, the goal of management has been limited to symptomatic relief and pain management. As there are still gaps in our understanding of glomerular hematuria, we opted to assess the histopathological features of kidney biopsies of 14 LPHS patients to evaluate the correlation of glomerular basement membrane (GBM) alterations with hematuria and pain.

METHOD
In this cross-sectional study, 14 patients with LPHS underwent kidney biopsies. Demographic data (sex, age, ethnicity, weight and height), renal biomarkers (urine blood, urine protein and serum creatinine) and comorbidities were obtained prior to the procedure. The kidney biopsies were investigated under light microscopy, immunofluorescence microscopy and electron microscopy. Descriptive statistics were used to report baseline characteristics and histology findings.

RESULTS
All 14 patients were female, with median age 37 years. About 78.6% of the patients were Caucasian. None of the 14 patients had an abnormal glomerular filtration rate or an elevated albumin creatinine ratio (&gt;3 mg/mmoL). 11/14 patients had macroscopic hematuria with 7/11 reporting gross hematuria with exacerbations of loin pain. 5/14 patients showed evidence of endothelial injury. Of the 14 patients, 1/14 had an insufficient sample, 1/13 had thick glomerular basement membrane, 1/13 had IgA nephropathy and 11/13 had normal GBM (Table 1). Regardless of GBM thickness, most patients had RBC cells ± casts implying glomerular leak. There was no evidence of podocyte injury. The presence of endothelial cell injury by electron microscopy may suggest a role for vascular damage in the pathogenesis of at least a subgroup of LPHS patients.

CONCLUSION
The array of histological changes identified in our study offers some understanding of the hematuria component but cannot explain pain as most patients did not have histological evidence of interstitial edema. In conclusion, our findings indicate that there is an urgent need for advanced understanding of molecular mechanisms underlying the heterogeneity of this disease. In our next phase of the study, we intend to compare gene signatures of LPHS patients with patients with isolated hematuria (without pain) to help enhance our understanding of unique genetic predisposing factors to this disease.
MO070: Noncanonical IKKS and the Type 1 Interferon Pathway Activate Inflammation and Cell Death in Tubular Cells and Contribute to Renal Injury
Authors: Marcela Córdoba David Gina , García-Giménez Jorge , Ortiz Alberto , Mario Ramos Cortassa Adrián 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Deleterious consequences of type 1 interferons (T1-INFs) in the renal tissue have been envisioned in the context of viral and autoimmune diseases and in clinical therapies dealing with their administration.(1–3) Moreover, a participation of the T1-INF pathway has been suggested in the acutely injured kidney. (4) However, the pathogenic processes triggered by the T1-INFs in the kidneys are still not well defined and hence they need to be better defined. Therefore, we aimed to address whether the T1-INF pathway and molecular routes leading to its activation regulate critical pathogenic mechanisms underlying kidney damage.

METHOD
The overall activation of the T1-INF pathway, which involves upstream signaling through TBK1/IKKε/IRF3 and downstream engagement of the INFα/β receptor (IFNAR) (5) was studied in models of cultured murine tubular cells (MCT) and mice challenged with the INFs α and β and the proinflammatory inducers TWEAK and LPS. Pharmacological, immune-modulator and genetic approaches were used to inhibit signaling from TBK1/IKKε/IRF3 or IFNAR in tubular cells as well as in murine models of kidney injury induced by LPS or folic acid.

RESULTS
INFs α and β activated the T1-INF pathway from their interaction with IFNAR thus stimulating intertwined antiviral ISG and inflammatory NF-κB-associated responses in tubular cells and kidney tissue. Both ISGs and NF-κB were also activated by TWEAK and LPS through the TBK1/IKKε/IRF3 signaling pathway, which also mediates cell death programs. Simultaneous pharmacological inhibition of TBK1/IKKε restrained the cytokine production and the ISG response elicited by TWEAK or LPS, and the TWEAK-dependent apoptosis triggered in the presence of proinflammatory cytokines. Moreover, TBK1 silencing also protected from inflammation and prevented the ISG reaction although it promoted cell death. The activity of IKKε accelerated the TBK1-induced NF-κB activation without showing relevant participation in this mechanism by itself, despite it having a contribution to cell death. An improvement of the kidney injury (inflammation and tubular cell death) in murine models of LPS and folic acid nephrotoxicity was observed by restraining the T1-INF pathway through pharmacological inhibition of TBK1/IKKε or IFNAR immune-neutralization. By contrast, fueling the TBK1/IKKε or the IFNAR signaling worsened the renal injury.

