bluuebunny/crossref_metadata_2025 huggingface dataset:
MO489: Weight Change and Risk of Depression in Patients With Diabetic Kidney Disease: A Nationwide Population-Based Study
Authors: Sang Choi Hong , Ryon Oh Tae , Heon Suh Sang , Seong Kim Chang , Hui Bae Eun , Kwon MA Seong , Wan Kim Soo
Published: May 2022

BACKGROUND AND AIMS

Several studies have reported that depression has a high prevalence in patients with diabetes or chronic kidney disease. However, the relationship between weight changes and the risk of depression has not been elucidated in patients with diabetic kidney disease (DKD).

METHOD

From the Korean National Health Insurance Service database, we selected 67 866 patients with DKD with body weight data from two consecutive health examinations with a 2-year interval between 2009 and 2012. The weight change >2 years was categorized into five groups: ≥10% weight loss, 5%–10% weight loss, <5% weight change, 5%–10% weight gain and ≥10% weight gain. The occurrence of depression was monitored through the end of 2018 by the ICD-10 codes.

RESULTS

During the 5.24-year follow-up, 17 023 patients with DKD developed depression. The weight change and the risk of depression showed a U-shaped relationship: patients with ≥10% weight loss [hazard ratio (HR): 1.116] and those with ≥10% weight gain (HR: 1.114) showed higher HRs than those with ≤5% weight change, even after adjusting for several confounding factors. In subgroup analyses, the risk of depression tended to increase as weight gain or weight loss increased in all subgroups.

CONCLUSION

Both weight loss and weight gain increased the risk of depression in patients with DKD
MO499: Incidence of Cause-Specific Cardiovascular Events in Men and Women With CKD
Authors: Faucon Anne-Laure , Lambert Oriane , Alencar de Pinho Natalia , Ayav Carole , Combe Christian , Fouque Denis , Frimat Luc , Jacquelinet Christian , Laville Maurice , Liabeuf Sophie , Massy Ziad , Nicolas Mansencal , Stengel Benedicte
Published: May 2022

BACKGROUND AND AIMS

Men are at higher risk of cardiovascular disease (CVD) than women in the general population, and chronic kidney disease (CKD) is a well-established cardiovascular (CV) risk factor [1–4]. However, the incidence of cause-specific CV events in men and women with CKD is poorly documented.

METHOD

All hospitalization and death reports for CV events of the 3033 patients (1983 men and 1050 women) with non-dialysis CKD (stage 3–5) included in the French CKD-REIN Cohort were reviewed and classified by cause using criteria from the Cardiovascular and Stroke Endpoint Definitions for Clinical Trials [5]. Cause-specific Cox proportional hazard models were used to estimate hazard ratios for death and each fatal or nonfatal CV event according to gender.

RESULTS

At baseline, in men (mean age: 68 years; mean eGFR 33 mL/min/1.73 m²), the prevalence of atheromatous CVD was 30% for coronary artery disease, 14% for cerebrovascular disease and 17% for lower limb artery disease, and that of non-atheromatous CVD was 14% for heart failure and 13% for atrial fibrillation. In women (65 years old, 32 mL/min/1.73 m²), these prevalences were 15%, 7%, 9%, 11% and 9%, respectively.

During a median follow-up of 5 (IQR: 3–5) years, 98 men and 43 women died from CVD {i.e. 1.3 [95% confidence interval (95% CI): 1.0–1.5] versus 1.0 (0.7–1.3)/100 person-years}, including 53% versus 46% from heart failure, 31% versus 19% from sudden death, and 16% versus 35% from other cardiovascular causes, respectively.

Crude incidence rates of death or hospitalization for coronary artery disease and lower limb artery disease were higher in men than in women, slightly higher for CV death, cerebrovascular disease and atrial fibrillation, but similar for both genders for heart failure (Fig. 1). History of CVD was strongly associated with subsequent CV events of any type.

In multivariable analyses, gender was no longer associated with any cause-specific CV event, whereas a lower eGFR was significantly associated with an increased risk of coronary artery disease and heart failure, but not with other CV events (Table 1).

CONCLUSION

In patients with moderate or advanced CKD, the burden of atheromatous CVD is higher in men than in women and explained by their higher prevalence of cardiovascular risk factors, but that for heart failure and atrial fibrillation appears to be similar for both genders.
MO508: Estimated Glomerular Filtration Rate and the Risk of Inflammatory Bowel Disease in Adults: A Swedish Population-Based Study
Authors: Yang Yuanhang , Ludvigsson Jonas , Olén Ola , Sjolander Arvid , Jesus Carrero Juan
Published: May 2022

BACKGROUND AND AIMS

Chronic kidney disease (CKD) and inflammatory bowel disease (IBD) share many risk factors. While kidney complications are seen in 4%–23% of patients with longstanding IBD, it is unknown whether low kidney function may predispose to developing IBD.

METHOD

We analyzed the association between estimated glomerular filtration rate (eGFR) and the risk of being diagnosed with IBD among 1 612 160 adults without prior IBD history who accessed healthcare in Stockholm during 2006–18. We categorized eGFR into five groups: <30,  30–59, 60–89, 90–104, 105 + mL/min/1.73m2 with 90–104 being the reference group. Flexible parametric survival models with stepwise adjustments and piecewise linear splines were used to investigate the association between eGFR, IBD and IBD-subtypes (Crohn's disease, ulcerative colitis and IBD unclassified). IBD cases were identified by two or more records with an IBD diagnosis. Subgroup analyses explored the consistency of the associations between age strata, sex, background education and the presence of selected comorbidities. To explore the possibility of detection bias and reverse causation, we estimated IBD risks from the first year after baseline eGFR.

