bluuebunny/crossref_metadata_2025 huggingface dataset:
MO572: Effects of Ketoanalogues on the Evolution of Bone Mineral Metabolism in Patients With Advanced Chronic Kidney Disease
Authors: Kosmadakis Georgios , Isnard Rouchon Myriam , Fuentes Fanny , Ramade Nathalie , Baudenon Julien , Deville Clemence , Enache Ioana , Gueret Claudine , Haskour Abraham , Necoara Aura , Rance Nicole
Published: May 2022

BACKGROUND AND AIMS

There is a mounting volume of evidence on the efficacy of ketoanalogues associated with low protein diets, concerning the nephroprotective effects in patients with advanced chronic kidney disease (CKD). The important number of capsules daily ingested associated with their important calcium content would potentially affect the bone mineral metabolism of this group of patients. The aim of this study is to investigate the effects of ketoanalogues on the evolution of the bone mineral metabolism parameters in patients with advanced CKD.

METHOD

This is a prospective non-randomized controlled comparative study of two groups of patients. The results are shown as mean ± ESM. The first group (intervention) (20 patients, 12/8 M/F, mean age 71.9 ± 2.9, 10 with diabetes) was treated with ketoanalogues associated with a low protein diet and the control group (17 patients, 9/8 M/F, mean age 68.2 ± 3.3, 8 with diabetes) had a conventional follow-up of CKD. We studied the evolution of the body weight, renal function (glomerular filtration rate measured by the CKD-EPI formula in mL/min/1.73 m2), 24 h proteinuria, salt and protein consumption, serum albumin, serum prealbumin, alkaline reserve, serum phosphate levels, serum parathormone levels and calcium levels corrected for serum albumin at baseline as well as 6, 12 and 24 months post-inclusion. We performed a T-test for independent groups in order to study the differences between the two groups in every time point of the study. P-values < 0.05 were considered statistically significant.

RESULTS

The results are shown in the Table 1. There were no differences between the two groups at baseline. There was a significant nephroprotective effect of the ketoanalogues after 12 and 24 months. Alkaline reserve and serum calcium levels were significantly higher in the intervention group after 6, 12 and 24 months. Serum phosphate and serum parathormone levels were significantly higher in the control group 6 months, 1 and 2 years after the baseline. All patients were treated with the appropriate agents for the correction of the perturbed study parameters. During the 2-year follow-up, four patients from the study group (two pre-emptive renal transplantations, one death from oncologic causes and one start of dialysis) and eight patients from the control group (three deaths and five dialysis initiations) quitted the study.

CONCLUSION

In conclusion, the treatment with ketoanalogues and low protein diet has a significantly positive impact on the bone mineral metabolism of the patients with advanced CKD. It is unknown whether this is due to the high calcium content of the capsules or from the fact that the renal function is better preserved in the intervention group
MO576: A Novel Application of Serum Creatinine and Cystatin C to Predict Sarcopenia in Advanced Chronic Kidney Disease
Authors: Teng Yi-Yen , Mitra Sari Santi , Lin Yu-LI , Hsu Bang-Gee
Published: May 2022

BACKGROUND AND AIMS

Sarcopenia is highly prevalent in patients with advanced chronic kidney disease (CKD), yet a reliable serum index has not been established. The product of serum creatinine and the estimated glomerular filtration rate based on cystatin C (Cr × eGFRcys) was recently proposed as a sarcopenia index (SI), approximately to 24-h filtered creatinine through the glomerulus. We aimed to evaluate the diagnostic and prognostic validity of the novel SI in advanced CKD. 

METHOD

In 297 patients with non-dialysis stage 3b-5 CKD, aged 68.8 ± 12.9 years, the total skeletal muscle mass (SMM), handgrip strength (HGS) and usual gait speed were assessed. Sarcopenia was defined based on the Asian Working Group for Sarcopenia 2019 consensus update. To validate the prognostic impact of the SI, the CKD registry database of our hospital was retrospectively analyzed.

RESULTS

The SI correlated moderately with SMM (r = 0.503, P < 0.001), HGS (r = 0.508, P < 0.001) and gait speed (r = 0.381, P < 0.001); the independency of the SI with three muscle metrics was confirmed after adjustment. For sarcopenia prediction, the SI had acceptable discriminative powers in men (area under the receiver operating characteristic curve [AUC] 0.646, 95% confidence interval [CI] 0.569–0.718) and women (AUC 0.754, 95% CI 0.670–0.826), with optimal cut-off values of 53.9 and 45.8, respectively. In the prognostic cohort, 113 (11.9%) of 946 patients died during a median follow-up of 36 months. Applying the cut-off values above, the low SI group was independently associated with all-cause mortality (hazard ratio [HR] = 2.15, 95% CI = 1.39–3.32, P = 0.001), compared with the normal SI group.

CONCLUSION

Cr × eGFRcys is a promising SI for sarcopenia detection and mortality prediction in advanced CKD. Further studies are needed to expand our investigation.
MO581: Hyperphosphatemia Induces Lung Fibrosis in OLD Mice
Authors: Asenjo-Bueno Ana , Alcalde-Estevez Elena , Martínez Miguel Patricia , Olmos Gemma , Piedad Ruiz-Torres Maria , López-Ongil Susana
Published: May 2022

BACKGROUND AND AIM

Hyperphosphatemia is a common condition associated with chronic kidney disease (CKD) and also with aging. Furthermore, lung dysfunction is described in both cases; however, the relationship between high phosphate levels and lung function is still unknown. The aim of this work is to analyze the effect of hyperphosphatemia in the development of lung fibrosis related to aging.

