bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO011: The Use of a 4-Point Scoring Scale in 18F-FDG-PET/CT Imaging Helps for Diagnosis of Renal and Hepatic CYST Infections in Patients with Autosomal Dominant Polycystic Kidney Disease: A Validation Cohort
Authors: Demuynck Selina , Lovinfosse Pierre , Seidel Laurence , Mekahli Djalila , Jouret François , Bammens Bert , Goffin Karolien 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Autosomal dominant polycystic kidney disease (ADPKD) is prone to multiple complications, including cyst infection (CyI). 18F-FDG PET/CT imaging proved useful in the diagnosis of renal and hepatic CyI. A 4-point scale comparing the uptake of 18F-FDG in the suspected infected cyst versus the hepatic physiological background has been proposed. We performed an independent validation of this semi-quantitative score system.

METHOD
All ADPDK patients hospitalized between January 2007 and March 2019 who underwent an 18F-FDG PET/CT for suspected CyI were retrospectively identified using computer-based databases. Medical files were systematically reviewed. CyI was conventionally defined by: fever (&gt;38°C), abdominal pain, increased plasma CRP levels (≥70 mg/dL), absence of any other cause of inflammation and favorable outcomes after ≥21 days of antibiotics. The 18F-FDG uptake around the suspected CyI was evaluated using the 4-point scale. Stats were performed using SAS version 9.4.

RESULTS
Our cohort included 51 18F-FDG PET/CT in 51 patients, including 11 cases of CyI according to the above-detailed definition. The agreement between the 4-point scale and the gold-standard criteria of CyI was significant, with an odds ratio of 6.03 for CyI in case of a score ≥3 (P, 0.014). The corresponding sensitivity and specificity of PET/CT using the 4-point scale were 63.3% and 77.5%, respectively.

CONCLUSION
Our independent validation cohort confirms that the use of a semi-quantitative 4-point scoring system helps in the diagnosis of CyI by 18F-FDG PET/CT imaging in patients with ADPKD.
MO015: The Interaction of Gender and Genotype in the Development of Polycystic Liver Disease in ADPKD
Authors: Cong Eugene Chen Wen , Ong Albert , Gittus Matthew 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Liver cysts are the most common extra-renal manifestation in autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD) may result in significant morbidity in a proportion of patients. The major objective of this study was to investigate the relationship between the incidence of liver cysts and PLD with age, gender and genotype in a longitudinal ADPKD patient cohort (n = 625) followed up between 2010 and 2021.

METHOD
A retrospective analysis of PLD was performed on all patients with available abdominal US (US, n = 565) or abdominal MRI/CT (n = 321) imaging. Liver cyst counts were obtained from routine clinical reports (US) or quantified by a single-blinded observer (MR/CT). Patients were divided into subgroups of different severity based on cyst numbers detected on US (QIAN 0–4) or MRI/CT (CHEN 0–3): QIAN 0 (0), 1 (&lt;10), 2 (10–20), 3/4 (&gt;20); CHEN 0 (0), 1 (&lt;20), 2 (21–40), 3 (&gt;40). Patients who were genotyped (n = 390) were classified into those with PKD1 (T, truncating or NT, non-truncating), PKD2, other genes (non-PKD1 or PKD2) or NMD (no mutation detected). The potential influence of genotype and gender on the incidence of liver cysts and the time to the development of PLD (defined as QIAN 3/4 or CHEN 3) was investigated by survival analysis (Kaplan–Meier plots). Hazard ratios (HR) were calculated and statistical significance was determined via Log-rank (Mantel-Cox) or Chi-square tests.

RESULTS
Liver cysts were detected in 61% of patients by US and 72% by MRI/CT, increasing with age. Kaplan–Meier plots showed a significant effect of gender for the presence of liver cysts (M: F HR of 0.74 US, 0.69 MR/CT). Genotype had a major effect on the prevalence of liver cysts (US, n = 344) with a median age of 46, 53, 59, 75 and 77 years for PKD1-T, PKD1-NT, PKD2, other genes or NMD, respectively. A similar trend was noted for patients with MR/CT imaging. The percentage of patients with PLD (QIAN 3/4 or CHEN 3) ranged between 26% (US) and 36% (MR/CT) with a median age for developing PLD of 51 (US; min-max range 23–80 years) and 50 years (MR/CT; min-max range 27–81 years), respectively. The incidence of PLD was more strongly influenced by gender (M: F HR 0.53 US, 0.56 MR/CT) and was highly enriched in patients with PKD1 or PKD2 mutations.