RESULTS

We detected 9663 new cases of IBD (Crohn's disease: n = 3299 and ulcerative colitis: n = 5072), over a median follow-up of 9 years. Linear splines suggested the association between eGFR and IBD to be J-shaped, with higher IBD risk at both eGFR extremes. After multivariable adjustment and compared with eGFR 90–104 mL/min/1.73 m2 lower eGFR strata were associated with higher IBD risk {adjusted hazard ratio (HR), 1.14; [95% confidence interval (95% CI) 0.99–1.32] for eGFR = 30–59 mL/min and 1.63; 1.14–2.33 for eGFR <30 mL/min}. This association was stronger in magnitude for Crohn's disease, with an HR of 1.32 (1.03–1.71) for eGFR = 30–59 mL/min and 2.22 (1.24–3.97) for eGFR <30 mL/min. Subgroup analyses showed consistency across age, education categories, presence of diabetes and of CVD, but suggested that the association between low eGFR and IBD was stronger in women and in the absence of hypertension (P for interaction <.05). Associations were slightly attenuated after excluding IBD cases during the first year of follow-up, indicating the presence of detection bias and/or reverse causation.

CONCLUSION

We observed an association between decreased eGFR and the risk of developing IBD, which was stronger in magnitude for Crohn's disease, but that could be partly explained by bias.
MO519: Ferric Citrate Hydrate Improves Levels of Transferrin Saturation in Hemodialysis Patients With Lower Levels of Transferrin Saturation
Authors: Yokoyama Keitaro , Inoue Ryo , Ito Kyoko , Mitobe Yuko , Matsumoto Yu , Yamada Ryoichi , Susai Hiroyuki , Nishino Noriaki
Published: May 2022

BACKGROUND AND AIMS

Iron deficiency identified by transferrin saturation (TSAT) is reported as a risk factor for all-cause mortality and cardiovascular events in non-dialysis dependent (NDD) chronic kidney disease (CKD) [1, 2] and for all-cause mortality in hemodialysis patients [3]. Ferric citrate hydrate (FC, Riona®), an oral iron-based phosphate binder in CKD patients, is also approved as an iron preparation for iron-deficiency anemia (IDA) in Japan in 2021. In the USA, ferric citrate (Auryxia®) is approved as a phosphate binder for dialysis-dependent CKD and an iron replacement product for the treatment of IDA in patients with NDD-CKD. FC or ferric citrate increased TSAT in patients with NDD-CKD and IDA [4]. However, a few data show that whether FC or ferric citrate has the similar effect in hemodialysis patients whose TSAT is <20%. Considering the additional indication of IDA in Japan, we investigated the FC's effect on TSAT by using the data obtained from the ASTRIO study [5], which was conducted in Japanese hemodialysis (HD) patients.

METHOD

We conducted a retrospective study using the data of ASTRIO study [5], which is a randomized, prospective, open-label, multicenter 24-week study to investigate the FC's effect on anemia management compared with non-iron-based phosphate binders (PBs) in Japanese HD patients with hyperphosphatemia. Ninety-three patients taking non-iron-based PBs were randomized 1:1 to continue PBs (control) or switch to FC. During 24-week study, serum phosphate and hemoglobin were controlled, 3.5–6.0 mg/dL and 10–12 g/dL, respectively. From 93 patients (FC, n = 48; control, n = 45), we extracted 41 patients (FC, n = 21; control, n = 20) whose TSAT at baseline was <20% and compared the levels of TSAT and other iron related parameters between FC group and control group.

RESULTS

In the ASTRIO study, the mean (SD) levels of TSAT (%) was 14.3 (4.0) at baseline and rapidly increased to 25.0 (11.1) at 4 weeks in the FC group. After that, the levels of TSAT were almost unchanged in the FC group, whereas, in the control group, the mean (SD) levels of TSAT were almost unchanged during the 24-week study. The mean (SD) levels of serum ferritin gradually increased until week 12 and subsequently showed to be stabilized in the FC group, whereas, in the control group, these were almost unchanged during the 24-week study (Table 1).

CONCLUSION

In Japanese HD patients whose TSAT was <20%, FC rapidly increased TSAT compared with control. We will also investigate the FC's effect on TSAT in HD patients from the post-marketing surveillance study, the prospective, multicenter and observational, up to maximum 2 years treatment.
MO533: Safety of Roxadustat versus Erythropoiesis-Stimulating Agents for Treatment of Anemia in Patients With Chronic Kidney Disease Incident to or not Receiving Dialysis: Pooled Analysis of Four Phase 3 Studies
Authors: Barratt Jonathan , Dellanna Frank , Portoles Jose , Choukroun Gabriel , De Nicola Luca , Reusch Michael , Young James , Dimkovic Nada
Published: May 2022

BACKGROUND AND AIMS

Patients with late-stage chronic kidney disease (CKD) who are non–dialysis-dependent (NDD) or incident to dialysis (ID) (e.g. initiated dialysis within the last 4 months) or dialysis-dependent (DD) represent a vulnerable population at increased risk for morbidity and mortality despite significant clinical advancements in recent years. The safety of roxadustat in patients with NDD or ID-DD CKD requires further elucidation.

METHOD

In this post-hoc exploratory analysis, safety results from eligible patients with anemia of CKD enrolled in four phase 3, randomized, open-label studies [NDD (DOLOMITES) or ID-DD (SIERRAS, HIMALAYAS, ROCKIES)] were pooled and compared roxadustat to an erythropoiesis-stimulating agent (ESA). Endpoints were time to major adverse cardiovascular event [MACE; myocardial infarction, stroke and all-cause mortality (ACM)] and MACE+ (MACE plus congestive heart failure or unstable angina requiring hospitalization), ACM, and treatment-emergent adverse events (TEAEs). MACE and MACE + were evaluated for non-inferiority using hazard ratios (HRs) at 1.8 and 1.3-upper margins, respectively, and 95% confidence intervals (CIs). TEAEs were descriptively summarized.

