bluuebunny/crossref_metadata_2025 huggingface dataset:
MO552PHARMACOLOGICAL HIF PROLYL HYDROXYLASE INHIBITION IMPROVES EXERCISE ENDURANCE CAPACITY IN CKD MICE
Authors: Takemura Koji , Nishi Hiroshi , Higashihara Takaaki , Nangaku Masaomi
Published: May 2021

Background and Aims

Erythropoietin (EPO) and hypoxia-inducible factor (HIF) stabilizers (prolyl hydroxylase (PH) inhibitors) are efficient therapeutic modalities against anemia in chronic kidney disease (CKD). Compared to EPO and EPO receptor system, extra-renal action of PH inhibitors has still not been fully investigated. Previous reports caution us about the actual misuse of PH inhibitors in doped athletes, but the drug nonhematopoietic effects of PH inhibitors on skeletal muscles remain controversial both in healthy subjects or in patients with CKD.

Method

To study direct pharmacological effects of PH inhibitors on skeletal muscles, one of PH inhibitors, roxadustat, was administered via oral gavage to healthy 8-week-old C57BL6 mice. Plasma EPO levels and HIF-targeted gene expression were analyzed after a single administration. Exercise ability was assessed by treadmill exhaustion test after a single dose or chronic 5-week treatment. Roxadustat was also administered for 2 weeks to CKD mice with 2-week 0.2% adenine diet. Endurance capacity was similarly assessed after 2-week roxadustat treatment.

Results

Even a single administration of roxadustat increased plasma EPO levels and gene expression downstream of HIF in skeletal muscles. Healthy mice treated with roxadustat for 5 weeks showed higher blood haemoglobin (Hb) levels and improved exercise endurance in treadmill exhaustion test, which was blunted by hemodilution procedure. Adenine-fed CKD mice showed lower blood Hb levels and worse endurance capacity compared to control mice. Roxadustat treatment improved endurance capacity in CKD mice without significant increase in blood Hb levels compared to control mice.

Conclusion

Treatment with HIF-PH inhibitor, roxadustat, improves exercise endurance principally via pharmacological erythropoiesis. However, roxadustat shows potential effects independent of erythropoiesis on endurance capacity in CKD.
MO557EFFICIENCY OF FERRIC CARBOXYMALTOSE IN NON-DIALYSIS CKD PATIENTS AND ITS IMPACT ON KIDNEY FUNCTION: A PROSPECTIVE OBSERVATIONAL STUDY
Authors: Roldão Marisa , Escoli Rachele , Gonçalves Hernâni , Lopes Karina
Published: May 2021

Background and Aims

Iron deficiency anemia occurs in the vast majority of patients with chronic kidney disease (CKD). The aim of this study was to investigate the efficacy of ferric carboxymaltose (FCM) iron deficiency anemia’s treatment in non-dialysis CKD patients and to clarify its impact on kidney function.

Method

Prospective observational study of non-dialysis CKD stage 3 to 5 patients, with anemia and iron deficiency treated with FCM from 01 January 2019 to 31 June 2020. FCM was administrated as a single IV infusion of 500mg or 1000mg. Baseline clinical, analytical and demographic data were recorded. FCM efficacy was evaluated by comparing hemoglobin (Hb), serum ferritin and transferrin saturation index (TSAT) 24 ± 8 weeks after the infusion with analytical values at baseline. Renal function was also assessed at baseline and at 24 ± 8 weeks using estimated glomerular filtration rate (eGFR), calculated by CKD-EPI formula. Statistical analysis was executed using SPSS (Version 23 for Mac OSX).

Results

The average age of 71 patients was 77.31 ± 9.68 years, 29 (40.8%) were male, 46 (64.8%) were diabetic and 41 (57.8%) had congestive heart failure. Sixteen (22.5%) patients had CKD stage 3, 41 (57.7%) stage 4 and 14 (19.7%) stage 5. Twenty-five (35.2%) patients were treated with 1000mg of FCM. At baseline, average hemoglobin level (Hb) was 10.16 ± 1.12g/dL, serum ferritin 83.25 ± 96.55µg/L, TSAT 14.48 ± 6.72mg/dL and eGFR 24.21± 13.09ml/min/1.73m2. At 24 ± 8 weeks, Hb showed an increase of 1.31 ± 1.49 g/dL (p=0.001) and TSAT 10.68 ± 10.40% (p=0.001). Serum ferritin showed also an increase of 4.75 ± 180.53µg/L but did not reach statistical significance. The increase in Hb was observed uniformly across all stages of CKD. A Pearson correlation revealed a positive correlation between the variation of Hb and eGFR during the study follow-up period (r=0.310, p=0.008). A subgroup analysis was performed, patients were classified in 2 groups according to FCM dose. At baseline, there was no age, comorbidities or eGFR difference among groups. Patients treated with 1000mg had lower Hb (p=0.03) and serum ferritin (p=0.01). At 24±8 weeks both groups showed increases in Hb (p=0.001) and TSAT (p=0.001). Patients treated with 1000mg showed also a significant increase in ferritin (p=0.004). The Pearson correlation confirmed a positive correlation between the variation of Hb and eGFR in the group of patients treated with 1000mg (r=0.467, p=0.019) but not in the group treated with 500mg.

Conclusion

FCM was effective in the treatment of iron deficiency anemia in non-dialysis CKD stage 3 to 5 patients. In our population, the increase of Hb levels correlated with an improvement in eGFR in patients treated with higher doses of FCM, suggesting a positive impact of FCM on kidney function.
MO562ACUTE IMPACT OF A SINGLE HIGH DOSE OF FERRIC CARBOXYMALTOSE ON ENDOTHELIAL FUNCTION IN CKD NON-DIALYSIS PATIENTS
Authors: Mehedinti Ana-Maria , Iosif Liviu , Stoian Irina , Andreiana Iuliana , Capusa Cristina-Stela , Mircescu Gabriel
Published: May 2021

Background and Aims

Anemia is highly prevalent in CKD, and most frequently is caused by iron deficiency. Intravenous iron therapy is often and efficiently used, even in non-dialysis CKD patients. Still, experimental data suggested that intravenous iron could alter endothelial function, rising concerns related to the possible cardiovascular long-term effects. In this regard, we clinically assessed the acute impact of a high dose of iron ferric carboxymaltose (FCM), a commonly used iron formulation, on endothelial function in CKD iron-naive non-dialysis patients.

