bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO384: Identifying Long Non-Coding RNA Biomarkers From Urinary Exosomes for Diabetic Nephropathy
Authors: Zhu Xiaoxiao , Feng Songtao , Jing Jing , Zhong Xin , Shen Anran , Liu Bicheng , LV Linli 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Diabetic nephropathy (DN) is the common cause of end-stage renal disease. However, the early and specific diagnostic biomarkers are still lacking. Urinary exosomes are a potential source of biomarkers for kidney disease due to their renal cell origination, stability, and noninvasive collection. Long non-coding RNAs (lncRNAs) are increasingly recognized to be involved in diverse pathophysiological processes including kidney disease. Here we set to characterize the lncRNAs profiles in urinary exosomes of DN with aims to identify novel non-invasive biomarkers of DN.

METHOD
First-morning urine was collected from 11 healthy people, 9 patients with diabetes mellitus (DM), and 8 patients with biopsy-proven DN. Urinary exosomes were pelleted by ultracentrifugation and total RNA was extracted for next generation sequencing (NGS). The lncRNA profile of urinary exosomes was first characterized in terms of the detectable RNA numbers, expression levels in different groups. Then differential gene expression analysis was performed to facilitate the discovery of potential biomarkers.

RESULTS
Similar tremendous number of lncRNAs was detected with a total number of 6439 transcripts present in urinary exosomes in each group. In terms of the expression levels, the percentage of transcripts with TPM above 1 was 31.4%, 32.8%, 33.2% in the healthy group, DM and DN patients respectively, suggesting that no significant alteration of lncRNAs numbers and distribution in DN and diabetes conditions. Next, the differential expression analysis was performed to identify the distinct differential lncRNAs. Compared with healthy people, 18 lncRNAs were upregulated and 67 lncRNAs were downregulated in DM group, while 37 unregulated and 80 downregulated lncRNAs were identified in DN group. Moreover, the profile of lncRNAs in urinary exosomes was significantly different in DN patients compared to DM group with 59 lncRNAs upregulated and 36 lncRNAs downregulated. To explore the candidate biomarkers, 12 upregulated lncRNAs and 4 downregulated lncRNAs from the two comparison sets (DN versus Healthy, DN versus Healthy) were identified, among which FLJ16779 was present with the most remarkable difference. Further analysis showed that the sensitivity and specificity of FLJ16779 for distinguishing DN from healthy people are both 87.5%, and the area under the curve (AUC) was 0.9531. Additionally, the sensitivity and specificity of FLJ16779 for distinguishing DN from DM were 75% and 87.5% respectively, and AUC was 0.9063.

CONCLUSION
Urinary exosomes contain rich lncRNAs information with differential expression profiles in DN patients compared to DM and healthy controls, suggesting the possible involvement of lncRNAs in the pathogenesis of DN. lncRNA FLJ16779 might be a promising non-invasive biomarker of DN which requires further validation.
MO389: Klotho Supplementation Reverses Renal Dysfunction and Interstitial Fibrosis in Remnant Kidney
Authors: Takenaka Tsuneo 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Several studies demonstrate that klotho shows renoprotective actions. However, it has not been assessed whether klotho supplementation is able to reverse the renal injury.

METHOD
In the present study, the effects of klotho protein supplementation on remnant rat kidneys were assessed using three groups: renal ablation for 4 weeks, renal ablation for 12 weeks and klotho supplementation (20 μg/kg/day).

RESULTS
Klotho supplementation suppressed blood pressure, albuminuria, renal renin-angiotensin system (RAS), serum phosphate and fibroblast growth factor (FGF) 23 levels, fibrosis index, renal expression of transforming growth factor β and collagen I. Klotho protein supplementation increased glomerular filtration rate (GFR), fractional excretion of phosphate, renal expression of klotho, bone morphogenetic protein (BMP) 7 and superoxide dismutase.

CONCLUSION
Our data indicated that klotho supplementation reduced blood pressure and albuminuria with inactivation of renal RAS in the remnant kidney. In addition, exogenous klotho protein supplementation increased endogenous klotho expression, facilitating phosphate excretion with reductions in serum phosphate and FGF23. Finally, klotho protein supplementation upregulated BMP7, at least partly contributing to an increase in GFR and reversal of fibrosis in the remnant kidney.
MO412: Impact of Body Mass Index on Mortality and End–Stage Kidney Disease in Patients With Non-Dialysis Dependent Chronic Kidney Disease
Authors: Al-Chalabi Saif , Nawaz Saira , Lodge Michelle , Sinha Smeeta , A. Kalra Philip , Chinnadurai Rajkumar 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Obesity is a major global problem affecting more than 1.9 billion adults [1]. The aetiological factors of obesity are complex and consist of genetic, social and environmental elements. Obesity can lead to chronic kidney disease (CKD) via both direct and indirect pathways. However, the effect of obesity on the progression of CKD remains unclear. This study aimed to investigate the impact of higher body mass index (BMI) on clinical outcomes in a large UK cohort of patients with non-dialysis dependent (NDD)-CKD.

