bluuebunny/crossref_metadata_2025 huggingface dataset:
MO527: The Active Ingredient in the Nuphar Lutea Plant, 6,6′: Dihydroxythiobinupharidine (DTBN) Ameliorates Kidney Fibrosis, Inflammation and Anemia in a Mouse Model of Chronic Kidney Disease (CKD)
Authors: Khalilia Jannat , Landau Daniel , Arazi Eden , Gopas Jacob , Segev Yael
Published: May 2022

BACKGROUND AND AIMS

EPO resistance and iron deficiency in CKD-related anemia are associated with an increase in inflammatory cytokines associated with the innate immune response, such as IL-6, IL-1 and TNF-α. Recently (Bandach et al. Sci Reports 2021) we reported that kidney fibrosis and anemia of CKD can be worsened or relieved when IL1 effects are enhanced or inhibited respectively.

The Water lily (Nuphar lutea) plant has been widely used as a traditional remedy for the treatment of rheumatism, scars, pain and more. Gopas, Golan-Goldhirsh et al. (Cancer Biology Therapy 2009) extracted an active ingredient from the family of nupharidines: 6,6′-Dihydroxythiobinupharidine (DTBN), which showed anti-inflammatory properties, mainly through the inhibition of NF-κB. The purpose of this study was to test the effects of DTBN in a mouse model of CKD-associated anemia.

METHOD

8 weeks old male C57BL/6 mice were divided into three groups: control, CKD (induced by adenine diet) and CKD-DTBN. CKD groups were injected with saline-DMSO or 30 µg DTBN, every 2 days and sacrificed after 3 weeks from dietary intervention.

RESULTS

Serum urea and kidney TGFβ mRNA were significantly decreased in CKD- DTBN versus CKD. Kidney histology in CKD mice showed macrophage infiltration and renal fibrosis, which was ameliorated in CKD-DTBN.

A significant improvement in inflammation indices (blood lymphocytes, kidney and liver IL-6 and p-STAT3, liver CRP), as well as kidney immunoreactive NF-κB and F4\80, which were increased in CKD, were decreased in CKD-DTBN. CKD anemia indices (hemoglobin, hematocrit and red blood cell (RBC) count) significantly improved in CKD-DTBN. Kidney HIF-2α and EPO mRNA were significantly decreased in both uremic groups, but was unchanged in CKD- DTBN versus CKD. However, serum iron and transferrin saturation significantly increased in CKD-DTBN versus CKD.

CONCLUSION

Uremic mice treated with DTBN show improvement in kidney fibrosis, inflammation and anemia indices. Thus, DTBN may be a novel therapeutic alternative for CKD and its complications.
MO544: Outcomes Associated With use of Phosphate Binders in Persons With Chronic Kidney Disease Stages 4 and 5 in Spain
Authors: Molina Pablo , D. Molina Mariola , Bover Jordi , Gimenez-Civera Elena , Castro Alonso Cristina , Escudero Quesada Veronica , Pantoja Jonay , Jesus Carrero Juan , Luis Gorriz Teruel Jose
Published: May 2022

BACKGROUND AND AIMS

Use of phosphate binders among non-dialysis chronic kidney disease (ND-CKD) patients remains controversial, since clinically relevant benefits have not been fully demonstrated. The goal of this study was to determine patterns of phosphate binders use and its associated outcomes in ND-CKD patients.

METHOD

PECERA (Collaborative Study Project in Patients with Advanced CKD) is a 3-year, prospective multicentre, open-cohort study of 966 adult patients with non-dialysed CKD stages 4–5 enrolled from 12 centres in Spain. The end of the follow-up was December 2012. At baseline and every 6 months, demographics, comorbidities, treatments and serum biochemical parameters were collected. Patients who received treatment with calcium-based and calcium-free phosphate binders were compared with those who had not. In a prespecified statistical approach, we assessed the association of phosphate binders use with all-cause mortality using time-dependent Cox proportional hazards models.

RESULTS

Sevelamer was the only calcium-free based binder prescribed during the study. Overall, 515 (53%) patients received some form of binder, with most of them using calcium-based binders (n = 360, 37%) and a minority (n = 111, 11%) using exclusively sevelamer (n = 111, 11%) or a combination of the two (n = 44, 5%). After a median follow-up of 29 months (IQR 13–36 months) there were 181 deaths (19%). Crude overall all-cause mortality was significantly lower in patients receiving sevelamer, but not in those receiving calcium-based binders (Figure). After multivariate adjustment for age, weight, blood pressure, diabetes, comorbidity, vitamin D treatment, renal function and levels of albumin, calcium, phosphorous and PTH, treatment with sevelamer was independently associated with lower mortality [adjusted hazard ratio (HR), 0.44 (95% confidence interval (95% CI), 0.22–0.88); P = 0.02]. Use of calcium-based phosphate binders did not predict death.

CONCLUSION

The administration of sevelamer is associated with lower all-cause mortality in advanced ND-CKD patient. Clinical trials are warranted to clarify the risks and benefits of phosphate binders in this population.
MO545: Estimated Proximal Tubule Fluid Phosphate Concentration: An Early Marker of CKD-MBD?
Authors: Rotondi Silverio , Mazzaferro Sandro , Pasquali Marzia , Tartaglione Lida , Tinti Francesca , Perrotta Adolfo
Published: May 2022

BACKGROUND AND AIMS

Chronic kidney disease (CKD) typically associates with mineral bone disorders (CKD-MBD), kidney damage progression and increased morbidity and mortality. CKD-MBD develops early in CKD and, if promptly detected, could receive therapeutic attention. However, early markers of CKD-MBD like fibroblast growth factor 23 (FGF23) and α-Klotho are not widely available in clinical practice. Recently, estimated proximal tubule fluid phosphate concentration (ePTFp) has been proposed as a novel early marker of MBD. In fact, in CKD patients, along with the progressive reduction of nephron number, FGF23 increments are necessary to reduce renal tubular phosphate reabsorption and to maintain phosphate balance. As a consequence, PTFp concentration per single nephron progressively increases, leading to renal tubular cells overload, interstitial inflammatory response and progression of kidney damage. For this reason, PTFp concentration could represent an early marker of CKD-MBD.

