bluuebunny/crossref_metadata_2025 huggingface dataset:
P1804DIALYSIS AFTERKIDNEY GRAFT LOST: DATA OF THE ITALIAN REGISTRY OF PEDIATRIC DIALYSIS
Authors: La Porta Edoardo , Conversano Ester , Zugna Daniela , Consolo Silvia , Labbadia Raffaella , Mattozzi Francesca , Parolin Mattia , Verrina Enrico Eugenio , Vidal Enrico
Published: June 2020

Background and Aims

An increasing number of patients are returning to dialysis after kidney allograft failure (KAF). These patients are at higher risk of complications and mortality compared with incident ESKD patients.. In the pediatric population these data are missing and outcomes have never been investigated before in a nationally representative sample. The aim of this study was to describe the characteristics and hard outcomes of children entering dialysis after KAF in a large population of pediatric dialysis patients.

Method

We retrospectively reviewed the files of patients receiving chronic dialysis at <18 years, recorded from January 1990 to June 2019 by the Italian Registry of Pediatric Chronic Dialysis (IRPCD), a nationwide population-based chronic dialysis network involving all 12 Italian pediatric dialysis centers. We identified 126 patients who had returned to dialysis after KAF. All patients were followed from (re)initiation of dialysis until death, re-transplantation or loss to follow-up. Multivariable regression and survival analysis were used to evaluate factors involved in the choice of dialysis modality and patient outcomes.

Results

After KAF, 45 (35.7 %) patients were treated with PD and 81 (64,3%) with HD. Prior to kidney transplantation (Ktx), 74 (58.7%) were on PD, 45 (35.7%) on HD, and 7 on conservative care (5.5%). Compared with PD patients, those on HD were older (median age of 14.8 years [IQR 11.4-17.5] vs. 10.8 [IQR 2-6.5] vs.; p=0.002), had a longer transplant vintage ([55.2 months [13.2-100.3]) vs. 33 [5.1-82.2], and reentered dialysis in more recent calendar years (2013 [2007-2017] vs. 2004 [2001-2009]). Significant predictors for being treated with PD after KAF were a younger age at dialysis start (OR 0.83 per year increase [95%CI 0.72-0.94]) and a history of PD use before Ktx (OR 12.74 [2.2-74.6]). Patients returning to dialysis in more recent eras (OR 0.87 per year increase [0.81-0.94]) and those who were treated with more than one dialysis modality before Ktx (OR 0.15 for being treated with PD [0.04-0.63]) were more likely to be initiated on HD.

Over the observation period, 6 PD (13.6%) and 3 HD (4.2%) patients died. After adjustment for several covariates, patients on PD exhibited an increased risk for mortality compared with HD (HR 4.65 [1.12-19.30], while the difference for modality failure and access to renal transplantation did not reach statistical significance (Fig.1)

Conclusion

Patients returning to dialysis after KAF in more recent years are more likely to be initiated on HD rather than PD. According to our registry data, the use of PD is associated with a lower survival among patients initiating dialysis after KAF.

Fig.1 Cumulative incidences for the competing events, death, transplant and other techniques (solid line: PD, dash line: HD)
P1816KIDNEY DAMAGE IN NECROTIZING ENTEROCOLITIS OF PREMATURE BORN INFANTS
Authors: Kyslova Iuliia , Chornopyshchuk Nataliia , Yablon Olga , Konoplitska Anastasiia , Chornopyshchuk Roman
Published: June 2020

Background and Aims

Neonatal kidney damage can be the result of hypoxic-ischemic events or nephrotoxic drugs. The long-term effects of hypoxia on the kidneys are still unclear. Unlike full-term infants, premature infants of less than 36 weeks of gestational age exhibit persistent nephrogenesis According to literature database, ischemia as well as reperfusion and infection (hypoxia, acidosis, hypotension, the action of free oxygen radicals) are also major risk factors for necrotizing enterocolitis (NEC). The aim is to establish the peculiarities of kidney damage in necrotizing enterocolitis of premature infants who died from it and infants with NEC surviving.

Method

The study involved 54 of premature infants: 21 infants with NEC stage II and III who died (group A), 43 infants who survived with similar stages of NEC (group B). Statistical processing of the data obtained was carried out on a personal computer using STATISTICA 6.1 and IBM SPSS.

Results

Infants in group A had significantly higher body weight - (1371.2±70.5) g than infants in group B - (1163.9±51.6) g (p<0.05). Gender peculiarities were established: boys (66.7%) were significantly more prevalent in group A, i.e. there were twice more boys among the dead (χ2 = 7.679; p = 0.006). In 85.7% children with NEC stage II and III who died was diagnosed perinatal hypoxia and 90.5% infants of this group have perinatal infections, p<0.01. The level of serum urea and creatinine in children with NEC who died was significantly higher (21.2±2.9 mmol/l and 175.8±23.7 μmol/l respectively) than in premature infants who survived with NEC (6.8±0.6 mmol/l and 76.0±6.9 μmol/l, respectively), (p<0.01). Odds ratio (OR) of lethal outcome in premature infants with NEC and elevated levels of urea (OR = 12.364; 95% CI: 3.415–44.768) and creatinine (OR = 8.267; 95 % CI: 2.447-27.589). In premature infants who died, one of the most frequent causes of death was acute kidney damage - in 8 (38.1%) infants, among other causes one of the most common causes was endogenous intoxication in 8 (38.1%) infants, rarely other causes.