CONCLUSION
T1-INFs and proinflammatory modulators activate related proinflammatory and antiviral signaling pathways in tubular cells that otherwise may favor kidney injury thus offering alternative targets for nephroprotection.
MO076: GLUT2 as a Key Factor in the Pathogenesis of Diabetic Kidney Disease
Authors: Ahmad Majdoleen , Hinden Liad , Hamad Sharleen , Abramovitch Rinat , Thorens Bernard , Tam Joseph 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Diabetic kidney disease (DKD) affects more than 30% of all diabetic patients. It is strongly associated with increased morbidity, mortality and global healthcare burden. Furthermore, it is considered the primary cause of end-stage kidney disease (ESKD). The renal proximal tubular cells (RPTCs) are highly susceptible to diabetes-induced hyperglycaemia, and glucose handling in these cells plays a central role in the pathophysiology of DKD; yet, the molecular mechanisms underlying hyperglycaemia-induced tubulopathy are poorly understood. Although glucose transporter 2 (GLUT2) is a major glucose transporter in the RPTCs, its exclusive role and the underlying mechanism by which it contributes to the pathogenesis of DKD are poorly known. Here, we reveal its fundamental role in the pathogenesis of DKD.

METHOD
By using the Cre-lox technique, we developed a novel mouse strain with reduced GLUT2 expression specifically in the RPTCs and crossed it with the Akita-diabetic mouse strain to generate diabetic RPTC-GLUT2-/- mice. We evaluated the renal phenotype of the null mice and compared it with their diabetic wild-type (WT) littermate controls by assessing renal patho-morphological changes, measuring blood and urine biochemical alterations, and testing renal function by qPCR, immunohistochemistry and ELISAs. Moreover, we measured glucose uptake by the kidney in the diabetic RPTC-GLUT2-/- mice and their WT controls by utilizing µPET-MRI imaging of tail vein-injected 18[F]-deoxy-D-glucose (FDG).

RESULTS
Whereas no significant changes were found in the weight or the diabetic status of the null mice in comparison with the WT animals, considerable improvements of renal function in the diabetic RPTC-GLUT2-/- mice were measured. These positive changes included significant reductions in urine creatinine, albuminuria, albumin-to-creatinine ratio (ACR) and urinary kidney injury marker 1 (KIM-1) levels. Interestingly, the hyperglycemia-induced patho-morphological changes in the kidney as well as renal injury, fibrosis and inflammation were significantly attenuated in the diabetic RPTC-GLUT2-/- mice. Moreover, the renal uptake of 18[F]-FDG was significantly decreased in the diabetic RPTC-GLUT2-/- mice compared with their WT littermate controls.

CONCLUSION
Fundamental novel observations regarding the contribution of GLUT2 in RPTCs to the development and pathogenesis of DKD have emerged. Our findings suggest that RPTC-GLUT2 not only affects glucose reabsorption but also modulates cellular function, eventually affecting the degree of renal inflammation, tubulointerstitial fibrosis, diabetic kidney injury and renal patho-morphology. Correspondingly, our results indicate that GLUT2-linked molecular mechanisms greatly affect DKD pathophysiology. Therefore, studying these cellular pathways have a major potential for therapeutic intervention of DKD and other kidney diseases.
MO104: Predictors for Early Mortality in Myeloma-Related Kidney Disease
Authors: Cadri Vilma , Saraci Armanda , Pasko Nevi , Imeraj Matilda , Toska Loriana , Straokosha Arjana , Rista Elvana , Cili Alma , Ivanaj Arben , Rroji (Molla) Merita , Barbullushi Myftar 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Renal failure severe enough to require dialysis is an independent predictor of poor survival outcomes in multiple myeloma (MM). Significant early mortality (EM) was also determined in patients with MM infected by COVID-19. To evaluate the EM rate and investigate the risk factors associated with EM in MM patients.

METHOD
Medical records of patients from the hematology unit of UHC ‘Mother Teresa’ with MM between January 2020 and March 2021 were reviewed. Out of 183 patients, 33.3% have in presentation myeloma-related kidney disease (MRKD). The statistical methods consisted of Kaplan–Meier survival curves, the log-rank test, logistic regression analysis and the ROC curve for mortality analysis.

RESULTS
We evaluated 61 patients with MRKD, with 67.2% men; the mean age was 66.2+ (8.7) years. The incidence of MRKD was 41%, and 19.7% of MRKD patients underwent haemodialysis treatment. The 1-year mortality rate was found 29.5% (P &lt; .01), where the EM rate was 13.1%, from which 62.5% needed dialysis. During follow-up, 10% of patients with MRKD had confirmed positive SARS-COV2 tests, associated with a high mortality rate of around 67%. AUC for creatinine value was 0.828, while it had a specificity of 88.37% and a sensitivity of 77.78% at a cut-off value &gt;4 mg/dL (Figure 1). Multivariate logistic regression found creatinine &gt;4 mg/dL, haemodialysis and COVID-19 remained independent predictors of high mortality in MRKD patients after being adjusted for cofounders (Figure 2).

