bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of dietary energy density and supplemental rumen undegradable protein on intake, viscera, and carcass composition of lambs recovering from nutritional restriction
Authors: Dougherty Holland C , Evered Mark , Oltjen James W , Hegarty Roger S , Neutze Stephen A , Oddy V Hutton
Published: May 2022

Variation in nutrition is a key determinant of growth, body composition, and the ability of animals to perform to their genetic potential. Depending on the quality of feed available, animals may be able to overcome negative effects of prior nutritional restriction, increasing intake and rates of tissue gain, but full compensation may not occur. A 2 × 3 × 4 factorial serial slaughter study was conducted to examine the effects of prior nutritional restriction, dietary energy density, and supplemental rumen undegradable protein (RUP) on intake, growth, and body composition of lambs. After an initial slaughter (n = 8), 124 4-mo-old Merino cross wethers (28.4 ± 1.8 kg) were assigned to either restricted (LO, 500 g/d) or unrestricted (HI, 1500 g/d) intake of lucerne and oat pellets. After 8 wk, eight lambs/group were slaughtered and tissue weights and chemical composition were measured. Remaining lambs were randomly assigned to a factorial combination of dietary energy density (7.8, 9.2, and 10.7 MJ/kg DM) and supplemental RUP (0, 30, 60, and 90 g/d) and fed ad libitum for a 12- to 13-wk experimental period before slaughter and analysis. By week 3 of the experimental period, lambs fed the same level of energy had similar DMI (g/d) and MEI (MJ/d) (P > 0.05), regardless of prior level of nutrition. Restricted-refed (LO) lambs had higher rates of fat and protein gain than HI lambs (P < 0.05) but had similar visceral masses (P > 0.05). However, LO lambs were lighter and leaner at slaughter, with proportionally larger rumens and livers (P < 0.05). Tissue masses increased with increasing dietary energy density, as did DMI, energy and nitrogen (N) retention (% intake), and rates of protein and fat gain (P < 0.05). The liver increased proportionally with increasing dietary energy density and RUP (P < 0.05), but rumen size decreased relative to the empty body as dietary energy density increased (P < 0.05) and did not respond to RUP (P > 0.05). Fat deposition was greatest in lambs fed 60 g/d supplemental RUP (P < 0.05). However, lambs fed 90 g/d were as lean as lambs that did not receive supplement (P0, P > 0.05), with poorer nitrogen retention and proportionally heavier livers than P0 lambs (P < 0.05). In general, visceral protein was the first tissue to respond to increased intake during refeeding, followed by non-visceral protein and fat, highlighting the influence of differences in tissue response over time on animal performance and body composition.
Reproductive status affects isotopic niches of Miniopterus natalensis in northeastern South Africa
Authors: Pretorius Mariëtte , Broders Hugh , Hall Grant , Keith Mark
Published: May 2022

The Natal long-fingered bat, Miniopterus natalensis, is an insectivorous, regional migrating species that exhibits sex-specific migration patterns. We explored the variability of isotopic niches using δ13C and δ15N ratios in fur from female and male bats in different reproductive states: pregnant, reproductive (but not pregnant at the time of this study), and nonreproductive females; nonscrotal and scrotal males using Bayesian standard ellipse areas and generalized linear models. Reproductive status was an informative predictor for the observed variation of both δ13C and δ15N ratios. Pregnant females displayed the highest mean δ13C and δ15N ratios and were distinct from other reproductive states. Reproductive females exhibited significantly higher δ15N ratios than nonreproductive females or nonscrotal and scrotal males, which may reflect state-dependent foraging and/or higher metabolic stress. Scrotal males displayed the lowest mean δ13C and δ15N ratios. Nonscrotal males exhibited the broadest isotopic niche, whereas reproductive females had the narrowest isotopic niche. Differences in isotopic niche sizes between the different reproductive groups may relate to variable individual feeding behavior and/or geographically different foraging areas/migratory stopover sites at individual and intraspecific levels in M. natalensis. This suggests that group-living, cave-dwelling bats may employ individual foraging specialization to facilitate coexistence in the broader geographic landscape.
Computational flow analysis with boundary layer and contact representation: II. Heart valve flow with leaflet contact
Authors: Terahara Takuya , Kuraishi Takashi , Takizawa Kenji , Tezduyar Tayfun E
Published: May 2022

In this second part of a two-part article, we provide an overview of the heart valve flow analyses conducted with boundary layer and contact representation, made possible with the space–time (ST) computational methods described in the first part. With these ST methods, we are able to represent the boundary layers near moving solid surfaces, including the valve leaflet surfaces, with the accuracy one gets from moving-mesh methods and without the need for leaving a mesh protection gap between the surfaces coming into contact. The challenge of representing the contact between the leaflets without giving up on high-resolution flow representation near the leaflet surfaces has been overcome. The other challenges that have been overcome include the complexities of a near-actual valve geometry, having in the computational model a left ventricle with an anatomically realistic motion and an aorta from CT scans and maintaining the flow stability at the inflow of the ventricle-valve-aorta sequence, where we have a traction boundary condition during part of the cardiac cycle.
A History of the Passive in Pre-modern Aramaic: An Outline
Authors: Kalinin Maksim , Loesov Sergey
Published: May 2022