RESULTS

In total, 2142 patients were evaluated (1083 roxadustat; 1059 ESA; 616 NDD; 1526 ID-DD). Roxadustat was non-inferior to ESA for risk of MACE [HR 0.79 (95% CI 0.61–1.02)] and MACE+ [HR 0.78, (95% CI 0.62–0.98)] with a consistent finding for ACM [HR 0.78 (95% CI 0.57–1.05)]. TEAEs were generally comparable between roxadustat and ESA groups, including any TEAE [incidence rate per 100 patient-exposure years (IR/100 PEY) 56.1 versus 53.5], TEAEs leading to discontinuation of study drug (IR/100 PEY 6.7 versus 5.1) and TEAEs leading to death (IR/100 PEY 6.9 versus 7.4). The most frequent (IR/100 PEY) TEAEs were hypertension (roxadustat 12.8, ESA 12.3), end-stage kidney disease (roxadustat 6.6, ESA 6.1), diarrhea (roxadustat 7.1, ESA 4.8) and hyperkalemia (roxadustat 4.3, ESA 4.8).

CONCLUSION

There was no evidence of an increased risk of cardiovascular events or mortality with roxadustat compared with ESA in patients with anemia who have NDD or ID-DD CKD. Although TEAE development occurred commonly in both the roxadustat and ESA groups, patients infrequently discontinued a study drug because of an adverse event.
MO553: Impact of the Internal Parathyroid Clock on the Regulation of Parathyroid Gene Expression
Authors: Egstrand Søren , Lerche Mace Maria , Morevati Marya , Nordholm Anders , Olgaard Klaus , Lewin Ewa
Published: May 2022

BACKGROUND AND AIMS

Proper rhythms in metabolism, hormone secretion and activity are maintained by a molecular circadian clock. The central clock in central nervous system (CNS) receives light input via retina to regulate timing of activity. Peripheral clocks are found in a number of tissues regulating an estimated 8–10% of all expressed genes[1]. We have previously shown that an internal circadian clock operates in the parathyroid gland (PTG) which is disturbed in a rat model of chronic kidney disease (CKD)[2].

Here, we examined the PTG transcriptome of wildtype mice over 24-h and compared with our novel mouse strain with PTG-specific circadian clock knockdown (by PTG-specific knockdown of core circadian clock gene Bmal1) to investigate the role of the PTG clock.

METHOD

PTG-specific knockdown of Bmal1 was generated by crossing PTHcre-mice with Bmal1flox/flox mice (WT) creating PTHcre; Bmal1flox/flox mice (KD). PTGs of WT and KD were harvested at 4-h interval and 24-h gene expression was examined by RNAseq. Circadian rhythmicity was assessed by cosinor-analysis and JTK_CYCLE algorithm. Cluster analysis was performed using the Mfuzz package in R. The clusterProfiler R package was used for gene ontology enrichment and gene set enrichment analysis (GSEA) with FDR-adjusted P-value at < 0.05.

RESULTS

A total of 6.85% of all expressed genes were significantly rhythmic in the wildtype PTG, including parathyroid signature genes Casr, Vdr, Klotho, Fgfr1 and Gcm2. Rhythmic genes were divided into nine clusters based on similar expression profile, indicating common regulation. Gene ontology analysis revealed that five clusters showed significant enrichment of genes involved in regulating transcription (cluster 1), mitochondrial ATP synthesis by oxidative phosphorylation (cluster 2), secretion (cluster 3), peptide biosynthesis (cluster 4) and cell cycle (cluster 5) (Figure 1).

KD mice had global dampening of rhythmicity of PTG circadian clock genes as well as parathyroid signature genes compared to WT and significant downregulation of genes involved in mitochondrial ATP synthesis at four consecutive timepoints compared to WT by GSEA analysis (Figure 2A + B). Gene ontology analysis of all downregulated genes across timepoints in KD mice revealed multiple interconnected enriched terms related to mitochondrial ATP synthesis (Figure 2C).

CONCLUSION

Dampened rhythm of PTG circadian clock genes also reduced rhythmicity of parathyroid signature genes and downregulated genes involved in mitochondrial function and ATP synthesis in four separate comparisons. This indicates importance of the internal PTG molecular clock for parathyroid function.
MO554: Roxadustat Improves Renal Osteodystrophy by Dual Regulating Bone Remodeling
Authors: LI Luyao , LI Afang , Zuo LI
Published: May 2022

BACKGROUND AND AIMS

Renal osteodystrophy (ROD) is a complication of chronic kidney disease (CKD) resulting in increased susceptibility to fractures. Therefore, developing effective drugs to prevent and treat ROD is vital. Accumulating evidence suggested stabilization of hypoxia-inducible factor-1α (HIF-1α) could promote bone formation. Roxadustat is a novel HIF stabilizer to treat renal anemia in CKD patients. This study aims to investigate the effects of roxadustat on bone remodeling using a CKD rat model.

