bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO051EFFECT OF TOLVAPTAN ON THE SUPPRESSION OF TOTAL KIDNEY VOLUME INCREASE IN PATIENTS WITH MODERATE-TO-SEVERE RENAL DYSFUNCTION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Authors: Nomi Hiroki , Mori Daisuke , Tamai Shinjiro , Tokuchi Maho , Inoue Natsumi , Kawai Hideaki , Shimada Naoyuki , Haga Ryota , Nagatoya Katsuyuki , Yamauchi Atsushi 
Published: May 2021

Abstract

Background and Aims
Tolvaptan (TV) slows down the increase in total kidney volume (TKV) in patients with autosomal dominant polycystic kidney disease (ADPKD). The efficacy of TV in patients with moderate-to-severe renal dysfunction (RD) in ADPKD remains unknown.

Method
This was a single-centre retrospective study involving 27 patients with ADPKD who took TV and visited our hospital in the past six years. The participants were divided into two groups: the normal-to-mild RD (estimated glomerular filtration rate (eGFR) ≥ 45mL/min/1.73m2) group and the moderate-to-severe RD (eGFR &lt; 45mL/min/1.73m2) group. Treatment effects were evaluated using ΔTKV, which was calculated as post-/pre-treatment annual TKV change. Continuous variables are presented using the median [interquartile range].

Results
The moderate-to-severe RD group comprised 11 patients. Baseline characteristics of the normal-to-mild vs. moderate-to-severe RD group were as follows: eGFR, 56 [50–69] vs. 29 [24–38] mL/min/1.73m2; age, 48 [39–55] vs. 49 [43–58] years; male gender, 57% vs. 36%; body mass index (BMI) , 26 [23–28] vs. 24 [22–27] kg/m2; TKV 1700 [1084–2574] vs. 1827 [1331–2424] mL; family history of ADPKD, 100% vs. 82%; history of cerebral aneurysm, 19% vs. 36%; hypertension, 81% vs. 82%; hyperuricemia, 13% vs. 27%; dyslipidaemia, 19% vs. 18%; diabetes, 6.1% vs. 9.1% and systolic blood pressure (sBP) on admission 138 [129–144] vs. 131 [128-137] mmHg. No significant differences were noted in all these parameters, except for renal function. The starting dose of TV was 60 mg/day in all cases (0.9 [0.7–1.0] vs. 0.9 [0.8–1.1] mg/kg; P = 0.35). Urine volume (7.5 [5.7–9.6] vs. 4.0 [3.3–4.7] L/day; P = 0.006) and urinary sodium excretion (163 [126–226] vs. 89 [81–120] mEq/day; P = 0.003) were higher in the normal-to-mild RD group. Between the groups, there were no differences in urine protein (0.12 [0.0–0.3] vs. 0.16 [0.08–0.29] g/day; P = 0.31) and ΔeGFR (98% [88–123] vs. 106% [102–112]; P = 0.45), which was calculated as post-/pre-treatment annual eGFR change. Although both groups experienced the therapeutic effects of TV, the efficacy was poorer in the moderate-to-severe RD group (ΔTKV, 82% [76–85] vs. 96% [86–97]; P = 0.001).

Conclusion
The efficacy of TV patients with moderate-to-severe RD in ADPKD might be modest.
MO062A RARE COMBINATION OF POLYCYTHEMIA VERA WITH A THROMBOPHILIA FACTOR V MUTATION IN A HEMODIALYSIS PATIENT :CASE REPORT
Authors: Ghabi Faten , Salma Toumi , Amouri Asma , Chaker Hanen , Agerbi Ikram , Damak Najla , Kammoun Khawla , Yaich Soumaya , Benhamida Mohamed 
Published: May 2021

Abstract

Introduction
Anemia is an almost constant complication in patients with end stage renal disease. In contrast, primary polycythemia is extremely rare, with only a few cases that have been reported in the literature. We report in this work a rare association of thrombophilia and acquired polycythemia in a chronic hemodialysis patient.