In Proto-Aramaic, the passive of transitive verbs belonging to all three principal stems—G, D and C—was formed internally. Some verbs of the G- and D-stems also possessed detransitive derivatives. Transitive verbs of the G-, D- and C-stems lost their internal passives early on, and the passives of G- and D-verbs were encoded by their respective t-stems. Against this general Aramaic picture, in Imperial Aramaic the passive forms of the G-stem were in complementary distribution: the passive Past was encoded by the internal passive of the Suffix Conjugation (Gp SC), while the passive non-Past was rendered by the Gt participle and the Gt Prefix Conjugation. Gp SC stopped being used with Imperial Aramaic once it was replaced, as a written language, by vernacular-based literary varieties. The Ct-stem, non-existent in Imperial Aramaic, must have first emerged among spoken varieties of Aramaic in the first half of the first millennium bce, and only within I-w and II-w/y roots. Within the Imperial Aramaic corpus, both the rare Gt SC passive forms and Ct-stem forms reflect the influence of spoken Aramaic varieties in the diglossic situation. In Syriac, the Ct-stem of sound roots is unattested during its golden age. The Ct-forms of sound roots appeared in original Syriac texts only after the Arab conquest, and these also come from spoken Aramaic varieties.
Culturing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for Diagnosis and Genome Sequencing
Authors: Zeng Zhiqi , Guo Hua , Chen Liping , Lin Zhengshi , Guan Wenda , Wang Yutao , Jiang Haiming , Wu Xiao , Yin Yong , Gao Zelong , Chen Canxiong , Yang Zifeng
Published: May 2022

Objective

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection “re-positive” phenomenon is encountered clinically. The accuracy of a viral nucleic acid test is crucial to prevent reintroduction of the virus into the community. This study evaluated the effect of virus culturing on increasing the sensitivity and specificity of real-time polymerase chain reaction (RT-PCR) detection and viral genomic sequencing.

Methods

A series of tenfold dilutions of a SARS-CoV-2 viral stock were conducted and cultured for either 24 or 48 hours. The viral load of cultured samples was determined by RT-PCR. The cultured and non-cultured samples of 1x 50% tissue culture infectious dose (TCID50) were sequenced using metagenomic next-generation sequencing. The depth and coverage of SARS-CoV-2 genome were measured.

Results

The lowest viral load detectable in a sample with RT-PCR was 0.01 TCID50. After a 24-h culture, the viral ORF 1ab and N-gene cycle threshold (CT) values were reduced by 4.4 points and 1 point, respectively. One TCID50 viral load of post 24-h culture revealed the sequence depth reached an average of 752 reads, compared with 0.15 in the nonculture; furthermore, the coverage was 99.99% while 6.42% in the nonculture.

Conclusion

These results indicate that virus culturing can significantly increase the viral load, which can increase the certainty of true-positive detection of the viral nucleic acids, and improve the quality of virus genomic sequencing.
Multi-epoch machine learning 1: Unravelling nature versus nurture for galaxy formation
Authors: McGibbon Robert J , Khochfar Sadegh
Published: May 2022

We present a novel machine learning method for predicting the baryonic properties of dark matter only subhalos from N-body simulations. Our model is built using the extremely randomized tree (ERT) algorithm and takes subhalo properties over a wide range of redshifts as its input features. We train our model using the IllustrisTNG simulations to predict blackhole mass, gas mass, magnitudes, star formation rate, stellar mass, and metallicity. We compare the results of our method with a baseline model from previous works, and against a model that only considers the mass history of the subhalo. We find that our new model significantly outperforms both of the other models. We then investigate the predictive power of each input by looking at feature importance scores from the ERT algorithm. We produce feature importance plots for each baryonic property, and find that they differ significantly. We identify low redshifts as being most important for predicting star formation rate and gas mass, with high redshifts being most important for predicting stellar mass and metallicity, and consider what this implies for nature versus nurture. We find that the physical properties of galaxies investigated in this study are all driven by nurture and not nature. The only property showing a somewhat stronger impact of nature is the present-day star formation rate of galaxies. Finally we verify that the feature importance plots are discovering physical patterns, and that the trends shown are not an artefact of the ERT algorithm.
Real-Time and Remote MCMC Trace Inspection with Beastiary
Authors: Wirth Wytamma , Duchene Sebastian
Published: May 2022

Bayesian phylogenetics has gained substantial popularity in the last decade, with most implementations relying on Markov chain Monte Carlo (MCMC). The computational demands of MCMC mean that remote servers are increasingly used. We present Beastiary, a package for real-time and remote inspection of log files generated by MCMC analyses. Beastiary is an easily deployed web-app that can be used to summarize and visualize the output of many popular software packages including BEAST, BEAST2, RevBayes, and MrBayes via a web browser. We describe the design and implementation of Beastiary and some typical use-cases, with a focus on real-time remote monitoring.
DDGun: an untrained predictor of protein stability changes upon amino acid variants
Authors: Montanucci Ludovica , Capriotti Emidio , Birolo Giovanni , Benevenuta Silvia , Pancotti Corrado , Lal Dennis , Fariselli Piero
Published: May 2022