METHODS

For in vivo studies, C57BL6 male mice of 5 months old (Young) and 24 months old (Old) fed with a standard diet containing 0.6% phosphate were used. Additionally, some old mice were fed with a hypophosphatemic diet containing 0.2% phosphate (Old-Low P) for the last 3 months. Serum phosphate levels were measured with DIPI-500 assay. Lung fibrosis was evaluated by Sirius Red staining and by expression of extracellular matrix proteins such as fibronectin or collagen V assessed by western blot. In vitro studies were performed on a human cell line from lung fibroblasts (Wi-38), which were treated with a phosphate donor called β-glycerophosphate (BGP, 10 mM) at different times. Fibrosis was detected by expression of fibronectin by western blot as in lung tissues. Oxidative stress was measured by confocal microscopy using the fluorogenic probe CellROX. EMSA assays was used to check the activation of fibronectin promoter by NFκB transcription factor.

RESULTS

Old mice that showed higher serum phosphate levels had more lung fibrosis than young mice. Old mice fed with the low phosphate diet, which had less serum phosphate levels, reduced significantly the lung fibrosis respect to old mice fed with the standard diet. In order to elucidate a possible mechanism, in vitro studies were performed in lung fibroblasts treated with BGP. BGP induced a significant increased on fibronectin expression. BGP also rose oxidative stress at short times. As NF-kB transcription factor can be activated by oxidative stress, we checked whether BGP induced the binding of this factor to fibronectin promoter to upregulate this gene. The EMSA analysis showed that BGP promoted the binding of NF-κB to fibronectin promoter. Besides, in the presence of an antioxidant such as catalase, BGP did not induce the binding of NF-kB to fibronectin promoter, suggesting a role for oxidative stress.

CONCLUSION

Old mice showed hyperphosphatemia and lung fibrosis, which both were improved using a low phosphate diet. In vitro studies in lung fibroblasts confirmed that fibrosis induced by BGP seems to be mediated by activation on NF-kB via oxidative stress. These results show a relationship between hyperphosphatemia and lung fibrosis in aging; however, more studies are necessary in order to elucidate the relationship with other chronic diseases related to aging.
MO583: Cafeteria Diet-Induced Obesity Worsens Experimental CKD
Authors: Muyor Karen , Duranton Flore , Cortijo Irene , Laget Jonas , Jover Bernard , Dominique Lajoix Anne , Argiles Ciscart Angel , Gayrard Nathalie
Published: May 2022

BACKGROUND AND AIMS

Obesity is an important risk factor for chronic kidney disease (CKD). It carries hemodynamic and morphologic changes in the kidney resulting in renal function reduction. CKD is associated with glomerulosclerosis and tubulointerstitial fibrosis that involve collagen deposition. The aim of the study was to evaluate the impact of obesity on kidney fibrosis in a model of 5/6th nephrectomized rats fed a cafeteria diet.

METHOD

Twenty four rats were fed acafeteria diet and 10 rats received a standard diet for 6 months. For each diet group, half of the rats underwent 5/6 nephrectomy (SNx) at 4 months. Expression of collagen type 1, 3, 4 was quantified by immunohistochemistry in kidney sections at 6 months. Adipocyte size was measured in epididymal adipose tissue (eWAT), and the presence of macrophages was determined by CD68 immunostaining.

RESULTS

Rats fed the cafeteria diet were hyperglycemic and hypertensive. Their body weight was higher than those fed the standard diet. SNx rats had increased serum creatinine levels, which were even higher in the cafeteria group (71 ± 10 µM) compared with standard diet group (54 ± 5 µM) (P < 0.05). Serum creatinine level was comparable in non-nephrectomized animals fed the cafeteria (32 ± 1 µM) or standard diet (29 ± 1 µM). Collagen 1 level in kidney tissue was increased in both SNx groups with no clear effect of the diet (respectively, 7.1 ± 0.6% and 8.9 ± 0.9% of tissue area with the standard and cafeteria diets). Renal expression of collagen 3 and 4 was significantly increased in SNx animals with cafeteria diet (8.6 ± 1.5 and 10.9 ± 1.9% tissue area, respectively) compared with control rats fed the same diet (5.2 ± 0.5 and 6.3 ± 0.6% tissue area, respectively). Adipocyte size of eWAT was significantly increased by cafeteria diet but reduced in nephrectomized rats. In the cafeteria-SNx group, CD68 immunostaining showed a significant increase in macrophage number in kidney (P = 0.01) and a consistent tendency in eWAT (Fig. 1).

CONCLUSION

Cafeteria diet-induced obesity worsened the 5/6 nephrectomy-induced CKD. The expression of collagens 3 and 4 as well as the number of macrophages were increased in kidneys from the cafeteria SNx group suggesting an exacerbation by pre-existing obesity of CKD-induced renal inflammation and fibrosis.
MO585: Effects of EPP-AF® Green Propolis Extract Supplementation on Inflammatory Markers in Patients With chronic Kidney Disease on Peritoneal Dialysis
Authors: Mafra Denise , G. Baptista Beatriz , Fanton Susane , M. Ribeiro Marcia , R. Paiva Bruna , Cardozo Ludmila , Alvarenga Livia , A. Berretta Andresa
Published: May 2022

BACKGROUND AND AIMS

Inflammation and oxidative stress are involved in the mortality of patients with chronic kidney disease (CKD) on peritoneal dialysis (PD). In this context, propolis may mitigate inflammation, reducing mRNA expression of nuclear factor-kB (NF-kB) and levels of inflammatory markers as tumor necrosis factor-α (TNF-α). Several studies have been performed in vitro and in animals showing that propolis (a resin made by bees) has excellent anti-inflammatory properties. Only one study evaluated the effects of propolis in patients with CKD (stages 3 and 4) and showed a reduction in proteinuria and urinary MCP-1, but there is no study in patients with CKD on peritoneal dialysis (PD). The present study aimed to evaluate the effects of propolis supplementation on inflammatory markers in patients with CKD on PD.