CONCLUSION
Female patients with a PKD1-T genotype appear to be at the highest risk of developing PLD. Genotypes other than PKD1 or PKD2 are unlikely to develop PLD. Further work is needed to improve risk stratification and treatments for PLD by identifying additional pathogenic factors.
MO029: Urinary biomarkers in the progression of autosomal dominant polycystic kidney disease
Authors: Carolina Santos Ana , Novais Carla , Matos Andreia , Bicho Manuel , Almeida Edgar 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease characterized by the formation and growth of renal cysts, affecting the decrease of renal function, which may lead to end-stage renal disease (ESRD). Due to the enormous intrafamilial phenotypic variability of ADPKD and since serum creatinine and glomerular filtration rate (GFR) have a limited ability to assess the disease and predict its progression at earlier stages, there is a need to find new biomarkers to predict disease progression. The α-glutathione s-transferase (GST-α) and haptoglobin (Hp) are produced mainly by the proximal convoluted tubule, and these enzymes are released into the urinary lumen in direct response to tubular damage.
This study aims to evaluate the urine concentration of α-GST and Hp biomarkers at different stages of ADPKD progression and correlate the levels of urinary biomarkers α-GST and Hp with traditional markers of renal dysfunction.

METHOD
Twenty-five patients with ADPKD, mean age of 41.57 ± 14.43 years, mostly female (56.0%), diagnosed according to the Ravine criteria and with a follow-up of at least 60 months. Demographic, hemodynamic, urinary creatinine (UCr) and serum creatinine (SCr) data were collected in baseline (T0) and at the end of the follow-up period (T1). GFR was determined using the CKD-EPI formula, grouping patients into early stages (CKD1 and CKD2) and advanced stages (CKD3 to CKD5). Biomarkers were determined by the ELISA method and indexed to UCr in T1. In addition, α-GST was determinate in a control sample composed of 17 individuals without diagnosed kidney disease.
Statistical analysis was performed by SPSS version 26 with a significant value of P &lt; 0.05.

RESULTS
Comparing the means of SCr and GFR between T0 and T1 were observed a decrease of renal function during the follow-up period (P = 0.013 and P = .017, respectively). About 14.4% of patients were in an advanced stage of kidney disease in T1, compared with 4.8% in T0.
ADPKD patients had increased values of α-GST in relation to the control group (P &lt; 0.001), but no difference in the SCr was found. We also found a trend for higher levels of HP in advanced stages of CKD (P = 0.071). In ADPKD patients, direct correlations were observed between the variation of SCr during the follow-up with α-GST and Hp (r = 0.606, P = 0.048 and r = 0.738, P = 0.037, respectively). A trend to correlation was found between the levels of Hp and the Scr in T1 (r = P = 0.058).

CONCLUSION
The levels of α-GST and Hp are associated with renal damage and may be helpful in the early identification of the decline in renal function in ADPKD patients.
MO034: Novel MUC1 variant identified by massively parallel sequencing explains interstitial kidney disease in a large Dutch family
Authors: de Haan Amber , Eijgelsheim Mark , Rump Patrick , Van der Zwaag Bert , Zivna Martina , Kmoch Stanislav , Bleyer Anthony , Kidd Kendrah , Van Eerde Albertien M , Knoers Nine , De Borst Martin 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Chronic kidney disease (CKD) can be caused by a wide variety of systemic and renal disorders. In approximately 20% of patients, the cause of CKD remains unknown. Previous studies have shown that massively parallel sequencing (MPS) can be a valuable diagnostic tool in patients with unexplained CKD. Here, we describe a large family with kidney failure of unknown origin, in which we aimed to identify the primary renal disease diagnosis with MPS in a routine healthcare setting.

METHOD
We conducted MPS in a large family in the Netherlands including six generations with documented kidney failure at young age. Affected individuals had a bland sediment and kidney biopsy revealed interstitial fibrosis in several family members. Whole exome sequencing followed by variant filtering and analysis based on the CKD-Y (CKD-young) gene panel (v18.1, 141 genes) was performed by the Genome Diagnostics Section of the University Medical Center Utrecht.