Observation
This is a 47-year-old man, non-smoking, hypertensive, with CKD in hemodialysis since 2015 secondary to undetermined nephropathy. The change in the patient's condition on hemodialysis was marked by the occurrence of repeated thrombosis of these arteriovenous fistulas(AVFs), including exploration that revealed a coagulation factor V mutation, hence his initiation of antivitamin K. The patient initially presented with severe anemia at the start of the extra renal purification , the average hemoglobin (Hb) level between 2015 and 2018 was 7.4 g / dl thus requiring the use of iron supplementation (IV iron) and stimulating agents erythropoiesis (ESA). In february 2019, erythropoietin requirements were reduced due to the increase in Hb levels and then stopped in April 2019. The Hb level continued to increase to reach 16.8 g / dl in february 2020 without receiving ESAs or iron supplements. From where an etiological investigation was initiated to search for the origin of this polycythemia going up to the genetic study for the JAK2V617F mutation which came back positive. Furthermore, gas scans, chest x-rays and abdominal ultrasounds are normal, hence polycythemia vera was retained in this patient. For fear of losing his AVF, the patient underwent intermittent phlebotomies during dialysis associated with the prescription of IEC and his Hb level rose to 14.5g / dl.

Conclusion
Primary erythrosis remains rare in dialysis, the pathophysiological mechanism of which remains poorly understood. Iterative phlebotomies remain the solution sometimes coupled with the prescription of IEC.
MO064ASSESSMENT OF KIDNEY SURVIVAL IN PATIENTS AFFECTED BY ADPKD
Authors: García Rabaneda Carmen , Morales García Ana Isabel , Bellido Díaz María Luz , Del Águila García María del Mar , Poyatos Andújar Antonio M , Martínez Atienza Margarita , Esteban de la Rosa Rafael Jose 
Published: May 2021

Abstract

Background and Aims
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary nephropathy that causes kidney failure and the need for renal replacement therapy (RRT). It has recently been established that there is a genotype-phenotype relationship for this disease, with differences in the age of access to TRS if the involvement occurs in the PKD1 or PKD2 gene and if the variant is truncating or not. Identifying patients at high risk for rapid progression has become increasingly important given the emergence of potential new treatments such as tolvaptan.

Method
Studies are carried out in 23 families affected in which a genetic study has previously been the variant identified. For the survival analysis, the Kaplan-Meier test was performed. Data are expressed in terms of mean ± SD, median and %.

Results
The data described in Table 1 show that there is huge variability of access to RRT according to the type of variant found in the family. We found families in which the age at which kidney failure occurred ranged from 48.03 (28.38-67.68) years to families in which RRT began with 78.04 (65.06-91.03).
We observed that those families that present a variant with a stop or frameshift codon suffer a loss of kidney function before those that present a missense variant. In the variants with a stop or frameshift codon, we observed that they ranged from 48.03 (28.38-67.68) for the variant c.7480G&gt; T (p.Glu2494 *) to 73.75 (61.52-85, 98) in variant c.9616C&gt; T p.Gln3203 *. In those missense variants, the age of access to RRT ranges from 62.17 (60.43-63.91) to 77.13 (71.56-82.71)

Conclusion
Advances in studies of the genes involved in ADPKD are expanding the identification of new variants and the knowledge about their involvement in the progression of the disease.
The correlation between genotype and kidney disease will provide a useful clinical prognosis for ADPKD and will allow us to establish current and future treatments.
MO036DAPAGLIFLOZIN RESCUES THE RENAL PHENOTYPE OF GLYCOGEN STORAGE DISEASE TYPE IB
Authors: D'Acierno Mariavittoria , Resaz Roberta , Siccardi Sabrina , Iervolino Anna , Sardella Donato , Capasso Giovambattista , Eva Alessandra , Trepiccione Francesco 
Published: May 2021