METHOD
The Salford Kidney Study is a longitudinal prospective cohort of more than 3000 patients with NDD-CKD. All patients with available BMI at baseline from October 2002 to December 2016 were included in this study. Patients were grouped according to their BMI into underweight [(BMI &lt; 18.5 kg/m2), n = 35], healthy weight [(BMI 18.5–24.9 kg/m2), n = 628], overweight [(BMI 25–29.9 kg/m2), n = 860] and obese [(BMI &gt; 30 kg/m2), n = 897]. Cox-regression analysis was performed to study the strength of association between BMI groups and major clinical outcomes [all-cause mortality, end-stage kidney disease (ESKD) and annual rate of progression of CKD (delta eGFR)] by using the healthy weight BMI group as a reference. The outcomes were also analysed in a 1:1 propensity score-matched analysis between patients in the healthy weight and obese groups (414 in each).

RESULTS
A total of 2420 patients with a median follow-up of 44.3 months were available for analysis. The median age of the cohort was 67 years and 58% were male. The prevalence of hypertension and diabetes increased with a higher BMI (84.0% and 18.8% in healthy weight, 91.7% and 31.0% in overweight and 94.2% and 46.8% in the obese groups, respectively). There was no significant difference in the baseline eGFR between the groups with a median of 29.3 mL/min/1.73 m2. There was an inverse association between a higher BMI and all-cause mortality [obese versus healthy weight: hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.81–0.96; P = 0.004] but there was no association observed with ESKD (HR 0.96; 95% CI: 0.87–1.06; P = 0.422). The delta eGFR was not significantly different between the different BMI groups (Table 1). A similar observation with all-cause mortality being better in the obese group was noted in the propensity-matched analysis (HR:0.88; CI:0.81–0.96; P = 0.004) (Table 2).

CONCLUSION
In our large cohort of patients, a higher BMI was seen to be protective against all-cause mortality. Furthermore, the annual rate of decline in eGFR was similar among the BMI groups. Patients with normal BMI had significantly higher all-cause mortality compared with the obese group.
MO413: Registration of Image Modalities for Analyses of Tissue Samples Using 3D Image Modelling
Authors: Hermann Juliane , Jankowski Vera , Jankowski Joachim 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Biopsies are a diagnostic tool for the diagnosis of histopathological, molecular biological, proteomic and imaging data, to narrow down disease patterns or identify diseases. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) provides an emerging state-of-the-art technique for molecular imaging of biological tissue. The aim of this study is the registration of MALDI MSI data sets and data acquired from different histological stainings to create a 3D model of biopsies and whole organs.

METHOD
The registration of the image modalities is achieved by using a variant of our global, deformable Schatten-q-Norm registration approach. Utilizing a connected-component segmentation for background removal followed by a principal-axis-based linear pre-registration, the images are adjusted into a homogeneous alignment. This registration approach is accompanied by the 3D reconstruction of histological and MALDI MSI data.

RESULTS
With this, a system of automatic registration for cross-process evaluation, as well as for creating 3D models, is developed and established. The registration of MALDI MSI data with different histological image data is evaluated by using the established global image registration system.

CONCLUSION
In conclusion, this multimodal image approach offers the possibility of molecular analyses of tissue specimens in clinical research and diagnosis.
MO424: Relationship Between Itch Intensity and Patient-Reported Disease Improvement in Patients With Chronic Kidney Disease-Associated Pruritus Treated With Difelikefalin
Authors: Mccafferty Kieran , Walpen Sebastian , Schaufler Thilo , Morin Isabelle , Menzaghi Frederique , Wen Warren , Fishbane Steven 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Chronic kidney disease-associated pruritus (CKD-aP) is a common condition in patients with CKD undergoing haemodialysis (HD), leading to poor sleep quality, reduced quality of life and depression. Difelikefalin is a selective kappa opioid receptor agonist approved in the United States for the treatment of moderate-to-severe pruritus in adults undergoing HD, which significantly reduced itch intensity in HD patients with CKD-aP in the Phase 3 KALM-1 and KALM-2 multicentre, placebo-controlled trials. The KALM trials used the Worst-Itching Numerical Rating Scale (WI-NRS) to assess itch-intensity [range from 0 (no itching) to 10 (worst itching imaginable)] and the Patient Global Impression of Change (PGIC) to assess the patient's overall perception of change in itch (range from ‘very much improved’ to ‘very much worse’) relative to the start of the study. The aim of this post hoc analysis was to establish how the WI-NRS score relates to the PGIC and to assess a clinically relevant change in WI-NRS.