RESULTS
MPS revealed a novel frameshift variant [c.326_350dup, p.(Ser119Profs*119), NM_001 204 286.1] in MUC1, which co-segregated with the renal phenotype in the family. This variant is positioned before the first variable number of tandem repeat (VNTR) domain of MUC1 and leads to a + 1 base frameshift in the open reading frame of the MUC1 mRNA. The predicted C-terminal amino-acid sequence of the resulting mutant protein is the same as the previously reported pathogenic cytosine insertions in the VNTR. Variants in MUC1 are associated with autosomal dominant tubulointerstitial kidney disease (ADTKD), which matches the clinical phenotype in this family. Immunohistochemical analysis in the index patient showed MUC1fs deposition in kidney tissue, confirming the diagnosis of ADTKD-MUC1.

CONCLUSION
We report a novel frameshift mutation in MUC1 identified with MPS. This study highlights that MUC1 variants positioned before the first VNTR region can lead to ADTKD and that genetic testing in patients with suspected ADTKD-MUC1 should also include regions outside of the VNTR. Additionally, this study confirms the relevance of MPS as a tool to screen adult patients with early-onset kidney failure.
MO037: Burosumab in adult patients with X-linked hyphophosphatemic rickets: an Italian Experience
Authors: Edvige Foligno Nadia , Arcidiacono Teresa , Bologna Arianna , Brioni Elena , Del Mastro Teresa , Avino Monica , Vezzoli Giuseppe 
Published: May 2022

Abstract

BACKGROUND AND AIMS
X-linked hypophosphoremic rickets (XLH) is a rare disease caused by mutations in the PHEX gene leading to an increase in the serum levels of FGF23, which inhibits the tubular reabsorption of phosphates and the production of 1,25(OH)2D. These alterations cause hypophosphatemia, rickets, bone deformities, growth retardation and muscle activity impairment.

METHOD
Burosumab (B) is a monoclonal antibody against FGF23, used for the treatment of XLH. In Italy B can be employed in adults only as compassionate use. In 2020, we treated four adult XLH patients with B (1 mg/kg sc every 4 weeks) for 24 weeks. These patients, V.M. (M, 32 years), S.T. (F, 47), E.R. (M, 46) and S.M. (F, 20) had legs deformities, musculoskeletal pain and severe disability.

RESULTS
In all patients, phosphorus levels were normalized by B 2 weeks after the B injection, but its levels decreased during the following 28 days; the effect of B on serum phosphate declined during the 24-week follow-up. Plasma values of 1,25(OH)2D and CTX (C-terminal telopeptide of type I collagen) increased after burosumab, but their increase was less marked after the first two injections. In contrast, PTH and bALP values did not change during B therapy.
Scores of BPI test, chair test and walking test confirmed an improvement in the fatigue resistance and physical performance. Other tests showed the improvement of self-reported well-being and quality of life in all patients. These effects were not observed in adult patients on conventional therapy with phosphate salts and active vitamin D.

CONCLUSION
Therefore, markers of physical conditions and life quality may be more indicative for the necessity of burosumab treatment than serum phosphate, which may not be a significant marker to initiate burosumab treatment in adult patients. Burosumab treatment of XLH patients is well-tolerated and leads to prolonged beneficial effects on general conditions of patients although the inconstant improvement of serum phosphate.
MO045: Kidney involvement in hereditary transthyretin amyloidosis: a cohort study of 103 patients
Authors: Solignac Justine , Delmont Emilien , Fortanier Etienne , Mancini Julien , Attarian Shahram , Daniel Laurent , Ion Ioana , Ricci Jean-Etienne , Robert Thomas , Habib Gilbert , Moranne Olivier , Jourde-Chiche Noemie 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Hereditary transthyretin amyloidosis (ATTR) is a disabling and life-threatening disease that primarily affects the nervous system and heart. Its kidney involvement has been poorly studied and is not well known to nephrologists.

METHOD
We conducted a retrospective study describing kidney phenotype of all prevalent patients with ATTR mutations, with symptomatic amyloidosis or asymptomatic carriers, followed-up in two university hospitals from the South of France, between June 2011 and June 2021.

