bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0877ASSOCIATIONS OF DISORDERS IN BONE MINERAL PARAMETERS WITH MORTALITY IN STAGE 4 AND 5 CKD: INSIGHTS FROM THE PECERA STUDY
Authors: Molina Pablo , Molina Mariola D , Pallardó Luis M , López-Menchero Ramón , Torralba Francisco Javier , Escudero Quesada Veronica , Castro Alonso Cristina , Del Pozo Carlos , Martín-Rivas Josefa , Sánchez-Pérez Pilar , Soldevila Amparo , González-Rico Miguel , Peris Ana , Sancho Calabuig Asunción , Gorriz Jose Luis 
Published: June 2020

Abstract

Background and Aims
Abnormalities of bone mineral parameters are associated with increased mortality in patients on dialysis, but their effects and the optimal range of these biomarkers are less well characterized in non-dialysis chronic kidney disease (CKD).

Method
PECERA (Collaborative Study Project in Patients with Advanced Chronic Kidney Disease) is a 3-year, multicentre, open-cohort, prospective study carried out in 995 adult patients with CKD stages 4-5 not on dialysis enrolled in 2007-09 from 12 centres in Spain. Associations between levels of serum calcium (corrected for serum albumin), phosphate, and intact parathyroid hormone (iPTH) and all-cause mortality were examined using time-dependent Cox proportional hazards models and penalized splines analysis adjusted by demographics and comorbidities, treatments and biochemical collected at baseline and every 6 months for 3 years.

Results
After a median follow-up of 30 months (IQR:14-37 months) there were 180 deaths (18%). The association of calcium and phosphate with all-cause mortality was U-shaped (Figure). The serum values associated with the minimum risk of mortality were 9.35 mg/dL for calcium and 3.56 mg/dL for phosphate, being the lowest risk ranges between 7.4 to 10.7 mg/dL and between 2.3 to 4.6 mg/dL for calcium and phosphate, respectively. For iPTH levels, the association was J-shaped, with an increased risk for all-cause mortality at levels &gt; 110 pg/mL.

Conclusion
As previously reported in dialysis patients, PECERA provided evidence on the association of serum calcium, phosphate and iPTH levels with all-cause mortality in stage 4 and 5 CKD patients, suggesting potential survival benefits of controlling bone mineral parameters in this population. Whereas the ranges of calcium and phosphate associated with the lowest mortality in the study were consistent with the current K-DIGO guidelines, our results suggested that the threshold for considering anti-parathyroid treatment might be lower than is currently recommended.
P1620PROGNOSTIC VALUE OF RENAL BIOPSY QUANTITATIVE HISTOLOGY IN LIVING KIDNEY DONORS AND RECIPIENTS OF KIDNEYS FROM LIVING DONORS
Authors: Buus Niels Henrik , Nielsen Cecilie Molgaard , Krag Soren , Ibsen Lotte , Skov Karin , Nyengaard Jens Randel 
Published: June 2020

Abstract

Background and Aims
Living kidney donors (LKD) have an increased risk of chronic kidney disease. Likewise, renal transplant recipients may experience early or unexplained loss of graft function. We examined the predictive value of stereology based on a CT-scan and a biopsy from the transplanted kidney in relation to renal function outcome in both LKD and recipients of kidneys from living donors.

Method
A pre-transplantation contrast-enhanced CT-scan was used to obtain cortical volume of both kidneys using the Cavalieri estimator. Glomerular number density in a baseline biopsy from the transplanted kidney (taken at the time of transplantation) was estimated by a model-based method and multiplied with cortex volume to estimate the total number of glomeruli in the donated kidney. Glomerular volume was estimated by the 2D nucleator (1). In addition, kidney fibrosis (point-counting), glomerular sclerosis, and arteriole dimensions (2D nucleator) were also calculated. Pre-donation single kidney glomerular filtration rate (GFR) was determined using 51chrome EDTA clearance together with a renography and the GFR measurement was repeated one year after transplantation in both donors and recipients. We examined the association between GFR at one-year follow-up and cortex volume and various histology parameters from the baseline biopsy after adjustment of age, sex, body mass index, smoking status, 24-hour mean blood pressure and single-kidney GFR before transplantation.