Conclusion

Hypoxia and infections during pregnancy and during the birth of premature infants played a significant role in develop of kidney damage. Elevated levels of urea and creatinine in premature infants with NEC one of the factors that associated with mortality.
P1820THE DEVELOPMENT OF TRANSITION SERVICES IN RENAL CARE IN SYNERGY WITH YOUNG PATIENTS, PARENTS AND PEDIATRIC AND ADULT HEALTH CARE PROVIDERS: A CO-CREATION APPROACH
Authors: Els Holvoet , Van Biesen Wim , Van Humbeeck Liesbeth
Published: June 2020

Background and Aims

Healthcare transition to adulthood is recognised as challenging for adolescents and young adults (AYA’s) diagnosed with chronic kidney disease. Therefore the implementation of a transition programme adjusted to the needs of this patient population is of great importance. However, rarely are the views of young people or their families sought about the process or relevant outcome of their transition process. The aim of this study was to co-develop a transition programme that (1) enables health care providers to facilitate improving transition outcomes from the perspective of all stakeholders, and (2) enhances self-management by young people with chronic kidney disease.

Method

The development of this programme involved (1) an extensive review of currently existing best-practices (published and unpublished), and (2) understanding the current state of transition practice at our centre by means of semi-structured interviews and focus groups with patients, parents and health care providers of both pediatric and adult side.

Results

A working group was established incorporating a reflective process designed to develop a community of practice. During the process, participants’ experiences, lessons learned from the review of current state of evidence and practice, and appreciation of the (changing) context within which participants were working were incorporated. Analysis revealed 6 core elements as the foundation of the transition program: the AYA as the main focus, involvement of the parents, holistic approach, flexibility, forward-looking approach, continuity in guidance and follow-up. We also identified the need to distinguish the difference between transitioning from child to teenager to young adult and the actual transfer between paediatric and adult care. The actual final proposed transition programme can be divided in 4 phases: (1) introduction of the transition process to parents and patients, (2) guiding the patient to become more independent and to gain insight in the disease and related themes, (3) managing the transfer to adult health care and (4) finalizing the transition care plan. Adequate on-going communication and collaboration between paediatric and adult care seems essential for achieving a successful program.

Conclusion

This study addressed the development of a transition programme as a multi-actor process wherein patients, parents and health care providers significantly contribute to the transition to adulthood and transfer to adult care.
P182125 YEARS OF GROWTH HORMONE TREATMENT IN CHILDREN WITH CHRONIC KIDNEY DISEASE IN POLAND - RESULTS OF NATIONAL MULTICENTER STUDY
Authors: Leszczyńska Beata , Daniel Maria , Majcher Anna , Pyrzak Beata , Szczepanska Maria , Zagozdzon Ilona , Jander Anna , Tkaczyk Marcin , Sikora Przemysław , Wasilewska Anna , Zachwieja Katarzyna , Miklaszewska Monika , Stankiewicz Roman , Jarmuzek Wioletta , Rubik Jacek , Makulska Irena , Pańczyk-Tomaszewska Małgorzata
Published: June 2020

Background and Aims

Growth retardation is one of considerable problems in children with chronic kidney disease (CKD) with a great impact on life activity and quality of life. Recombinant human growth hormone (rhGH) treatment has been used for more than 30 years to improve growth velocity and final growth in children with CKD. In Poland rhGH therapy in children with CKD is available since 1994.

The aim of the study was to assess growth velocity in all children with CKD treated with rhGH in Poland since 1994.

Method

We retrospectively analyzed 321 polish children with CKD (mean age: 10.2±7.60, 210 ♂ (65%) qualified to the rhGH therapy between 1994 and 2019. Among 321 children, 180 (56.1%) were on conservative treatment (CT), 118 (36.7%) on chronic dialysis (RRT) and 23 (7.2%) after kidney transplantation (KTx). In 240 (75%) patients who were treated continuously for at least 12 months we have evaluated: growth velocity and mean annual values of selected biochemical parameters.

Results

Mean height SDS at the beginning of the treatment was -2.73±1.04 SD, among children on CT -2.22±1.20, on RRT -2.9±1.11, after KTx -3.07±1.30. Mean time of rhGH treatment was 23±10.7 months. During one-year rhGH treatment mean growth velocity in 240 children was: 8.5 ± 2.7 cm (ΔSDS 0.78±1.02) and mean height SDS increased significantly

(-2,73±1.04 vs. -1.92±1.11, p<0.0001). Children on CT did not differ significantly in age vs. children on RRT (10.66±3.40 vs. 10.26±3.61 years, p =0.972), and growth velocity was slower in RRT group expressed in cm (7.52±2.59 vs. 9.2±2.30, p<0.0001) and in ΔSDS (0.4±0.83 vs. 0.72±1.15, p=0.045). Growth velocity (ΔSDS) correlated negatively with age of rhGH initiation in children on CT (r=-0.40, p=0.008) and on RRT (r=-0.28, p=0.03). We found no significant relation between growth velocity and sex, cause of CKD, hemoglobin, total protein, albumin, urea, creatinine, calcium, phosphorus, Ca x P, PTH and alkaline phosphatase.

Conclusion

1. Growth hormone treatment is highly effective in children with CKD especially those who are treated consevatively. 2. Early initiation of rhGH therapy is the crucial factor determining response to the treatment in children with CKD.
P1849ANALYSIS OF ASSOCIATION BETWEEN URBANIZATION AND REDUCED RENAL FUNCTION IN INDIAN POPULATION
Authors: Kumar Rahul
Published: June 2020

Background and Aims

While chronic kidney disease (CKD) is a growing public health concern in low- and middle-income countries, such as India, few studies have investigated the association between urbanization and the occurrence of CKD in those countries.