Estimating the functional effect of single amino acid variants in proteins is fundamental for predicting the change in the thermodynamic stability, measured as the difference in the Gibbs free energy of unfolding, between the wild-type and the variant protein (ΔΔG). Here, we present the web-server of the DDGun method, which was previously developed for the ΔΔG prediction upon amino acid variants. DDGun is an untrained method based on basic features derived from evolutionary information. It is antisymmetric, as it predicts opposite ΔΔG values for direct (A → B) and reverse (B → A) single and multiple site variants. DDGun is available in two versions, one based on only sequence information and the other one based on sequence and structure information. Despite being untrained, DDGun reaches prediction performances comparable to those of trained methods. Here we make DDGun available as a web server. For the web server version, we updated the protein sequence database used for the computation of the evolutionary features, and we compiled two new data sets of protein variants to do a blind test of its performances. On these blind data sets of single and multiple site variants, DDGun confirms its prediction performance, reaching an average correlation coefficient between experimental and predicted ΔΔG of 0.45 and 0.49 for the sequence-based and structure-based versions, respectively. Besides being used for the prediction of ΔΔG, we suggest that DDGun should be adopted as a benchmark method to assess the predictive capabilities of newly developed methods. Releasing DDGun as a web-server, stand-alone program and docker image will facilitate the necessary process of method comparison to improve ΔΔG prediction.
Reconstructing physical cell interaction networks from single-cell data using Neighbor-seq
Authors: Ghaddar Bassel , De Subhajyoti
Published: May 2022

Cell-cell interactions are the fundamental building blocks of tissue organization and multicellular life. We developed Neighbor-seq, a method to identify and annotate the architecture of direct cell–cell interactions and relevant ligand–receptor signaling from the undissociated cell fractions in massively parallel single cell sequencing data. Neighbor-seq accurately identifies microanatomical features of diverse tissue types such as the small intestinal epithelium, terminal respiratory tract, and splenic white pulp. It also captures the differing topologies of cancer-immune-stromal cell communications in pancreatic and skin tumors, which are consistent with the patterns observed in spatial transcriptomic data. Neighbor-seq is fast and scalable. It draws inferences from routine single-cell data and does not require prior knowledge about sample cell-types or multiplets. Neighbor-seq provides a framework to study the organ-level cellular interactome in health and disease, bridging the gap between single-cell and spatial transcriptomics.
CB-Dock2: improved protein–ligand blind docking by integrating cavity detection, docking and homologous template fitting
Authors: Liu Yang , Yang Xiaocong , Gan Jianhong , Chen Shuang , Xiao Zhi-Xiong , Cao Yang
Published: May 2022

Protein-ligand blind docking is a powerful method for exploring the binding sites of receptors and the corresponding binding poses of ligands. It has seen wide applications in pharmaceutical and biological researches. Previously, we proposed a blind docking server, CB-Dock, which has been under heavy use (over 200 submissions per day) by researchers worldwide since 2019. Here, we substantially improved the docking method by combining CB-Dock with our template-based docking engine to enhance the accuracy in binding site identification and binding pose prediction. In the benchmark tests, it yielded the success rate of ∼85% for binding pose prediction (RMSD < 2.0 Å), which outperformed original CB-Dock and most popular blind docking tools. This updated docking server, named CB-Dock2, reconfigured the input and output web interfaces, together with a highly automatic docking pipeline, making it a particularly efficient and easy-to-use tool for the bioinformatics and cheminformatics communities. The web server is freely available at https://cadd.labshare.cn/cb-dock2/.
MO006: Identifying the Main Predictors of Urine Output in Autosomal Dominant Polycystic Kidney Disease (ADPKD) Patients taking Tolvaptan
Authors: Borrego-Utiel Francisco-Jose , Isabel Morales García Ana , Polo Moyano Aurora , Roca Oporto Francisco , Merino Garcia Enoc , Jose Esteban de la Rosa Rafael
Published: May 2022

BACKGROUND AND AIMS

Tolvaptan (TVP) blocks vasopressin V2 receptors causing severe polyuria. Few works have analyzed factors associated with urine output in autosomal dominant polycystic kidney disease (ADPKD) patients taking TVP.

METHOD

We selected 24 h urine samples from ADPKD patients treated with TVP. Urine osmolality/creatinine ratio was used as estimator of urine daily osmolar load.

RESULTS

We included 122 urine samples from 54 patients. After TVP, urine output doubled with a parallel reduction in solutes in urine with parallel reduction in urine solute concentration. However, when they were expressed as urine solute/creatinine ratios, no significant changes were observed. Daily osmolar load and osmolality/creatinine ratio did not change significantly.

Before TVP, urine output was positively correlated with body weight and urine osmolality/creatinine ratio and negatively with estimated glomerular filtration rate (eGFR), urine morning osmolality and 24 h urine calculated osmolality. After TVP, urine output was positively correlated with body weight, eGFR and negatively with age. There was a poor correlation with urine calculated osmolality.

We built a predictor model using general linear modeling, and we found that urine output was related to lower age, higher body weight, higher eGFR and greater doses of TVP. When body weight was removed, urine output was also related to male sex and higher daily osmolar excretion.

CONCLUSION

Patients taking TVP will undergo an increase about twice in urine production from baseline. Greater doses of TVP cause a progressive increase in urine output independent of renal function. GFR and specially age and body weight are the most important predictors of future urine output in patients taking TVP.
MO031: Long-term safety of treatment with tolvaptan in patients with autosomal dominant polycystic kidney disease
Authors: Martins Muñoz Judith , Espinel Laura , De Lorenzo Alberto , Tarragon Blanca , Teresa Naya Maria , Cubas Alfonso
Published: May 2022

BACKGROUND AND AIMS

Tolvaptan, a vasopressin antagonist, is a drug that acts by slowing the progression of autosomal dominant polycystic kidney disease (ADPKD). Its administration is not free of side effects. To assess the long-term safety profile of ADPKD patients treated with tolvaptan.

METHOD

Retrospective observational study was undertaken of ADPKD patients on treatment with tolvaptan.