METHOD
A post hoc analysis of data from KALM-1 and KALM-2 was performed. Studies enrolled maintenance HD patients with mean baseline 24-h WI-NRS score &gt; 4 in KALM-1 or ≥ 5 in KALM-2. Patients were randomized 1:1 to intravenous difelikefalin 0.5 mcg/kg or placebo three times/week for 12 weeks. Patients completed the PGIC at the end of the 12-week, double-blind treatment period, as well as completing the WI-NRS daily. Cumulative distribution function (CDF) analyses were performed at Week 12. Results are reported for 50% CDF at week 12.

RESULTS
For the overall population, ‘very much improved’ corresponded to a 5-to-6-point WI-NRS reduction; ‘much improved’ corresponded to a 3-to-4-point WI-NRS reduction; and ‘minimally improved’ corresponded to a 1-to-2-point WI-NRS reduction (Figure 1).

CONCLUSION
There is a clear relationship between the PGIC and the WI-NRS, with greater reductions in itch severity corresponding to perceptions of better overall improvement in itch following treatment with difelikefalin. A 3-point reduction in WI-NRS can be considered clinically relevant, since it was perceived by patients as equivalent to their itch being ‘much improved’. This analysis further corroborates similar clinically meaningful changes in pruritus, previously reported in patients with CKD-aP, as ≥ 3-points [1, 2].
MO443: Accumulation of REG-1Α in Proximal Tubules of a Rat Model of Chronic Kidney Disease: A New Biomarker at the Interface Between Renal Impairment and Neurodegenerative Diseases
Authors: Cortijo Irene , Muyor Karen , Laget Jonas , Jover Bernard , Reynaud Fabrice , Duranton Flore , Fontès Pascaline , Trousse Françoise , Marcilhac Anne , Mestre-Francés Nadine , Argiles Ciscart Angel , Gayrard Nathalie 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Chronic kidney disease (CKD) increases the risk of developing cognitive dysfunction and it has been identified as a modifiable risk factor for Alzheimer's disease (AD) [1]. Regenerating family member 1 alpha (Reg-1α) protein, originally identified as a 16 kDa polypeptide in the pancreas, is increased in cerebrospinal fluid (CSF) and in neurons of AD patients [2, 3]. Reg-1α is also elevated in blood in inflammatory conditions and chronic illnesses such as diabetes and interestingly, in patients with renal function impairment [4, 5]. It is not known whether Reg-1α is synthesized in the kidney or the modifications observed in CKD are merely due to a decline in the glomerular filtration rate. The aim of our study was to localize and quantify the Reg-1α protein in the kidneys of normal rats or CKD rats (5/6 nephrectomized rats) and determine, in a second time, if serum Reg-1α level is a suitable marker for assessment of renal function. As Reg-1a is able to cross the altered blood-brain barrier, it might be a new interesting biomarker at the interface between renal impairment and neurodegenerative diseases.

METHOD
A total of 16 3-month-old rats were randomly allocated to 5/6 nephrectomy (Nx) or Sham operation. Three months after surgery, serum creatinine and urea, systolic blood pressure (SBP) were measured and renal fibrosis (Sirius Red) was quantified. The expression of Reg-1α was evaluated by double-immunofluorescence using anti-Reg-1α and anti-Aquaporin-1 (Aqp-1) (as a proximal tubule marker) antibodies to determine the localization of Reg-1α in the kidney.

RESULTS
5/6Nx rats showed increased serum creatinine levels (97.3 ± 17.6 versus Sham 26.3 ± 0.8 µmol/L; P &lt; 0.05) and serum urea levels (23.9 ± 8.9 versus Sham 4.7 ± 0.1 mmol/L). They also had a higher SBP (158 ± 12 versus Sham 133 ± 5 mmHg) and renal fibrosis increased in the 5/6Nx group (8.1 ± 1.5 versus Sham 2.7 ± 0.2% staining). The double-immunofluorescence revealed an increased expression of Reg-1α of 5/6Nx rats compared with the Sham group. This expression seemed to be specific to the cytoplasm of the proximal tubules, with a ring-shaped distribution (preliminary results, Figure 1).