METHODS

We investigated the association between urbanization and estimated glomerular filtration rate (eGFR), an important CKD risk marker. Data came from the India Health and Nutrition Survey wave 2017, in which we collected fasting serum, individual and household data along with community level urbanization data, which was used to derive a study-specific urbanization measure, in 218 communities across fifteen states. A total of 8754 men and 8566 women participants aged 18 years or older were included in the analysis. Reduced renal function was defined as eGFR of less than 60 mL/min/1.73 m2 measured using serum creatinine concentration (mg/dL).

RESULTS

After adjusting for socio-demographic (e.g., age, education and household income), a sex-stratified multilevel logistic model revealed that living in a more urbanized community was associated with higher odds of reduced eGFR (odds ratio [OR] = 1.38 per one-standard deviation [SD] increase in the CHNS specific urbanization index, 95% confidence interval [CI] = 1.11-1.73 for men; OR = 1.35, 95% CI = 1.11-1.62 for women). After adjusting for behavioral variables (i.e., alcohol consumption, smoking, physical activity and diet), as well as obesity and cardiometabolic risk factors, the association was attenuated in men (OR = 1.25, 95% CI = 0.98-1.59), but remained statistically significant in women (OR = 1.24, 95% CI = 1.01-1.52).

CONCLUSION

Our findings suggest that living in an urban environment is linked with higher odds of reduced renal function independently of behavioral and cardiometabolic risk factors, which have been shown to increase along with urbanization.
P1858PSYCOEDUCATIONAL TEAM IN PRE- HEMODIALYSIS FOR PATIENTS AND CAREGIVERS
Authors: Mulè Marica , Gaggia Paola , Movilli Ezio , Manenti Chiara , Appiani Miriam , Zani Orietta , Bertoni Anna , Scolari Francesco
Published: June 2020

Background and Aims

The aim of this work is to explain the training to create a multidisciplinary team that in the future will activate the psychoeducational groups in nephrology. These groups will be support to patients and caregivers already in the waiting period from the intervention of the fistula at the beginning hemodialysis.

Method

The training of five meetings was realized from March 2019 to May 2019. The training for a team composed by 3 nephrologist, 4 nurses, 1 dietician, 1 nursing coordinator was conducted of a psychologist to established modalities and aims of a psychoeducational pathway for patients that will begin hemodialysis and their caregivers. In the first meeting, through a focus group, the participants discussed the word “to cure”. In the second meeting participants defined patient and caregiver’s needs after the diagnosis of Chronic Kidney Disease. In the third meeting the team work defined the objectives and methods of conducting future groups psychoeducational. In the fourth meeting participants decided the duration and modalities of the psychoeducational pathway for patient and caregiver. Finally, in the fifth meeting, the team reviewed the objectives, recipients and thematic areas of the meetings for patients and caregivers. In addition, an evaluation questionnaire was administered to verify the benefit and satisfaction of the training. All the contents of the training were transcribed in a diary and analyzed with a pencil and paper mode.

Results

In the first meeting the team discussed the need to accompany and educate patients even before the onset of haemodialysis. In the second meeting team decided that the therapeutic education is not only for patients waiting to start haemodialysis but also on their caregivers often uninformed and not involved by doctors and nurses. In this focus the caregiver appears an important figure that support the patient at home and if not properly informed it can become an obstacle in patient care. In the fourth and fifth meetings have been defined a possible psychoeducational training in three total meetings so named:

The participants in the satisfaction questionnaire to the question “how much did this training respond to the needs of your job?” on nine answers collected, the outcome it was M = 4.7 on Likert scale 1(few)-5 (much).

Conclusion

The training has managed to build a multidisciplinary team ready to care patients and caregivers that will begin haemodialysis in a more informed and aware way. Currently, two psychoeducational groups have been created for patient and caregiver. As shared in the multidisciplinary team’s training these psychoeducational groups are activated to help the patient to accept dialysis at the same time help the family member to take on the role of caregiver. This project has made it possible to improve not only teamwork but overall patient and caregiver care.
P1861ARTIFICIAL PHOSPHATE- HOW DIFFICULT IS IT TO AVOID IT?
Authors: Smith Oonagh , Kiernan Sarah
Published: June 2020

Background and Aims

Hyperphosphataemia has been independently associated with increased morbidity and mortality across the lifecycle of chronic kidney disease. Dietary phosphate restriction is the corner stone of hyperphosphataemia management. Traditionally the focus was on limiting foods that are naturally high in phosphate such as meats, dairy, wholegrain and nut products. However, phosphate-containing additives are a growing concern. Artificial phosphates are thought to be readily absorbed by the body and are increasingly being added to processed foods, at a time when there is an increased desire and reliance on convenience foods. It has been shown that educating patients with end stage renal disease to avoid phosphate-containing food additives can result in a modest but clinically significant improvement in serum phosphorus levels. 1 The aim of this study was to evaluate how feasible it is for a patient to source convenience packaged cooked meats/poultry that are free from artificial phosphate and if such products are a suitable option for the renal patient in relation to salt and protein content.

Method

Data was manually collected in a branch of the five leading supermarket chains. The ingredient list of each product food label was checked for artificial phosphate (phos), artificial potassium (K) or the corresponding E numbers and the nutrition table examined for salt and protein content (per 100g / 25g portion or slice). The price was checked in store and manually calculated per 7g protein exchange.