Results
CT-scans, GFR measurements and kidney histology from 49 LKD and 38 recipients of kidneys from living donors were available for analysis. Mean age of donors was 50±12 years (55% women) and of recipients 46±13 years (26% women). In donors, GFR decreased from 113±24 to 71±16 ml/min while in recipients GFR was 61±18 ml/min at one-year follow-up (all with a functioning graft).
In donors, GFR at follow-up of the remaining kidney had increased by 28% as compared to baseline. Follow-up GFR correlated to cortex volume (P&lt;0.001), but not to any of the histological parameters (total glomerular number, glomerular volume, % sclerosed glomeruli, % kidney fibrosis or arteriolar dimensions).
In recipients, GFR at follow-up had increased by 8% as compared to single-kidney GFR before donation. Follow-up GFR correlated to % kidney fibrosis (P=0.02) and % sclerosed glomeruli (P=0.05), but not any of the other histological parameters or cortex volume.

Conclusion
When adjusted for relevant clinical confounders the estimation of cortex volume had predictive value for renal function outcome in LKD while % kidney fibrosis and % sclerosed glomeruli had predictive value in recipients of kidneys from living donors.
P0044THE BIOLOGICAL AND FUNCTIONAL CHARACTERISATION OF GENES RESPONSIBLE FOR MONOGENIC DISORDERS OF THE KIDNEY
Authors: Salehi Mahan , Jiang Xiao , Xu Xiaoguang , Eales James , Tomaszewski Maciej 
Published: June 2020

Abstract

Background and Aims
Single mutations in over 620 genes are known as drivers of approximately 330 monogenic disorders of the kidney. These disorders are estimated to account for up to 10% of chronic kidney disease cases. Due to their disease-causing nature, these genes are particularly clinically relevant targets for molecular analysis, but, so far, there has been no systematic analysis of their expression profile and biological functions in the human kidney. We aimed to characterise and compare the genes responsible for monogenic disorders of the kidney with other non-monogenic protein-coding genes.

Method
We used RNA-sequencing profile of 430 kidneys to explore the characteristics of 530 monogenic genes whose expression was available for analysis in the dataset. The property of genes was characterised using in silico databases such as Genome Reference Consortium Human Build 37 (GRCh37), Drug Gene Interaction database (DGIdb) and the Human Protein Atlas (HPA). The PANTHER (protein analysis through evolutionary relationships) database was used to determine the biological network of interactions between the monogenic genes. A Fast Gene Set Enrichment Analysis (FGSEA) was carried out using single-cell RNA-sequencing data for eight cell types of the kidney from Young et al. Finally, we carried out a two-stage mendelian randomisation to discover a causal link between gene expression and estimated glomerular filtration rate (eGFR) and blood pressure (BP). We used the summary statistics from UK Biobank and the CKDGen consortium for BP and eGFR respectively.

Results
The expression of monogenic genes was both higher and more specific to the kidney, than other protein-coding kidney genes. The pathway analysis found both fetal and organ development to be overrepresented in this set of genes, when compared to non-monogenic kidney genes. We also found that monogenic genes are significantly overrepresented for cell-type specific expression in the proximal tubule and underrepresented in podocytes. Our Mendelian randomisation analysis identified a causal effect between the expression of 50 monogenic genes and either eGFR, systolic or diastolic blood pressure.