METHODS

This is a longitudinal, randomized, double-blind, placebo-controlled trial with 19 patients randomized into two groups: propolis (4 capsules of 500 mg/day containing concentrated and standardized dry EPP-AF® green propolis extract) or placebo (4 capsules of 500 mg/day of magnesium stearate, silicon dioxide and microcrystalline cellulose as placebo) for 2 months. The inflammatory cytokines plasma levels such as TNF-α and interleukin-6 (IL-6) were evaluated by ELISA, and quantitative real-time PCR analyses were performed to evaluate the mRNA expression of NF-kB in peripheral blood mononuclear cells (PBMCs). Plasma malondialdehyde (MDA) levels, a peroxidation lipid marker, was measured as thiobarbituric acid reactive substances (TBARS). Routine parameters, including C-reactive protein (CRP), were analyzed using commercial kits.

RESULTS

All patients concluded the study: 10 patients in the propolis group [57.2 ± 13.7 years, five men, 6 (6–36) months on DP] and 9 in the placebo group [56.6 ± 14.7 years, two men, 6 (6–57) months on DP]. The obtained data revealed that the intervention did not affect the mRNA expression of NF-κB. However, the plasma levels of TNF-α reduced significantly after propolis supplementation (Table 1 and Fig. 1). There were no significant differences in the placebo group.

CONCLUSION

Short-term EPP-AF® propolis dry extract supplementation seems to mitigate inflammation, reducing the plasma levels of TNF-α in patients with CKD on PD.
MO598: Coping Strategies During the COVID-19 Pandemic: Influence of Patient Activation in People Living With Kidney Disease
Authors: Patel Naeema A , Wilkinson Thomas , Smith Alice , Lightfoot Courtney J
Published: May 2022

BACKGROUND AND AIMS

Patient activation refers to the knowledge, skills and confidence needed to manage one's health [1]. Higher patient activation is associated with better health outcomes in long-term conditions [2] such as kidney disease (KD). The COVID-19 pandemic has presented a myriad of additional challenges for people living with KD. Individuals may display different coping strategies in response to stressful and difficult circumstances such as health management during the pandemic [3]. Our group conducted a multicentre survey to evaluate the impact of the pandemic on kidney patient experiences, lifestyle and health care. As part of this larger study, we hypothesized that higher patient activation may be associated with more effective coping strategies. The purpose of this analysis was to explore coping styles utilised during the pandemic across different levels of patient activation in people with nondialysis CKD (ND-CKD) and kidney transplant recipients (KTR).

METHOD

214 ND-CKD and KTR participants [50.9% male, mean age 60.71 (SD 14.15) years, 56.1% KTRs] completed the Patient Activation Measure (PAM-13). Participants were categorised into ‘low’ and ‘high’ activation based on their PAM-13 score (levels 1–2 as low; 3–4 as high). Coping strategies were assessed using the Brief-COPE questionnaire and categorised into adaptive coping (active coping, information support, positive reframing, planning, emotional support, humour, acceptance and religion) and maladaptive coping (venting, self-blame, self-distraction, denial, substance use and behavioral disengagement) strategies. Chi-square tests were conducted to compare coping strategies used by low- and high-activated patients.

RESULTS

Most participants were classified as having ‘high’ activation levels (n = 164, 77%). Table 1 shows the three most frequently used adaptive and maladaptive coping strategies across activation levels. A significantly greater proportion of those with high activation used acceptance (P = 0.006), active coping (P = 0.045) and positive reframing (P = 0.031) as coping strategies. No significance was observed between maladaptive coping strategies and activation level.

CONCLUSION

The most commonly reported coping strategy was ‘acceptance’ for individuals with high and low activation. The findings suggest that a higher proportion of people with high patient activation used adaptive coping strategies. Worryingly, regardless of activation level, about a third of participants used substance use (i.e. alcohol and drugs) as a form of coping. Identifying people with lower activation in KD can indicate the need for additional support to help them cope in challenging circumstances. Interventions to improve activation may assist in developing effective coping strategies.
MO599: Efficacy and Safety of Optimized Sodium Thiosulfate Therapy for Calciphylaxis in Chinese Patients
Authors: Yang Xin , Liang Zhang Xiao
Published: May 2022

BACKGROUND AND AIMS

Calciphylaxis is a rare life-threatening syndrome. Although sodium thiosulfate (STS) showed clinical improvement, some patients presented with serious adverse events and withdrew from treatment. The optimized STS approach included four features: repeated treatment courses, small initial dose, once daily, and escalating low-to-moderate dose. The optimized STS approach, named ‘Zhong Da STS Therapy’ (Zhong Da: the name of a hospital, affiliated with Southeast University, School of Medicine, Nanjing, Jiangsu, China), was generalized with four features: repeated treatment courses, small initial dose, daily medicine, and daily escalating low-to-moderate dose of STS. STS from the initial dose (5 g) was administered intravenously once daily escalating to the highest daily dose as a maintenance dose (no more than 10 g). This study retrospectively evaluated the efficacy and safety of optimized STS therapy for calciphylaxis in China.

METHOD

The medical records of maintenance hemodialysis or CKD patients who were first diagnosed with calciphylaxis and received STS treatment at Zhong Da Hospital affiliated to Southeast University between October 2017 and October 2019 were retrospectively evaluated. The exclusion criteria of this retrospective study were death at the time of diagnosis (retrospectively confirmed cases) and did not receive the optimized STS approach treatment. The data to evaluate the efficacy included the changes in skin lesions, pain relief, survival rate and laboratory data. Adverse events were summarized as safety parameters.