Results
P1863KNOWLEDGE ABOUT CHRONIC KIDNEY DISEASE AND THE WAYS OF PREVENTION: A POPULATION-BASED STUDY IN NORTHEAST BRAZIL
Authors: Bezerra da Silva Junior Geraldo , Cavalcante Oliveira Michelle Jacintha , Silva Pedrosa Alyne Suellen , Araújo Pereira Gabriel , Holanda Pinheiro Vilela Isis , Santiago Veloso Felipe Camilo , Lima de Oliveira Leticia , Melo Oliveira Fernanda , Alcântara Jordão Diandra , Arrais Lima Costa Ana Beatriz , Brito de Aguiar Castro Sarah Maria , Sanders Costa Clarissa , Gomes Ramalho de Oliveira Juliana , Askari Marjan , De Francesco Daher Elizabeth
Published: June 2020

Background and Aims

The incidence and prevalence of chronic kidney disease (CKD) is increasing worldwide, and health literacy is an important goal of any program of health care. The aim of this study is to investigate the knowledge of the population in Brazil about CKD and the ways of prevention, as well as the use of novel technologies to achieve knowledge and get awareness on CKD.

Method

This is a population-based study conducted in two large urban centers in Northeast Brazil (Fortaleza city, Ceara, and Maceio city, Alagoas). We have applied a questionnaire with questions regarding the knowledge about CKD, its preventive measures, causes, and ways of diagnose (for example, what is “creatinine”?). We have also investigated the use of novel technologies, focused on applications (apps) to achieve information related to health (if the interviewed) already uses to get health information through apps and if they would like to. Sociodemographic information was also collected. Exclusion criteria were: people from the healthcare sector (because they would already have specialized knowledge about CKD, and we aimed to know what the general population know about CKD), people with CKD, other kidney diseases or medical conditions that could lead to the knowledge about CKD.

Results

A total of 1,147 individuals were interviewed, with a mean age of 38.7±16.0 years, and 621 (54.1%) were female. Regarding the questions about the knowledge about CKD (“Do you know what is chronic kidney disease?”), 442 (38.5%) was found to answer yes. When asked if they know what is creatinine, only 176 (15.3%) said yes. In relation to the risk factors for CKD, 466 (40.6%) answered to know which factors were associated with increased risk for CKD, and 587 (51.1%) said to know how to prevent CKD. Another question was about the use of applications (app) to healthcare, and 358 individuals (31.2%) said to use some type of app to take care of their health. We have also questioned if the interviewed would use applications to get information regarding CKD, and 773 (67.3%) said yes, they would like to.

Conclusion

CKD is a Public Health problem in Brazil, with huge costs to the health system. Prevention is the key determinant to decrease the disease burden to everyone, people, society and healthcare players. Awareness of CKD seem to be slowly increasing in our country, once a significant percentage of interviewed said to know the ways of prevention, but it is still far from ideal. Technology seem to be an interesting solution to achieve our goals in terms of prevention and treatment of CKD.
P0511ENHANCER AND SUPER-ENHANCER DYNAMICS IN REPAIR AFTER ISCHEMIC ACUTE KIDNEY INJURY
Authors: Wilflingseder Julia , Willi Michaela , Lee Hye Kyung , Olauson Hannes , Jankowsky Jakub , Ichimura Takaharu , Erben Reinhold , Valerius M Todd , Hennighausen Lothar , Bonventre Joseph Vincent
Published: June 2020

Background and Aims

The endogenous repair process of the mammalian kidney allows rapid recovery after acute kidney injury (AKI) through robust proliferation of tubular epithelial cells. There is currently limited understanding of which transcriptional regulators activate these repair programs and how transcriptional dysregulation leads to maladaptive repair. Here we investigate the existence of enhancer dynamics in the regenerating mouse kidney.

Method

RNA-seq and ChIP-seq (H3K27ac, H3K4m3, BRD4, POL2 and selected transcription factors) were performed on samples from repairing kidney cortex 2 days after ischemia/reperfusion injury (IRI) to identify activated genes, transcription factors, enhancer and super-enhancers associated with kidney repair. Further we investigated the role of super-enhancer activation in kidney repair through pharmacological BET inhibition using the small molecule JQ1 in vitro and in acute kidney injury models in vivo.

Results

Response to kidney injury leads to genome-wide alteration in enhancer repertoire in-vivo. We identified 16,781 enhancer sites (H3K27ac and BRD4 positive, H3K4me3 negative binding) active in SHAM and IRI samples; 6,512 lost and 9,774 gained after IRI. The lost and gained enhancer sites can be annotated to 62% and 63% of down- and up-regulated transcripts at day 2 after kidney injury, respectively. Super-enhancer analysis revealed 164 lost and 216 gained super-enhancer sites at IRI day 2. 385 super-enhancers maintain activity before and after injury. ChIP-seq profiles of selected transcription factors based on motif analysis show specific binding at corresponding enhancer sites. We observed lost enhancer binding of HNF4A and GR mainly at kidney related enhancer elements. In contrast, STAT3 showed increased binding at injury induces enhancer elements. No dynamic was observed for STAT5. Both transcription factor groups show corresponding mRNA changes after injury. Pharmacological inhibition of enhancer and super-enhancer activity by BRD4 inhibition (JQ1: 50mg/kg/day) before IRI leads to suppression of 40% of injury-induced transcripts associated with cell cycle regulation and significantly increased mortality between days 2 and 3 after AKI.

Conclusion

This is the first demonstration of enhancer and super-enhancer function in the repairing kidney. In addition, our data call attention to potential caveats for use of small molecule inhibitors of BET proteins that are currently being tested in clinical trials in cancer patients who are at risk for AKI. Our analyses of enhancer dynamics after kidney injury in vivo have the potential to identify new targets for therapeutic intervention.
P0512SKLB023 ATTENUATED LIPOPOLYSACCHARIDE-INDUCED ACUTE KIDNEY INJURY VIA INHIBITION OF NF-KAPPPAB AND MAPKS PATHWAYS
Authors: Ren Qian , Ma Liang , Fu Ping
Published: June 2020

Background and Aims

Excessive nitric oxide (NO) production by the activation of inducible nitric oxide synthase (iNOS) during sepsis was considered to contribute to acute kidney injury (AKI) and selective inhibition of iNOS activity may be a promising strategy for the treatment of sepsis-induced AKI. The novel small molecule compound (Z)-N-(3-Chlorophenyl)-2-(4-((2,4-dioxothiazolidin-5-ylidene) methyl) phenoxy) acet-amide (SKLB023) as a selective iNOS inhibitor was designed, synthesized by our lab and exhibited therapeutic potential in arthritis and non-alcoholic steatohepatitis models with potent anti-inflammatory effects. This study aimed to evaluate whether SKLB023 as a drug candidate could offer renal protective effect against sepsis-induced AKI.