CONCLUSION
High incidence of MRKD indicates under recognition of MM. Mortality from COVID-19 infection in MRKD was relatively high, 22.2%. Renal failure is the second most common cause, after infection, of EM in MM patients. It is potentially reversible, so it is of high-interest early diagnosis and management of MRKD for more prolonged survival. Prophylactic measures in patients with preexisting-kidney failure may further reduce this risk.
MO105: Study of 45 Cases of Membranous Nephropathy from a Kidney Biopsy Record at the Level of the Nephrology Department in Marrakech
Authors: Mikdam Najoua 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Membranous nephropathy is the most common cause of nephrotic syndrome in adults. However, the epidemiological data of this disease are not yet sufficiently known in our country. The aim of our study was to determine the clinical, biological and histological profile of MN and to evaluate its therapeutic approaches and evolutive aspects.

METHOD
We conducted a single-centre retrospective study in the nephrology department of the University Hospital Center Mohammed VI, over a period of 3 years (2016–2019) including 45 cases of MN confirmed by renal biopsy, with a minimum follow-up of 6 months. All patients were started on supportive therapy and then reassessed at 6 months. The nature of the next treatment was determined on an individual basis according to the risk of progression of each patient. The primary endpoint of the study was to obtain a remission of nephrotic syndrome. Complete remission was defined as proteinuria &lt;0.3 g/day, and normal renal function partial remission was defined as proteinuria of 0.3–3 g /day and a stabilization of creatininemia.

RESULTS
The mean age of the patients was 45.24 ± 10.98 years. The clinical presentation was dominated by edematous syndrome found in 75.8% of cases. Systemic manifestations were found in 50% of cases. Nephrotic syndrome was objectified in 66.67% of cases. The histological study showed a predominance of the stage 3 in 56.7% of cases. Membranous lupus nephritis was found in 20.1% of cases, viral hepatitis B in 3% of cases, secondary syphilis in 3% of cases and primary MN in 73.9% of cases. Anti-PLA2R antibodies were positive in four patients with primary MN. After a minimal 6-month follow-up, we achieved remission in 74% of patients. Eighteen patients received aetiopathogenic treatment. Total remission was found in 48% of patients, partial in 39.4% of patients and an aggravation was noted in 15.1% of the cases progressing towards end-stage renal failure.

CONCLUSION
The evolution of membranous nephropathy is highly variable, but it remains a considerable cause of end-stage renal failure; hence, the need for rapid and continuous management is high in order to achieve remission and reduce the morbimortality related to membranous nephropathy.
MO113: Estimation of Hypocalcaemia, Hypoalbuminemia and Hypomagnesaemia Prevalence in Patients with COVID-19 and its Relationship with Clinical Manifestations and Disease Progression
Authors: Hashemi Samaneh , Salmanzadeh Shokrollah , Mobarak Sara , Yahyavi Sahzabi Reza , Hazbehnejad Alireza , Noorshahi Nooshin , Hashemi Fatemeh , Maghsudi Fatemeh 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Electrolyte abnormalities are common among patients with coronavirus disease 2019 (COVID-19). This study aims to investigate the electrolyte changes in severe and non-severe COVID-19 patients. Hypocalcaemia, hypomagnesaemia and hypoalbuminemia and their relationship with the severity of symptoms and prognosis will also be determined.

METHOD
We enrolled 270 COVID-19 patients. Serum tests were taken from each patient on the day of admission to check the level of variables. Thereon, calcium, magnesium and phosphorus levels were measured twice a week and albumin levels were measured once a week. Variables such as PTH and 25 (OH) D were measured once at the beginning of the study. Other laboratory results like complete blood count, C-reactive protein and clinical data such as arterial blood oxygen levels, length of stay in the ICU and the treatment regimen were extracted from patients' medical records and history. Finally, patients were categorized as mild, moderate, severe and critical group based on the severity of the disease. The data analyses were carried out via SPSS software (version 21.0).

RESULTS
Of 270 patients, 135 people (50%) were men. The mean age of patients was 46.7 years. Based on the severity of the disease, 91 patients had mild disease, 90 patients presented with moderate disease, 54 patients were in severe condition and 35 patients were critical. Hypocalcaemia (Ca 2+ ≤8.6 mg/dL) was detected in 49 patients (18.1%) on admission. The mean of serum magnesium, phosphorus and albumin levels on admission was 2.2 ± 0.22 mEq/L, 3.39 ± 0.79 mg/dL and 4.49 ± 0.66g/dL, respectively. Phosphorus level was lower than 2.63 mg/dL in 11 patients (4.07%) and 43 patients (15.92%) had hypoalbuminemia. The mean 25(OH) D level was 32.92 ± 10.29 μg/L; therefore, 182 patients (67.40%) fall within the normal range (&gt;30 μg/L).

CONCLUSION
Patients with mild and moderate disease tend to develop hypocalcaemia, hypoalbuminemia and hypomagnesaemia more often than severe and critical COVID-19 patients during treatment. 25(OH) D deficiency rate was higher in the moderate group. Patients with hypocalcaemia during treatment had higher mortality than other patients. We recommend electrolytes be measured at initial presentation and serially monitored during hospitalization in order to establish timely and appropriate corrective actions and prevent the serious complications of the disease.