Abstract

Background and Aims
Glycogenosis I type b (GsdI-b) is a rare metabolic disease and immune disorder characterized by hepato-renal glycogen accumulation caused by a deficiency in the Glucose-6-phosphate transporter (G6PT). G6PT transports glucose-6-phosphate (G6P) from cytoplasm to endoplasmic reticulum (ER) where a G6Pase catalyses the hydrolysis of G6P in glucose and phosphate. G6PT deficiency lead to impaired glucose homeostasis, myeloid disfunction and long-term risk of hepatocellular adenomas. No causal therapy is so far available for GSDI-b patients besides a dietary approach to control glycemia and the use of Granulocyte Colony-Stimulating Factor (GCSF) to improve neutropenia. Over time, these supports increase the chronicity of GSDI-b with some complications. A mouse model recapitulating the GDSI-b has been recently generated by inducing G6PT suppression after tamoxifen injection. Here, we characterized the renal phenotype of TM-G6PT-/- mice model focusing on the molecular mechanisms that lead to renal dysfunction. Finally, we evaluated the efficiency of Dapagliflozin, a selective inhibitor of SGLT2, on kidney functions in terms of therapeutic effect.

Method
Machine learning approach to computer based evaluation of renal morphology was used to analyze the renal sections from TM-G6PT-/- treated with or without dapagliflozin.
Results: G6PT is expressed in all renal zones and a severe downregulation of G6PT mRNA expression in whole kidney of TM-G6PT-/- mice can be observed. TM-G6PT-/- mice show tubular vacuolization and overall cellular dysfunction of PT due to a high glycogen accumulation. TM-G6PT-/- mice manifest glycosuria, phosphaturia and polyuria associated with a down regulation of main transporters of PT cells. The urine concentrating defect is due to a primarily role of G6PT in CNT/CD cells confirmed by a downregulation of AQP2, main water channel along CD segments. This mouse model recapitulates the human GSD-Ib renal phenotype characterized by a disfunction of PT but also CNT/CD cells. In order to evaluate whether targeting the glucose metabolism would improve the renal phenotype of these mice we limited glucose flux across the apical membrane of PT cells, applying the SGLT2-inhibitor dapagliflozin to reduce new glycogen formation. After one month of treatment, Dapagliflozin prevents glycogen accumulation in TM-G6PT-/- mice and ameliorates the main dysregulated markers of PT function. This finding was paralleled by an improvement of the histological features of kidney morphology in dapagliflozin treated TM-G6PT-/- mice.

Conclusion
Our data provide evidence that treatment with dapagliflozin ameliorates intracellular glycogen storage and improves the renal functions in TM-G6PT-/- mice.
MO021ENHANCED MCP-1 RELEASE IN EARLY AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Authors: Janssens Peter , Decuypere Jean-Paul , De Rechter Stéphanie , Breysem Luc , Van Giel Dorien , Billen Jaak , Hindryckx An , De Catte Luc , Baldewijns Marcella , Claes Kathleen , Wissing Karl Martin , Devriendt Koenraad , Bammens Bert , Meyts Isabelle , Torres Vicente , Vennekens Rudi , Mekahli Djalila 
Published: May 2021

Abstract

Background and Aims
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either the PKD1 or PKD2 gene. While kidney failure typically occurs in adulthood, the disease starts in utero. The best change of preserving renal function long term might be the use of agents with few side effects as early as possible. For this approach, both better early prognostic stratification and novel treatment options are needed. The pediatric phase of ADPKD, while kidney function is still normal and before significant tissue destruction has occurred could be the best stage both to identify and study prognostic biomarkers as well as to identify novel targets for early treatment. Copeptin (a surrogate for vasopressin), epidermal growth factor (EGF) ( a measure for functional tubular mass) and monocyte chemoattractant protein-1 (MCP-1) ( a chemoattractant for macrophages) are associated with severity and hold prognostic value in adults but remain unstudied in the early disease stage. Kidneys from adults with ADPKD exhibit macrophage infiltration, and a prominent role of MCP-1 secretion by tubular epithelial cells is suggested from rodent models.