Method

21 C57BL6 mice (20-22g, 6-8 weeks old) were randomly divided into three groups: control, model, SKLB023 pretreatment. AKI was induced by a single injection of 10mg/kg LPS, and SKLB023 was orally administrated at the dose of 50 mg/kg for three consecutive days and one hour before LPS injection. All mice were sacrificed 16h after LPS injection and blood and kidney tissues were collected for further evaluation. LPS-induced renal dysfunction was assessed by measurement of blood creatinine and urea nitrogen (BUN) as well as histopathological changes. Moreover, the kidney mRNA and protein expression of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1(KIM-1), newly identified kidney injury markers, were tested by polymerase chain reaction (PCR) and western blot. To explore underlying mechanisms, the renal expression of inflammatory cytokine genes IL-1β, IL-6, mcp-1 and proteins iNOS, COX-2, IL-1β, TNF-α, IL-6, HMGB1 in were measured. The total expression of nuclear factor-kappa B (NF-κB), IκBα and MAPKs proteins (ERK1/2, p38 MAPK) and their corresponding phosphoproteins (p-NF-κB, p-IκBα, p-ERK1/2, p-P38 MAPK) in mice kidneys were subsequently analyzed by western blot.

Results

16hours following LPS challenge, mice developed AKI as evidenced by elevated creatinine and BUN levels and corresponding pathological changes. Additionally, kidney expression of NGAL and KIM-1 were remarkably increased after LPS injection. SKLB023 pretreatment, however, alleviated LPS-induced renal dysfunction. Moreover, the excessive production of inflammatory cytokines during sepsis was significantly suppressed by SKLB023. Further observation from PCR and immunoblot results indicated that SKLB023 attenuated the activity of NF-kB and the phosphorylation of ERK1/2 and p38 MAPK in septic AKI mice.

Conclusion

These data demonstrated that SKLB023 exhibited renoprotective effect in LPS-induced AKI, which was associated with its anti-inflammatory activities by inhibiting the NF-kappaB and MAPK signaling pathways
P0869EXOGENOUS OSTEOGENIC FACTOR 1 ADMINISTRATION ATTENUATED VASCULAR CALCIFICATION AND IMPROVED BONE DISORDERS IN CHRONIC UREMIC RATS
Authors: Lee Chien-Te , Ng Hwee-Yeong , Chen Wen-Lin , Lee Yuai-Ting
Published: June 2020

Background and Aims

Hyperphosphatemia and secondary hyperparathyroidism are frequent complications in chronic kidney disease (CKD) which both contribute to increased morbidity and mortality in CKD. Osteogenic factor-1 (OP-1) is an important member of BMPs subfamily and its effects on CKD-associated mineral and bone disorders (MBD) is controversial. The study examined whether exogenous OP-1 administration can modulate disturbed CKD-MBD in adenine-induced chronic uremic rats

Method

Chronic renal failure was induced in adult male SD rats by feeding adenine-containing diet. After adenine diet feeding 3 weeks, animals were injected with OP-1 (5μg/kg/day) intraperitoneally for 2 weeks. The serum and urine phosphorus levels and associated mineral parameters, including fibroblast growth factor 23(FGF-23), DKK-1 and sclerostin were measured. Vascular calcification was assessed by immunohistochemistry staining on aortic tissue. Bony structure was evaluated by microCT (Bruker-microCT, Kontich, Belgium).

Results

A significant decrease of body weight and deteriorated renal function was observed in adenine and OP-1 treatment groups during study period and serum creatinine levels were similar (5.23 ±1.1 mg/dL vs. 5.4 ±1.2 mg/dL, p>0.05). Animals in OP-1 group had lower serum phosphorous (18.7±5.1 vs. 29.0±9.6 mg/dL, p<0.05) and intact parathyroid hormone levels (2906.1±1206.9 vs. 4669.7±2505.9 pg/dL, p<0.05) compared to adenine group. Decreased urine phosphorous excretion was noted in both groups without significant difference. Levels of serum FGF-23, sclerostin and DKK-1 were significantly lower in OP-1 treatment group (all p< 0.05). OP-1 administration diminished the staining of RUNX2 (59.1±3% of adenine-treated group), alkaline-phosphatase (49.4±5.7%), β-caterin (39.3±1.8%), BMP2 (43.2%±6.7%), and BMP7 (51.9±10%, all p <0.05). MicroCT revealed that bone mineral density was increased by OP-1 treatment (0.46±0.1 vs.0.39±0.06 g/cm3). Total volume was increased but bone volume was not changed. OP-1 administration did not affect trabecular thickness and trabecular number.