METHOD

A total of 24 8-week-old male Sprague–Dawley rats were divided into three groups (n  = 8/group): the normal group (Normal), CKD group and CKD + Roxadustat group. For induction of CKD, the diet containing 0.5% (w/w) adenine was given to the rats for the first 4 weeks. Roxadustat (10 mg/kg, by gavage) was given every other day from the third week of CKD induction for 4 weeks. Then blood was collected to test hemoglobin (Hb) concentrations, serum levels of creatinine (Cr), calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH) and bone turnover markers including bone alkaline phosphatase (BAP), osteocalcin (OCN) and tartrate-resistant acid phosphatase 5b (TRACP-5b). Left femurs were subjected to micro-computed tomography (micro-CT) to evaluate bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). Left tibiae were collected to calculate osteoclast surface/bone surface (Oc.S/BS), osteoclast number/bone surface (N.Oc/BS), osteoblast surface/bone surface (Ob.S/BS) and osteoblast number/bone surface (N.Ob/BS). One-way analysis of variance followed by Tukey HSD post hoc test was used for comparisons. P < 0.05 was statistically significant.

RESULTS

CKD rats exhibited remarkably higher serum Cr, P, iPTH, TRACP-5b levels and obviously lower Hb and serum Ca levels compared with the normal group. Whereas roxadustat treatment significantly decreased iPTH, TRACP-5b and increased Hb, BAP and OCN levels in CKD rats. CKD induced remarkably decreased BMD, BV/TV, Tb.N, Tb.Th and dramatically increased Tb.Sp compared with the normal group. However, roxadustat treatment improved these changes in CKD rats. CKD rats had increased Oc.S/BS, N.Oc/BS, Ob.S/BS and N.Ob/BS compared with the normal group. Roxadustat decreased Oc.S/BS, N.Oc/BS but further increased Ob.S/BS and N.Ob/BS in CKD rats.

CONCLUSION

Roxadustat alleviated bone loss and bone microstructure deterioration of CKD rats by promoting bone formation and inhibiting bone resorption.
MO555: Exosomes From Endothelial Cells to Smooth Muscle Cells Induce Vascular Calcification in Early Chronic Kidney Disease
Authors: Liao Ruoxi , Qin Zheng , Jiang Luojia , Xiong Yuqin , LI Jiameng , Wang Liya , LI Yupei , Han Mei , Su Baihai
Published: May 2022

BACKGROUND AND AIMS

Vascular calcification can occur in the early stages of chronic kidney disease (CKD) and result in a poor prognosis. How the calcification signal in the blood is transduced from endothelial cells in the tunica intima to vascular smooth muscle cells in the tunica media in the early stages of CKD is still unknown. The aim of this study was to explore the role of exosomes in signal transduction in vascular calcification.

METHOD

Exosomes were isolated from normal phosphate- and high phosphate-stimulated human umbilical vein endothelial cells (HUVECs) by superspeed centrifugation. We used transmission electron microscopy, molecular size analysis and Western blot analysis of exosome markers to identify exosomes (Figure 1). VSMC calcification was assessed by Alizarin Red Staining and Western blot. Proteomics analysis and miRNA microarray analysis were carried out to detect the differences in exosomal proteins and miRNAs. The results were analysed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

RESULTS

Fluorescence microscopy verified that VSMCs took up exosomes from HUVECs. Exosomes isolated from high phosphate-stimulated HUVECs (HP-HUVEC-exos) induced VSMC calcification (assessed by Alizarin Red Staining), increased osteopontin expression and increased alkaline phosphatase activity (Figure 2). Proteomics analysis showed different protein expressions including STAT1, STAT3, HDAC1, PARP1, WDR5 et al. MiRNA microarray analysis showed different miRNA levels including miR-223–3p, miR-6776–5p, miR-6851–5p, miR-2116–3p, miR-6849–5p et al. (Figure 3). Target GO analysis showed that both miRNA and protein difference focused on some biological processes (RNA splicing, mRNA processing, RNA targeting), molecular function (cadherin binding, cell adhesion molecule binding, ubiquitin-like protein ligase binding) and cellular component (focal adhesion, cell-substrate junction, spliceosomal complex). KEGG analysis revealed that both miRNA and protein differences were focused on pathways associated with the cell cycle, virus infection and protein processing in the endoplasmic reticulum.

CONCLUSION

Exosome-mediated miRNA and protein transfer from endothelial cells to VSMCs may induce vascular calcification via RNA processing, protein processing and cell adhesion.
MO558: Chronic Kidney Disease and Gastroparesis: What is the Association?
Authors: Sandoval Terra Campos Guelli Mariana , Correa Tulio , Silva Isabella , Zampier Daniela , Costa Leticia , Dias Lorena , Guidoreni Angela
Published: May 2022

BACKGROUND AND AIMS

Chronic kidney disease (CKD) can predispose individuals to multiple extrarenal manifestations, such as anemia, bone disease, heart disease and electrolyte disorders. In addition, some patients with CKD can present with gastrointestinal (GI) symptoms, but the pathogenesis of this condition is still unclear. Symptoms of gastroparesis include early satiety, pyrosis, epigastric pain, nausea and vomiting, which may lead to caloric and electrolyte deficiencies as well as significant weight loss. Therefore, the aim of this study was to analyze the association between CKD and gastroparesis.

METHOD

A systematic literature review was conducted following the PRISMA guidelines. Papers were selected searching PubMed/Medline, SciELO and LILACS databases using the terms (chronic kidney disease OR CKD) and (gastroparesis OR gastric emptying) in January 2022. The inclusion criterion was limited to observational studies that evaluated the association between CKD and gastroparesis. There were no language or publication date restrictions.