RESULTS

Of the 182 ADPKD patients under follow-up in our hospital, 18% (n = 33) started treatment. Of these, 60.6% (n = 20) were male, with an age of 47.64 ± 8.64 years, a baseline Fg of 65.24 ± 20.14 mL/min, TKVh of 1137.45 ± 667.58 mL and a mean follow-up time of 39.85 ± 10.04 months. A total of 72.7% reached the maximum dose (120 mg), the mean maximum dose reached being 108.18 ± 22.42 mg. At the time of the study, 100% of the patients had reached the maximum dose, the mean time to reach it being 5.8 ± 9.3 weeks. A total of 90.9% (n = 30) presented with side effects: 81.8% (n = 27) aquaretic and 12.1% (n = 4) hepatotoxicity. Others being hypernatremia in 9.1% (n = 3) and hyperuricemia in 24% (n = 8). No other side effects were described. A total of 39.4% (n = 13) of the patients temporarily discontinued treatment after 3.01 ± 2.17 months. The reasons were as follows: aquaretic effects 35.7% (n = 5), hepatotoxicity 35.7% (n = 5), 3.03% desire for pregnancy (n = 1), 3.03% cerebral hemorrhage (n = 1) and 3.03% (n = 1) worsening of renal function. Some 30.76% (n = 4) of the patients restarted treatment at 5.5 ± 6.76 months. Therefore, the treatment discontinuation rate was 27.2%.

The profile of patients with side effects were mostly male (60%) with mean age of 46 ± 8.65 years and TKVh of 1829.93 ± 1172.83 mL .The maximum dose reached in these patients was 107 ± 23.2 mg with a mean time to reach it of 6.19 ± 9.7 ± weeks.

Patients who had more aquaretic side effects were characterized by better baseline prior to renal function and a greater decrease in GFR throughout follow-up. No differences in TRV variations were observed.

CONCLUSION

Tolvaptan treatment is shown to be safe in the long term. However the patient profile to receive treatment must be considered given that a high percentage present aquaretic effects. Regarding hepatotoxicity, although it is another potentially serious effect to consider, it is easily managed and reversible in our studied sample.
MO069: Therapeutic Effects of Semaglutide as Mono and Combination Treatment with Lisinopril in a Mouse Model of Hypertension-Accelerated Diabetic Kidney Disease
Authors: Christensen Michael , Dalbøge Louise S , Secher Thomas , Gravesen Salinas Casper , Ida Rune , Björk Hansen Henrik , Fink Lisbeth N , Viberg Østergaard Mette
Published: May 2022

BACKGROUND AND AIMS

Obesity, hyperglycemia and hypertension are critical risk factors for the onset and progression of diabetic kidney disease (DKD). Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular and renal outcomes in type 2 diabetes patients. We have recently profiled the effects of SGLT2 and angiotensin-converting enzyme (ACE) inhibition in a model of advanced DKD facilitated by adeno-associated virus (AAV)-mediated renin overexpression in uninephrectomized (UNx) diabetic db/db mice (Østergaard et al., AJP Renal Physiol 321: F149–F161, 2021). In the present study, we evaluated the nephroprotective effects of the long-acting GLP1R agonist semaglutide, a long-acting GLP1R agonist currently approved for diabetes and obesity treatment and in clinical development for DKD. Semaglutide was profiled with and without combination treatment with lisinopril, a standard ACE inhibitor, in the db/db UNx-ReninAAV mouse model of DKD.

METHOD

Female db/db mice received a single intravenous injection of reninAAV 1 week prior to UNx. Six weeks post-nephrectomy, mice were randomized into treatment groups based on body weight and blood glucose in the fed state, and received vehicle (SC, QD), semaglutide 30 nmol/kg or semaglutide 30 nmol/kg (SC, QD) in combination with lisinopril 30 mg/kg (PO, QD) for 11 weeks. Treatment endpoints included blood pressure, plasma/urine biochemistry and histomorphometric markers of kidney injury.

RESULTS

Vehicle-dosed db/db UNx-ReninAAV mice developed hallmarks of hypertensive DKD characterized by severe albuminuria and advanced glomerulosclerosis. Compared with vehicle, semaglutide significantly reduced fed blood glucose and hemoglobin A1C levels, whereas no significant effect on plasma insulin was observed. Semaglutide significantly reduced both diastolic and systolic blood pressure as well as albuminuria and urine kidney injury molecule-1 (KIM-1) levels. Semaglutide improved kidney histopathology with notable reductions in glomerulosclerosis severity and percent area of KIM-1 staining. Combined lisinopril treatment led to further improvements in blood pressure, albuminuria and glomerulosclerosis. Semaglutide with and without lisinopril coadministration did not influence plasma urea, cystatin C and kidney CD11 expression.

CONCLUSION

Semaglutide improved disease hallmarks in the db/db UNx-ReninAAV mouse model of advanced DKD. Further benefits on renal functional and histological markers were obtained by combination with antihypertensive standard-of-care treatment.
MO112: Clinical Features of Allopurinol-Induced DRESS/DIHS in 46 Patients
Authors: Liu Qianling , Zhao Sumei
Published: May 2022

BACKGROUND AND AIMS

Allopurinol is the first-line prescribed agent for hyperuricemia and gout. Allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious and potentially life-threatening drug hypersensitivity syndrome. This study aimed to investigate the clinical features, treatment, outcome and prognostic factors of allopurinol-induced DRESS.