OBJECTIVE

To evaluate the relationship between ePTFp and early markers of MBD in patients with CKD stage G2–4.

METHOD

In CKD patients stage G2–4, we evaluated serum FGF23, α-Klotho, parathyroid hormone (PTH) and ePTFp [ePTFp = (phosphaturia/creatininuria) x creatininemia x 3,33]; 30 healthy subjects (age 40 ± 5 years) were the control group for normal value of ePTFp.

RESULTS

In 68 CKD patients (age 58.9 ± 15.6 years eGFR 45 ± 21 mL/min), ePTFp averaged 2.4 ± 1.3 mg/mg which was significantly higher than in the control group (ePTFp = 1.2 ± 0.5; P < 0.01). ePTFp increased progressively along with the increasing CKD stages (stage 2: 1.6 ± 0.6; stage 3: 2.3 ± 0.9; stage 4: ± 1.5; P < 0.001) with values significantly higher than the control group since CKD stage 2 (ePTFp: Control group = 1.2 ± 0.5 versus stage 2 = 1.6 ± 0.6; P < 0.05). ePTFp showed a positive correlation with FGF23 (r: 0.69; P < 0.001) and PTH (r:0.310; P < 0.05) and a negative correlation with α-Klotho (r: −237; P < 0.05) and eGFR (r: −647; P < 0.001).

CONCLUSION

Our data showed early and progressive increments of ePTFp in CKD patients since CKD stage 2. These increments are paralleled by increased FGF23 and PTH and decreased α-Klotho, suggesting reciprocal pathophysiologic dependence. Accordingly, ePTFp could represent a surrogate of renal tubular cells phosphate overload, indicative of CKD-MBD development. ePTFp can be easily obtained in everyday clinical routine and could represent a reference to make therapeutic choices (e.g. dietary phosphate control).

In conclusion, ePTFp could identify patients at risk of developing the CKD-MBD maladaptive response with increased risk of kidney damage progression.
MO549: Chronic Kidney Disease and Vascular Calcification Result in Inflammation and Dysfunction of Colon Tissue in Rats
Authors: Bartochowski Piotr , Muyor Karen , Laget Jonas , Cortijo Irene , Castel Laura , Duranton Flore , Bornes Stéphanie , Argiles Ciscart Angel , Jover Bernard , Cordaillat - Simmons Magali , Gayrard Nathalie
Published: May 2022

BACKGROUND AND AIMS

Chronic Kidney Disease (CKD) results in modifications in the activity and/or structure of many organs. One of them is the intestine. Intestinal barrier dysfunction may result in turn, in gut leakage and aggravation of the course of CKD. The interaction between the colon and kidneys may be relevant for both, the kidneys as well as the colon. This study aimed to evaluate the impact of CKD and vascular calcification on colon tissue and function.

METHOD

Sprague–Dawley rats underwent 5/6 nephrectomy (SNx, n = 18) or sham surgery (Control, n = 6). A total of 8 weeks after surgery, SNx rats were divided into three groups: normal chow (SNx, n = 6); high phosphate (1.2%) with high vitamin D; 5 days/week at a dose of 0.1 µg/day (SNx-VC1, n = 6) or 0.4 µg/day (SNx-VC2, n = 6) to induce vascular calcification. Four weeks after dietary intervention, rats were sacrificed and colon tissue was sampled for analysis. The inflammation of colon tissue was scored on haematoxylin-eosin staining (score 1–4) and the presence of macrophages was quantified by immunostaining with CD68 antibody. The mucus production was also quantified by Alcian blue staining.

RESULTS

Haematoxylin-eosin staining showed increased inflammation in SNx-VC2 rats (2.47 ± 0.26) compared with the Control group (1.52 ± 0.14) (P < 0.05), Figure 1. The number of CD68 + cells did not differ between groups. Compared with the Control group (19.87 ± 2.20), mucus production was reduced significantly in SNx-VC2 rats (11.98 ± 2.61) (P < 0.05) and close to significance (P < 0.0505) in SNx-VC1 (13.21 ± 1.22).

CONCLUSION

CKD was associated with a decrease in mucus production and an increase in inflammation in colon tissue. These changes are more marked in the animals with associated vascular calcification (high vitamin D and high phosphate diet).
MO562: Prevalence and Determinants of Predialysis Dietitian Follow-Up-Results From the Brazilian Dialysis Registry
Authors: Nerbass Fabiana , Lima Helbert , Merege Vieira Neto Osvaldo , Sesso Ricardo , Lugon Jocemir
Published: May 2022

BACKGROUND AND AIMS

There are lacking of data regarding predialysis dietitian follow-up of CKD patients considering large populational datasets. We aimed to evaluate the prevalence and socio-demographic determinants of predialysis dietitian follow-up in a large cohort of Brazilian dialysis patients.

METHOD

We evaluated retrospectively data from all incident adult dialysis patients included in the Brazilian Dialysis Registry from January 2011 to September 2021. Predialysis dietitian follow-up was said to be present when a period >6 months of dietitian care was reported. Gender, age, skin color, education, body mass index, chronic kidney disease (CKD) etiology, first chronic dialysis program, healthcare provider and geographic regions were considered in the logistic regression model.

RESULTS

A total of 10 382 patients met the inclusion criteria and 1254 (12.1%) reported predialysis dietitian follow-up, and most of them referred by nephrologist (94.2%). The independent determinants of dietitian follow-up were older age, white skin color, higher education level, not having diabetes, living in North/Northeast and South (compared with Southeast), and having a nonpublic healthcare provider. When considered only patients with predialysis nephrologic care, higher education, hemodialysis as the first dialysis modality and living in the North/Northeast and South regions (compared with Southeast) were associated with dietitian follow-up.