Conclusion
Our studies revealed differences in the renal expression profile of monogenic genes and protein-coding genes. The proximal tubule segment of the nephron is a particularly enriched segment of the nephron for monogenic disorders. Kidney expression of 50 of the monogenic genes is causally related to changes in eGFR and blood pressure in the general population.
P0178COMPARATIVE EFFECTIVENESS OF RENIN-ANGIOTENSIN SYSTEM INHIBITORS AND CALCIUM CHANNEL BLOCKERS IN INDIVIDUALS WITH ADVANCED CHRONIC KIDNEY DISEASE: A NATIONWIDE COHORT STUDY
Authors: Fu Edouard L , Clase Catherine M , Evans Marie , Lindholm Bengt , Rotmans Joris , Van Diepen Merel , Dekker Friedo W , Carrero Juan Jesus 
Published: June 2020

Abstract

Background and Aims
There is a lack of data that could help to guide the choice of antihypertensive agents in patients with advanced chronic kidney disease (CKD). We evaluated whether initiating treatment with a renin-angiotensin system inhibitor (RASi) is superior to calcium channel blockers (CCB) in preventing mortality, major adverse cardiovascular events (MACE) or kidney replacement therapy (KRT) in patients with advanced CKD.

Method
Observational study from the Swedish Renal Register, 2007-2017. We identified all nephrologist-referred patients in Sweden who initiated RASi or CCB treatment and had non-dialysis dependent advanced CKD (eGFR &lt;30 ml/min/1.73m2). The associations between RASi vs CCB initiation, mortality, MACE and KRT were assessed by Cox regression. Analyses were adjusted with propensity score weighting for a wide range of confounders, including demographics, blood pressure, laboratory measures, comorbidities and medications. As a positive control we evaluated new use of the same drugs in patients with CKD G3 (N = 2608; eGFR between 30-60 ml/min/1.73m2). Furthermore subgroup, as-treated and competing risk analyses were performed.

Results
The propensity-score weighted cohort included 2479 RASi and 2327 CCB initiators who were well-matched for baseline confounders (all standardized differences &lt;0.1). Median follow-up was 4.1 years, with a maximum follow-up of over 10 years. Compared to CCB, initiation of RASi was associated with a similar risk of mortality (adjusted HR 0.94; 95% CI 0.85-1.03) and MACE (0.99; 0.87-1.13), but with a lower risk of KRT (0.87; 0.78-0.98). Results were consistent across subgroups, in as-treated analyses and after accounting for the competing risk of death. In the control cohort of patients with CKD G3, initiation of RASi (versus CCB) was associated with lower KRT risk (adjusted HR 0.67; 0.47-0.96), and similar risk of mortality (0.91; 0.76-1.08) and MACE (1.06; 0.82-1.35).

Conclusion
Compared with CCB, initiation of RASi in patients with advanced CKD was associated with a lower risk of KRT, but no different risk of mortality or MACE.
P0339URINE METABOLOMIC ASSAY IN EARLY IGA NEPHROPATHY PATIENTS REVEALS URINE GLYCINE AS A PROGNOSTIC BIOMARKER
Authors: Park Sehoon , Yang Seung Hee , Joo Kwon Wook , Kim Jung-Hyun , Kim Dong Ki 
Published: June 2020

Abstract

Background and Aims
A urine metabolomic biomarker from early immunoglobulin A nephropathy (IgAN) can be a useful tool for early detection or prognostic prediction of the disease.

Method
We profiled the urine metabolomes, using nuclear magnetic resonance (NMR) spectrometry, from 197 IgAN patients with eGFR ≥ 60 mL/min/1.73 m2, and the patients with same kidney function range but have diagnosis of membranous nephropathy (n=81) and minimal change disease (n=50) were included as the disease-control group. Additional 146 healthy controls who received routine health screenings and donated urine samples were included. We calculated the creatinine-adjusted urine concentrations of 27 urine metabolites. Urine metabolites specifically increased in urines from IgAN patients were identified, and their associations with the prognosis of the disease, determined with the outcome of eGFR 30% reduction from baseline, were investigated. Additional kidney biopsy samples from independent patients and controls were stained for molecules included in related biological process for experimental validation.