RESULTS

Among the 111 papers initially identified, 14 were eligible for this review after full texts were read. Dysmotility-like dyspeptic complaints and delayed gastric emptying can be prevalent in CKD patients. Gastric hypomotility appears to be an important factor in the generation of GI symptoms in patients with CKD. Different pathophysiological mechanisms, such as electrolyte imbalance, gastric mucosal edema and direct toxicity of uremic retention molecules can play a role in inducing gastroparesis in patients with CKD. Serum levels of several polypeptide hormones involved in the modulation of GI motility [e.g. gastrin, cholecystokinin (CCK) and neurotensin] and the regulation of hunger and satiety (e.g. glucagon, CCK) were significantly altered as a consequence of renal insufficiency and may play a major role in gastrointestinal dysmotility. Patients with CKD showed impaired gastric myoelectrical activity in response to food and high levels of GI hormones. Delayed gastric emptying contributes to malnutrition, which may potentially have a broad impact in the prevention and treatment of CKD and its complications. Gastric emptying tests are valuable in identifying occult gastroparesis in high-risk patients and may guide the selection of prokinetic therapy, which can significantly increase levels of serum albumin and improve general prognosis. Electrogastrography is an interesting noninvasive technique to evaluate gastric motility in patients with severe chronic renal failure.

CONCLUSION

The studies suggest that patients with CKD are at higher risk of developing gastroparesis and dysmotility-like dyspeptic complaints. Nevertheless, more studies are needed to provide high-quality evidence.
MO566: Relationship Between Cholesterol Intake and Development of Chronic Kidney Disease: A Community-Based Prospective Cohort Study
Authors: Park Joonbyung , Kim Hyoungnae , Noh Hyunjin , Seok Jeon Jin , Hyo Kwon Soon , Lee Haekyung , Cheol Han Dong
Published: May 2022

BACKGROUND AND AIMS

Globally, the incidence and prevalence of CKD have been increased. Also, CKD DALYs and death due to CKD have been increased (DALYs: The disability-adjusted life-year).[1] CKD puts a lot of mental and economic burden on an individual’s life and lowers the quality of life.[2] As CKD progress, kidney-specific risk factor for cardiovascular events and disease are increased.[3] Dyslipidemia is generally known to be associated with the development and progression of chronic kidney disease.[4] However, it is unclear whether limiting cholesterol intake helps prevent CKD. Recent studies have reported that there is no association between cholesterol intake and cardiovascular disease.[5] The aim of our study is to analyze the relationship between cholesterol intake and the development of CKD in a general population.

METHOD

We included 9226 subjects without CKD from the Korean Genome and Epidemiology Study. The amount of daily cholesterol intake was assessed by food frequency questionnaire. The primary outcome was the development of CKD, which was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 and/or proteinuria (≥1+).

RESULTS

The mean age was 55.7 ± 8.8 years and 39.6% of subjects were men. The cholesterol intake was only significantly correlated with serum HDL cholesterol but not with total and non-HDL cholesterol. Moreover, this significant relationship was disappeared after adjusting for daily fat intake. During median follow-up duration of 11.4 years, 778 (8.5%) CKD events occurred. In multivariable Cox analysis, serum total cholesterol was significantly associated with incident CKD (hazard ratio [HR] 1.005, 95% confidence interval [CI]: 1.003–1.007; P < 0.001). However, cholesterol intake was not associated with incident CKD both in subjects with dyslipidemia (HR: 1.001; 95% CI: 1.000–1.002; P = 0.205) and without dyslipidemia (HR: 0.999; 95% CI: 0.997–1.000; P = 0.134).

CONCLUSION

Cholesterol intake was not correlated with serum cholesterol levels with considering fat intake. In addition, cholesterol intake was not associated with increased risk of CKD in the general population. Therefore, it may not be necessary to limit cholesterol intake to prevent CKD in this population.
MO570: Effects of Dark Chocolate on Inflammation and Oxidative Stress in Patients With Chronic Kidney Disease on Hemodialysis
Authors: Mafra Denise , M. Ribeiro Marcia , Fanton Susane , R. Paiva Bruna , G. Baptista Beatriz , Alvarenga Livia , Cardozo Ludmila
Published: May 2022

BACKGROUND AND AIMS

Patients with chronic kidney disease (CKD), especially on hemodialysis (HD), have a high prevalence of cardiovascular mortality, with oxidative stress (OE) and inflammation as the main contributors. Persistent inflammation from the early stages of CKD is caused by several factors, including increased production of reactive oxygen species (ROS), leading to OE, which in turn induces inflammation by activating the nuclear factor-kB pathway, causing the overproduction of inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α) and interleukins (IL). Dark chocolate is rich in polyphenols, which have antioxidant, anti-inflammatory and cardioprotective properties, and it could be an alternative nonpharmacological to mitigate inflammation and complications of CKD. Therefore, this study aimed to evaluate the effects of dark chocolate on oxidative stress and inflammation in patients with CKD on HD.

METHODS

This is a longitudinal clinical trial performed with 46 patients with CKD on a regular dialysis program (3 dialysis sessions per week). A group received 40 g of dark chocolate during HD sessions, totaling 120 g per week, for 2 months, and a group did not receive any intervention. Plasma levels of TNF-α and IL-6 were evaluated using the ELISA method. Thiobarbituric acid reactive substances were performed to evaluate lipid peroxidation as malondialdehyde (MDA). Routine parameters were also analyzed using commercial kits. Changes in parameters were evaluated between the pre- and post-treatment.

RESULTS

Thirty-five patients performed the chocolate group (18 men, 53.4 ± 12.9 years old and 43.2 ± 30 months on HD) and 11 patients (7 men, 46.7 ± 10.9 years old and 55.2 ± 18.7 months on HD) the control group. Although TNF-α plasma levels did not reduce significantly after chocolate, the levels were increased in the control group (Table 1 and Fig. 1). The potassium plasma levels were reduced (from 5.9 ± 0.8 to 5.5 ± 0.8 mg/dL, P < 0.05) and phosphorus plasma levels did not change in the chocolate group (5.9 ± 1.7 to 5.8 ± 1.6 mg/dL). In the control group, both parameters did not change after 2 months.