Method
A monocentric cross-sectional study in a tertiary referral center was performed. All consenting genotyped ADPKD patients attending the outpatient pediatric ADPKD clinic of the university hospital of Leuven and age, sex and BMI matched healthy controls were included between June and October 2017. Plasma copeptin, urinary EGF and urinary MCP-1 were evaluated. MCP-1 was studied in mouse collecting duct cells, human proximal tubular cells and fetal kidney tissue.

Results
53 genotyped ADPKD patients and 53 controls were included. Mean (SD) age was 10.4 (5.9) vs 10.5 (6.1) years (P=0.543), and eGFR 122.7 (39.8) vs 114.5 (23.1) ml/min/1.73 m2 (P= 0.177) in patients vs controls respectively. Outcome parameters in table. Plasma copeptin and EGF secretion were comparable between both groups. Median (IQR) urinary MCP-1 (pg/mg creatinine) was significantly higher in ADPKD patients (185.4 (213.8)) compared to controls (154.7 (98.0)) (P= 0.010). Human proximal tubular cells with a heterozygous PKD1 mutation and mouse collecting duct cells with a PKD1 knockout exhibited increased MCP-1 secretion triggered by fetal bovine serum. Human fetal ADPKD kidneys displayed prominent MCP-1 immunoreactivity and M2 macrophage infiltration.

Conclusion
An increase in tubular MCP-1 secretion is an early event in ADPKD, long before kidney function decline and in children with few kidney cysts. MCP-1 is a promising early disease severity marker and a potential treatment target.
MO022EVALUATION OF THE EFFECT OF TOLVAPTAN ON OXIDATIVE STRESS IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)
Authors: Rigato Matteo , Bertoldi Giovanni , Ravarotto Verdiana , Carraro Gianni , Calò Lorenzo 
Published: May 2021

Abstract

Background and Aims
Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent monogenic kidney disease, with approximately 12.5 million affected people worldwide, and it is responsible for over 10% of patients with end-stage renal disease (ESRD) with an important impact on public health. It causes progressive renal failure and other extrarenal manifestations, including endothelial dysfunction and hypertension. These complications are both linked to reduced nitric oxide levels related to excessive Oxidative Stress (OxSt) that different studies confirm occurring in the early stages of ADPKD.
This study aims to evaluate ex vivo through a molecular biology approach the OxSt status of ADPKD patients under treatment with tolvaptan (Jinarc) and compare with both a group of untreated young ADPKD subjects with preserved renal function (eGFR&gt; 80 mL/min/1.73m2) and a cohort of healthy subjects as controls.

Methods
In mononuclear cells of 9 ADPKD patients treated with tolvaptan, 9 untreated ADPKD patients with preserved renal function (eGFR&gt; 80 mL/min/1.73m2) and 9 healthy subjects we evaluated the state of OxSt in terms of protein expression of p22phox, subunit of NADH/NADPH oxidase essential for the production of superoxide; protein expression of Heme oxygenase (HO)-1, protective from OxSt and anti-inflammatory and MYPT-1 phosphorylation, marker of Rho kinase activation, deeply involved in OxSt signaling for the induction of cardiovascular-renal remodeling;

Results
In patients with tolvaptan treated ADPKD, protein expression of p22phox and phosphorylation state of MYPT-1 were significantly reduced compared to untreated young ADPKD subjects with normal GFR (p=0.01 and p=0.03, respectively). Phosphorylation of MYPT-1 was significantly reduced in patients treated with tolvaptam vs untreated patients and also when compared to healthy controls (p=0.01 for both). HO-1 levels of treated ADPKD patients were significantly higher both vs untreated ADPKD patients with normal GFR (p=0.04) and vs healthy controls (p=0.01)