Results
Among the 15 metabolites higher in the urines from IgAN patients than those from the healthy controls, only glycine was the metabolite that the median level was significantly higher also than that of the disease-control group. We found that the higher levels of glycine, alanine, citrate, threonine, and valine were significantly associated with higher risks of 30% eGFR reduction in IgAN patients. Among the molecules related to metabolism of glycine, expressions of T and H proteins from glycine cleavage system were significantly reduced in the kidney biopsy slides from independent IgAN patients when compared to the controls.

Conclusion
Urine glycine may be a prognostic and pathophysiology-related biomarker of IgAN. A further study confirming the clinical usefulness and pathophysiologic significance of urine metabolites in IgAN patients is warranted.
P0969PARKIN INHIBITS THE PROGRESSION OF DIABETIC NEPHROPATHY BY PROMOTING GATA4 DEGRADATION TO REDUCE THE SENESCENCE OF RENAL TUBULAR CELLS
Authors: Chen Kehong , Chen Jia , He Yani 
Published: June 2020

Abstract

Background and Aims
Diabetic nephropathy (DN) can cause end-stage renal disease. During the progression of DN, hyperglycemia accelerates the senescence of renal tubular epithelial cells (RTECs), leading to the tubulointerstitial inflammation and fibrosis. E3-ubiquitin ligase Parkin can regulate several pathophysiological processes. This study explored the role and mechanisms of Parkin in the progression of diabetic nephropathy (DN).

Method
149 cases of patients with DN diagnosed by renal biopsy were recruited in our study. 32 normal kidney samples were obtained from renal carcinoma as control. Renal Parkin expression was detected by immunohistochemistry. The correlation between Parkin expression and renal pathological injury scores, renal function injury parameters were analyzed. In vivo, we generated Parkin overexpressed streptozotocin-induced DN mice using ultrasound- mediated adenovirus transfection. In vitro, knockdown and overexpression experiments were performed by parkin siRNA or Parkin overexpressed adenovirus in high glucose (HG) stimulated mouse primary RTEC. Moreover, we used co-immunoprecipitation and pull down experiments to evaluate the interaction of GATA4 with parkin.

Results
We found that Parkin expression gradually decreased and was inversely associated with IL-6, TGF-β1 and GATA4 expression in the kidney during the progression of DN. Parkin over-expression (OE) reduced inflammation, fibrosis, premature senescence of RTECs and improved renal function while Parkin knockout (KO) had opposite effects in DN mice. Parkin-OE decreased GATA4 protein, but not its mRNA transcripts in the kidney of DN mice and high glucose (HG)-treated RTECs. Immunoprecipitation indicated that Parkin directly interacted with GATA4 in DN kidney. Parkin-OE enhanced GATA4 ubiquitination. Furthermore, Parkin-KO up-regulated growth arrest specific gene 1 (GAS1) expression in renal tubular tissues of DN mice and GATA4-OE enhanced the HG-up-regulated GAS1 expression in RTECs. Conversely, GAS1-OE mitigated the effect of Parkin-OE on HG-induced P21, IL-6 and TGF-β1 expression in RTECs. These results indicate that Parkin inhibits the progression of DN by promoting GATA4 ubiquitination and downregulating the GATA4/GAS1 signaling to inhibit premature senescence, inflammation and fibrosis in DN mice. Thus, these findings uncover new mechanisms underlying the action of Parkin during the process of DN.