RESULTS

The mean age was 51.10 ± 14.85 years old and 71% of patients were male. By October 2019, 87.1% of patients survived, 74.2% markedly improved and 41.9% of patients were followed up for more than 1 year with 100% survival. About 27 (87.10%) patients had typical skin lesions with 66.70% ulceration and skin lesions showed a predominantly peripheral distribution. After the first course, skin lesions improved by 77.8%, and 38.1% of pain sufferers were free from analgesics. The reduction of the Numerical Pain Rating Scale (NPRS) (P < 0.001) is related significantly to the treatment course. Furthermore, during the entire treatment session, more than half of the patients (54.84%) never experienced adverse events, only one withdrew treatment and no one died from complications. And most adverse events appeared in the course of increasing the STS dose and would be relieved when we stopped adding it or decreased to the day-before dose.

CONCLUSION

Optimized STS therapy is a promising approach for calciphylaxis patients because it is relatively safe and associated with good outcomes.
MO602: Combined and Progressive Intradialytic Exercise Training Keeps Stable the Systemic Inflammation, Endothelial Function Markers and Redox State: A Secondary Analysis of a Randomized Controlled Trial
Authors: Porcher Andrade Francini , Pires Dorneles Gilson , Vaz Leal Diogo , Viana João , Rovedder Paula
Published: May 2022

BACKGROUND AND AIMS

Chronic inflammatory conditions and disturbances in oxidative stress are hallmarks of renal damage and may be a trigger to non-pharmacological therapeutic options, such as exercise training, in chronic kidney disease[1,2]. This study aimed to evaluate the effects of 12-week combined and progressive intradialytic exercise training on systemic inflammation, endothelial function markers, and redox state in hemodialysis (HD) patients.

METHOD

This is a secondary analysis of a randomized controlled trial with HD patients[3] randomly allocated into two groups: exercise group (EXG) (n = 19) and usual care/control group (CON) (n = 19). EXG performed a 12-week combined and progressive intradialytic training period 3 times a week. CON maintained their normal HD routine during the same timeframe. Blood samples were obtained before and after the 12-week period to analyze C-reactive protein (CRP), interleukin (IL)-4, IL-6, IL-10, IL-17A, tumoral necrosis factor-alpha (TNF-α), reactive oxygen species (ROS), total antioxidant capacity (TAC), monocyte chemoattractant protein-1 (MCP-1), interferon-gamma (IFN-γ), vascular endothelial growth factor (VEGF), and nitric oxide (NO). The inflammatory balance was evaluated by IL-6/TNF-α, TNF-α/IL-4 and TNF-α/IL-10 ratios.

RESULTS

A significant effect was only observed in CON but not EXG, with decreased IL-6 (median of 9.93 [IQR: 8.31–14.79] to 8.86 [7.88–9.61] pg/mL; P = 0.044), IL-17A (62.26 [48.87–102.44] to 53.33 [45.29–59.58] pg/mL; P = 0.044), and IFN-γ (28.19 [26.44–31.15] to 27.09 [25.85–27.89] pg/mL; P = 0.006) and an increase in ROS (485.98 [333.17–604.83] to 507.31 [443.48–637.04]; P = 0.049).

CONCLUSION

The HD patients who undertook the 12-week combined and progressive intradialytic exercise training did not experience an alteration in systemic inflammation, endothelial function markers and redox state, in contrast with the increased oxidative stress state observed in CON.

FUNDING SOURCES

Hospital de Clínicas de Porto Alegre–Research Incentive Fund (FIPE) (Grant No. 2015–0151) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
MO605: Exploring the Relationship Between Cardiorespiratory Fitness and Cardiovascular Risk in Kidney Transplant Recipients
Authors: Billany Roseanne E , Mubaarak Zahra , Bishop Nicolette , Smith Alice , Graham-Brown Matthew
Published: May 2022

BACKGROUND AND AIMS

Cardiovascular disease (CVD) remains a leading cause of mortality for kidney transplant recipients (KTR). Traditional risk factors include smoking, obesity, hypertension and hyperlipidemia. Nontraditional risk factors include creatinine levels, previous transplants and total time on renal replacement therapy. High levels of physical inactivity have long been known to link with poor cardiovascular outcomes. The first United Kingdom Clinical Practice Guidelines for Exercise and Lifestyle in Chronic Kidney Disease recommend that KTRs aim for 150 min of moderate to vigorous physical activity a week (or 75 min vigorous physical activity) plus two strength training sessions in line with current World Health Organisation recommendations for the general population. However, evidence suggests that only 27% of KTRs are sufficiently active for health.

We aimed to explore the relationship between cardiorespiratory fitness and the 7-year risk of major adverse cardiac events (MACE) and 7-year risk of mortality in KTRs.

METHOD

49 KTRs (31 male; mean [±SD]; 59 [±19] eGFR mL/min/1.73 m2; age 49 [±14] years) completed a continuous ramp cardiopulmonary exercise test (1W increase every 4 s) to volitional exhaustion on a cycle ergometer. The cardiovascular risk calculator for renal transplant recipients (CRCRTR-MACE) was used to calculate 7-year risk of MACE and 7-year risk of mortality. Cardiorespiratory fitness categories were defined in accordance with the American College of Sports Medicine guidelines. Data were analyzed using hierarchical multiple regression adjusting for gender.