METHOD

Case reports of allopurinol-induced DRESS published by China from January 2000 to August 2021 were retrieved from CNKI, Wan Fang, Wei Pu and PubMed databases for analysis.

RESULTS

This study included 46 patients, consisting of 34 (73.9%) males and 12 (26.1%) females (M: F = 2.8:1). The mean of age was 56.1 ± 17.4 years (range: 23–86 years). The mean of latency periods was 24.0 ± 14.8 days (range:1–60 days). Most patients presented with fever, cutaneous eruption, eosinophilia, lymphadenopathy and facial oedema. All patients showed at least one internal organ injury. A total of 35/46 (76.1%) patients showed two or more internal organs involved. Liver and kidney injury were the most common visceral manifestations. One patient showed central nervous system involved, presenting as leukoencephalopathy. HLA*B 58:01 allele was tested in 19/46 (41.3%) patients. A total of 18/19 (94.7%) patients were positive. A total of 45/46 (97.8%) patients were treated with systemic corticosteroids. Patient outcomes were known for 45 of the 46 patients. A total of 13 (28.9%) patients were cured, 24 (53.3%) patients received partial recovery and 8 (17.8%) patients died. Septic shock and multiple organ failure were the leading causes of death. Patients with older age, underlying cardiovascular disease, chronic kidney disease, infection and internal organ involvement (including kidney, heart and lung) were associated with poorer outcomes.

CONCLUSION

We explored clinical features, treatment, outcome and prognostic factors of 46 allopurinol-induced DRESS cases in China. Early identification and discontinuation of the causative drug are crucial to the management of DRESS. For patients with severe disease, corticosteroids are recommended as the first-line therapy. However, further studies are needed to address diagnostic criteria of DRESS for early diagnosis, as well as to develop standardized corticosteroid treatment regimens.
MO136: Histological Findings in Checkpoint Inhibitor-Induced Nephropathy
Authors: Gerakis Alexander , Kaitantzoglou Christine , Giatras Ioannis , Stauridi Flora , Labropoulos Stefanos , Athanasiadis Ilias , Kosmidis Paraskeuas , Gakiopoulou Harikleia
Published: May 2022

BACKGROUND AND AIMS

Immune checkpoint inhibitors (CPIs)—a landmark in cancer therapy—has been occasionally associated with immune-related nephropathy [1]. Acute interstitial nephritis is considered to be the most common underlying histological entity, according to recent literature [2].

METHOD

We report on six patients, 58–73 years old, three women and three men who presented with acute kidney disease, while on immunotherapy with CPIs. Five of them carried the diagnosis of non-small cell lung carcinoma (NSCLC) and one the diagnosis of renal cell carcinoma. All received proton pump inhibitors and experienced one or more of immune-related adverse events (dermatitis, arthritis, colitis, hepatitis and pneumonitis), prior to nephropathy. All underwent kidney biopsy.

RESULTS

Two female patients, both with NSCLC, developed heavy nephrotic syndrome (serum albumin: 1.7–1.8 mg/dL and 24-h urine protein:  12–16 g), after 23–28 months on pembrolizumab monotherapy, which was withdrawn. In the first patient, kidney biopsy demonstrated histology consistent with a lupus like membranous nephropathy (Figure 1). She received corticosteroids with partial recovery. Rechallenge with pembrolizumab was attempted and well tolerated. Renal biopsy of the second patient demonstrated a secondary AA (+) amyloidosis (Figure 2). She showed increased levels of SAA (114 mg/L) and IL-1b (22.9 pg/mL). She received colchicine and moderate dose of corticosteroids with partial remission.

Two other patients, with NSCLC and clear cell renal carcinoma respectively, demonstrated renal biopsy findings consistent with acute interstitial nephritis (serum creatinine 1.5–1.6 mg/dL). The first one was on pembrolizumab along with cisplatin and pemetrexed, while the second one was on pembrolizumab along with axitinib. Both received prednisolone (10–20 mg for 3 months approximately). Pembrolizumab was restarted thereafter. Their renal function remained stable.

Finally, two patients with NSCLC, both men, disclosed acute renal failure (serum creatinine: 3.6- 5 mg/dL) without considerable albuminuria. Acute tubular injury (ATI) was the predominant histological finding (along with focal and mild interstitial inflammation). Both were on combined chemo- and immune- therapy. One on ipilimumab and nivolumab along with platinum and pemetrexed and the other on pembrolizumab and pemetrexed. ATI was attributed most probably to pemetrexed which was withdrawn. Corticosteroids were promptly stopped in the first patient. The second patient showed gradual improvement of his renal function without corticosteroid therapy.

CONCLUSION

CPIs can induce nephropathy other than acute interstitial nephritis. Renal biopsy showed diverse and unusual histological findings. Renal biopsy along with the clinical setting was helpful in choosing appropriate therapy and deciding on CPI's continuation or withdrawal.
MO208: De Novo Glomerulonephritides Following BNT162B2 COVID-19 Vaccine: A Case Series
Authors: Fornara Laura , Musetti Claudio , Guglielmetti Gabriele , Cantaluppi Vincenzo
Published: May 2022

BACKGROUND AND AIMS

The development and massive use of mRNA COVID-19 vaccine BNT162b2 has raised new concerns on triggering de novo immune-mediated diseases, in particular rare diseases as glomerulonephritis (GN), even if the security profile is excellent and severe reactions have been rare. In literature few similar cases were recently described [1, 2]. We report six cases of newly diagnosed GN after a two-dose regimen of SARS-CoV-2 vaccine, from a single tertiary care institution in Northern Italy.