CONCLUSION

Predialysis dietitian follow-up for more than 6 months in a country in which the public health system is the main dialysis provider is still very low. The nephrologist is pivotal for referral to dietitians but socioeconomic factors also seem to play a role in this regard.
MO573: Diet Quality Components and Gut Microbiota of Peritoneal Dialysis Patients
Authors: Ishikawa Ramos Christiane , S. Andrade Laila , R. Teixeira Renata , Hoffmann Christian , Cuppari Lilian
Published: May 2022

BACKGROUND AND AIMS

Diet has been recognized as an important determinant of microbiota composition. In CKD, nutrients such as fiber and protein have been shown to influence the microbiota profile. However, since nutrients are not ingested in isolation, the overall assessment of diet, reflecting the synergy of nutrients, may potentially modify the relationship between the diet and gut microbiota. Therefore, our aim was to evaluate whether the quality of diet and its components associate with alpha diversity of gut microbiota and phyla composition in peritoneal dialysis (PD) patients.

METHOD

In this cross-sectional study, patients undergoing automated PD for at least 3 months, aged 18–75 years and clinically stable were enrolled. Those who were using prebiotics, probiotics, symbiotics and antibiotics within a period of 30 days before the study were not included. Participants received sterile materials to collect the feces sample and were instructed to keep it refrigerated and bring to the clinic within a period of 12 h. To evaluate α-diversity and phyla microbial profile, 16S ribosomal DNA was PCR-amplified and sequenced on an IlluminaMiSeq platform. The diet quality index (DQI), validated for the healthy Brazilian population, was calculated from a 3-day food record. This index is based on the energy density of 11 components (sugars and sweets; beef and pork; refined grains and breads; animal fat; poultry, seafood and eggs; whole grains, breads, tubers and roots; fruits; non-starchy vegetables; legumes and nuts; milk and dairy products and vegetable oils). Each component is scored from 0 to 5 or 10, and a final score ranged from 0 (worse) to 100 (better) is obtained.

RESULTS

Thirty-seven patients were included [52.4 ± 13.7 years; 54% men; 70% with diabetes; PD vintage 18.0 (5.0–46.5) months]. The distribution of gut microbiota's phyla is presented in Figure 1. Mean DQI was 47.8 ± 12.2, indicating that most of the patients (76%) were in an intermediate quality of diet. DQI was not associated with age, gender, PD vintage, BMI or the presence of diabetes. As can be seen in Table 1, although no association was found between DQI total score with the gut microbiota α-diversity indexes, the energy density of some components of DQI tended or was associated with those indexes. DQI total score was also not associated with any specific phyla, but the energy density of the components ‘sugars and sweets’ was negatively associated with Bacteroidetes (r= −0.389, P = 0.017) and positively with Firmicutes (r = 0.468, P = 0.003), while the inverse was observed for ‘legumes and nuts’, Bacteroidetes (r = 0.358, P = 0.029) and Firmicutes (r = −0.333, P = 0.044).

CONCLUSION

A healthier diet, with a larger amount of ‘whole grains, breads, tubers and roots’ and ‘legumes and nuts’ and, lower in ‘sugars and sweets’, seems to contribute to the α-diversity or Bacteroidetes colonization in peritoneal dialysis patients.
MO574: Use of The Highly Hypoproteic Supplemented DIET in the Therapy of Patients With Advanced Chronic Renal Failure
Authors: Cecchi Sofia , DI Stante Silvio , Baldini Federica , DI Luca Marina
Published: May 2022

BACKGROUND AND AIMS

A low-protein diet has shown to be effective in slowing the progression of chronic kidney disease (CKD) and allows a later start to dialysis treatment [1]. However, the very low protein diet (0.3 g/kg/day) supplemented with aminoacids and ketoanalogues (sVLPD), but it is difficult to implement for the high number of tablets to take [2]. In order to increase compliance, we decided to prescribe balanced sVLPD to all patients with eGFR < 15 mL/min or with specific indications (e.g. renal transplantation program and conservative therapy) supplemented with amino acids without ketoanalogues.

The aim of this approach was to evaluate the efficacy, compliance and safety of the personalized sVLPD, developed by a trainer dietitian mainly focused on nitrogen, acid–base, hydroelectrolytic balances and malnutrition [3].

METHOD

During last 2 years, 91 patients were initiated into diet therapy. They were 58.2% males, all hypertensive, 33% diabetic, 65.9% on EPO therapy. At the beginning and quarterly were detected characterizing blood chemistry tests, anthropometrich measures and body composition (with impedance analysis) in all the patients.

RESULTS

The average observation time was 9.1 ± 5.1 months. Laboratory tests have shown improvement in mean azotemia (Fig. 1) values (144.2 ± 44.2 versus 94.6 ± 19.7 mg/dL; T0 versus T18; P < 0.005), phosphorus (4.4 ± 0.9 versus 4 ± 0.7 mg/dL; T0 versus T15; P < 0.05), bicarbonate (24.6 ± 5.7 versus 27 ± 4.7 mmol/L; T0 versus T6, P < 0.005); eGFR (Fig. 2) remained stable during follow-up (12.1 ± 3.6 versus 12.4 ± 4 mL/min; T0 versus T18; NS). Hemoglobin, uricemia, serum albumin, glycemia (downward trend NS), potassium, sodium, chlorum, calcium, magnesium, pH and lipids remained within normal values; average TSAT always >20% and average ferritin >100 mg/dL.

The body mass index (BMI) was always on average within the normal range with an increase in patients with adequate hydration and lean mass (Fig. 3); improvement trend (NS) of the PAS, PAD within limits. Reduction of effective protein intake (0.85 ± 0.29 versus 0.61 ± 0.20 g/kg/die; T0 versus T9 P < 0.05). During the observation, 8 deaths occurred (7 patients over 85 years old), 10 admissions on dialysis peritoneal, 4 in hemodialysis and 3 pre-emptive transplants from living donors. To date, we estimated that the initiation of dialysis was delayed on average by 8.7 months/patient.