CONCLUSION
Our data show, for the first time, a proximal tubule-specific accumulation in Reg-1α in CKD suggesting an influence of impaired renal function on Reg-1α accumulation. Further assessment of Reg-1a in the blood, the blood-brain barrier and neuroinflammation status in this model is needed to better understand the potential effect of kidney accumulation of Reg-1α on brain dysfunction. Should this effect be confirmed, Reg-1α would be a new actor involved in the kidney-brain dialogue.
MO449: Polycystins are Upregulated in Fibrotic Kidneys and Promote Renal Fibrosis
Authors: Wang Yanzhe , Wu Ming , Ye Chaoyang 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Mutations in PKD1 or PKD2 gene, which encodes polycystin-1 or polycystin-2, cause autosomal polycystic kidney disease (ADPKD). The development of ADPKD is associated with the progression of renal fibrosis. Whether renal fibrosis in ADPKD is a direct effect of PKD mutation or a consequence of cyst growth-induced tubular obstruction is currently unknown. Polycystin-2 has been identified as a direct target of triptolide and we used triptolide as a probe to study the role of polycystin-2 in renal fibrosis.

METHOD
Unilateral ureteral obstruction (UUO), unilateral ischemia-reperfusion injury (UIRI) and aristolochic acid nephropathy mouse models were established. Mice were treated with vehicle or triptolide. Western blotting and Masson's trichrome staining were performed to evaluate renal fibrosis. Moreover, human kidney 2 (HK2) cells and normal rat kidney 49F (NRK-49F) cells were used as in vitro models.

RESULTS
Here we showed that polycystin-2 is up-regulated in these three mouse models and tightly correlated with the expression of collagen-I in a time-dependent manner. Treatment with triptolide inhibited the expression of polycystin-2 and pro-fibrotic markers in UUO and UIRI models. Moreover, triptolide dose-dependently inhibited the expression of polycystin-2 and pro-fibrotic markers in rat renal fibroblasts or in TGF-β stimulated human renal epithelial (HK2) cells. Knockdown of PKD2 reduced the expression of pro-fibrotic markers in TGF-β stimulated or unstimulated HK2 cells. Moreover, we showed that knockdown of PKD2 attenuated the inhibitory effect of triptolide on the expression of pro-fibrotic markers in TGF-β stimulated HK2 cells. Finally, using Pkd2 conditional knockout mice, we showed that heterozygous or homozygous deletion of Pkd2 reduced the expression of pro-fibrotic markers in UUO kidneys. Polycystin-1 was also up-regulated in three renal fibrotic models and conditional deletion of Pkd1 reduced the expression of pro-fibrotic markers in UUO or folic acid-induced fibrotic kidneys. Furthermore, conditional knockout of the methyltransferase EZH2 attenuated the anti-fibrotic responses induced by PKD1 deletion in UUO kidneys.

CONCLUSION
Polycystins are pro-fibrotic proteins in injured kidneys suggesting that renal fibrosis in ADPKD kidneys is not a direct effect of PKD mutation.
MO485: Chronic Kidney Disease in Patients With Lung Transplant
Authors: Luisa Serrano Salazar Maria , Rubio Arboli Lucia , Sánchez-Sobrino Beatriz , De Valdenebro Recio Maria , López Paula , Aguilar Myriam , Teresa Lazaro Carrasco de la Fuente Maria , Portoles Jose' M 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The incidence of chronic kidney disease (CKD) in patients with lung transplantation (LTx) has increased over the last decades.
Progression factors recognized in the development of CKD are: older age and comorbidity of recipients, immunosuppressive (IS) toxicity and longer survival. There is a lack of specific information about other risk factors or specific preventive management of CKD.

METHOD
Retrospective, single-centre study including all patients with LTx on Nephrology outpatient clinic among 2007 and 2020. Demographic, comorbidity and intercurrent events, renal function impairment, proteinuria and IS treatment were analyzed. We defined composite renal event (MARE) as renal replacement therapy (RRT), death or doubling serum creatinine.