METHOD

We described six cases of de novo GN occurring after massive use of Pfizer-BioNTech BNT162b2 COVID-19 vaccine from March 2021 to December 2021. All cases were biopsy proven. Baseline characteristics and laboratory findings, treatments and outcomes were based on review of medical records.

RESULTS

From April 2021, we observed two IgA nephropathies (IgA-N), one membranous nephropathy (MN), one membranoprolipherative GN (MPGN), one acute interstitial nephritis (aTIN) and one minimal change disease (MCD). Of note, one IgA-N presented with diffuse purpura as in IgA-vasculitis. The median age at vaccination was 52.8 years (min–max 18–67) and three (50%) were female; arterial hypertension was the most common comorbidity (50%). Only one subject contracted COVID-19 before vaccine (16.6%). None of the points showed any sign of renal disease before vaccine; at the time of disease onset, the median creatinine was 1.49 mg/dL (min–max 0.6–10.5 mg/dL) and proteinuria 3.0 g/24 h (min–max 0.9–13.8 g/24 h). All cases presented after the second dose (1 day to 6 months thereafter) and three (50%) were within 3 weeks from the vaccine. Of note, the aTIN developed after the vaccine during a long-time therapy with statins and relapsed after a rechallenge with a statin few months later. All the nephropathies were treated as per center practice, with an overall good response (four partial remissions and one complete remission). Given a target population of about 100 000–200 000 residents in our area, we could estimate an incidence rate of 4–8 cases/100 000 patient-years.

CONCLUSION

This small series has a lot of limitations including the small number of patients and we probably missed some cases in our area. Furthermore, we could not investigate a causal association, even if the timing of disease onset might be suspicious in three cases and the incidence seemed to be almost twice as the expected in Europe (about 2–4/100.000 patient-years). As for SARS-CoV-2 vaccines, it is likely that the mRNA vaccine will result in a more potent inflammatory stimulus than the one observed after inactivated virus-vaccine: maybe some patients had already a subclinical GN and the vaccine constituted a flare leading to the full-blown disease [3].
MO285: FOSL1 Preserves Klotho Expression and Limits Acute Kidney Injury
Authors: Cuarental Leticia , Ignacia Ceballos Darnaude Mª , Valino Lara , Pintor-Chocano Arancha , Ortiz Alberto , Dolores Sanchez-Nino Maria
Published: May 2022

BACKGROUND AND AIMS

Fosl1 (FRA1, Fos-related-antigen 1) is a transcription factor of the AP-1 complex (activator protein 1) that regulates the expression of genes that regulates processes involved in acute kidney injury (AKI) such differentiation, inflammation, proliferation and cell death. We have now explored the role of Fosl1 in AKI and repair.

METHOD

The function of Fosl1 was explored in murine nephrotoxic AKI induced by folic acid or cisplatin in wild type and genetically modified mice tubular cell Fosl1 deficient mice (Fosl1Δtub). RT-qPCR, western blot, and immunohistochemistry were used to assess gene and protein expression. Direct regulation of Klotho by Fosl1 was explored by chromatin immunoprecipitation (ChIP). Murine tubular cells were cultured in an inflammatory milieu promoted by TWEAK and Fosl1 was targeted by siRNA.

RESULTS

Fosl1 was one of the most upregulated transcription factors in experimental nephrotoxic AKI transcriptomics and also one the transcription factors binding to the Klotho promoter (Panel A). Fosl1 upregulation was confirmed in experimental nephrotoxic AKI and in human AKI and localized to tubular cell nuclei at early times points (panel B). Fosl1 deficient (Fosl1Δtub) mice developed more severe folic acid- or cisplatin-induced AKI and higher proinflammatory cytokine expression and kidney macrophage infiltration (Panel C). Additionally, kidney expression of the nephroprotective and antiaging factor Klotho was more severely depressed in Fosl1Δtub mice (Panel D). Enrichment of AP1 binding sites was found in the Klotho promoter and we confirmed direct Fosl1 binding to the Klotho promoter in a ChIP assay. Moreover, Fosl1Δtub mice had disturbed expression of cell cycle regulators and PCNA expression, suggesting a dysregulation in kidney repair. In tubular cells cultured in an inflammatory milieu, Fosl1 expression was also upregulated. Fosl1 siRNA targeting in cultured tubular cells increased inflammatory gene expression and cell death and decreased Klotho expression.

CONCLUSION

Fosl1 contributes to an adaptive kidney response during AKI that limits kidney injury and includes Klotho expression and Fosl1 deficiency promotes an accelerated loss of klotho and more severe AKI.
MO313: Haematological Ratios as Risk Factor for Acute Kidney Injury in Patients Suspected of an Infection at the Emergency Department
Authors: de Hond Titus , Khairoun Meriem , Haitjema Saskia , Kaasjager Karin A H
Published: May 2022

BACKGROUND AND AIMS

Evidence exists that inflammation plays an important role in the pathogenesis of acute kidney injury (AKI) in sepsis patients. Haematological ratios can be used to measure systemic and silent inflammation. Therefore, we investigated what haematological ratios could be identified as risk factors to predict AKI < 30 days in patients suspected of infection at the emergency department (ED).