Method

In this prospective crossover single center study, forty CKD iron-deficient non-dialysis patients [median age 66.5 (56;73) years, 62% female, median estimated glomerular ﬁltration rate 24 (11;36) mL/min, 78% in the very high-risk category according to KDIGO, 90% with hypertension and 40% with diabetes mellitus] were included. The study was approved by Ethics Committee of the UMF “Carol Davila” Bucharest. Pregnancy and breast feeding, anemia of other cause, history of erythropoietin therapy, high-degree inflammation, active malignancies, glomerulonephritis or liver diseases, immunosuppressive therapy, hemoglobin <7g/dl, ferritin > 500 ng/ml and/or transferrin saturation > 50%, baseline flow mediated dilatation (FMD) < 7%, antioxidant supplements and active smoking were exclusion criteria. The effect on endothelial function was clinically assessed by comparing FMD at 15 minutes before and 15 minutes after 2 infusions: first, the comparator (250 mL 0.9% saline), and 24 hours apart, FCM (1000 mg in 250 mL 0.9% saline). FMD was measured using a Doppler ultrasound system according to guidelines recommendations. Wilcoxon paired test was used to test the post- and pre-infusion differences.

Results

Flow mediated vasodilatation and blood pressure at baseline was similar before each intervention. Neither comparator nor FCM infusion had any effect on acute changes in systolic and diastolic blood pressure. Arterial reactivity was not acutely affected after FCM [ΔFCM 0.01 (-0.35;0.15) versus saline solution 0.001 (-0.4;0.5), p=0.9].

Conclusion

A single high dose of ferric carboxymaltose did not acutely impaired endothelial function evaluated by flow mediated vasodilatation, in a CKD non-dialysis cohort.
MO544EFFECT OF DIFFERENT FREQUENCY OF FG-4592 ON CHRONIC KIDNEY DISEASE
Authors: Yin Di , Li Zuolin , Ding Zhao-ying , Liu Bicheng
Published: May 2021

Background and Aims

Hypoxia inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) is a novel small molecule inhibitor in clinical treatment for renal anemia. Several studies have shown that sustained HIF activation may also have deleterious effects, such as tubulointerstitial fibrosis. Here, the potential effects of different treatment frequency of HIF-PHI (FG-4592) on CKD (chronic kidney disease) mice were investigated.

Method

Male C57BL/6J mice were constructed by subtotal nephrectomy of 5/6 to serve as a model for CKD. We then compared four different strategies based on the frequency of FG-4592(intragastric administration, 30mg/kg) over 9 weeks: once a week (qw), twice a week (biw), three times a week (tiw), and every day (qd).

In vitro, HK-2 cells were divided into three groups according to the different administration methods of FG-4592(30μM): FG-4592 for 20h (FG0); FG-4592 for 8h, followed by washing with medium for 12h(FG1); twice FG-4592 for 8h, followed by washing twice with medium for2h(FG2).

Results

Hemoglobin in the biw group, tiw group or qd group was significantly higher than that in vehicle group. EPO, HIF-1α and HIF-2α of tiw group, biw group and qd group were significantly higher than those in vehicle group. Makers of fibrosis and inflammation in qd group were higher than that in vehicle group, while there was no statistical difference in the changes of the above indicators in tiw group and biw group. HIF-1α and HIF-2α were increased in intermittent administration, but the expression of VEGF, makers of fibrosis or inflammation were not affected. In HK2, HIF-1α and HIF-2α were activated by continuous administration of FG-4592. At the same time, the expression of VEGF, inflammatory and fibrosis indicators were increased significantly during continuous administration. In HepG2, EPO was increased in intermittent administration in HepG2 cells without VEGF increasing.

Conclusion

Taken together, our studies demonstrated that FG-4592 administration 2-3 times a week can effectively improve renal anemia without side effects on inflammatory and fibrosis.
MO576ASSOCIATION OF BONE MATERIAL STRENGTH WITH BONE DENSITY IN PATIENTS WITH END-STAGE RENAL DISEASE
Authors: Johnsson Matilda , Qureshi Abdul Rashid Tony , Jankowska Magdalena , Lindholm Bengt , Haarhaus Mathias
Published: May 2021

Background and Aims

Patients with end-stage renal disease (ESRD) have an increased risk of skeletal complications, including an increased fracture risk, which is only partially identified by determination of bone mineral density (BMD). Experimentally, the complex bone-and mineral disorders in ESRD cause disturbances of bone material properties, but these have not been studied in vivo. Determination of bone material strength index (BMSi) by reference point indentation (RPI) is a novel method to determine bone material quality in vivo and can identify patients at increased fracture risk, even in the presence of normal BMD. We determined BMSi in ESRD patients and investigated its association with BMD and serum markers of mineral metabolism.

Method

15 Adult patients with ESRD, scheduled for a living-donor kidney transplantation, were included in this cross-sectional study. Laboratory analyses included calcium, phosphate, PTH 1-84 and alkaline phosphatase. BMSi was determined by RPI with the OsteoProbe RUO in the tibia. Bone mineral density was measured by dual X-ray absorptiometry.