Conclusion

Our data indicated administration of exogenous OP-1 improved hyperparathyroidism and attenuated vascular calcification. OP-1 treatment was also associated with beneficial effects on bony structure in animals with renal failure.
P1371HEART FAILURE HOSPITALISATIONS IN THE PIVOTAL TRIAL OF IV IRON IN HAEMODIALYSIS PATIENTS: A PRE-SPECIFIED SECONDARY ANALYSIS
Authors: Jhund Pardeep , Petrie Mark , Robertson Michele , Mark Patrick , Macdonald Michael , Connolly Eugene , White Claire , Reid Chante , Anker Stefan D , Bhandari Sunil , Farrington Kenneth , Kalra Philip A , Tomson Charles R V , Wheeler David , Ford Ian , McMurray John , Macdougall Iain
Published: June 2020

Background and Aims

Heart failure (HF) is a common and potentially deadly complication in patients receiving haemodialysis which is difficult to diagnose and treat. The impact of a proactive high-dose strategy compared to a reactive low-dose strategy of IV iron administration was investigated in the PIVOTAL randomised trial in incident haemodialysis patients, with fatal HF and HF hospitalisation being components of the composite primary cardiovascular endpoint as well as a pre-specified key secondary event.

The aim of this analysis was to examine the effect of a proactive high-dose strategy compared to a reactive lower dose strategy on HF events in patients recruited to PIVOTAL.

Method

As with the primary composite cardiovascular endpoint, HF hospitalisations in PIVOTAL were recorded prospectively via an electronic database, and events were then adjudicated by a blinded Endpoint Adjudication Committee. The time-to-event analyses of the primary, secondary and post hoc outcomes were performed in the intention-to-treat population using Cox proportional hazards regression, with treatment group as the only explanatory variable. The Kaplan–Meier method was used to estimate event rates. Both fatal and non-fatal HF events were analysed as time to first event, and a recurrent event analysis was also performed for non-fatal events.

Results

Overall, 2141 participants were followed for a median of 2.1 years. A first fatal or non-fatal HF event occurred in 51 of 1093 patients (4.7%) in the high-dose iron group and in 70 of 1048 patients (6.7%) in the low-dose iron group (hazard ratio 0.66, 95% confidence interval 0.46 to 0.94; P<0.001) (Figure). There was a total of 63 HF events (including first and recurrent events) in the high-dose iron group and 98 in the low-dose iron group, giving a rate ratio of 0.59 (0.40-0.87); p=0.0084. A history of HF and diabetes were independent predictors of a heart failure event.

Conclusion

Compared with a low-dose regimen, high-dose intravenous iron decreased the occurrence of first and recurrent heart failure events in incident patients undergoing haemodialysis, with large relative and absolute risk reductions.
P0338CRUMBS HOMOLOG2-EZRIN SIGNALING INDUCED PODOCYTE INJURY, LEADING TO MINIMAL-CHANGE DISEASE(MCD) AND FOCAL SEGMENTAL GLOMERULOSCLEROSIS(FSGS)
Authors: Hada Ichiro
Published: June 2020

Background and Aims

The etiology and cellular pathogenesis of podocyte injury leading to minimal-change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remain largely obscure. Genetic mutation of crumbs homolog 2 (CRB2) is a cause of congenital nephrotic syndrome. Type-1 transmembrane proteins including CRB2 transduce outside-in signals that are involved in various cellular events including changes in the cytoskeletal network. The aim of the present study is to determine whether alteration of CRB2-mediated signaling in podocytes causes MCD and FSGS.

Method

Mice were immunized with a partial recombinant protein including the extracellular part of mouse CRB2. Urinalysis was obtained, and the kidney was subjected to histopathology. Kidney samples were also subjected to immunofluorescence microscopy and glomerular isolation to determine whether activation of the ezrin/radixin/moesin (ERM) family of cross-linkers between plasma membrane proteins and the actin cytoskeleton is involved in the pathogenesis of this nephrotic model. A CRB2-expressing mouse podocyte cell line was generated and incubated with anti-CRB2 antibody, and cell lysates were subjected to immunoblot analysis of ERM phosphorylation. The presence of anti-CRB2 antibody in the serum was determined by Western blot analysis.

Results

Apparent anti-CRB2 antibody was detected in the serum from 4 weeks onward. Immunized mice developed proteinuria at 4 weeks, which continued at least until 29 weeks. Mice developing extremely heavy proteinuria also developed hematuria from 18 weeks onward. Light microscopy revealed MCD in mice with proteinuria alone and FSGS in mice with heavy proteinuria and hematuria. Immunofluorescence microscopy revealed positive granular IgG staining in podocyte foot processes, but not complement C3. Electron microscopy and immuno-electron microscopy revealed alteration of actin organization associated with prominent foot process effacement. Strong phosphorylation of ezrin was observed in the glomerulus from the proteinuric stage and in the cellular lysates from the CRB2-expressing podocyte cell line incubated with anti-CRB2 antibody.

Conclusion

The current data revealed that binding of anti-CRB2 antibody to the extracellular domain of CRB2 on the podocyte foot process activated the ezrin-cytoskeleton network, leading to podocyte injury. Our data also indicated that signaling by this one molecular can induce two different phenotypes of glomerular injury: MCD and FSGS. In our model, the signaling was activated by anti-CRB2 antibody, but in patients with nephrotic syndrome the CRB2 ligands remain unknown. Therefore, it will be important to identify the soluble factors interacting with CRB2, which may be novel factors contributing to the pathogenesis of MCD and FSGS.
P0768NOVEL URINARY PROTEIN BIOMARKERS FOR UROTHELIAL CANCER IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Huang Chiu-Ching , Chou Che-Yi , Shu Kuo-Hsiung , Chen Hung-Chun , Wang Ming-Chang , Chang Chia-Chu , Hsu Bang-Gee , Wu Mai-Szu , Yang Yuan-Lung , Chen Chao-Jung
Published: June 2020

Background and Aims

Introduction: Chronic kidney disease (CKD) patients are known to have greater risk of urothelial cancer (UC) than general population. Urine is the most non-invasive examination and is directly linked to UC. Urinalysis and urine cytology are the major screening tools; however, these tests have low sensitivity or specificity in early disease. In this study, we used both normal and Non-UC CKD patients as controls to discover novel and more specific protein biomarkers in urine for early UC diagnosis.