RESULTS

84% of participants were classified as having ‘poor’ or ‘very poor’ cardiorespiratory fitness (VO2; ml/kg/min). Cardiorespiratory fitness was a significant predictor of 7-year risk of MACE after adjusting for gender (F(2, 40) = 10.64, P < 0.001, adj. R2 = 0.315). Each 1 mL/kg/min increase in VO2 was associated with a 0.5% decrease in 7-year risk of MACE (B = −.523, 95% CI [−0.794, −0.252]). Cardiorespiratory fitness was also a significant predictor of 7-year risk of mortality (F(2, 40) = 8.50, P < 0.001, adj. R2 = 0.263). Each 1 mL/kg/min increase in VO2 was associated with a 1% decrease in 7-year risk of mortality (B = −0.961, 95% CI [−1.483, −0.439]).

CONCLUSION

This exploratory analysis shows that cardiorespiratory fitness explains 31.5% and 26.3% of the variance in the 7-year risk of MACE and the 7-year risk of mortality, respectively. Various interventions have been shown to improve cardiorespiratory fitness in KRTs. Improving levels of physical activity and subsequently cardiovascular fitness provide a low cost strategy to partially attenuate some of widespread impact of CVD-related morbidity and mortality. These results highlight the importance of incorporating physical activity as part of post-transplant care.
MO614: Modified Lipid Metabolism and Cytosolic Phospholipase A2 Activation in Mesangial Cells Under Pro-Inflammatory Conditions
Authors: Boi Roberto , Ebefors Kerstin , Henricsson Marcus , Johansson Alva , Borén Jan , Nyström Jenny
Published: May 2022

BACKGROUND AND AIMS

Diabetic kidney disease (DKD) is thought to be a consequence of hyperglycemia and driven by early glomerular hemodynamic changes and progressive expansion of the mesangium. The molecular mechanism behind the pathophysiological alterations of the mesangium is yet to be elucidated. This study aimed at investigating whether lipid signaling might be the missing link.

METHOD

Human mesangial cells (HMCs) were stimulated with high glucose, IL-1β or PDGF-BB. Production of IL-1β and PDGF-BB, COX-2 induction and cPLA2 activation and prostaglandin secretion were investigated using a combination of ELISA, western blot, lipidomics, qPCR and activity assays. Inhibition of cPLA2 was evaluated using ELISA, migration and proliferation assays. Validation of data was performed in silico using the Nephroseq database [1] and a recently published glomerular transcriptomic DKD database. [2]

RESULTS

Stimulation of HMCs with high glucose primed IL-1β secretion through inflammasome NLRP3 signaling. In turn, IL-1β was able to stimulate PDGF-BB release. PDGF-BB increased IL-1β secretion synergistically. Both IL-1β and PDGF-BB stimuli caused lipid metabolism variations and in particular triggered the formation of phosphorylated sphingoid bases (PSBs) and the activation of the enzymes cPLA2 and COX-2. This led to the formation of prostanoids from arachidonic acid produced by cPLA2. As a result, prostaglandins were secreted. Another product of cPLA2 activation was lysophosphatidic acid (LPA), a proliferation effector. Blocking cPLA2-mediated release of arachidonic acid could in fact reduce HMCs’ proliferation and secretion of prostaglandins.

CONCLUSION

Hyperglycemia primes glomerular inflammatory and proliferative stimuli triggering lipid metabolism modifications in HMCs. The upregulation of cPLA2 was found to be critical in this setting. cPLA2 inhibition with AACOCF3 reduced mesangial secretion of prostaglandins and proliferation, making it a potential target for DKD therapy.
MO617: Liraglutide Improves Both Diabetic Nephropathy and Cardiomyopathy in the SDT Fatty Rat, A Cardiorenal Model of Type 2 Diabetes
Authors: Briand Francois , Shinohara Masami , Brousseau Emmanuel , Maupoint Julie , Dubroca Caroline , Kageyama Yasushi , Sulpice Thierry
Published: May 2022

BACKGROUND AND AIMS

The Glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide (LIRA) has cardioprotective effects and may reduce the development of kidney disease in type 2 diabetic patients. We here evaluated the effects of LIRA on both kidney and heart function in the Spontaneously Diabetic Torii (SDT) fatty rat, a type 2 diabetic cardiorenal model.

METHOD

SDT fatty male rats were treated subcutaneously with vehicle or LIRA 0.4 mg/kg QD for 10 weeks. To measure the effects of LIRA on glomerular hyperfiltration, rats were injected with FITC-sinistrin to measure glomerular filtration rate (GFR) at 4 weeks of treatment. At 5 weeks of treatment, rats underwent unilateral nephrectomy and were put on a 0.3% salt diet to induce a GFR decline. GFR was then measured at 10 weeks of treatment, before hemodynamics measurement and echocardiography.

RESULTS

Compared with vehicle, LIRA induced significant body weight loss, as well as blood glucose levels reduction by up to ∼20%. During the hyperfiltration phase, LIRA attenuated hyperfiltration, with a 19% lower GFR versus vehicle (P < 0.05). In vehicle-treated animals, unilateral nephrectomy and 0.3% salt diet induced a major reduction (−56%) in GFR, as expected. After 10 weeks of treatment, LIRA markedly attenuated this GFR decline (vehicle: 9.3 ± 0.5 mL/min/kg; LIRA: 13.3 ± 0.9 mL/min/kg, P < 0.001 versus vehicle). Compared with vehicle, LIRA also lowered urine albumin-to-creatinine ratio both in the hyperfiltration and GFR decline phases, and significantly reduced kidney inflammation and fibrosis histology scores. LIRA showed significant reduction in cardiac hypertrophy, as well as both arterial and left ventricle end-systolic pressures. Moreover, LIRA normalized the diastolic dysfunction with preserved ejection fraction observed in SDT fatty rats (P < 0.001 versus vehicle).