RESULTS
A total of 69 LTx receptors (79.4% double LTx) were followed in a dedicated outpatient nephrology clinic. A total of 52.2% male, mean age at LTx 48.3 years (SD 16.6).
Etiology of lung disease: cystic fibrosis (30.4%), obstructive lung disease or emphysema (33.3%) and interstitial disease (30.4%). After LTx, as complications, infection was the most frequent event (89.7%) and 49.3% presented neoplasic illness.
The mean time from LTx until first nephrologist evaluation was 6.6 years (2 months–19.9 years) and main comorbidities were: hypertension (81.2%), diabetes mellitus (52.2%), dyslipidemia (50.7%), 60.3% former smokers and 26.1% had suffer from a previous CV event.
After 1 year of LTx, mean eGFR decreased to 49.8 mL/min, which means that only in the first year after LTx there is a loss of ∼50% of mean kidney function. Factor associated with impaired kidney function at the first year after LTxw was cystic fibrosis (higher percentage in the rapid progression group).
At first evaluation by Nephrology, the mean eGFR was 30.9 mL/min (SD 15.3), with a CKD distribution: 39.4% CKD 3; 45.5% CKD 4 and 12.1% CKD 5 (&lt;15).
Clinical study and biopsy define CKD etiologies: CNI toxicity (68.1%) thrombotic microangiopathy (11.6%), tubular (10.1%), vascular (7.3%) and glomerulopathies (2.9%).
A total of 88.4% patients reached MARE at the end of the study. A total of 24 patients required RRT (mean time since LTx 9.2 years) and thereafter, 10 received a kidney transplantation (KTx).
In Dyalisis group, a higher mortality was observed versus no dialysis group (24 versus 2.2%), a higher percentage of vascular origin disease with a further deterioration of eGFR at the time of referral to Nephrology.
At the end of follow-up, 15 patients died (14 were in RRT), 5 continued on HD and 5 with a functional KTx, and 44 patients were still without RRT.

CONCLUSION
MO487: Rates of Hyperkal a EMIA and Management Patterns in a Tertiary Outpatient Renal Clinic
Authors: Rosati Erica , D'ambrosio Viola , Baccaro Rocco , Bargagli Matteo , Manuel Ferraro Pietro 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The optimal ambulatory management of hyperkalaemia (HK) in patients with chronic kidney disease (CKD) is still an important unmet challenge. Common strategies include dose reduction or discontinuation of nephroprotective medications (e.g. renin-angiotensin-aldosterone system inhibitors [RAASi]), dietary restriction of potassium (K), loop diuretics, bicarbonate and sodium polystyrene sulfonate; all the above interventions are characterized by specific pitfalls and limitations. However, new potassium binders are available that might improve the management of chronic hyperkalaemia. In the light of their widespread use, it will be important to increase our knowledge of the incidence, characteristics and current real-life management patterns of hyperkalaemia in CKD patients.

METHOD
We performed a retrospective analysis of patients followed at our tertiary outpatient renal clinic from 1 April 2016 to 31 December 2021. HK was defined as serum K &gt; 5.0 mmol/L and stratified according to severity. eGFR was estimated with the CKD-EPI equation and stratified according to the KDIGO criteria. The time span between each episode of HK was assessed with Poisson regression models. A sample of 100 HK events was selected at random for manual chart review of the management strategies performed: Information was abstracted using a standardized form.

RESULTS
The final analysis included 1844 patients, contributing 4480 occasions. Baseline characteristics by hyperkalaemia status are reported in Table 1. Patients with HK were older, with lower eGFR and a higher prevalence of diabetes.
At least one episode of HK was documented in 525 patients (28.5%) and among them, 166 patients (31.6%) had at least two HK episodes (on average, 1.55 episodes/patient). HK events were more frequent among patients with more advanced stages of CKD. The time span between episodes decreased significantly (Fig. 1): on average, each episode was 17% [95% confidence interval (95% CI), 3%–29%) closer to the subsequent (P = .016). Of the 100 HK episodes randomly reviewed, 79% received no intervention, whereas 21% triggered at least one intervention. The probability of intervention increased with increasing severity of HK: 8.6%, 35.9%, 50.0% and 100% for K-values 5.0–5.4, 5.5–5.9, 6.0–6.4 and ≥6.5 mmol/L, respectively. Most interventions included dose reduction or discontinuation of RAASi. One patient was sent to the emergency department for urgent examination and treatment (K 7.0 mmol/L).

CONCLUSION
Hyperkalaemia is a common and recurring problem for patients with renal impairment: It occurs in almost one-third of the overall population of this study, and many hyperkalaemic patients experience recurring events. As expected, the prevalence rates of hyperkalaemia increase with worsening CKD severity. Furthermore, the decreased time span between consecutive episodes highlights an accelerated recurrence pattern of hyperkalaemia despite interventions.