Results

Patients with bone mineral strenght index above median had higher bone mineral density of the right hip and total body than patients below median (p = 0.04). Alkaline phosphatase was lower in patients with BMSi below the median (47 (35-71) U/L vs. 103 (53-318) U/L, p = 0.009). There was a trend towards a significant relationship between length and BMSi (p = 0.09).

Conclusion

We identified for the first time an association of BMSi with BMD and alkaline phosphatase in patients with ESRD. Our findings of an association of BMSi with BMD are in accordance with findings in other populations with increased fracture risk.
MO577EXPANDING THE POTENTIAL BENEFITS OF FERRIC CITRATE FOR IMPROVING IRON-DEFICIENCY ANAEMIA AND MINERAL BONE DISORDER PARAMETERS IN NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE PATIENTS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Putra Boby Pratama , Putra Felix Nugraha
Published: May 2021

Background and Aims

Most of non-dialysis-dependent chronic kidney disease (NDD-CKD) patients will suffer from iron-deficiency anaemia (IDA) also mineral and bone disorders (CKD-MBD) as consequences of CKD progression. Ferric citrate (FC) is an iron-based phosphate binder that based on previous studies showed efficacies in improving IDA and CKD-MBD parameters although the results were still inconclusive. This study aims to establish the overall efficacies of FC in improving IDA and CKD-MBD parameters in NDD-CKD patients.

Method

We did comprehensive searching using predefined keywords in online databases of Pubmed, EMBASE, ScienceDirect, and The Cochrane Library, to include all relevant studies from 2000-2020. We included all randomized controlled trials (RCTs) accessing the efficacies of FC in improving IDA and CKD-MBD parameters compared with standard care (SC) in NDD-CKD patients. The CKD-MBD parameters analysed in this study are changes in serum phosphorus (P), serum calcium ions (Ca), alkaline phosphatase (ALP), intact fibroblast growth factors-23 (iFGF-23), C-terminal fibroblast growth factors-23 (cFGF-23), and intact parathyroid hormone (iPTH), while the IDA parameters analysed are changes of haemoglobin (Hb), serum iron (Fe), transferrin saturation (TSAT), and ferritin. Bias risk was accessed by using the revised Cochrane Risk-of-bias (RoB-2) tool. Analysis was performed to provide standard mean difference (SMD) with 95% confidence interval (CI) using random-effect heterogeneity test.

Results

We included six RCTs with total of 1,082 participants met our inclusion criteria. The FC significantly improve CKD-MBD parameters of P (SMD = -0.84. 95% CI = -1.21 to -0.07, p<0.00001, I2 = 74%), iFGF-23 (SMD = -0.43. 95% CI = -0.73 to -0.13, p = 0.005, I2 = 73%), cFGF-23 (SMD = -0.74. 95% CI = -1.12 to -0.35, p = 0.0002, I2 = 78%), and iPTH (SMD = -0.23. 95% CI = -0.40 to -0.06, p = 0.008, I2 = 0%), while the improvement of Ca (SMD = 0.16. 95% CI = -0.07 to 0.38, p = 0.17, I2 = 0%) and ALP (SMD = 0.03. 95% CI = -0.22 to 0.28, p = 0.81, I2 = 14%) are not statistically significant compared with the SC group. The FC also significantly improve IDA parameters of Hb (SMD = 1.10. 95% CI = 0.06 to 2.14, p = 0.04, I2 = 97%), TSAT (SMD = 1.18. 95% CI = 0.67 to 1.69, p<0.00001, I2 = 72%), and ferritin (SMD = 1.10. 95% CI = 0.34 to 1.86, p = 0.004, I2 = 87%) compared with the SC group, unless the improvement of Fe is not statistically significant (SMD = 1.34. 95% CI = -0.28 to 2.95, p = 0.11, I2 = 97%).

Conclusion

The ferric citrate shows potential benefits for improving iron-deficiency anaemia and CKD-MBD parameters in NDD-CKD patients. Nevertheless, further trials are needed to establish the efficacies.
MO578OSTEOCALCIN AND VASCULAR CALCIFICATION IN HEMODIALYSIS PATIENTS: AN OBSERVATIONAL COHORT STUDY
Authors: Keryakos Hesham Kamal Habeeb , Salama Ahmed , Okaily Nagwa , Boulis Mariam
Published: May 2021

Background and Aims

Vascular calcification contributes to morbidity and mortality in patients with ESRD on maintenance hemodialysis. to study the relationship between osteocalcin and vascular calcification.

Method

160 patients with ESRD on maintenance hemodialysis and 60 age-and sex-matched healthy controls were recruited. Serum vitamin K2 and osteocalcin both intact and undercarboxylated were measured. Transthoracic echocardiography was done for valvular calcification and thickening, and carotid duplex was done for carotid intimal medial calcification and thickening.

Results

Hemodialysis patients have higher median serum vitamin K2 (p<0.001), higher undercarboxylated osteocalcin (p<0.001). Only older age, duration of hypertension, and duration of established cardiovascular disease are associated with carotid media-intimal calcification. Old age is a strong predictor of carotid media intimal thickening. Female sex is associated with valvular thickening.

Conclusion

Functional vitamin K deficiency is present in maintenance hemodialysis patients and serum osteocalcin is not associated with cardiovascular calcification.
MO583IN VITRO AND EX VIVO EXPERIMENTS OF VASCULAR CALCIFICATION
Authors: Holmar Jana , Noels Heidi , Jankowski Joachim , Orth-Alampour Setareh
Published: May 2021

Background and Aims

Vascular calcification (VC) is one major complication in patients with chronic kidney disease whereas a misbalance in calcium and phosphate metabolism plays a crucial role. The mechanisms underlying VC have not been entirely revealed to date. Therefore are the studies aiming at the identification and characterization of the mediators/uremic toxins involved in VC ongoing and highly relevant. However, currently many different protocols being used in the studies of vascular calcification processes. This complicates the comparison of study outcomes, composing systematic reviews, and meta-analyses. Moreover, the reproducibility of data is hampered, and the efficiency in calcification research through the lack of a standardized protocol is reduced. In this study, we developed a standardized operating protocol for in vitro and ex vivo approaches to aiming at the comparability of these studies.