Aims

To discover novel and more specific urinary protein biomarkers for screening of urothelial cancer (UC) in CKD patients.

Method

This is a multicenter prospective cohort study, carried out at 10 nationwide hospitals covering different regions of Taiwan from 2013-2018. Subjects were Taiwanese healthy adults (healthy controls, n=210), patients with CKD but without UC (disease controls, n=273) and patients with ongoing UC (n=211). For non-UC patients, urine and blood specimens were collected at the time of the structured interview. For UC patients, urine and blood samples were collected before operation. iTRAQ-LC-MS/MS approach was applied to compare protein expression among normal, CKD and UC cohorts.

Results

A total of 3838 proteins in urine were identified and 2497 proteins of them can be quantified. By filtering with fold changes, published papers and Human ATLAS, 27 candidates were selected as potential biomarkers and were validated with ELISA assay in a large sample size of urine specimens. Among the 27 candidates, we found BRDT, CYBP, GARS and HDGF were highly-expressed in the UC cohort when compared to normal and CKD cohorts (Figure 1). To increase the diagnostic value of UC, we combined ROC of our newly discovered 4 protein biomarkers. The AUC values of our newly discovered 4-biomarker panel were higher than the AUC values of the published biomarker panel, including the FDA-approved protein biomarkers (Figure 2).

Conclusion

We discover and validate a highly specific urinary protein biomarker panel (BRDT, GARS, HDGF and CYBP) to distinguish UC from CKD and healthy controls. It may be used for high throughput screening of subjects, such as CKD patients, who are at high risk to develop UC.
P0966PLACENTAL GROWTH FACTOR DEFICIENCY AGGRAVATES DIABETIC NEPHROPATHY
Authors: Lim Ji Hee , Kim Yaeni , Kim Eun Nim , JIN YONGJIE , Kim Hyung Duk , Ban Tae Hyun , Choi Bum Soon , Park Cheol Whee
Published: June 2020

Background and Aims

Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family. PlGF exerts favorable angiogenetic and lymphangiogenic activity by binding to VEGF-R1 and -R3, respectively. Due to its functional synergy with VEGF-A, it is required for a correct neovascularization during pathological conditions while inactivation of PlGF contributes to decrease of pathological angiogenesis. Because reduced angiogenesis and lymphagiogenesis that contribute to defective lipid drainage are implicated in the progression diabetic kidney disease, we investigated the role of PlGF in the development of diabetic nephropathy by using PlGF-knockout mice.

Method

Diabetes was induced by a low-dose streptozotocin injection in 9-week-old male C57BL/6J PlGF-KO and wild-type mice and biochemical and morphological parameters were examined at 12 weeks later.

Results

In diabetic PlGF-KO mice, fasting blood glucose and HbA1c levels increased significantly and the development of glomerular sclerosis and mesangial area expansion were accompanied by albuminuria. Diabetic PlGF-KO mice exhibited increased expression of type IV collagen, transforming growth factor-β1 and glomerular IHC staining for nephrin, PECAM-1 and WT-1-positive cells and VEGF-R1,-R2,-R3 expression decreased, suggesting decreased endothelial cell and podocyte structure. Intrarenal expression of pLKB1, and pAMPK decreased and that of PPARα, PGC1α, ERRα, p-eNOS, and urinary Nox concentration decreased while iNOS increased, indicating disturbed lipid metabolism and endothelial dysfunction in the same group. Increased intrarenal FFA, TG, and cholesterol concentration represents presence of lipid accumulation. F4/80- and TUNEL-positive cells increased, suggesting increased inflammatory cell infiltration and apoptosis. CD68 and arginase-II increased indicating that macrophage subtype M1 polarization is involved in the inflammatory process. Expression of Bcl2/bax decreased and that of SOD1 and 2 decreased, indicating increased apoptosis and oxidative stress, respectively. Increased expression of intrarenal 8-OHdG and urinary isoprostane level indicates increased oxidative stress.

Conclusion

Impaired angiogenesis and lymphangiogenesis are implicated in PlGF deficiency and this promotes lipotoxicity-induced inflammation, oxidative stress and deteriorates renal functional and phenotypic parameters in the diabetic kidney.
P1000URINE MYO-INOSITOL AS A NOVEL PROGNOSTIC BIOMARKER FOR DIABETIC KIDNEY DISEASE
Authors: Lim Chun Soo , Kwon Soie , Lee Jung Pyo
Published: June 2020

Background and Aims

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESRD). Metabolomics has been increasingly applied to identify the cause of CKD, as it can present epigenetics and suggest corresponding treatment options. Only a few metabolomics studies were conducted in DKD patients, and the results are inconclusive. We investigated the association between urine metabolites and renal disease progression and mortality in DKD, using 800 MHz NMR spectroscopy based targeted metabolomics profiling.

Method

Prospectively stored urine samples from consecutive patients with DKD stage 1 to 5 (n=208) and their healthy controls (n=26) were analyzed. Cross-sectional associations were evaluated between eGFR or urine protein creatinine ratio (UPCR) and 26 urinary metabolites. Multivariable adjusted Cox models were conducted for the risk prediction of ESRD and mortality. The receiver-operating characteristic (ROC) analyses were used to assess the additive effect of each metabolite to predict the progression to ESRD.