CONCLUSION

In the SDT fatty rat, LIRA shows significant benefits by reducing renal hyperfiltration, preventing GFR decline, and improving cardiac hypertrophy, blood pressure and diastolic dysfunction. This preclinical model will be useful to evaluate drugs targeting the cardiorenal axis in type 2 diabetes.
MO629: The Baseline Risk Factors of Covid-19 Adverse Outcomes in Patients with Advanced Stages of Diabetic Kidney Disease: The Single Center Experience
Authors: Klochkova Nataliya , Lysenko Mariana , Zeltyn-Abramov Eugene , Poteshkina Nataliya , Markova Tatyana , Frolova Nadia , Belavina Natalya , Kondrashkina Svetlana , Sokolova Natalya , Manchenko Oxana , Smolentseva Valeria
Published: May 2022

BACKGROUND AND AIMS

The patients with diabetic kidney disease (DKD) due to type 2 diabetes mellitus (T2DM) are at a high risk of adverse outcomes of COVID-19. The causes of high mortality in this cohort are the subject of debate.

Identification of the risk factors (RF) of adverse COVID-19 outcomes in patients with T2DM and advanced stages of DKD at hospital admission.

METHOD

The patients with laboratory-confirmed COVID-19 were included in the retrospective observational study during the hospitalization in MCCH №52, the observation period being 04 January 2020 to 31 October 2020. The study endpoints were the outcomes of hospitalization—discharge or lethal outcome. Data were collected from electronic medical database. The following independent variables were analyzed at hospital admission: gender, age, duration of T2DM, general comorbidity (Charlson Index, CCI), the insulin demand (InsD), fasting blood glucose (FBG), body mass index (BMI), NEWS scale points, white blood cell (WBC), lymphocytes and platelet count, CPR, serum albumin (SA), ferritin, LDH, and GFR.

RESULTS

A total of 120 patients were included. Mediana age was 69 years (IQR 63.5–79.5), females 53%. The observation group was divided into subgroups: (i) patients with advanced DKD according to GFR values not requiring maintenance hemodialysis (MHD) and (ii) patients on MHD. All patients were distinguished by high general comorbidity and duration of T2DM more than 10 years. The mortality in both subgroups was high (38.2% versus 38.5%, respectively). The results are presented in Table 1.

CONCLUSION

The patients with T2DM and advanced DKD are very vulnerable to adverse outcomes of COVID-19. High FBG, lymphopenia and high ferritin value on admission seem to be the most significant RF of lethal outcome regardless of MHD.
MO632: Impact of Diabetic Kidney Disease on Coronary Artery Plaque Progression
Authors: Yabushita Sayaka , Kishi Satoru , Tanaka Tetsu , Aihara Hideaki , Ogura Yoshiyasu , Tsukada Hiroyuki , Furuse Satoshi , Mise Naobumi
Published: May 2022

BACKGROUND AND AIMS

The aim of this study was to evaluate the relationship between diabetic kidney disease (DKD) and change in coronary plaque volume in asymptomatic diabetes patients.

METHOD

In this prospective observational study, we analyzed 79 asymptomatic type 2 diabetes patients (age, 63.7 ± 8.1 years; male, 69.3%) without prior history of coronary artery disease who underwent serial 320-row computed tomography coronary angiography with an interscan interval of more than 24 months (median 37.7 months). Total coronary plaque volume was assessed at baseline and after 3 years, using QAngio CT (MEDIS) for vessel diameters greater than 1.5 mm in the three main branches. The primary endpoint was coronary plaque progression (PP), which was defined as the absolute change in coronary plaque volume during the 3 years. PP was compared among four groups, which were divided according to the presence or absence of DKD at baseline and after 3 years, as follows: Group 1 (no DKD at baseline, no DKD after 3 years), Group 2 (DKD at baseline, no DKD after 3 years), Group 3 (no DKD at baseline, DKD after 3 years), Group 4 (DKD at baseline, DKD after 3 years)]. DKD was defined as albuminuria >30 mg/g Cr or eGFR <60 mL/min/1.73 m2. We conducted univariate linear regression analysis to assess the association of DKD groups with PP.

RESULTS

Plaque volumes were significantly greater in Group 4 than in Group 1 both at baseline and after 3 years (Table 1). PP was also significantly greater in Group 4 than in Group 1 (β-coefficient: 293.6, P < 0.01). Group 4 had greater PP compared with Group 1 after adjustment (β-coefficient: 181.6, P < 0.05).

CONCLUSION

DKD may be an independent risk factor for coronary plaque progression in asymptomatic type 2 diabetic patients without a history of cardiovascular disease. Early therapeutic intervention in such patients may prevent the onset of coronary artery disease.
MO633: Survival Comparison Between CVVHDF and CVVH for Septic Acute Kidney Injury
Authors: Jang Mun , Woo Lee Seung
Published: May 2022

BACKGROUND AND AIMS

The mortality rate of septic acute kidney injury (AKI) remains high despite improvements in renal replacement technology. Adding dialysis to continuous veno-venous hemofiltration (CVVH) can increase survival in these patients, although hemofiltration leads to better clearance of inflammatory mediators in sepsis than hemodialysis. We tested whether continuous veno-venous hemodiafiltration (CVVHDF) is more effective than CVVH with the same net effluent according to body weight in intensive care unit (ICU) patients with septic AKI.

METHOD

The mortality rate of septic acute kidney injury (AKI) remains high despite improvements in renal replacement technology. Adding dialysis to continuous veno-venous hemofiltration (CVVH) can increase survival in these patients, although hemofiltration leads to better clearance of inflammatory mediators in sepsis than hemodialysis. We tested whether continuous veno-venous hemodiafiltration (CVVHDF) is more effective than CVVH with the same net effluent according to body weight in intensive care unit (ICU) patients with septic AKI.