Conclusion
Parkin inhibited the progression of DN by promoting GATA4 ubiquitination and downregulating the GATA4/GAS1 signaling to inhibit premature senescence, inflammation and fibrosis. Our findings uncover a novel endogenous protective mechanism by which Parkin regulates the senescence of RTECs, inflammation and fibrosis during the pathogenesis of DN.
P1800RITUXIMAB ENHANCES THE EXPRESSION OF INTERLEUKIN-6 VIA TOLL-LIKE RECEPTOR 3 SIGNALING IN HUMAN PODOCYTE
Authors: Watanabe Shojiro , Hirono Koji , Aizawa Tomomi , Tsugawa Koji , Tanaka Hiroshi 
Published: June 2020

Abstract

Background and Aims
The etiology of idiopathic nephrotic syndrome (INS) in children remains unclear, but it is well known that viral infections often cause relapses of INS. Since toll-like receptor 3 (TLR3), a ligand of viral dsRNA exists in podocytes, dysregulation of TLR3 signaling in podocytes may be involved in the pathogenesis of INS. Recently, rituximab (RTX) a specific antibody to human CD20, has been successfully used to treat children with intractable nephrotic syndrome (frequent relapse nephrotic syndrome, FRNS, and steroid dependent nephrotic syndrome, SDNS). It has been reported that depletion of B cell is main mechanism of RTX treatment. However, some patients experienced recurrence before peripheral blood B cell recovery, whereas selected patients have sustained remission even after peripheral blood B cell recovery. Considering that dramatic effects of RTX in the treatment of INS, it is speculated that some B cell-independent mechanisms of RTX exist. In this context, some recent studies have reported a direct effect of RTX on podocyte, targeting sphingomyelinase phosphodiesterase acid-like 3b (SMPDL3b), but detailed mechanisms remain to be determined. In this study, we examined whether RTX influences TLR3 signaling in cultured human podocyte.

Method
Immortalized human podocytes in culture were treated with polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of viral dsRNA. RTX were added before or after the treatment of poly IC. Then, expression of interleukin (IL)-6 were measured using real time RT-PCR and ELISA. Direct binding of RTX to podocyte were confirmed by immunofluorescence.

Results
Poly IC induced the expression of IL-6 in cultured human podocyte in a concentration and time-dependent manner. IL-6 expression induced by poly IC were enhanced in both mRNA and protein level by pretreatment of RTX. RTX itself were apparently stained on podocyte by immunofluorescence.

Conclusion
RTX binds directly to cultured human podocyte and enhances the IL-6 expression induced by poly IC. Since IL-6 from podocyte was reported to be engaged in regulating glomerular inflammation by cross-talk with endothelial cells, exploring the role of enhanced IL-6 from podocyte by RTX, at least in a part, suggests a direct mechanism of RTX in treating intractable nephrotic syndrome in children.
P1838THE CONTRIBUTION OF MICROSCOPE IN THE KNOWLEDGE OF KIDNEY DISEASES AS DESCRIBED BY GIULIO BIZZOZERO
Authors: Bellinghieri Guido , Gembillo Guido , Savica Vincenzo , Satta Ersilia , Salvo Antonino , Santoro Domenico 
Published: June 2020

Abstract

Background and Aims
Giulio Bizzozero (20 March 1846 - 8 April 1901) was an eminent Italian scientist, the father of the modern microscopy. In 1879 he published his masterpiece “Manuale di Microscopia Clinica “(Handbook of Clinical Microscopy). Here he underlined how the microscopic examination of the urine gave to the physicians of the time indicative criteria of alteration of the kidney, often essential for diagnosis.

Method
Bizzozero operates in his book a detailed analysis of the methods of time, laying the foundations of microscopy and diagnosis of renal diseases. He proposed a classification of pathological urine and gave large space to the role of the presence of red blood as a great diagnostic sign in urinary sediment (Figure 1 and Figure 2).
The author emphasized the use of microscopy against the obsoleted vision of old academics and promulgated the experimental methods in opposition to the vitalistic philosophy of the time. Bizzozero underlined the idea of “teamwork” and the strong connection with his close collaborators, he says that on a laboratory “a mind should give the idea and the direction of work while other minds join together dealing with particular executions”.