CONCLUSION

Two months of dark chocolate intervention seem to modulate the TNF-α plasma levels (inflammation marker) in patients with CKD on hemodialysis. It is important to emphasize that dark intervention in this study did not increase the phosphorus plasma levels in patients with CKD on HD.
MO575: Possible Benefits of a Low Protein Diet in Older CKD Patients at Risk of Malnutrition: A Pilot Randomized Controlled Trial
Authors: Vettoretti Simone , Caldiroli Lara , Armelloni Silvia , Mattinzoli Deborah , Ikehata Masami , Molinari Paolo , Alfieri Carlo , Messa Piergiorgio , Castellano Giuseppe
Published: May 2022

BACKGROUND AND AIMS

Current guidelines do not clarify whether older patients with advanced chronic kidney disease may benefit of low protein diet if they are at risk of malnutrition. We compared the effects of normo-calorie/normo-protein (NP) and normo-calorie/low protein diet (LP) on nutritional status and metabolic complications related to the progression of kidney damage in these patients.

METHOD

This pilot study had an open label randomized-controlled design (ClinicalTrials.gov Id: NCT05015647). Thirty-five patients were treated for six months with two different diets (LP = 17) and (NP = 18). Malnutrition was assessed by Malnutrition Inflammation Score and International Society of Renal Nutrition and Metabolism criteria. Renal function was assessed by creatinine and cystatin C based eGFR.

RESULTS

At the end of the study, Malnutrition Inflammation Score was improved in both LP and NP groups (respectively: 3 ± 3 versus 6 ± 1.5, P = 0.020 and 3 ± 2.5 versus 6 ± 2, P = 0.012), and prevalence of protein energy wasting syndrome decreased only in LP. LP group had higher eGFRcys-C (17 ± 6 versus 12 ± 4 mL/min/1.73 m2; P < 0.05), lower serum urea (105 ± 65 versus 138 ± 30 mg/dL; P < 0.05) and lower PTH (68 ± 10 versus 99 ± 61 ng/L; P < 0.05) than NP. Serum and urinary phosphorous did not change while FGF23-intact and FGF23 c-terminal increased in both groups (FGF23-intact in LP: 70[48;98] versus 126[90;410] pg/mL, P < 0.01 and in NP: 86[57;194] versus 143[119;186] pg/mL, P < 0.01; FGF23 c-terminal in LP: 77[30.3;112] versus 111[63;384] RU/mL, P < 0.01 and in NP: 142[56.6;175] versus 157[76.7;281] RU/mL, P < 0.01).

CONCLUSION

LP diet has a favorable impact on nutritional status as much as NP diet with possible greater benefits on the progression of kidney disease and some of its metabolic complications.
MO577: The Role of Nutritional Therapy in CKD: Low Protein Diet VERSUS Mediterranean Diet, A Multicentric Study
Authors: Gembillo Guido , Calabrese Vincenzo , Siligato Rossella , Longhitano Elisa , Metro Daniela , Santoro Domenico
Published: May 2022

BACKGROUND AND AIMS

Nutritional therapy exerts a positive role for the prevention, progression and treatment of chronic kidney disease (CKD) and cardiovascular diseases. An individualized, stepwise approach is essential to guarantee high adherence to nutritional patterns and to reach therapeutical goals. Which is the best dietary regimen is still a matter of discussion.

METHOD

We performed an observational, multicentric study on 75 non-diabetic patients with CKD stage III-IV with a one-year follow-up (Table 1). We compared two of the most used dietary regimens for CKD patients: low protein diet (LPD) and the Mediterranean diet (MD).

RESULTS

Our results showed a significant renal function preservation in LPD compared with the MD cohort patients. An unadjusted model with a general linear model for repeated measures demonstrated a MD significant effect on creatinine clearance compared with LPD with an estimate marginal mean of −9.98 mL/min (95% CI: −15.6 to −4.3). Adjusted model for age, BMI and sex confirmed this significance in between-group in the joint mean difference (9.34, 95%CI: −15.44 to −3.24) (Fig. 1).

CONCLUSION

An adequate dietary strategy is of pivotal importance in the treatment of chronic diseases like CKD. Our study aimed to bring more evidence in the contest of nutritional therapy, demonstrating that beside the central importance of the MD for selected patients, LPD seems to have superior therapeutical benefits on kidney function preservation.
MO578: UBE-1099, A Novel Non-Covalent Keap1-NRF2 Inhibitor, Protects Against Renal Ischemia-Reperfusion Injury
Authors: Ogi Sayaka , Sunamoto Hidetoshi , Fukiya Hirohiko , Nara Futoshi , Onuma Kazuhiro
Published: May 2022

BACKGROUND AND AIMS

Bardoxolone methyl is a covalent Kelch-like ECH-associated protein 1 (Keap1) inhibitor that induces nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Bardoxolone methyl improved glomerular filtration rate (GFR) in clinical trials for chronic kidney disease (CKD), although the mechanism remains unclear. Bardoxolone imidazole, an analog of Bardoxolone methyl suppressed tubular damage in a mouse acute kidney injury (AKI)-to-CKD model of unilateral ischemic reperfusion without contralateral nephrectomy (U-IR). Here, we evaluated the renal protective effect and the mechanism of a novel non-covalent Keap1 inhibitor, UBE-1099 in the U-IR mice.