CONCLUSION

The approach we have adopted allowed to achieve good adherence to the diet, a slowdown in the progression of the CKD, improve and maintain good metabolic control, electrolytic and acid–base and body composition. A personalized sVLPD resulted in delayed starting of dialysis treatment, allowing patients to continue pre-dialysis education-program, increasing the choice for home peritoneal dialysis.
MO584: Effect of Probiotic Supplementation on Endothelial Injury and Inflammation Biomarkers Among Patients with Chronic Kidney Diseases on Hemodialysis
Authors: Érica Maria Rodrigues de Araújo , Gdayllon Cavalcante Meneses , Alice Maria Costa Martins , Elizabeth De Francesco Daher , Geraldo Bezerra Da Silva Junior
Published: May 2022

BACKGROUND AND AIMS

The use of probiotics in chronic kidney disease (CKD) is hypothesized to contribute to decrease inflammation and endothelial injury, thus preventing cardiovascular disease. The aim of this study was to investigate the effects of probiotics supplementation on biomarkers of endothelial injury (syndecan-1) and inflammation (C-reactive protein), as well as overall biochemical parameters of patients with CKD on hemodialysis.

METHOD

This is a double-blind, randomized clinical trial, with 80 patients with CKD on hemodialysis in a specialized healthcare clinic at Fortaleza, northeast Brazil, from February to June 2021, of which 40 were allocated to the placebo group and 40 were allocated to receive the probiotics supplementation. The supplementation consisted of the following encapsulated Gram-positive bacteria: Lactobacillus Plantarum A87, Lactobacillus Rhamnosus, Bifidobacterium bifidum A218 and Bifidobacterium Longum A101 in a concentration of 1 billion colony-forming unity (CFU), totaling 4 billion CFU in each capsule. The dosage consisted of ingesting 1 capsule of the supplement daily, after dinner, for 3 months. Pre-dialysis blood collections were performed before and after the treatment period. The ELISA technique was applied to measure the serum syndecan-1 biomarker and PCR. Total blood count, fast glucose and body mass index (BMI) were also investigated.

RESULTS

About 80% of the recruited patients in the study group completed the trial. When compared with the placebo group, the group that received the probiotics had a significant reduction in syndecan-1 levels (184.3 ± 106 versus 239.48 ± 113.6 ng/mL; P = 0.005) and PCR (1626 ± 617.5 versus 898 ± 313 ng/mL; P = 0.001), increase in hematocrit and hemoglobin, respectively (33.5 ± 5.1 versus 37.1 ± 5.4; P = 0.011; 11.1 ± 1.8 versus 12 ± 1.5; P = 0.036) and decrease in fast glucose levels (146.5 ± 74.6 versus 162.7 ± 112.6 mg/dL; P = 0.026). The BMI classifications did not present significant differences between the groups.

CONCLUSION

Probiotics supplementation for patients with CKD on hemodialysis evidenced benefits, including a decrease in endothelial injury biomarker (syndecan-1) and inflammation (PCR), as well as improvement in biochemical parameters (hematocrit/hemoglobin and fast glucose). Further studies are required to investigate long-term effects of probiotics among CKD patients, including all stages of the disease.
MO593: Study of Cardiopulmonal Parameters in Patients with CKD During Renal Rehabilitation
Authors: Saipova Durdona , Egamberdieva Dano
Published: May 2022

BACKGROUND AND AIMS

Chronic kidney disease is a global health problem in which patients’ performance decreases as renal dysfunction progresses. However, no evidence-based lifestyle recommendations for the primary prevention of CKD have yet been developed.

The aim of the study was to study cardiorespiratory parameters in patients with CKD during aerobic exercise of light and moderate intensity.

METHOD

The study included 130 patients with CKD stages 2–3, aged 45– 65 years, whose average age was 58.7 ± 0.73 years, and the proportion of women in the sample was 47.7%. All patients underwent determination of urea, serum creatinine, measurement of blood pressure and heart rate. To determine exercise tolerance, a cardiorespiratory exercise test was performed. Patients of the main group, depending on the initial cardiorespiratory parameters, were divided into 2 subgroups: 1 subgroup—67 patients who performed light intensity exercises; 2 subgroups—33 patients who performed medium-intensity exercises for 12 weeks 3 times a week. The choice of training intensity was made according to the level of individual or subjective perception of the load and was calculated using the approximate heart rate. The control group consisted of patients with CKD stages 2–3 who did not perform physical training.

RESULTS

When studying the indicators of systolic and diastolic blood pressure before and after physical training, moderately severe arterial hypertension was revealed. After 12 weeks of physical training in the group with medium-intensity training in patients, the blood pressure level significantly decreased compared with the baseline values ​​(SBP from 147 mm Hg to 129 mm Hg, DBP from 99 mm Hg) up to 79 mm Hg, P < 0.001), while in the group with physical training of light intensity this indicator practically did not change (SBP decreased from 147 to 138 mm Hg, DBP 93 to 89 mm Hg, respectively). A hypertensive reaction to physical activity was also confirmed, with positive dynamics at the stages of physical rehabilitation.

After 12 weeks, except for the VO2 in VT, the HR in VT and the RCP, all other cardiopulmonary parameters increased in the main group (P < 0.05). The maximum oxygen consumption in the study group before the start of training peak VO2 (mL/kg/min) was 22.8 ± 0.3 after training 26.1 ± 0.4 (P < 0.05). In the control group, it was 23.6 ± 0.8 and 24.2 ± 0.7, respectively. In addition, the dynamics of the indicator of maximum oxygen consumption VO2 peak in the main group was significantly higher compared with the control group and with the baseline values(P < 0.001).