Results

ESRD occurred in 103 (44.0%) patients and 65 (27.8%) deaths occurred during median 4.5 years (IQR, 2.06–6.58) follow-up period. The median fold change in 9 metabolites (glucose, mannose, myo-inositol, glycerol, lactate, fumarate, creatine, taurine and choline) in patient group revealed a trend corresponding to DKD stages. Linear regression showed that myo-inositol had a strongest association with eGFR. The relationship between the competitive metabolites and outcomes (ESRD and mortality) was investigated by multivariate Cox models after adjusting for the baseline covariates. Of these, 4 metabolites (myo-inositol, glycerol, fumarate, oxoisocaproate) had predictive values for ESRD, and among them, only myo-inositol retained predictive significance in mortality (adjusted HR 1.004, 95% confidence interval 1.002-1.006, P < 0.001). At ROC analysis, urinary myo-inositol had additive effect to serum creatinine concentration and UPCR in the prediction for ESRD progression (NRI = 2.9%, P = 0.03; IDI = 35.1%, P = 0.02).

Conclusion

These results suggest that myo-inositol can be a predictive biomarker for the risk of ESRD progression and mortality in DKD. Further studies are needed to elucidate the pathophysiological roles of myo-inositol in DKD.
P1431MULTI-CENTER REGISTRY ANALYSIS COMPARING SURVIVAL ON HOME HEMODIALYSIS AND KIDNEY TRANSPLANT RECIPIENTS IN AUSTRALIA AND NEW ZEALAND
Authors: Ethier Isabelle , Cho Yeoungjee , Hawley Carmel , Pascoe Elaine M , Roberts Matthew A , Semple David , Nadeau-Fredette Annie-Claire , Wong Germaine , Lim Wai , Sypek Matthew P , Viecelli Andrea , Campbell Scott , Van Eps Carolyn , Isbel Nicole M , Johnson David W
Published: June 2020

Background and Aims

In the era of organ shortage, home hemodialysis (HHD) has been identified as the possible preferential bridge to kidney transplantation. Data are conflicting regarding the comparability of HHD and transplantation outcomes. This study aimed to compare patient and treatment survival between HHD patients and kidney transplant recipients.

Method

The Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry was used to include incident HHD patients on day 90 after initiation of kidney replacement therapy and first kidney-only transplant recipients in Australia and New Zealand from 1997 to 2017. Survival times were analyzed using the Kaplan-Meier product limit method comparing HHD patients to subtypes of kidney transplant recipients using the log-rank test. Adjusted analyses were performed with multivariable Cox proportional hazards regression models for time to all-cause mortality. Time-to-treatment failure or death was assessed as a composite secondary outcome.

Results

The study compared 1411 HHD patients to 4960 living donor (LD) recipients, 6019 standard criteria donor (SCD) recipients and 2427 expanded criteria donor (ECD) recipients. While LD and SCD recipients had reduced risks of mortality compared to HHD patients (LD adjusted hazard ratio [HR] 0.57, 95%CI 0.46-0.71; SCD HR 0.65 95%CI 0.52-0.79), the risk of mortality was comparable between ECD recipients and HHD patients (HR 0.90, 95%CI 0.73-1.12). LD, SCD and ECD kidney recipients each experienced superior time-to-treatment failure or death compared to HHD patients.

Conclusion

This large registry study showed that kidney transplant offers a survival benefit compared to HHD but that this advantage is not significant for ECD recipients.
Working Memory for Signs and Gestures
Authors: Rudner Mary , Rönnberg Jerker
Published: June 2020

Working memory (WM) for signs and words is similar at the behavioral level, but differences emerge at the neural level. We have illuminated WM for sign language by studying behavior and neural activation in signers and nonsigners performing sign- and gesture-based n-back WM tasks. This work has shown that deaf signers have a performance advantage over hearing nonsigners on sign-based WM tasks probably due to their signing expertise. It has also shown that lexical but not phonological knowledge of sign language leads to better WM for sign language. Cross-modal plasticity driven by congenital deafness can be dissociated into sensory and cognitive components, and we have shown that deaf signers recruit the posterior portion of the superior temporal lobe for WM processing. These findings are discussed in relation to the Ease of Language Understanding (ELU) model.
Developmental, Cognitive, and Neurocognitive Perspectives on Language Development in Children Who Use Cochlear Implants
Authors: Rinaldi Pasquale , Pavani Francesco , Caselli Maria Cristina
Published: June 2020

Newborn hearing screening programs and early diagnosis allow deaf children to receive hearing aids and/or cochlear implants very early in life. However, even within these early intervention scenarios, deaf children remain at risk of delays in spoken language acquisition despite what is expected based on their hearing recovery scores. The first part of this chapter offers an overview of recent studies on the role of specific factors (i.e., age at diagnosis, age at cochlear implant activation, family environment, and exposure to sign language) in affecting communicative and linguistic development. The second part examines to what extent current cognitive neuroscience research is contributing to refinement of the concept of critical or sensitive periods for the development of the acoustic system and language in deaf children. Clinical and educational implications for promoting language development in deaf children are discussed.
Theory of Mind and Conversation in Deaf and Hearing Children
Authors: Peterson Candida C.
Published: June 2020

Conversation in a shared language (spoken or signed) is not only a pleasurable social activity but also a fundamental building block for the growth of social cognition, including theory of mind (ToM). Participating in informal conversations at home and at school fosters cognitive development of ToM, which, in turn, fosters reciprocated friendship, peer-group popularity, leadership, and social skills, while protecting against loneliness and social isolation. These interconnections between ToM and conversation are explored with a special focus on deaf children, a population of key theoretical significance for the understanding of ToM development generally. Timely ToM growth is linked with (a) having access from birth to a language (spoken or signed) that all family members can fluently share, (b) frequent family discussions of cognitive mental states, (c) school-based access to varied peer and adult conversational partners, and (d) children’s own eagerness to participate in conversations exposing them to different mental viewpoints.