METHOD

Data from the SPACE-cohort (SePsis in the Acutely ill patients in the ED) were used. This cohort consists of all patients ≥ 18 years, that present at the ED of the UMC Utrecht for the internal medicine with suspicion of infection. AKI was defined based on the KDIGO criteria. Haematological markers were determined with the Abbott Cell-DYN Sapphire haematology analyser. In total, 7 haematological ratios were included. A Cox regression was performed after the ratios were divided into tertiles. Consequently, Kaplan–Meier curves for 30-day mortality were constructed for the significant predictors from the Cox analysis.

RESULTS

In univariate Cox regression, neutrophil-to-lymphocyte ratio (NLR), segmented neutrophil-to-monocyte ratio (SeMo) and neutrophil-to-lymphocyte-and-platelet ratio (NLPR) were all significant risk factors for the occurrence of AKI < 30 days after ED presentation (Fig. 1). After correction for multiple confounders, NLR, SeMo and NLPR remained significant. There were significant differences in survival for all these three ratios (Fig. 2).

CONCLUSION

In this study, we show that several haematological ratios are risk factors for AKI and mortality in patients suspected of infection at the ED. Using these risk factors in prediction models might enable ED physicians to treat AKI in an early phase and prevent any short- and long-term complications. A limitation of this study is the retrospective character. Because of this, not all patients in the cohort had follow-up creatinine levels, and the occurrence of AKI could not be determined in these patients.
MO371: Should We Systematically Look for Urine Alterations in all Patients With Monoclonal Gammopathy of Undetermined Significance?
Authors: Iturralde Ros Marta , Maiztegi Azpitarte Ainhoa , Ortiz Espejo María , Montes Gaisan Carmen , María Ocio San Miguel Enrique , Carlos Ruiz San Millán Juan , Rodrigo Emilio
Published: May 2022

BACKGROUND AND AIMS

Monoclonal gammopathy of undetermined significance (MGUS) has a high prevalence in the elderly population, being as high as 9% in subjects over 85 years. Population aging leads to an increase in the number of patients with MGUS. In 2012, monoclonal gammopathy of renal significance (MGRS) was described to identify MGUS patients with renal alterations but without overt hematological disorders. Despite an increasing number of cases and case series being reported, the prevalence and natural history of MGRS are not known with precision, in part because a systematic search for kidney damage is not standardized in all patients in whom MGUS is diagnosed. Our objective was to analyze in how many MGUS patients urine has been systematically analyzed and in how many of them any alterations suggestive of MGRS were detected.

METHOD

A retrospective observational study was carried out in our center of all patients in whom a paraprotein had been detected in the blood during the first trimester of 2018 and who did not present a known underlying hematological disorder. Glomerular filtration rate (GFR) was estimated using the CKD-EPI equation. The percentage of patients with a urine test using dipstick and urine sediment was analyzed, as well as the presence or any alteration suggestive of MGRS in them.

RESULTS

Three hundred and sixty patients were recorded, 44% females and with a mean age of 74 ± 12 years. Mean GFR was 69 ± 22 mL/min/1.73 m2 being 32% below 60 mL/min/1.73 m2. Urine dipstick and urine sediment were performed in only 42% and 24% of patients, respectively. Urine dipstick was more frequently performed in patients with worse GFR (72 ± 20 versus 64 ± 24 mL/min/1.73 m2P = 0.001) and in older patients (73 ± 13 versus 76 ± 11, P = 0.027). Similarly, urine sediment was more frequently performed in patients with worse GFR (72 ± 20 versus 59 ± 25 mL/min/1.73 m2 P < 0.001). Significant hemoglobinuria was found in 38% and dipstick albuminuria in 29% of them. Among those patients with urine sediment analysis, significant hematuria was detected in 56% and leukocyturia in 52%. Patients with significant dipstick hemoglobinuria (70 ± 21 versus 55 ± 26 mL/min/1.73 m2 P < 0.001) and albuminuria (68 ± 21 versus 54 ± 28 mL/min/1.73 m2 P = 0.005) showed worse GFR (figure 1).

CONCLUSION

Despite the risk of suffering some pathologic renal conditions included in the term MGRS, in most of our patients with MGUS, a urine dipstick or sediment analysis is not performed. MGUS patients with urine alterations show worse renal function. We advocate that all MGUS patients should have a dipstick and sediment urinalysis to rule out any possible associated kidney damage.
MO373: How to Decide Whether Creatinine or Cystatin C is More Accurate for Kidney Function Assessment in Older Adults
Authors: Potok Alison , Rifkin Dena , IX Joachim , Shlipak Michael , Satish Anita , Schneider Alice , Mielke Nina , Schaeffner Elke , Ebert Natalie
Published: May 2022

BACKGROUND AND AIMS

The gold standard for evaluation of kidney function is measured GFR [mGFR] which is challenging to perform in clinical practice. Serum creatinine and cystatin C are used to estimate GFR clinically, but neither is a perfect marker. Within any given individual, the estimated glomerular filtration rate (eGFR) can be widely different when using serum creatinine [eGFRCr] vs. cystatin C [eGFRCys]. We investigated which was closest to mGFR in elderly outpatients when results between these two eGFRs were discrepant.

METHOD

About 657 older ambulatory participants of the population-based Berlin Initiative Study (BIS) had GFR measured by iohexol plasma clearance (mGFR), as well as serum creatinine and cystatin C levels. eGFRCr and eGFRCys were calculated using the 2009 and 2012 CKD-EPI equations, respectively. The cohort was divided into two groups based on which of these eGFR estimates was lowest. Bias (defined as ‘eGFR-mGFR’), imprecision (standard deviation [interquartile range] of bias), as well as proportion within 30% (P30) were calculated.