CONCLUSION

Training intensity is essential for improving cardiorespiratory parameters in patients with CKD. When choosing the intensity of training, it is necessary to take into account the baseline cardiorespiratory parameters. The use of physical training in combination with standard therapy improves cardiorespiratory parameters in patients with CKD.
MO603: Effects of Intradialytic Bicycle Ergometer Exercise on Inflammation Transcription Factors in Patients with Chronic Kidney Disease
Authors: Mafra Denise , de Brito Jessyca S , Borges Natalia A , V. Vargas Reis Drielly C M , Santos Da Silva Greicielle , Fonseca Larissa S , Ribeiro Marcia M , Chermut Tuany R , Paiva Bruna R , Cardozo Ludmila , Oliveira Leonardo C , Moura Mariana , Capistrano Estelina S M
Published: May 2022

BACKGROUND AND AIMS

Oxidative stress and inflammation are involved in the pathophysiological mechanisms in patients with chronic kidney disease (CKD) on hemodialysis (HD). In this context, the therapeutic potential of targeting the gene transcription factors associated with these mechanisms has been studied; for instance, nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of antioxidant responses and, nuclear factor κappa B (NF-κB) that promotes the inflammatory response. However, the effects of physical exercise on the modulation of these factors are under investigation in CKD patients. Therefore, the aim of the present study was to evaluate the effects of an intradialytic aerobic exercise training program on the expression of transcription factors (Nrf2 and NF-κB) in patients with CKD on HD.

METHODS

This is a longitudinal, randomized clinical trial with a washout period and crossover performed with 18 patients randomized into two groups: Exercise (individualized intradialytic aerobic exercise on an adapted stationary exercise bike) three times per week for 3 months and control (without exercise). After the washout period (1 month), the exercise group became the control, and the other group performed the exercises for another 3 months. Peripheral blood mononuclear cells (PBMCs) were isolated, and quantitative real-time PCR analysis was performed to evaluate Nrf2, NF-kB and NAD(P)H: quinone oxidoreductase-1 (NQO1) mRNA expression. The plasma levels of inflammatory cytokines, tumour necrosis factor-α (TNF-α), C-reactive protein (CRP) and interleukin-6 (IL-6) were evaluated by ELISA.

RESULTS

Eighteen patients [11 men, 44.1 ± 8.4 years, 17.3 (6.6–124) months on HD] completed all the study. The obtained data revealed that the intervention did not affect the mRNA expression of Nrf2, NQO1 and NF-κB (Table 1). Also, TNF-α levels were not changed. However, IL-6 showed a tendency to decrease after the exercise intervention (P = 0.054).

CONCLUSION

Three months of intradialytic aerobic exercise were insufficient for modulating the transcription factors associated with antioxidant activity (Nrf2 and NQO1) and inflammation (NF-κB) in patients with CKD.
MO612: Relationship of Renal Timp-1, Stat3 and Inflammatory Factors in Diabetes
Authors: Manzeger Anna , Mikone Krisztina , Mozes Miklos , Stepanova Ganna , Kokeny Gabor
Published: May 2022

BACKGROUND AND AIMS

The balance of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMP) is disrupted in diabetic nephropathy and renal TIMP-1 overexpression is observed in both animal experimental models and human biopsies. The STAT3 transcription factor participates in several inflammatory pathways; however, its interaction with TIMP-1 in diabetes remains unknown. We aimed to investigate the progression of nephropathy and its relationship to renal STAT3 activation in type-1 diabetic TIMP-1 knock-out (KO) mice.

METHOD

Diabetes was induced in 6-week-old male TIMP-1 KO (DM-KO, n = 8) and C57Bl6 wild type (DM, n = 5) mice by intraperitoneal streptozotocin injections (50 mg/kg/day for 5 days). Control mice (CTL, n = 6) received citrate buffer injections. Eight weeks after onset of diabetes blood and urine chemistries, renal histology, renal mRNA and protein expression were assessed. Statistical significance was evaluated using Kruskal–Wallis test and Tukey post-hoc analysis.

RESULTS

Despite similar hyperglycemia, DM-KO mice developed significantly less proteinuria (P <0.01) and histologically milder glomerulosclerosis and tubular damage as compared with wild type DM mice. Kidneys of DM mice depicted 4-fold STAT3 phosphorylation, but DM-KO kidneys had similar values as CTL nondiabetic controls. DM kidneys also showed 20-fold CCL2, 10-fold C3 and 2.5-fold C4 overexpression, which in DM-KO kidneys remained all near control (CTL) levels.

CONCLUSION

Based on our results, we conclude that TIMP-1 influences the progression of diabetic kidney disease in mice not solely through the inhibition of MMP-s, but also by influencing the extent of renal inflammation via STAT3 phosphorylation. Therefore, TIMP-1 might emerge as promising future therapeutic target.

FUNDING

Hungarian Academy of Sciences BO/00 304/20/5, ÚNKP-21–5-SE-1.
MO615: The Lund Mets Rat, An Obese Type 2 Diabetic Preclinical Model, Develops Non-Alcoholic Steatohepatitis, Diabetic Nephropathy and Heart Failure with Preserved Ejection Fraction Under High Fat/Cholesterol/Fructose Diet
Authors: Briand Francois , Dubroca Caroline , Maupoint Julie , Brousseau Emmanuel , Sulpice Thierry
Published: May 2022

BACKGROUND AND AIMS

Beyond the glucose control, anti-diabetic drugs need to demonstrate benefits on metabolic comorbidities. An animal model that recapitulates obesity and type 2 diabetes (T2D) comorbidities [i.e. non-alcoholic steato-hepatitis (NASH), nephropathy and heart failure with preserved ejection fraction (HFpEF)] is still needed for preclinical drug development. To overcome this limitation, we evaluated the effects of a high fat/cholesterol/fructose (HFCF) diet in the Lund MetS rat, a congenic BBDR.cg-lepr.cp model generated by introgression of the Koletsky leptin receptor mutation into the BioBreeding Diabetes Resistant (BBDR) rat.