METHOD

A fluorescence polarization-based (FP) assay and NQO1 activity-induction assay were performed to evaluate an inhibitory activity of Keap1 inhibitors. An U-IR mice were orally administered either the inhibitor (30 mg/kg, 10 mL/kg, once a day) or vehicle for 14 days and efficacy was evaluated. The whole transcriptome analysis with RNA-seq was conducted with whole kidney of the U-IR mice after 14 days treatment. A pathway analysis of the significantly differentially expressed genes detected was performed using Ingenuity Pathway Analysis (IPA) software.

RESULTS

UBE-1099 directly inhibited the interaction of Nrf2-Keap1 and induced NQO1 activity. The oral administration of UBE-1099 to the U-IR mice upregulated NQO1 expression in the kidney. UBE-1099 inhibited the decline in GFR and renal weight and significantly improved tubular damage and atrophic lesions in the U-IR model as effective as CDDO-Im without body weight loss. In addition, UBE-1099 significantly decreased the number of macrophages in the kidney.

CONCLUSION

A novel non-covalent Keap1 inhibitor, UBE-1099 improved the atrophic pathology, reduced tubular damage and inflammation resulting from Nrf2 activation in the U-IR mice. The compound has been suggested to be a promising drug for the renal diseases. Currently, the mechanism of action in improving renal function is being analyzed through RNA-seq analysis.

Figure:
MO592: Evolution of Body Composition During a Intradialysis Exercise Program Using Virtual Reality
Authors: Cana Poyatos Alicia , Segura-Ortí Eva , Vercher Narbona Verónica , Antonio Gil-Gómez José , José Martínez-Olmos Francisco , Valtueña-Gimeno Noemi , Benavent Caballer Vicente , Toquero Correa Marina , Garcia-Maset Rafael , Royo-Maicas Pilar , Garcia-Testal Alicia
Published: May 2022

BACKGROUND AND AIMS

There are few follow-up studies on the composition body by bioimpedance in exercise programs in different population. It is necessary to know if the body composition measured by bioimpedance change during a intradialysis exercise program using virtual reality. The aim is to determine evolution of body composition of patients on intradialysis exercise program using virtual reality.

METHOD

This is a subanalysis in a clinical trial with intradialysis exercise intervention. Intradialysis exercise consists in a video game adapted to dialysis: Treasure hunting. It is a nonimmersive virtual reality game in which the patient must catch some objectives avoiding obstacles by moving the lower limbs. The exercise lasts from 20 to 40 min. Intensity was checked through the rate of perceived exertion. The body composition is determined by multi-frequency stereoscopic bioimpedance . The study started in September 2019 (Baseline) but due to the COVID-19 pandemic it was paused for 1 year and started again in March 2021 (Restart). Body composition was determined basal, at 3th and 6th month in program. This study is funding from Programa Estatal de I + D + i Orientada a los Retos de la Sociedad, del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020 del Gobierno de España.

RESULTS

This is an open recruitment study, 49 patients have been recruited as of September 2021, mean (SD) age 72 (13) years, females 18. About 17 patients dropped out (16 of them don’t return after the pandemic start). To date, 32 patients are in exercise program.

Paired data analysis showed no difference in normohydrated weight, lean tissue index, or overhydration. The fat tissue index increased significantly (P 0.04) during the pause period in the first year of the pandemic. At the time of this communication, only 12 patients have completed 6 months of the program. We await the evolution of all included patients to report results at 6 months.

CONCLUSION

The evolution of body composition measured by bioimpedance during an intradialysis exercise program by virtual reality did not show relevant changes. Considering our results and those of previous studies, it’s possible that bioimpedance is not a very sensitive test to evaluate an intradialysis exercise program in the short to medium term. Longer and larger studies are needed.
MO596: Intradialysis Exercise at the Beginning Versus end of the Dialysis Session: Effect on the Dialysis Dose
Authors: Ortiz Sáez Natalia , Segura-Ortí Eva , Antonio Gil-Gómez José , Cana Poyatos Alicia , Garcia-Maset Rafael , Rico-Salvador Inmaculada , José Martínez-Olmos Francisco , Valtueña-Gimeno Noemi , Benavent Caballer Vicente , Toquero Correa Marina , Jose Cañada Martínez Antonio , Garcia-Testal Alicia
Published: May 2022

BACKGROUND AND AIMS

There is controversy over whether intradialysis exercise has an effect on the dialysis dose. Moreover, theoretical models indicate that intradialytic exercise performed at the end of session may have a beneficial effect in postdialysis rebound. Perhaps this effect of exercise at the end of dialysis can improve the dialysis dose. The aim in this study is to determine the effect of intradialysis exercise on dialysis dose, as well as its effect on dialysis dose when performed during the first two or the last two hours of dialysis session.

METHOD

This study is a randomized clinical trial. Patients were randomized to exercise in the first (Start group) or last two hours (End group) of dialysis session. Intradialysis exercise consists of a video game adapted to dialysis: Treasure hunting. It is a non-immersive virtual-reality game in which the patient must catch some objectives avoiding obstacles by moving the lower limbs. The exercise session lasts from 20 to 40 min. Intensity was checked through the rate of perceived exertion. Dialysis dose was measured through Kt/V single pool (Kt/V sp), urea reduction percentage (URP), KT and dialisance Kt/V (Kt/Vds) in the short period between dialysis, midweek. These was determined in two different weeks, in one week patients were at rest and in the other week patients did intradialysis exercise. The lean tissue mass (LTM) was determined by multi-frequency stereoscopic bioimpedance. This study is funding from Programa Estatal de I + D + i Orientada a los Retos de la Sociedad, del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020 del Gobierno de España.