RESULTS

Mean (±SD) age was 78 (±6) years, eGFRCys was 59 (±23), mean eGFRCr was 64 (±20) and mGFR was 55 (±20) mL/min/1.73 m2. Mean (±SD) body mass index was 28 (4) kg/m2 58% were men, and 26% had diabetes mellitus. Two-thirds of participants (448/657 = 68%) had eGFRCys < eGFRCr. Regardless of which group participants were in, the lower of the two eGFR estimates was the one less biased compared to mGFR. Among those in whom eGFRCr ≤ eGFRCys, 80% (=168/209) had eGFRCr closer to mGFR than eGFRCys; among those in whom eGFRCys < eGFRCr, 74% (=333/448) had eGFRCys closer to mGFR than eGFRCr (Figure). P30 was 86% for eGFRCr when it was the lower estimate, and was 90% for eGFRCys when it was the lower estimate (Table).

CONCLUSION

In a population of community-dwelling older adults, the lower value between eGFRCys and eGFRCr was closest to mGFR in 76% of participants.
MO500: Increased Mortality and Readmission Rates Among Hospitalized Covid-19 Patients With Varying Stages of Chronic Kidney Disease
Authors: Appelman Brent , Oppelaar Marjet , Broeders Lani , Wiersinga Joost , Peters-Sengers H , Vogt Liffert
Published: May 2022

BACKGROUND AND AIMS

Chronic kidney disease (CKD) has been recognized as a highly prevalent risk factor for both the severity of coronavirus disease 2019 (COVID-19) and COVID-19 associated adverse outcomes. In this multicentre observational cohort study, we aim to determine the mortality and readmission rates of patients hospitalized for COVID-19 across varying CKD stages.

METHOD

We performed a multicentre cohort study among COVID-19 patients included in the Dutch COVIDPredict cohort consisting of hospitalized COVID-19 patients (PCR-confirmed or CORADS score >4). Seven groups of CKD were defined based on a previously reported medical history of CKD and pre-admission eGFR (CKD-EPI), which was also used to categorize CKD-stages. Patients without CKD were classified as controls. The primary outcome was a composite endpoint of all-cause mortality, readmission or palliative hospital discharge in a 12-week follow-up period. Logistic regression was used to adjust the association between CKD groups and primary outcome in a stepwise procedure for the following confounders: age, sex, ethnicity, number of comorbidities and designated COVID-19 treatment wave.

RESULTS

From March 2020 until July 2021, a total of 4151 hospitalized COVID-19 patients were included, of whom 389 had a history of CKD before admission. After adjusting for all confounding covariables, in patients with CKD stage 3a, stage 3b, stage 4 and patients with NTX, odds ratios of death and readmission compared with patients without CKD ranged from 1.96 to 8.94 (Fig. 1).

CONCLUSION

We demonstrate an evident increased 12-week mortality and readmission rate in patients with CKD stage 3a and 4. Besides justified concerns for kidney transplant patients, clinicians should also be aware of more severe COVID-19 outcomes and increased vulnerability in all CKD patients.
MO524: Gender Differences in Intravascular Volumes Vanish if Expressed per Lean Body Mass
Authors: Lundby Carsten , Oberholzer Laura
Published: May 2022

BACKGROUND AND AIMS

Blood volume (BV) is an important clinical parameter and is usually expressed relative to body weight (BW), but is inappropriate with elevated fat mass. We hypothesized that established differences in BV and hemoglobin mass (Hbmass) between male and female would vanish if expressed per lean body mass (LBM) instead of BW. We furthermore aimed to establish reference values for BV, plasma volume, red blood cell volume and Hbmass in women and men for clinical use.

METHOD

Blood volumes (carbon monoxide rebreathing) and body composition (DXA scan) were determined in 225 female and 280 healthy men (18–93 years, BMI range: 16.4–40.6).

RESULTS

As expected, female absolute BV was 1570 mL [CI 95% (1429.66–1709.87)]; P-value ≤.001) less than in male, and also when expressed per BW female had lower values than male (Figure 1A) [CI 95% (8.06–12.02); P-value ≤.001]. However, when expressed to LBM, females had 6.3 mL higher value than males [CI 95% (−8.80 to −3.86); P-value ≤ .001] (Figure 2A). In a similar manner, absolute Hbmass was 303 g greater in male [CI 95% = (283.99–322.09); P-value ≤ .001] and also greater when expressed pr BW [CI 95% (2.37–2.88); P-value ≤ .001] (Figure 1D). However, when normalized to LBM, differences were greatly diminished −0.84 [CI 95% (0.53–1.15); P-value ≤ .001] (Figure 2B). Per year of older age, a man gains 0.14 [0.06–0.22] mL blood/LBM (P = .0012) and a woman gains 0.13 [0.04–0.22] mL (P = .0032), but the increase in blood volume is not different between men and women (no interaction effect, P = .92). Similar observations as for BV and Hbmass were also made for red blood cell volume and plasma volume (See Figs. 1 and 2).

CONCLUSION

The principal finding is that when BV and Hbmass are expressed relative to LBM, the known differences in intravascular volumes and Hbmass between male and female largely disappear. Furthermore, the relation between LBM and intracvascular volumes and Hbmass is preserved with advancing age. Taken together, LBM is a very strong predictor for intravascular volumes and Hbmass in healthy humans and could be considered a valuable clinical matrix in medical care aiming to normalize intravascular volumes in patients such as chronic kidney failure and heart failure.