Method

We analysed in vitro and ex vivo experimental conditions to study VC.

Vascular smooth muscle cells (HAoSMCs) were used for in vitro experiments and aortas from Wistar rats were used for ex vivo experiments.

The influence of the following conditions was studied in detail:

• Phosphate and calcium concentrations in calcifying media.

• Incubation time.

• Fetal calf serum (FCS) concentration.

The degree of calcification was estimated by quantification of calcium concentrations that were normalized to protein content (in vitro) or to the dry weight of the aortic ring (ex vivo). Additionally, the aortic rings were stained using the von Kossa method.

Optimal conditions for investigating medial vascular calcification were detected and summarized in the step-by-step protocol.

Results

We were able to demonstrate that the degree and the location of VC in vascular smooth muscle cells and aortic rings were highly dependent on the phosphate and CaCl2 concentration in the medium as well as the incubation time. Furthermore, the VC was reduced upon increasing fetal calf serum concentration in the medium.

An optimized protocol for studying vascular calcification in vitro and ex vivo was developed and validated. The final protocol (Figure 1) presented will help to standardize in vitro and ex vivo approaches to investigate the processes of vascular calcification.

Conclusion

In the current study, we developed and validated a standardized operating protocol for systematic in vitro and ex vivo analyses of medial calcification, which is essential for the comparability of the results of future studies.
MO587PREVALENCE OF MINERAL AND BONE DISORDERS MAKERS AMONG RECIPIENTS OF KIDNEY TRANSPLANT: SINGLE-CENTER EXPERIENCE
Authors: Vatazin Andrey , Parshina Ekaterina , Kantaria Rusudana , Stepanov Vadim , Zulkarnaev Aleksei
Published: May 2021

Background and Aims

Mineral and bone disorders (MBD) are common after successful kidney transplantation in patients with chronic kidney disease (CKD). We aimed to evaluate the prevalence of biochemical abnormalities among recipients of kidney transplant.

Method

We performed a cross-sectional study of 236 patients underwent successful kidney transplantation in our clinic between 2007 and 2019. Median age was 49 [Q1-Q3: 39; 58] years, mean estimated glomerular filtration rate (eGFR) was 51,1±21,8 ml/min/1,73 m2. Most of the patients received hemo- or peritoneal dialysis treatment, pre-emptive transplantation was performed in 6% cases. For those previously received dialysis, median duration of any type of dialysis was 21 [Q1-Q3: 11; 36] months. Median time after transplantation reached 42 [Q1-Q3: 19; 75] months. We evaluated serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P) and alkaline phosphatase (AP) levels. Target ranges were defined according to National guidelines on CKD-MBD as follows: 2,1 - 2,5 mmol/l for total Ca, 0,87 – 1,49 mmol/l for P; normal AP level is defined considering a gender (53-128 Е/l for men, 42-98 Е/l for women). Target iPTH level for optimal and slightly decreased transplant function (corresponding chronic kidney diasease (CKD) stage 3T) was defined as 35-70 pg/ml, for eGFR corresponding CKD 4T – as 70-110 pg/ml, for CKD 5T – as 70-150 pg/ml.

Results

In our cohort normal iPTH level was observed only in 13% cases, whereas 84% of the patients had hyperparathyroidism. iPTH inversely correlated with eGFR (ρ= -0,454 [95%CI: -0,55; -0,34], р<0,0001 – fig.1) and its level differed significantly between groups with different CKD stage (р<0,0001, Kruskall-Wallis test) – fig.2. However, fraction of patients with target iPTH did not differ in recipient groups with normal and decreased eGFR (p=0,118). Hypercalcaemia was observed in 29% cases; there was a weak correlation of serum total Ca level with iPTH (ρ= 0,282 [95%CI: 0,15; 0,4], р<0,0001) and AP (ρ=0,181 [95%CI: 0,05; 0,31], р=0,006) – fig.3. Hypophosphatemia was seen much more frequently during the first year after transplantation than in long-term period (30,3% vs 6,4% respectively, р=0,0002). Serum P level varied significantly in groups with different eGFR (p<0,0001, Kruskall-Wallis test), increasing in parallel with declining of transplant function – fig.4. The percentage of patients within a target range of AP amounted to 54%, above the target range – 40,7%. In total, only 6,8% of our cohort had all laboratory parameters within the target range.

Conclusion

We observed a high prevalence of biochemical abnormalities in kidney transplant patients confirming that transplantation itself does not cure mineral and bone disorders in CKD patients.
MO565M2 MACROPHAGES REGULATE MOUSE AORTIC SMOOTH MUSCLE CELL CALCIFICATION BY TRANSMITTING SENESCENCE INFORMATION
Authors: Fang Yaping , Zhu Xiaodong , Zhao Yu , Zhang Xiao liang
Published: May 2021

Background and Aims

Vascular calcification is highly prevalent in chronic kidney disease (CKD)with high morbidity and mortality. Complex pathological mechanisms are involved in the development of vascular calcification, including aging. Previous work have indicated that M2-macrophage promote mouse aortic smooth muscle cells (MAoSMCs) calcification. The present study aimed to understand the contribution of M2-macrophage to MAoSMCs calcification by focusing on the mechanisms underlying the transmitting senescence information

Method

The expression of IFITM3 and P16, marker of aging, in aging macrophages were confimed by RT-qPCR, western blotting and immunofluorescence staining. Then, the MAoSMCs were co-cultured with the supernatant of M2 macrophages. The expression of IFITM3 and P16 in MAoSMCs also were detected. Alizarin red staining and calcium content assay were used to analyse MAoSMCs calcification. We modulated the expression of IFITM3 using siRNAs to study M2-macrophages function in regulating MAoSMCs calcification.We detected the expression of IFITM3 and P16 in co-cultivate MAoSMCs and validate intracellular calcium contents by calcium test kit.