RESULTS

This is an open recruitment study, at the time of this communication 29 patients are active, 14 in Start group and 15 in End group. Age mean (SD) 74 (12) years, males 17, Charlson's Index 8.1 (2.24), time on hemodialysys treatment 55.72 (57.67) months, central venous catheter 8, HDFOL 8. A mixed analysis of repeated measures has been developed with each measure of dialysis dose as the dependent variable (Kt/Vsp, URP, KT and Kt/V ds) and independent variables: group (Start versus End), duration of exercise session and LTM. There were no differences in dialysis dose between Start and End groups. Duration of exercise session significantly increased the dialysis dose (Kt/Vsp + 0.015, P = 0.007, URP + 0.23 P = 0.01 and Kt/V ds + 0.015, P = 0.01).

CONCLUSION

The time of the dialysis session in which physical exercise is performed does not influence the dialysis dose. Longer duration of the intradialysis exercise session increases the dialysis dose.
MO624: The Relationship Between Renal Tubular Epithelial Cell Necroptosis and The Severity of Diabetic Nephropathy
Authors: Yu Qi , Chen Ying , Qu Lei , Wu Wenyan , Huang Shuo , Wang Hui , Wang Suxia , Liu Gang , Yang L I
Published: May 2022

BACKGROUND AND AIMS

Diabetic nephropathy (DN), a common complication of diabetic patients, usually contributes to end-stage renal failure. Accidental cell death (ACD) and regulated cell death (RCD) cause renal cell loss and deteriorate renal function during the progression of DN. MLKL is the executor of necroptosis, a major form of RCD. The multimer of phosphorylated MLKL (p-MLKL) gather at the cell membrane and form the leaking pores, performing the last step of necroptosis. This study aims to study the relationship of p-MLKL expression and the disease severity in DN patients, providing promising treatment target.

METHOD

A total of 30 patients who diagnosed with DN clinical-pathologically in the Peking University First Hospital from January 1998 to August 2018 were enrolled (excluding DN with primary or secondary glomerular diseases, DN combined with thrombotic microangiopathies and small vasculitis). p-MLKL were stained on renal biopsy kidney sections by immunohistochemistry. Image-Pro Plus 6.0 software (IPP) was used to analyze the expression of p-MLKL on 10 randomly taken images for each patient. The relationship between p-MLKL expression and clinical-pathological parameters was explored. Clinical parameters of plasma creatinine, peak plasma creatinine during renal biopsy period, estimated glomerular filtration rate (eGFR) were used. DN pathological changes contained: (i) glomerular lesions, (ii) arteriole lesions (iii) tubular lesions and (iv) tubules chronic interstitial lesions.

RESULTS

Compared with normal control, the positive expression of p-MLKL could be detected in the renal tubular interstitium of patients with DN. However, no p-MLKL positive signal was seen in the glomeruli. Patients with p-MLKL positive signals accounted for 73.33% (22/30) of the enrolled patients. Among the 30 patients, the value of p-MLKL kidney tissue IOD (integrated optical density) was positively correlated with peak serum creatinine (r = 0.373, P = 0.042), the pathological score of spherical sclerosis (r = 0.364, P = 0.048) and tubular brush border (TBB) loss (r = 0.363, P = 0.049).

CONCLUSION

The expression of necroptosis marker p-MLKL was significantly correlated with the clinical-pathological changes of DN patients. Its role in the progression of DN deserves further exploration.
MO628: A Clinical Score for Identifying Non-Diabetic Nephropathy in Patients with Diabetes and Kidney Disease
Authors: Bermejo Garcia Sheila , Agraz Irene , Vergara Ander , Jose Soler Romeo Maria
Published: May 2022

BACKGROUND AND AIMS

Between 50% and 60% of diabetics with renal involvement have nondiabetic nephropathy (NDN). Renal biopsy is crucial for renal diagnosis that includes diabetic nephropathy (DN), NDN or mixed form. The objective of the current study is to provide a tool in the daily clinical practice through a predictive model of NDN that is clue for the indication of renal biopsy.

METHOD

Observational, retrospective and multicenter study was undertaken of the pathological results of kidney biopsies in patients with diabetes from 2002 to 2014. A logistic regression analysis and the probability of presenting NDN was calculated using a punctuation score.

RESULTS

The cohort of 832 patients includes 621 men (74.6%), median age 61.7 ± 12.8 years, creatinine 2.8 ± 2.2 mg/dL and proteinuria 2.7 (1.2–5.4)g/24 h. Time of evolution of diabetes was 10.8 ± 8.6 years. 26.6% (n = 221) of patients presented diabetic retinopathy, 18.8% (n = 156) peripheral vasculopathy and 17.7% (n = 147) ischemic heart disease. A total of 288 patients (34.6%) presented microhematuria. A total of 39.5% (n = 329) presented DN, 49.6% (n = 413) NDN and 10.8% (n = 90) mixed forms.

In the multivariate analysis, age (OR: 1.03; 1.01–1.04; P < 0.001), absence of microhematuria (OR: 0.6; 0.4–0.86; P = 0.005), absence of diabetic retinopathy (OR: 3.97; 2.7–5.82; P < 0.001) and absence of peripheral vasculopathy (OR: 1.61, 1.03–2.52, P = 0.038) were identified as independent risk factors for NDN. A ROC curve with an area under the curve of 0.724 was obtained. A predictive model obtaining a score (see Figure 1) for each variable and finally a NDN prediction score was performed. In our new score, the number increased as increased the probability of NDN.

CONCLUSION

In our study, ∼66% of biopsied patients with diabetes presented NDN. Microhematuria, absence of diabetic retinopathy, absence of peripheral vascular disease and older age were identified as independent risk factors for NDN. We obtained a score that increased as increased the probability of NDN. This could be in a next future a useful tool for renal biopsy indication in patients with diabetes and kidney disease.