METHOD

17-week-old, male, lean control (ctrl) or Lund MetS obese T2D rats were fed a control chow (CC) diet or a HFCF diet, respectively for 8 weeks. Blood biochemistry was measured at 0, 4 and 8 weeks of diet. Kidney, heart and liver parameters were assessed at the end of the 8-week diet period.

RESULTS

Compared with ctrl, Lund MetS rats were obese (56% higher body weight) and diabetic with significantly higher %HbA1c (up to + 3%) and blood glucose levels (up to 3-fold higher) during the 8-week HFCF diet period. Significantly higher plasma insulin (up to 11-fold), total cholesterol (up to 5-fold), triglycerides (up to 8-fold), transaminases (up to 10-fold higher) levels were also observed in Lund MetS rats, as compared with ctrl. Hepatic total cholesterol, triglycerides and fatty acids levels were significantly higher in Lund Mets rats (14-, 7.3- and 6.7-fold higher as compared to ctrl, respectively). Liver histopathological scoring confirmed a NASH phenotype in Lund MetS rats fed the HFCF diet with strong liver steatosis, hepatic inflammation and portal to bridging fibrosis. Kidney function was substantially altered with a 60% decline in glomerular filtration rate and a 16-fold increase in urine albumin-to-creatinine ratio (both P < 0.0001 versus ctrl). Finally, echocardiography indicated diastolic dysfunction with significantly reduced E/A and greater E/e’ ratios, along with a preserved ejection fraction in Lund MetS rats, as compared with lean ctrl.

CONCLUSION

The present data demonstrate that the Lund MetS rat fed an HFCF diet that recapitulates the major metabolic comorbidities of obesity/T2D and may be a useful model for preclinical drug development.
MO623: Risk Factors of Diabetic Nephropathy Among Newly Detected Type 2 Diabetic Subjects: Preliminary Report from A Tertiary Care Hospital of Bangladesh
Authors: Abdur Rahim Muhammad , Humaira Habib Samira , Mohosin Ul Haque Wasim M D , Afsana Faria , Zaman Shahana , Iqbal Sarwar
Published: May 2022

BACKGROUND AND AIMS

Patients with type 2 diabetes mellitus may present with different macro- and micro-vascular complications including diabetic nephropathy. This preliminary study was designed to evaluate the risk factors for diabetic nephropathy among type 2 diabetic patients at the time of diabetes diagnosis.

METHOD

A case-control study was done at a tertiary care hospital in Dhaka, Bangladesh from January to September 2017. Adult (≥18 years), type 2 diabetic patients, who were detected as diabetic for the first time within the previous 3 months and who tested, at least, two urine samples for urine albumin-to-creatinine ratio (UACR), at least 6 weeks apart, within a 6-month period, were consecutively enrolled for the study. Pregnant ladies, patients with diagnosed kidney disease, patients having features of glomerulonephritis and systemic diseases including systemic lupus erythematosus and vasculitis, history of recent fever, urinary tract infection and menstruation were excluded. Patients having UACR ≥30 mg/g in at least two (out of 3, if tested) samples were taken as cases and those with UACR <30 mg/g were taken as controls. Data were analyzed by statistical package for social sciences (SPSS) version 20.

RESULTS

Total patients were 224 with female predominance (150, 67%). Fifty one (22.8%) patients had diabetic nephropathy (microalbuminuria = 47 and overt proteinuria = 4). Multivariate regression analysis revealed that hypertension {odds ratio (OR) = 3.71 [95% confidence interval (CI) 1.23–4.31], P = 0.003}, smoking [OR = 3.27 (95% CI 2.91–4.79), P = 0.003], family history of diabetes [OR = 2.31 (95% CI 1.84–3.14), P = 0.005] and diabetic nephropathy [OR = 3.34 (95% CI 2.40–4.97), P = 0.001], dyslipidaemia [OR = 2.31 (95% CI 1.98–3.91), P = 0.023], increased body mass index (BMI) [OR = 2.11 (95% CI 1.54–4.87), P = 0.001] and high glycated haemoglobin (HbA1c) [OR 3.21 (95% CI 1.71–5.97), P = 0.034] were significant risk factors for diabetic nephropathy.

CONCLUSION

Almost 23% of type 2 diabetic patients had diabetic nephropathy during diabetes diagnosis in this study and most patients had microalbuminuria. Presence of hypertension, dyslipidaemia, smoking, family history of diabetes and diabetic nephropathy, increased BMI and high HbA1c were significant risk factors for diabetic nephropathy among patients with type 2 diabetes at diagnosis.
MO625: Effects of Dietary Sodium and Protein Intake on Early DIP of GFR Levels in Subjects with Type 2 Diabetes Treated with SGLT2 Inhibitors
Authors: Gaudio Costanza , Colombi Claudia , Merciai Chiara , Seghieri Marta , Spatoliatore Giuseppe , Rosati Alberto
Published: May 2022

BACKGROUND AND AIMS

SGLT2 inhibitors (SGLT2i) are able to decrease proteinuria and slow down eGFR decline in DKD patients. The effect is mainly obtained by increase of natriuresis and glucose-induced osmotic diuresis, resulting in a reduction in intraglomerular pressure. These hemodynamic changes are beneficial in long-term period, but up to 28% of patients treated with SGLT2i experience an acute, usually transient, eGFR reduction of more than 10% [1]. Moreover, in some case, the decrease of eGFR can be more pronounced and compromise the maintenance of therapy. High sodium and protein intake can lead to intraglomerular pressure increase and predispose to a deeper fall of eGFR. We aimed at investigating whether measured creatinine clearance (CrCl) is a more sensitive method to detect the initial dip of GFR in patients with T2D treated with SGLT2i, and if dietary sodium and protein intake can influence the extent of the early change in GFR.

METHOD

Subjects with type 2 diabetes (T2D) were consecutively recruited among those referring to the inpatients of combined Nephrology and Diabetology clinic in years 2020–2021. Those eligible for treatment with SGLT2i were asked to collect 24-h urinary samples for sodium and urea determination, to estimate sodium and protein intake, respectively, before and 1, 3 and 6 months after treatment initiation.