Results

In the present study, we observed a significant increase in the expression of IFITM3 and P16 expression in M2 macrophages.Compared with M0 and M1 macrophages, the expression of IFITM3 and P16 at lowlevel. Alizarin red staining and calcium content assay revealed that M2 macrophage-mediated IFITM3 and P16 overexpression led to an apparent VSMC calcification in the presence of M2 macrophages medium.By contrast, inhibition of IFITM3 by siRNAs significantly blocked calcification of VSMCs in vitro. Moreover, we found that aging macrophages that overexpressed of IFITM3 and P16 increased in rats with CKD. Furthermore, pharmacological inhibition of aging signal was shown to block IFITM3-induced VSMC calcification. These findings demonstrate for the first time that M2 macrophage-mediated IFITM3 contributes to vascular calcification through a mechanism involving transmitting Senescence signalling.

Conclusion

Collectively, our present study demonstrated that the functional importance of M2 macrophage-IFITM3 dependent vascular calcification and provided a novel mechanistic insight to the macrophage senescence in CKD.
MO570PULSE PRESSURE: A PREDICTOR OF CARDIOVASCULAR CALCIFICATION AND CARDIOVASCULAR MORTALITY IN HEMODIALYSIS PATIENTS
Authors: Rroji (Molla) Merita , Seferi Saimir , Cafka Majlinda , Likaj Erjola , Cadri Vilma , Barbullushi Myftar
Published: May 2021

Background and Aims

The mortality rate is extremely high in chronic kidney disease (CKD), primarily due to the high prevalence of cardiovascular disease (CVD). Increased pulse pressure (PP), defined as the difference between inappropriately elevated systolic blood pressure (SBP) and reduced diastolic blood pressure (DBP) at any value of mean arterial pressure (MAP), is a surrogate measure of increased arterial stiffness of central elastic arteries (aorta and its major branches). CKD-MBD anomalies leading to calcification contribute to increased arterial stiffness and pulse pressure. This study aimed to evaluate the relationship of pulse pressure parameter with valve calcification and abdominal aortic calcification in hemodialysis patients and its impact on cardiovascular mortality.

Method

We performed a prospective case series study with 3 years follow- up. Plain X-ray images of the lateral lumbar spine from all subjects were studied to obtain images of the lower abdominal aorta using semiquantitative scores as described by Kauppila et al. Cardiac valve calcifications were evaluated by two-dimensional echocardiography with an HDI 5000 Sono CT echocardiographic machine with a 3.3-MHz multiphase array probe in subjects lying in the left decubitus position an according to the recommendations of the European Association of Echocardiography. The patient was evaluated as having vascular calcification if he had the presence of calcification in at least one of the site examined: a mitral valve, aortic valve or abdominal aorta.

Results

We studied 85 chronic stable hemodialysis patients. Mean age and meantime is therapy was 49.9±12.4 years and 51.5±28.7 months, respectively. Mean pulse pressure was 55.72±14.2 mmHg. Fifty-nine patients (69.4%) were identified with aortic abdominal calcification, and the mean Kauppila score was 4.91 ± 4.05. Sixty patients (70.5%) had at least one valve calcified, while thirty-three patients (38.8%) had both valves calcified. Univariate analysis revealed that every 1 mmHg increase in pulse pressure was associated with increased cardiovascular calcification risk p=0.020. In multivariate analysis, after adjustment for age, gender, diabetes mellitus, cholesterol, and triglyceride serum levels, the association also remained strong, where every increase of 1 mm Hg in pulse pressure was associated with increased risk for cardiovascular calcification (HR 1.02, 95% CI (1.00-1.03), p= 0.038). Besides, pulse pressure was an independent predictor for cardiovascular mortality (HR 1.03, 95% CI (1.02-1.05), p=0.002).

Conclusion

Pulse pressure may identify hemodialysis patients with subclinical cardiovascular calcification who need further evaluation. Wide pulse pressure is associated with increased cardiovascular mortality.
MO490SYMPTOM BURDEN AND ITS IMPACT ON QUALITY OF LIFE IN PATIENTS WITH MODERATE TO ADVANCED CKD
Authors: Speyer Elodie , Tu Charlotte , Zee Jarcy , Sesso Ricardo , Lopes Antonio , Hoshino Junichi , Ayav Carole , Pisoni Ronald , Pecoits-Filho Roberto , Stengel Benedicte
Published: May 2021

Background and Aims

It is generally considered that the early stages of CKD are asymptomatic, and that CKD becomes apparent once kidney function is significantly impaired, but large-scale studies in real-world non-dialysis CKD patients under nephrology care are still scarce. We evaluated symptom burden and its impact on quality of life in patients with moderate to advanced CKD.

Method

4423 patients with CKD Stage 3 to 5 from Brazil (N=548), France (N=2691), and the US (N=1184) enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) from 2013-2019 completed the Kidney Disease Quality of Life (KDQOL) questionnaire at baseline to assess how much they were bothered by 13 symptoms. Response options ranged from “not at all” to “extremely” bothered. From these Symptoms/Problems of Kidney Disease items, a score was calculated, ranged from 0 to 100, and analyzed in 3 categories: low (≥90), intermediate (66-90), or high symptom burden (<66). Poisson regressions were used to estimate prevalence ratios for each symptom and to study associations between CKD stage and a high symptom burden before and after adjusting for demographics and major comorbidities. Multiple linear regression accounting for clustering at the clinic level was used to examine associations between high symptom burden and physical and mental component summary (PCS and MCS, respectively) scores, with lower scores indicating poorer quality of life.