RESULTS

In this prospective randomized pilot study, 100 patients were assigned to CVVH (n = 47, M: F = 25:22, age 64 ± 15 years) or CVVHDF (n = 49, M: F = 30:19, age 65 ± 11 years). Baseline characteristics including age, sex, body weight, serum creatinine, blood urea nitrogen (BUN), beta-2 microglobulin, Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores did not vary between the two groups. There were no significant differences in the reduction ratios of serum creatinine, BUN, beta-2 microglobulin, APACHE II and SOFA scores between the two groups. Seven-, 28- and 60-day survival also did not vary.

CONCLUSION

In conclusion, CVVH and CVVHDF led to similar clearance of waste products and survival at the same net effluent in this study. Future large-scale randomized prospective studies will be needed to confirm these results in critically ill patients with septic AKI.
MO639: Evaluation of Glycemic Control and Interday Glucose Variability Using Continuous Glucose Monitoring in Diabetic Hemodialysis Patients
Authors: Divani Maria , Georgianos Panagiotis , Liakopoulos Vassilios , Didangelos Triantafillos , Makedou Kali , Savopoulos Christos , Grekas Dimitrios
Published: May 2022

BACKGROUND AND AIMS

Continuous-glucose-monitoring (CGM) facilitates the assessment of interday glucose variability and identification of acute excursions of hyper- and hypoglycemia [1–4).

METHOD

Among 37 diabetic hemodialysis patients who underwent 7-day CGM with the iPRO2 device (Medtronic Diabetes, Northridge, CA, USA), we explored the accuracy of GA and hemoglobin A1c (HbA1c) in assessing glycemic control, using CGM-derived metrics as the reference standard.

RESULTS

In receiver-operating-characteristic (ROC) analysis, the area under the curve (AUC) in diagnosing a time in target glucose range of 70–180 mg/dL (TIR70-180) in <50% of readings was higher for GA {AUC 0.878; [95% confidence interval (CI)] 0.728–0.962} as compared with HbA1c [AUC 0.682 (95% CI 0.508–0.825)] (P < 0.01). The accuracy of GA [AUC 0.939 (95% CI 0.808–0.991)] in detecting a time above target glucose range >250 mg/dL (TAR >250) in >10% of readings did not differ from that of HbA1c [AUC 0.854 (95% CI 0.699–0.948)] (P = 0.16). GA [AUC 0.712 (95% CI 0.539–0.848)] and HbA1c [AUC 0.740 (95% CI 0.570–0.870)] had a similarly lower efficiency in detecting a time below target glucose range <70 mg/dL (TBR <70) in >1% of readings (P = 0.71). Although the mean glucose levels were similar, the coefficient of variation of glucose recordings (39.2% ± 17.3% versus 32.0% ± 7.8%, P < 0.001) and TBR <70 [median (range): 5.6% (0, 25.8) versus 2.8% (0, 17.9)] were higher during the dialysis-on than during the dialysis-off day.

CONCLUSION

The present diagnostic test study shows that among diabetic hemodialysis patients, GA had higher accuracy than HbA1c in detecting a 7-day CGM-derived TIR70-180 in <50% of readings. However, both GA and HbA1c provided an imprecise reflection of acute excursions of hypoglycemia and interday glucose variability.
MO645: Does Sodium Magnetic Resonance Imaging Help for Initiation of Incremental Dialysis?
Authors: Lemoine Sandrine , Akbari Alireza , Penny Jarrin , Mcintyre Christopher
Published: May 2022

BACKGROUND AND AIMS

Incremental hemodialysis (HD) (twice a week) can be proposed to some patients who had a significant residual renal function (RRF) when HD is initiated. However, renal urea clearance is a very limited tool to predict the ability of the kidney to extract significantly water and sodium. We hypothesized that corticomedullary gradient (CMG) measurement with 23NaMRI could provide a new tool to select HD patients for incremental dialysis. We have already validated the use of 23NaMRI in healthy control. However, we had to prove first the feasibility of such a measure for HD patients.

METHOD

We conducted a prospective observational study to better characterize CMG in HD patients with 23NaMRI. We performed blood (urea, creatinine, sodium), urine collection (osmolarity, creatinine, sodium) and CMG with 23NaMRI in fasting patients. All MR experiments were carried out on a GE MR750 3T (GE Healthcare, WI). A custom-built two-loop (18 cm in diameter) butterfly radiofrequency surface coil tuned for 23Na frequency (33.786 MHz) was used to acquire renal 23Na images. We compared CMG in healthy controls (n = 15) and HD patients (n = 4) with or without RRF.

RESULTS

For healthy controls, median (IQR) age was 50 (32–60) years, 46% men, estimated glomerular filtration rate (eGFR) 103 (84–108) mL/min/1.73m2 urinary osmolarity (osmU) 786 (587–938) osm/L, sodium excretion fraction (FeNa) 0.27% (0.21–0.49). For HD patients, median (IQR) age was 68 (60–73) years, 50% men, creatinine 499 (366–606) umol/L, urinary osmolarity (osmU) 279 (193–317) osm/L, sodium excretion fraction (FeNa) 1.14% (0.44–2.21). Corticomedullary gradient for controls [1.53 (1.47–1.61)], was significantly different to HD 1.28 (1.17–1.4) (P = .001) as expected. There was a significant correlation between osmolarity and CMG (r = 0.73, P < .001). We showed a significant association between CMG and age (P = .03). The patient with RRF (diuresis to 1.3L/day) didn't display a different CMG compared with patients without RRF.

Figure 1 shows the difference in corticomedullary pictures (A) control and (B) HD patients.