Conclusions
Tolvaptan is reported to reduce the rate of GFR deterioration of 1.20 mg/mL/year compared to placebo. Several animal studies have demonstrated the ability of tolvaptan to reduce OxSt and increase HO-1. Our study showed “ex vivo” in humans that in ADPKD patients tolvaptan reduces the OxSt state compared to untreated ADPKD with normal GFR and increases the antioxidant HO-1, in addition to reduce Rho kinase activation, further supporting its renoprotective effect also in terms of OxSt inhibition.
This study confirms for the first time in humans that tolvaptan is effective on the reduction of intracellular OxSt and may impair the biochemical/molecular mechanisms that contribute to the worsening of renal function, endothelial damage and hypertension.
MO023FLANK PAIN HAS A MAJOR NEGATIVE IMPACT ON HEALTH-RELATED QUALITY OF LIFE IN ADPKD: THE CYSTIC I STUDY
Authors: Winterbottom Jean , Simms Roslyn , Caroli Anna , Cornec-Le Gall Emilie , Demoulin Nathalie , Furlano Monica , Meijer Esther , Devuyst Olivier , Gansevoort Ronald , LeMeur Yannick , Perico Norberto , Torra Roser , Ong Albert 
Published: May 2021

Abstract

Background and Aims
ADPKD is the most common inherited kidney disease in man, a major cause of end-stage renal disease and is a significant medical and economic burden worldwide. However, the impact of this major disease on the quality of life of patients with preserved kidney function has not been systematically explored.

Method
The CYSTic I study was an observational, prospective study designed to study the natural history of ADPKD in adult patients with preserved kidney function (eGFR ≥30 ml/min/1.73m2). 465 patients were recruited from six expert centres across Europe (Belgium, France, Italy, Netherlands, Spain and UK) with baseline data recorded including HR-QoL (Health-Related Quality of Life) incorporating a Kidney Disease QOL short form questionnaire (KDQoL-SF v1.3), MRI for Total Kidney Volume (TKV) and DNA for genotyping. The cohort was stratified by baseline eGFR, Ht-TKV or genotype and correlated with HR-QOL scores. Bivariate and multivariate analyses were applied to examine the relationship between HRQoL and variables of interest. KDQoL-SF scores were calculated using an online tool provided by the Rand organisation.

Results
Mean age of the participants was 44 years, 54.6% were female with a mean eGFR of 77ml/min/1.73m2 and Ht-TKV of 849ml/m. 72.3% had PKD1 mutations. 32.5% of participants reported flank pain that was not significantly correlated with eGFR, Ht-TKV or genotype. Of all the variables examined, flank pain showed significant negative associations with the highest number of KDQoL-SF subscale scores assessed (12/20).

Conclusion
Our results indicate that flank pain is common, likely to be under-reported in routine care but has a major negative impact on patient-reported quality of life.
MO024THE ROLE AND MECHANISM OF DECOY RECEPTOR DCR2 IN EMBRYONIC KIDNEY DEVELOPMENT
Authors: Chen Jia , He Yani 
Published: May 2021

Abstract

Background and Aims
Decoy receptor 2 (DcR2), a transmembrane receptor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), has been regarded as a hallmark of cell senescence. This study aimed to explore the role and the potential mechanism of DcR2 in the embryonic kidney development.

Method
The 12.5d, 16.5d, 20.5d embryonic kidney and mature renal tissue (8w) form WT and DcR2-KO mice were obtained. The ureteric buds, S-shaped bodies, renal vesicles were observed by periodic Acid-Schiff staining. The expression of DcR2 were detected by IHC. The co-expression of DcR2 and proximal tubular markers (AQP-1, villin), distal tubular markers (AQP-2), senescent markers (P16, LaminB1), proliferation markers (Ki-67, PCNA, Edu) were analyzed by confocal.