Results

Patients (mean age 68±13 years, 40% women, mean eGFR at baseline 30.4±12.2 mL/min/1.73m²) were very much to extremely bothered by a number of symptoms, the prevalence of three of which - washed out or drained, nausea or upset stomach, and lack of appetite – significantly increased in more advanced CKD stages before and after adjusting for confounders (Figure). Nearly one in four patients reported a high symptom burden, which was more prevalent in women, those with obesity, anemia, or albumin<3.5 g/dL; it was also more common in France than in the US and Brazil. In adjusted models, as compared to patients with low symptom burden, those with high symptom burden had a worse quality of life with PCS and MCS scores 14.6 (95% confidence interval [95% CI], 15.7 to 13.5) and 7.2 (95% CI, 8.3 to 6.1) points lower, respectively.

Conclusion

Our findings demonstrate a high symptom burden even in nondialysis CKD stages 3-5 with a substantial impact on physical and mental health-related quality of life. Several symptoms, particularly fatigue, and gastrointestinal symptoms, appeared to worsen with increasing CKD stage, independent of patient comorbidities.
MO499CKD-MBD BIOMARKERS AND CKD PROGRESSION: AN ANALYSIS BY JOINT MODELS
Authors: D'Arrigo Graziella , Mallamaci Francesca , Pizzini Patrizia , Versace Maria Carmela , Tripepi Giovanni Luigi , Zoccali Carmine , Mauro Working Group Of behalf of
Published: May 2021

Background and Aims

Biomarkers of the Chronic Kidney Disease – Bone Mineral Disorder (CKD-BMD)-including serum phosphate, calcium, PTH, 1,25 vitamin D, alkaline phosphatase and FGF23- have been implicated in CKD progression in follow up studies focusing on single measurements made at baseline only. The relationship between the time trend of these biomarkers over the course of CKD and renal outcomes has never been tested.

Method

In this study we applied the joint model, an approach combining the mixed linear model (MLM) and Cox’s regression analysis, to investigate the longitudinal relationship between repeated measurements (median 3, interquartile range 2-5) of serum phosphate, calcium, PTH and alkaline phosphatase and a composite renal outcome measure (eGFR reduction >30%, dialysis or transplantation) cohort of 729 stage 2-5 CKD patients (average eGFR = 36±13 ml/min/1.73 m2) over a 2.4 year follow up. Data were adjusted for traditional and CKD specific risk factors in models including also baseline serum 1,25 vitamin D and FGF23.

Results

On univariate MLM analyses, serum PTH was the sole CKD-BMD biomarker which significantly changed over time [b=0.030 (95% CI from 0.018 to 0.041), p<0.001]. In the multivariate mixed linear sub-model of the Joint Model, repeated measurements of PTH were related directly with male gender (P=0.033), alkaline phosphatase (P<0.01) and systolic BP (P=0.004) and inversely with calcium (P<0.001), baseline eGFR (P<0.001), and CRP (P<0.045). In the survival analysis sub-model of the joint model, the longitudinal series of PTH valuesover time were directly related to the incidence rate of renal events [HR (1 ln increase in PTH)=3.358 (95% CI from 2.628 to 4.293), p<0.001] and this was also true after data adjustment for a series of potential confounders [HR (1 ln increase in PTH)=2.25 (95% CI from 1.524 to 3.321), p<0.001]. In this analysis, also serum phosphate, baseline FGF23, proteinuria, baseline 1.25 vit D, calcium, and haemoglobin were significantly related to the incidence rate of renal events and these relationships were all independent of the baseline eGFR.

Conclusion

In this longitudinal study in stage 2-5 CKD patients investigating the links of CKD-MBD biomarkers with a composite renal outcome, PTH was the sole variable to show a linear increase overtime and to be directly related with the same outcome. Even though stable over-time, also the longitudinal series of serum phosphate (in a direct fashion) and calcium (in an inverse fashion) values were related to the same outcome as it were baseline FGF23 and 1.25 vit D. Findings in this longitudinal study further underscore the potential relevance of CKD-MBD biomarkers as risk factors for CKD progression.
MO501INCREASED ALBUMINURIA RISK IN CHRONIC KIDNEY DISEASE PATIENTS WHOSE WHITE COAT-, MASKED-, AND SUSTAINED HYPERTENSION: SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Putra Boby Pratama , Putra Felix Nugraha
Published: May 2021

Background and Aims

Latest classification of hypertension based on ambulatory blood pressure measurement was normotension (NT), white coat hypertension (WCHT), masked hypertension (MHT), and sustained hypertension (SHT). Recent studies suggest that WCHT, MHT, and SHT increase risk of target organ damage, particularly albuminuria, although the results were still inconsistent. Albuminuria is not only the sign of early glomerular damage in CKD patients, but also the signs of hypertension progression and predictors for cardiovascular events mortality. This study aims to compare the albuminuria risk among NT and WCHT, MHT, also SHT in CKD patients.

Method

We searched the literature comprehensively in online databases of Pubmed, EMBASE, ScienceDirect, and Cochrane Library to include all relevant studies using predefined terms until December 2020. We included studies that analyzed the albuminuria risk and compared the log2 urinary albumin-to-creatinine ratio (ACR) among NT and WCHT, MHT, or SHT in CKD patients. We used the Newcastle-Ottawa Scale for Observational Study checklist for evaluating bias risks. Analysis of the studies was conducted to provide pooled Odds Ratio (OR) for albuminuria risk and standard mean difference (SMD) for log2 ACR comparison with 95% Confidence Interval (CI) with random-effect heterogeneity test.