CONCLUSION

We showed that it is possible to assess corticomedullary gradient in HD patients. More patients are needed to explore the ability of the 23NaMRI to discriminate patients who could benefit from incremental dialysis.
MO649: Monitoring of Ionized Magnesium in Haemodialysis Patients: A Useful Tool to Allow a Personalized Prescription of Dialysate Composition
Authors: Bargnoux Anne-Sophie , Morena Marion , Rodriguez Annie , Coulon Caroline , Kuster Nils , Chalabi Lotfi , Cristol Jean-Paul
Published: May 2022

BACKGROUND AND AIMS

In healthy subjects, normal values of magnesium (Mg) are in the range 0.75–0.95 mmol/L. In the circulation, 65–70% of the Mg is present in the free, ionized and dialyzable form (i.e. 0.45– 0.60 mmol/L), 20% is bound to proteins and 15% is complexed. In chronic kidney disease (CKD) dialysis patients, the dialysate Mg concentration is a major determinant of Mg balance. The aim of this study was to assess the systemic variations of ionized Mg (iMg), as well as that of ionized calcium (iCa), before and after a dialysis session.

METHOD

A total of 121 dialysis patients [median age = 70 (62.5–78.2) years; 74 male/46 female] in maintenance haemodialysis three times per week, for at least 6 months and with no residual function, were included. Patients were assigned to a single dialysis session with either control fluid (group 1: 3 mM acetate, 1.5 mM Ca, 0.5 mM Mg), or citrate dialysis fluid containing 0.5 mM Mg (group 2: 0.8 mM citrate, 0.3 mM acetate, 1.65 mM Ca) or 0.75 mM Mg (group 3: 0.8 mM citrate, 0.3 mM acetate, 1.65 mM Ca). Blood samples were drawn before and after the midweek dialysis sessions as part of the routine patient follow-up and quality assurance process. iMg and iCa concentrations were measured by direct ion-selective electrode on Nova Stat Profile Prime Plus® (Nova Biomedical). Total Mg (tMg) and Ca (tCa) were assessed by colorimetric method c702/Cobas 8000 analyzer (Roche). Dialytic balance was assessed by the median intra-dialytic difference between pre-dialysis and post-dialysis.

RESULTS

The use of all types of dialysates (whatever their composition was) was associated with a calcium load during the session (Table). In addition, an Mg loss was observed in both control and citrate dialysis fluid groups containing 0.5 mM Mg. The dialysis session induced a significant decrease in iMg (13 and 22% in group1 and group 2 respectively). By contrast, the use of citrate dialysis fluid with 0.75 mM Mg led to a positive balance with a median intra-dialytic increase of 0.08 and 0.02 mmol/L in tMg and iMg respectively (Table), corresponding to a median increase of 8 and 3% in tMg and iMg respectively.

CONCLUSION

The iMg fraction represents 70% of tMg in CKD stage 5D patients. While a dialysate Mg concentration at 0.5 mM leads to a negative balance, increasing the concentration to 0.75 mM significantly raises post-dialysis circulating Mg levels in these patients. Therefore, monitoring of iMg should allow a personalized prescription in dialysate Mg composition.
MO672: Covid-19 in Patients on Peritoneal Dialysis: A Case-Series
Authors: Alfano Gaetano , Fontana Francesco , Morisi Niccolò , Cappelli Gianni , Magistroni Riccardo , Donati Gabriele
Published: May 2022

BACKGROUND AND AIMS

A great amount of information has been divulged on the epidemiology and outcome of coronavirus disease 2019 (COVID-19) in patients with ESRD. The majority of the studies have been conducted in patients on maintenance hemodialysis (HD) and kidney transplant recipients. Unfortunately, few studies focused on the outcome of peritoneal dialysis (PD) patients. Information regarding this subset of the population has been extrapolated from aggregated data including a higher percentage of HD patients. As a result, the impact of COVID-19 is indefinite in patients receiving PD. We conducted a study to better understand how patients on PD have been affected by COVID-19.

METHOD

We conducted a single-center retrospective analysis of 141 PD patients followed at the University Hospital of Modena, Italy from 1 March 2020 to 31 December 2021. The diagnosis of COVID-19 was performed through nasopharyngeal swab RT–PCR testing. Duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding measured the time elapsed from diagnosis of COVID-19 to one or two (if available) negative nasopharyngeal PCR tests. Median and interquartile range or mean and standard deviation were used for continuous variables and percentage for categorical variables. A P-value <0.05 was considered statistically significant.

RESULTS

During the pandemic, 18 out of 141 (12.7%) patients receiving PD dialysis contracted COVID-19. Median age was 60 (50.2–66.5) years with a predominance of males (72.2%)

The percentage of patients on APD accounted for 33.3%.

The infection was symptomatic in out of 18 (94.4%) patients. Fever (94.4%) and cough (55.6%) were the most common symptoms. Viral shedding, traced with nasopharyngeal swabs lasted 26 (14.5–3.5) days. Two patients were inactive on the waiting list for kidney transplantation for a mean of 43 ± 1.4 days.

COVID-19 caused hospital admission of seven (38.9%) patients. During hospitalization two (11.1%) patients switched from PD to HD for ultrafiltration failure and inadequate solute clearance and two (11.1%) died for septic shock with multiorgan failure. In our cohort of patients, excess death due to COVID-19 was 22.2%.

Half of the patients contracted the infection before the availability of SARS-CoV-2 vaccine. There were no statistically significant differences between vaccinated and unvaccinated patients in terms of symptoms, viral shedding and hospital admission or (Table 1). We underline that COVID-19 was fatal only in two unvaccinated patients.

CONCLUSION

This study reports the monocentric experience of a large PD center during the COVID-19 pandemic. COVID-19 was symptomatic in the majority of patients and led to hospitalization of about 40% of the patients. The rate of symptoms, viral shedding and hospital admission was similar between vaccinated and unvaccinated patients. Two unvaccinated patients died for the severe consequence of COVID-19.