Results
In WT kidneys, DcR2 were specifically expressed in the tubules and the percentage of DcR2 expression were higher than mature renal tissue. In addition, the expression of tubular DcR2 were significantly decreased in DcR2-KO kidney than WT. The number of ureteric buds, S-shaped bodies, renal vesicles were decreased in DcR2-KO kidney than WT. And the cortex of DcR2-KO kidney were thinner and medullar were enlarger than WT. DcR2 were co-expressed with proximal tubular markers AQP-1 and villin, but not with distal tubular markers AQP-2. Furthermore, DcR2 were co-expressed with senescent markers P16 and LaminB1, but not with proliferation markers Ki-67, PCNA, Edu.

Conclusion
DcR2 is specifically expressed in proximal tubular cells in embryonic kidney, and DcR2 is involved in early renal development. The potential mechanism is related to cell senescence participating in tissue remodeling and inhibiting cell proliferation.
MO025TREATMENT WITH TOLVAPTAN IN ADPKD PATIENTS: RESULTS FROM AN OBSERVATIONAL, MULTICENTRIC STUDY
Authors: Galliani Marco , Vitaliano Elio , Chicca Silvana , Paone Antonio , Pistolesi Valentina , Morabito Santo , Di Lullo Luca , Floccari Fulvio , Marrocco Fulvio , Cioffi Massimiliano , Rifici Nunzio , Iacono Rossella , Feriozzi Sandro , Pasquarelli Cynthia , Morosetti Massimo , Bernabei Eleonora , Ferrazzano Maria Teresa , Orossi Antonella , Fini Riziero , Lai Silvia , Mazzaferro Sandro , Fulignati Pierluigi , Grandaliano Giuseppe 
Published: May 2021

Abstract

Background and Aims
In recent years, treatment of ADPKD (Autosomal Dominant Polycystic Kidney of the Adult) has been based on the antisecretive and antiproliferative effect of several drugs. Tolvaptan, a vasopressin receptor antagonist, has been shown to slow disease progression in the face of side effects such as aquaresis and liver damage. Currently, the drug's reimbursability is allowed in patients aged up to 55 years, CKD 2-4 (GFR ≥ 25 ml/min) with evidence of rapid disease progression.

Method
We report the experience with Tolvaptan in 62 patients with ADPKD who were recruited from 11 Nephrology Units in Lazio (Italy).
Baseline characteristics of patients are reported in Table 1.
Renal volume was evaluated by MRI (26 patients), CT scan (3 patients), or ultrasonography (28 patients).
Rapid progression’s criteria were the following: Mayo Clinic classification, PRO-PKD score and the annual loss of GFR. Mean duration of Tolvaptan’s treatment was 522 days (range 56-867).
The Tolvaptan dosage used at the beginning of therapy was 60 mg/day in 95% of patients; at the end of follow-up, 37% were still taking 60 mg/day, while 38.7% were taking 90 mg/day and 16.1% were taking 120 mg/day.

Results
Median diuresis was 5-6 liters over 24 hours. A mean reduction in GFR of 12.5% (which was maintained for the next 12 months) was observed after initiation of therapy as a likely effect of tubulo-glomerular feedback.
Monthly blood tests were performed to monitor side effects (hyper/hyponatremia, increased bilirubin and/or transaminases, etc.).
Therapy was withdrawn by 2 patients (3.2%) due to aquaresis, while it was discontinued in 3 patients (4.8%) according to clinicians’ decision due to hepatic damage (3-fold increase in transaminases and/or bilirubin normal values). No significant alteration in natremia was observed in any patient. An increase in CK was observed in one patient, leading to momentary discontinuation of therapy. One patient withdraw therapy because of CKD’s progression to stage 5 after 2 years of therapy.

Conclusion
Results of this observational study show that Tolvaptan therapy was well tolerated and the incidence of liver damage was superimposed on that described in the literature.
It will be necessary to continue clinical observation over the time and apply Tolvaptan’s therapy to a larger population in order to assess its effects on disease progression.