RESULTS
103 patients were included, among whom 79 were symptomatic and 24 asymptomatic carriers, and 54% carried a V30M mutation. After a mean follow-up of 7.9 ± 25.7 years, 30.4% of the symptomatic patients had developed chronic kidney disease (CKD) and 20.7% had a urinary protein/creatinine ratio ≥0.5 g/g. None of the asymptomatic carriers had CKD or proteinuria. Median CKD-free survival in the global cohort was 81.0 years, and the average age of CKD onset was 69.3 ± 13.0 years. In a multivariate analysis, late onset of ATTR symptoms (after 60 years), the V122I mutation and proteinuria were significantly associated with CKD. In a 38-year-old V30M female, who presented a kidney-predominant phenotype, treatment with Patisiran resulted in remission of the nephrotic syndrome.

CONCLUSION
CKD affects almost one-third of patients with symptomatic ATTR amyloidosis. The role of ATTR amyloidosis per se in the development of CKD in this population remains to be determined, but some patients may benefit from specific therapies.
MO048: Genome-wide studies reveal factors associated with circulating uromodulin and its relations with complex diseases
Authors: LI Yong , Cheng Yurong , Consolato Francesco , Schiano Guglielmo , Chong Michael , Pietzner Maik , Quynh Nguyen Ngoc , Scherer Nora , Biggs Mary , Kleber Marcus E , Haug Stefan , Göçmen Burulça , Pigeyre Marie , Sekula Peggy , Steinbrenner Inga , Schlosser Pascal , Joseph Christina , Brody Jennifer , Grams Morgan , Hayward Caroline , Schultheiß Ulla T , Kraemer Bernhard , Kronenberg Florian , Peters Annette , Seissler Jochen , Steubl Dominik , Then Cornelia , Wuttke Matthias , Maerz Winfried , Eckardt Kai-Uwe , Gieger Christian , Boerwinkle Eric , Psaty Bruce , Coresh Josef , Oefner Peter , Pare Guillaume , Langenberg Claudia , Scherberich Juergen E , Yu Bing , Akilesh Shreeram , Devuyst Olivier , Rampoldi Luca , Köttgen Anna 
Published: May 2022

Abstract

BACKGROUND AND AIMS
UMOD is a major risk gene for monogenic and complex forms of kidney disease. The encoded kidney-specific protein uromodulin is the most abundant protein in urine and related to chronic kidney disease, hypertension and pathogen defense. Through basolateral release from kidney epithelial cells, uromodulin also reaches the blood, where its function is largely unknown. To gain insights into potential systemic roles, we performed genome-wide screens of circulating uromodulin in seven cohorts using two complementary assays.

METHOD
Separate genome-wide association study meta-analyses for circulating uromodulin were conducted for the antibody-based assay (five cohorts, N = 13 985) and the aptamer-based SOMAscan assay (two cohorts, N = 18 070). Genome-wide significant loci were placed into their functional genomic context using RNA-seq, ATAC-seq and Hi-C data generated from primary human kidney tissue. An array of downstream genetic analyses was then performed for significant loci, including fine-mapping, colocalization analyses and gene-by-gene interaction analyses. The B4GALNT2 p.Cys466Arg allele was expressed in MDCK cells and studied by immunofluorescence and Western blotting analyses.

RESULTS
We detected and replicated 13 genome-wide significant loci (P &lt;5e−8; 12 novel). At the UMOD locus, functional genomics data of primary human kidney tissue highlighted an upstream regulatory variant with differential accessibility and UMOD transcription in uromodulin-synthesizing kidney cells. Shared association patterns with complex traits, including chronic kidney disease and blood pressure, placed the PRKAG2 locus in the same context as UMOD. Experimental validation of another locus, B4GALNT2, showed that the detected p.Cys466Arg variant of the encoded N-acetylgalactosaminyltransferase has a loss-of-function effect leading to higher serum uromodulin levels. Lastly, our results point to enzymes writing glycan marks present on uromodulin and to their receptors in the circulation.

CONCLUSION
This study provides human genetic evidence of new pathway members of uromodulin and delivers novel insights into its determinants and systemic role in the circulation.
MO051: Single-Cell Transcriptomics of Lupus Nephritis with ANCA Positive
Authors: Meng Ting , Lin Wei , Ooi Joshua , Eggenhuizen Peter , Zhong Yong , Xiao Xiangcheng 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Lupus nephritis (LN) is one of the most common complications of SLE that can lead to worsened kidney function or renal failure. Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies that are against antigens in the cytoplasm of neutrophils and monocytes and can lead to an autoimmune disease characterized by vascular necrotizing inflammation. The presence of ANCA in serum can also be found in SLE. Positive ANCA serology in patients with LN is associated with distinct histopathologic features on renal biopsy and seems to affect outcome of LN. Deeper understanding of the molecular pathogenesis in LN with ANCA positive is needed to identify novel targets improve the outcome of LN.