RESULTS

At baseline, 27 patients (M 23/F 4; age 69 ± 7 years; BMI 28.2 ± 3.6 kg/m2; HbA1c 56 ± 16 mmol/mol) had a CrCl of 83.23 ± 25.52 mL/min/1.73 m2 (eGFR 67.32 ± 16.07), which dropped by 19% at month 1 (eGFR by 6%, although not significantly) and then increased to comparable baseline values at month 6. Exploring the potential correlation between changes in renal function and salt intake, ΔCrCl and baseline urinary sodium were inversely related at month 1 (r = −0.61; P <0.01), at month 3 (r = −0.51; P = 0.01) and month 6 (r= −0,48; P < 0.05) (Fig. 1). Likewise, an inverse correlation between ΔCrCl and baseline urinary urea (Fig. 2) was demonstrated at month 1 and 3 (r = −0.46; P <0.05 for both), at month 6 a similar, not significant, trend was observed (r = −0.47; P = 0.054). Proteinuria showed a significant reduction from baseline (P < 0.05); no significant relationship between change in proteinuria and urinary sodium or urea was observed.

CONCLUSION

The present study suggests that a higher dietary sodium and protein intake may amplify the extent of early dip in glomerular filtration rate, detected with measured CrCl, in diabetic patients undergoing SGLT2i treatment. We believe that measured creatinine clearance is a very sensitive method to detect it. Further studies are needed to confirm the results of our pilot study.
MO646: Effect of a High-Flux Dialyzer Applied to HFR Supra on the Removal of Large Uraemic Toxins in Haemodialysis Patients: Results from a Randomized Controlled Study
Authors: Molina Pablo , Valero Alejandro , Vizcaíno Belén , González Moya Mercedes , García-Valdelvira María , Montesa Marín María , Molina Mariola D , Beltrán Sandra , Estañ Nuria , Sancho Asunción
Published: May 2022

BACKGROUND AND AIMS

HFR-Supra (haemodiafiltration with the regeneration of the ultrafiltrate) is a highly biocompatible dialysis technique characterized by an adsorptive resin cartridge with high protein-bound toxin adsorption capacity without removal of albumin, mimicking both glomerular and tubular functions. However, the low-flux dialyzer contained in the second diffusive stage of the HFR Supra system may hamper the removal of large uraemic toxins. This study assessed the large uraemic toxin removal ability of a new HFR system (HFR-H) which combines adsorption such as in HFR-Supra, with a high-efficiency high-flux haemodialysis membrane.

METHOD

In an open, randomized, cross-over, single-center, controlled study, 16 adult chronic haemodialysis patients were treated by haemodiafiltration with the regeneration of the ultrafiltrate with the HFR-Supra or the HFR-H system. All other dialysis parameters were kept constant in both study arms. All the treatments were delivered with Flexya dialysis monitor (Medtronic) in the middle-week session, lasting 4-h. The reduction rate (RR) of urea, creatinine, phosphate, β2-microglobulin, kappa (κFLC) and lambda (λFLC) free light chains and albumin, was intra-individually compared for the two dialysis types with linear mixed models.

RESULTS

The RRs for β2-microglobulin, κFLC and λFLC were significantly higher with the HFR-H system than those obtained with HFR-Supra (Figure). There were no significant differences in the RR for urea, creatinine, phosphate, interleukin-6 and albumin.

CONCLUSION

This study demonstrates that treating patients with an HFR-H instead of an HFR-Supra system significantly increases the elimination of middle and large molecules.
MO655: Anti-Inflammatory Approach in Chronic Dialysis Patients with SARS-CoV-2: ATA or PMMA Dialyzers?
Authors: Gasperoni Lorenzo , Donati Gabriele , Scrivo Anna , Zappulo Fulvia , Abenavoli Chiara , Hu Lilio , Napoli Marianna , Angelini Andrea , Nunzio Miriam D I , Tringali Edoardo , Cingolani Alessandra , Marchegiani Beatrice , Rigotti Angelo , Manna Gaetano L A
Published: May 2022

BACKGROUND AND AIMS

High flux haemodialysis membranes may modulate the cytokine storm of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their impact in chronic haemodialysis (CHD) patients is not assessed [1, 2]. The aim of the study was the evaluation of asymmetric cellulose triacetate (ATA) and polymethylmethacrylate (PMMA) dialyzers on inflammatory markers in CHD patients with SARS-CoV-2.

METHOD

A prospective, observational study on CHD patients (age ≥18 years) affected by SARS-CoV-2 was carried out. Patients were enrolled from March 2020 to May 2021 and dialysis was performed at S. Orsola University Hospital (Bologna, Italy) Dialysis Unit. Mechanical ventilation at diagnosis was exclusion criteria. Pre- and post-dialysis C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) were determined at each session and corrected for haemoconcentration during the complete SARS-CoV-2 period.

Patients who underwent online haemodiafiltration (OLHDF) with PMMA dialyzer (Filtryzer BG-U™, Toray, surface area 2.1 m2 cut-off 20 kDa, KUF 43 mL/h/mmHg) were compared with those who underwent OLHDF with ATA dialyzer (SolaceaTM Nipro, surface area 2.1 m2 cut-off 45 kDa, KUF 72 mL/h/mmHg). The primary endpoint was to assess the differences in the reduction ratio/session (RR) of CRP, PCT and IL-6.

RESULTS

A total of 74 patients were enrolled, 48 were treated with ATA and 26 were with PMMA (420 versus 191 dialysis sessions). The main results are shown in Table 1. Median IL-6RR% was higher for ATA [17.08%, interquartile range (IQR) −9.0 to 40.0 versus 2.95%, IQR −34.63 to 27.32]. CRP and PCT showed higher RR with ATA in comparison to PMMA. When IL-6RR > 25% was the dependent variable in the multiple logistic regression analysis only ATA showed a significant correlation [odds ratio (OR) 1.891, 95% confidence interval (95% CI) 1.273–2.840, P = .0018) while higher CRP favoured the risk of lower IL6RR (OR 0.9101, 95% CI 0.868–0.949, P < 0.0001) (Table 2).