Results
Bizzozero's revolutionary vision of medicine had the purpose to allow every scientist to reach new discoveries in their field, previously being the privilege of an elite, making him a model both as a doctor as a humanist. In one of his memorable speeches he declared: “We need to undress the science of the cloak of mystery and authority: the professor in the school must not offer a series of dogmas supported by the prestige of his name, he must instead expose science in the real state in which it is found, with its doubts and its unresolved mysteries”.

Conclusion
This Bizzozero’s masterpiece definitely represents a milestone of scientific literature, a witness of the radical evolution of modern medicine and experimental research.
Olfactory Dysfunction in Coronavirus Disease 2019 Patients: Observational Cohort Study and Systematic Review
Authors: Chung Tom Wai-Hin , Sridhar Siddharth , Zhang Anna Jinxia , Chan Kwok-Hung , Li Hang-Long , Wong Fergus Kai-Chuen , Ng Ming-Yen , Tsang Raymond King-Yin , Lee Andrew Chak-Yiu , Fan Zhimeng , Ho Ronnie Siu-Lun , Luk Shiobhon Yiu , Kan Wai-Kuen , Lam Sonia Hiu-Yin , Wu Alan Ka-Lun , Leung Sau-Man , Chan Wai-Ming , Ng Pauline Yeung , To Kelvin Kai-Wang , Cheng Vincent Chi-Chung , Lung Kwok-Cheung , Hung Ivan Fan-Ngai , Yuen Kwok-Yung 
Published: June 2020

AbstractBackgroundOlfactory dysfunction (OD) has been reported in coronavirus disease 2019 (COVID-19). However, there are knowledge gaps about the severity, prevalence, etiology, and duration of OD in COVID-19 patients.MethodsOlfactory function was assessed in all participants using questionnaires and the butanol threshold test (BTT). Patients with COVID-19 and abnormal olfaction were further evaluated using the smell identification test (SIT), sinus imaging, and nasoendoscopy. Selected patients received nasal biopsies. Systematic review was performed according to PRISMA guidelines. PubMed items from January 1, 2020 to April 23, 2020 were searched. Studies that reported clinical data on olfactory disturbances in COVID-19 patients were analyzed.ResultsWe included 18 COVID-19 patients and 18 controls. Among COVID-19 patients, 12 of 18 (67%) reported olfactory symptoms and OD was confirmed in 6 patients by BTT and SIT. Olfactory dysfunction was the only symptom in 2 patients. Mean BTT score of patients was worse than controls (P = .004, difference in means = 1.8; 95% confidence interval, 0.6–2.9). Sinusitis and olfactory cleft obstruction were absent in most patients. Immunohistochemical analysis of nasal biopsy revealed the presence of infiltrative CD68+ macrophages harboring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen in the stroma. Olfactory dysfunction persisted in 2 patients despite clinical recovery. Systematic review showed that the prevalence of olfactory disturbances in COVID-19 ranged from 5% to 98%. Most studies did not assess olfaction quantitatively.ConclusionsOlfactory dysfunction is common in COVID-19 and may be the only symptom. Coronavirus disease 2019-related OD can be severe and prolonged. Mucosal infiltration by CD68+ macrophages expressing SARS-CoV-2 viral antigen may contribute to COVID-19-related OD.
Vibrio fluvialis Liver Abscess and Bacteremia in a Sashimi Lover: A Case Report and Review of the Literature
Authors: Kitaura Satoshi , Okamoto Koh , Wakabayashi Yoshitaka , Okada Yuta , Okazaki Aiko , Ikeda Mahoko , Hakuta Ryunosuke , Nakai Yousuke , Okugawa Shu , Koike Kazuhiko , Moriya Kyoji 
Published: June 2020

Abstract
Vibrio fluvialis is a foodborne pathogen known to cause a cholera-like gastroenteritis syndrome. Here we report the first case of V. fluvialis liver abscess and bacteremia presumed to be from sashimi, a Japanese raw seafood delicacy. We also provide a literature review of reported cases of V. fluvialis extra-intestinal diseases including bacteremia.