METHOD
Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from one LN patient with PR3-ANCA positive and a healthy adult kidney. We identified distinct cell clusters through unsupervised clustering analysis. Identification of the differentially expressed genes (DEGs) and enrichment analysis as well as the interaction between cells were also performed.

RESULTS
Unsupervised clustering analysis identified 15 distinct cell types including all of the renal intrinsic cells and major immune cells. The DEGs in kidney endothelial cells and intercalated cells were primarily enriched in genes involved in the regulation of inflammation and immune response including IL-17 signaling, TNF signaling, NOD-like receptor signaling and Th17 cell differentiation. Macrophages displayed increased expression of HLA-DRB5, which plays a central role in the immune system by presenting peptides derived from extracellular proteins. TYROBP, a gene plays a role in signal transduction and inflammation, was also high-expressed in macrophages from kidney of LN with PR3-ANCA positive. The receptor-ligand crosstalk analysis highlighted the interactions between endothelial cells and other cells in LN, which infers great importance in LN.

CONCLUSION
We provide a searchable resource of single-cell RNA sequencing to LN with PR3-ANCA positive to uncover intercellular interactions, elucidate key pathways underlying the pathogenesis and offer new insight into therapeutic targets of this unique type of LN.
MO052: New Trend in the Diagnosis of Kidney Disease in Cancer Patients: A Multicenter Study
Authors: Bolufer Mónica , Garcia Carro Clara , Blasco Miquel , Fernando Quintana Porras Luis , Shabaka Amir , Rabasco Cristina , Draibe Juliana , Merino Ribas Ana , Rosa Melero Martin Maria , Alonso Garcia Fabiola , Buxeda Anna , Batalha Paula , Teresa Visus Maria , José Soler Romeo Maria 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The new advances in cancer treatments and the increasing prevalence of kidney disease in the population with cancer have extended the indication of kidney biopsies. The purpose of the study is to analyze clinical and histological characteristics of patients with active solid organ malignancy that underwent kidney biopsy.

METHOD
Multicenter collaborative retrospective registered study supported by two working groups GLOSEN/Onconephrology from the Spanish Society of Nephrology. Clinical, demographical and histological data were collected. Comparison of continuous variables between two groups was performed by Student’s T-test, and Cox survival analysis adjusted for clinical conditions was performed to identify risk factors associated with mortality.

RESULTS
A total of 148 patients with cancer who underwent a kidney biopsy from 12 hospitals were included. About 64.3% men and mean age 66.9 years old. The indications for biopsy were acute renal failure (67.1%), proteinuria (17.1%) and acute on top of chronic kidney disease (8.2%). The most frequent malignancies were lung (29.1%) and abdominal (25%), with 49.7% metastatic cancer. As oncospecific treatment, 28.3% received chemotherapy, 29.9% immunotherapy, 19.3% specific therapies and 2.1% conservative treatment (Figure 1)
At the time of kidney biopsy, median creatinine was 2.58 mg/dL [1.81–4.1(IQ 25–75)], median urine protein/creatinine, 700 mg/g [256–2463 (IQ 25–75)] and 53.1% presented hematuria. The renal biopsy diagnosis most frequent was acute interstitial nephritis (39.9%), followed by acute tubular necrosis (8.8%) and IgA nephropathy (7.4%). Acute interstitial nephritis was more frequent in the period from 2017 to 2021 as compared with the period from 2010 to 2016 (P = 0.001). About 67.1% received corticosteroids and 18.9% required kidney replacement therapy. Median follow-up was 15.2 months [5.7–31.4 (IQ 25–75)]. The only factor associated with mortality was the presence of the metastasis at the time of kidney biopsy (P = 0.006).

CONCLUSION
There is a new trend in kidney disease and patients with cancer in terms of diagnosis and treatment. At present, acute interstitial nephritis has consolidated as the most common kidney pathology in this population. Renal biopsy is valuable tool for diagnosis, treatment and prognosis of solid organ cancer patients with kidney damage.