CONCLUSION

In SARS-CoV-2 CHD patients treated with OLHDF, ATA showed a better anti-inflammatory profile than PMMA, in particular regarding IL-6 RR.
MO657: Low Incidence of Intradialytic Hypotension During Online Post-Dilution High-Volume Haemodiafiltration: A Randomized Cross-Over Trial between Four Intermittent Dialysis Modalities
Authors: Rootjes Paul A , Charaa Sabrine , de Roij van Zuijdewijn Camiel , Nubé Menso J , Wijngaarden Gertrude , Grooteman Muriel
Published: May 2022

BACKGROUND AND AIMS

Compared with standard haemodialysis (S-HD), online post-dilution haemodiafiltration (HDF) is associated with improved survival, especially when high convection volumes [high-volume (HV)-HDF] are achieved [1]. A superior intradialytic haemodynamic stability may play an important role in this respect. Therefore, we assessed whether the intradialytic haemodynamic profile differs between four dialysis modalities, including S-HD and HV-HDF.

METHOD

In the current randomized cross-over trial (NCT03249532, ClinicalTrials.gov), 40 prevalent dialysis patients were subjected to S-HD [dialysate temperature (Td) 36.5°C], HD with cool dialysate (C-HD; Td 35.5°C), low-volume (LV)-HDF [convection volume (CV) 15 L/1.73 m2/session) and HV-HDF (CV ≥23 L/1.73 m2/session) (both Td 36.5°C). Blood pressure (BP) was measured 4x/hour. The primary endpoint was the total number of intradialytic hypotensive (IDH) episodes. IDH was defined as a nadir in systolic BP (SBP) <90 mmHg for a pre-dialysis SBP <160 mmHg and <100 mmHg for a pre-dialysis SBP ≥160 mmHg, independent of symptoms and interventions. In addition, an explorative analysis was performed on the incidence of early-onset IDH, which has recently been related to mortality [2]. Secondary endpoints included the intradialytic courses of SBP, diastolic BP (DBP) and mean arterial pressure (MAP).

RESULTS

IDH occurred significantly less frequent during C-HD (0.21 episodes/session) and HV-HDF (0.27/session) compared with S-HD (0.68/session, both P < .0005) (Figure 1). Furthermore, early-onset of IDH was also observed more frequently during S-HD (0.32/session) than during C-HD (0.07/session, P<.0005) or HV-HDF (0.10/session, P = .001) (Figure 1). After correction for multiple testing, the intradialytic courses of SBP, DBP and MAP declined only significantly during S-HD (−6.8, −5.2, −5.2 mmHg/session; P = .004, <.0005, .002 resp.) whereas these remained stable in the other modalities (Table 1).

CONCLUSION

In conclusion, during both C-HD and HV-HDF, IDH occurred least frequent and the intradialytic haemodynamic stability was best preserved. In contrast, intradialytic haemodynamic stability is most dysregulated during S-HD. Therefore, it is conceivable that the survival benefit of HV-HDF over S-HD is (at least partly) due to a more stable intradialytic haemodynamic profile and consequently less repetitive tissue injury.
MO681: Association of Framingham Risk Score with Mortality in Kidney Failure Patients from China and Sweden
Authors: LI Xiejia , Chen Zhimin , Rashid Tony Qureshi Abdul , Mukai Hideyuki , Suliman Mohamed , Heimbürger Olof , Peter Barany Franz , Chen Jianghua , Stenvinkel Peter , Lindholm Bengt
Published: May 2022

BACKGROUND AND AIMS

The Framingham risk score (FRS) was developed to estimate an individual`s risk of coronary heart disease over the next 10 years in the general population by using traditional cardiovascular disease (CVD) risk factors age, sex, systolic blood pressure, treatment of hypertension, total cholesterol, high-density lipoprotein cholesterol and smoking status. However, the utility of FRS in predicting CVD mortality in kidney failure patients is not clear. We examined the association between FRS and all-cause and CVD mortality in two cohorts of kidney failure patients from China and Sweden, respectively.

METHOD

In 1276 Chinese incident peritoneal dialysis [median age 50 years, 56% males, BMI 21 (19–23); incident peritoneal dialysis] and 559 Swedish incident or prevalent dialysis patients [median age 58 years, 62% males, BMI 24 (22–28)], FRS and baseline biochemical and metabolic biomarkers were analysed in relation to mortality during follow-up period of up to 5 years. All-cause and CVD mortality risk of were analysed with competing-risk regression models with transplantation as competing risk adjusting for BMI, serum albumin, hemoglobulin and calendar year.

RESULTS

Chinese patients were significantly younger (P < 0.01) and had lower BMI (P < 0.01) and FRS (P < 0.01) than Swedish patients but their sex distribution was similar. ‘In the Chinese patients,’ during median 3.6 years of follow-up, all-cause mortality rate was 16%, and 91 (46%) of the 199 deaths were caused by CVD. Both middle and high tertiles of FRS were associated with higher all-cause (Fig. 1A) and CVD mortality (Fig 1B) risk after adjusting for confounders. ‘In the Swedish patients,’ after median 2.1 years of follow-up, all-cause mortality rate was 36%, and 89 (44%) of the 204 deaths were caused by CVD. Both middle and high tertiles were associated with higher all-cause (Fig. 2A) and CVD mortality (Fig. 2B) risk after adjusting for confounders.

CONCLUSION

Higher FRS (both middle and high tertiles of FRS) was independently associated with significantly higher all-cause and CVD mortality risk in Chinese as well as in Swedish patients with kidney failure. These results underline the importance of traditional CVD risk factors in kidney failure patients and suggest that FRS may be a useful risk-assessment tool for predicting clinical outcomes in these patients.