Results

We included 7 observational studies met our inclusion criteria. WCHT increases albuminuria risk although not statistically significant (pooled OR = 1.72, 95%CI 0.97 to 3.07, p = 0.06, I2 = 75%), while MHT and SHT significantly increase albuminuria risk with pooled OR respectively 1.62 (95%CI 1.03 to 2.53, p = 0.04, I2 = 82%) and 3.17 (95%CI 1.66 to 6.05, p = 0.0005, I2 = 94%). Controlled hypertension significantly protects CKD patients against albuminuria risk based on log2 ACR comparison with WCHT (SMD = 0.52, 95%CI 0.38 to 0.67, p<0.00001, I2 = 0%), MHT (SMD = 0.34, 95%CI 0.19 to 0.49, p<0.0001, I2 = 39%), and SHT (SMD = 0.63, 95%CI 0.31 to 0.95, p=0.0001, I2 = 76%).

Conclusion

White coat hypertension, masked hypertension, and sustained hypertension increase albuminuria risks in CKD patients. However, further studies are needed to determine the causality.
MO503SAFETY AND EFFICACY OF ANTICOAGULATION IN PATIENTS WITH EGFR<30 ML/MIN/1.73 M2 AND ATRIAL FIBRILLATION
Authors: Freese Ballegaard Ellen Linnea , Bjerring Olesen Jonas , Kamper Anne Lise , Feldt-Rasmussen Bo , Gislason Gunnar , Torp-Pedersen Christian , Carlson Nicholas
Published: May 2021

Background and Aims

Net benefit of anticoagulation in patients with eGFR <30 ml/min/1.73 m2 and atrial fibrillation remains uncertain. The aim of this study was to evaluate the use, efficacy and safety of anticoagulation therapy in patients with eGFR<30 ml/min/1.73m2 (including dialysis treated patients) and atrial fibrillation.

Method

In a retrospective cohort study, all patients with atrial fibrillation and eGFR<30 ml/min/1.73 m2 were identified in nationwide Danish registers between 2008 and 2018. Cumulative incidences of stroke and major bleeding stratified on anticoagulation treatment were computed using the Aalen-Johansen estimator. One-year risks of stroke and major bleeding were calculated with comparison of treatment vs. no treatment based on Cox regression models adjusted for age, sex and dialysis status with G-computation of one-year risks standardized to the distribution of risk factors in the sample. Major bleeding was defined as any diagnosis of bleeding leading to hospitalization.

Results

A total of 2,452 patients with eGFR <30 ml/min/1.73 m2 and de novo atrial fibrillation were identified. Mean age was 78.8 years, 51.3% were male and 20% received dialysis therapy. Anticoagulation therapy was initiated in 877 patients (35.8%), with warfarin accounting for 58.6% of all prescriptions.

Overall, one-year standardized risk of bleeding was 10.6% (95% confidence interval (CI) 8.7%-12.7%) and 8.2% (95% CI 6.9%-9.5%) in patients with and without anticoagulation, while the risks of stroke were 3.6% (95% CI 2.6%-4.5%) and 5.1% (95% CI 4.1%-6.1%), respectively.

In subgroup analyses of patients dependent vs. non-dependent on dialysis, the standardized one-year risk of bleeding was 13.3% (95% CI 9.0%-19.8%) vs. 10.4% (95% CI 8.6%-12.4%) in patients with anticoagulation and 9.0% (95% CI 6.5%-12.0%) vs. 7.8% (95% CI 6.5%-9.2%) in patients without anticoagulation. While the risk of stroke was 3.5% (95% CI 0.8%-6.7%) vs. 3.5% (95% CI 2.5%-4.9%) in patients with anticoagulation and 5.7% (95% CI 3.5%-7.8%) vs. 4.9% (95% CI 3.7% vs. 6.3%) in patients without anticoagulation. Cumulative incidences of major bleeding and stroke are shown in the figure.

Conclusion

Use of anticoagulation was associated with increased risk of bleeding and reduced risk of stroke in patients with eGFR<30 ml/min/1.73 m2 and atrial fibrillation. Randomized controlled trials are needed to establish the benefit and harm of anticoagulation in this population.
MO504LOW BIRTH WEIGHT ASSOCIATES WITH SMALLER KIDNEY SIZE IN MIDDLE-AGED WOMEN
Authors: Lillås Bjørn Steinar , Qvale Tor Hatlestad , Richter Blazej Konrad , Vikse Bjørn Egil
Published: May 2021

Background and Aims

Low birth weight is associated with increased risk of kidney disease due to lower nephron endowment leading to hyperfiltration and subsequent nephron loss. Nephron number is thought to associate with kidney size. We compared kidney size measured by magnetic resonance imaging (MRI) with ultrasonography and measured glomerular filtration rate (mGFR) in adults with normal versus low birth weight.

Method

Healthy individuals aged 42-52 years with Low birth weight (LBW – 1100-2300g) and normal birth weight (NBW - 3500-4000g) were invited. GFR was measured using plasma clearance of iohexol. Kidney volume was measured on MRI images using axial T2 images and coronal T1 images with fat saturation without contrast enhancement, calculations were performed according to the ellipsoid formula - π/6 x Length x Width x Depth. Ultrasonographic imaging was done using a dorsal approach. In the maximal longitudinal view the parenchymal area was calculated subtracting the area of a manual tracing around the renal pelvis from the area of a manual tracing of the whole kidney. Volume and area from the two kidneys were added and total value was used for analyses. Kidney size measurements were compared between the two groups of LBW vs NBW, and analysis using Pearson’s correlation coefficient R between kidney volume and measured GFR and parenchymal area was performed.

Results

We included 102 individuals (54 LBW, 48 NBW). Total kidney volume was 302 ± 51 ml for female NBW vs 258 ± 48 ml for female LBW (p=0.002). For men, total kidney volume was 347 ± 51 ml vs 340 ± 65 ml (p=0.7). Measured GFR was significantly associated with kidney volume with R=0.52 (p<0.001) for women and R=0.39 (p=0.007) for men. Kidney parenchymal area measurements using ultrasonography showed similar results with an R=0.77 between the MRI and the ultrasonography measurement and similar differences for sex and birth weight were seen.

Conclusion

Healthy middle-aged females born with LBW have smaller kidneys than healthy middle-aged females born with NBW, no difference were seen for males. Kidney volume associate with measured GFR.
MO505IMPACT OF THE COVID-19 PANDEMIC ON SYMPTOMS OF ANXIETY AND DEPRESSION AND HEALTH-RELATED QUALITY OF LIFE IN OLDER PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Voorend Carlijn , Van Oevelen Mathijs , Nieberg Margot , Meuleman Yvette , Franssen Casper , Joosten Hanneke , Berkhout-Byrne Noeleen , Abrahams Alferso C , Bos Willem Jan W , Van Buren Marjolijn
Published: May 2021

Background and Aims

Older patients with advanced chronic kidney disease (CKD) are at increased risk for a severe course of the coronavirus disease-2019 (COVID-19) and vulnerable to mental health problems. We aimed to investigate prevalence and associated patient (demographic and clinical) characteristics of mental wellbeing (health-related quality of life [HRQoL] and symptoms of depression and anxiety) before and during the COVID-19 pandemic in older patients with advanced CKD.

Method

An ongoing Dutch multicentre prospective cohort study enrols patients of ≥70 years with an eGFR <20 mL/min/1.73m2 from October 2018 onward. With additional questionnaires during the pandemic (May-June 2020), disease-related concerns about COVID-19 and general anxiety symptoms were assessed cross-sectionally, and depressive symptoms, HRQoL, and emotional symptoms longitudinally.

Results

The 82 included patients had a median age of 77.5 years (inter-quartile range 73.9-82.1), 77% was male and none had tested positive for COVID-19. Cross-sectionally, 67% of the patients reported to be more anxious for COVID-19 because of their kidney disease, and 43% of the patients stated that their quality of life was reduced due to the COVID-19 pandemic (Figure 1). Higher COVID-19-related stress was associated with a lower education level (p=0.036), and patients who reported to feel more down due to COVID-19 were more often female (p=0.020). Anxiety scores were higher among females compared to males (median 4.0 [IQR 3.0-9.0] versus 2.0 [0.0-6.0], p=0.020), and weakly associated to a decline in eGFR (correlation coefficient 0.197, p=0.023).

Compared to pre-COVID-19, presence of depressive symptoms had increased (11% to 22%; p=0.022) and physical HRQoL declined (40.4±10.1 to 36.1±10.4, p<0.001). Mental HRQoL (50.3±9.6 to 50.4±9.9; p=0.913) and emotional symptoms remained similar. Males showed a greater decline in physical HRQoL (mean -5.3, SD 8.5) compared to females (mean -0.9, SD 5.7; p=0.039).

Conclusion

Our findings show that older patients with advanced CKD suffered from disease-related anxiety for COVID-19, increased depressive symptoms, and reduced physical HRQOL during the COVID-19 pandemic. The impact of the pandemic on this vulnerable patient group extends beyond increased mortality risk, and awareness of mental health problems during the pandemic is essential. More in-depth investigation on disease-related COVID-19 concerns and its implications for the CKD population is needed.
MO506RELATIONSHIP BETWEEN SODIUM CONSUMPTION, PRO-INFLAMMATORY PARAMETERS AND KIDNEY DISEASE IN THE JACKSON HEART STUDY
Authors: Wenstedt Eliane , Vogt Liffert
Published: May 2021

Background and Aims

Kidney disease is thought to be linked to inflammation. Pro-inflammatory parameters like C-reactive protein (CRP), endothelin-1, and TNF-a inversely associate with kidney function cross-sectionally and some have predictive value for longer-term kidney outcomes. Given the recently argued pro-inflammatory effect of sodium, we questioned whether sodium consumption has a role in the relationship between pro-inflammatory parameters and renal outcomes.

Method

Our research question was investigated using the Jackson Heart Study, which is a large prospective cohort study involving n=5301 Afro-Americans residing in Jackson, Mississippi, US. Spot urine sodium was used to estimate 24-hour sodium excretion with the Kawasaki formula, serving as a proxy for sodium consumption, and was available for n=1831 participants (depicting a random sample of the total population) that had a median follow-up of 8 years. Multiple linear regression was used to assess the relationship between sodium consumption and pro-inflammatory parameters. The parameters available for this cohort involved endothelin-1, high-sensitivity CRP, and leukocyte subsets (monocytes, neutrophils, and lymphocytes). Models were adjusted for potential confounders, involving sex, age, body mass index, estimated potassium intake, smoking status, and presence of diabetes. Subsequently, linear regression analyses between pro-inflammatory parameters and baseline estimated glomerular filtration rate (eGFR CKD-EPI) and change during follow-up were carried out with and without adjustment for sodium consumption as a confounder, to explore the possibility of a causal mediating pathway.

Results

Increased sodium consumption significantly associates with increased serum endothelin-1 levels in both unadjusted and adjusted models (Table 1). There was no association between sodium consumption and leukocyte subsets. There was a negative association between sodium consumption and CRP (Table 2). CRP was not associated with eGFR at baseline (p=0.20) or eGFR change from baseline (p=0.20). Endothelin-1 was inversely associated with eGFR at baseline (beta -0.06, p<0.001) and with eGFR change from baseline (beta 2.3 p=0.03). However, when these models were corrected for sodium consumption, endothelin-1 was no longer a significant predictor (beta -0.01 p=0.4 for eGFR at baseline) or was inversed (beta -0.1; p=0.001 eGFR during follow-up).

Conclusion

In this prospective cohort of Afro-Americans, increased sodium consumption is associated with increased circulating endothelin-1 levels. If this relationship proves to be causal (as suggested by animal sodium loading studies), this implies that sodium consumption may (at least partly) be underlying the relationship between endothelin-1 and worse renal outcomes.