bluuebunny/crossref_metadata_2025 huggingface dataset:
P0935ASSOCIATION OF DIETARY INTAKE WITH SERUM LEVELS OF PHOSPHORUS AND POTASSIUM IN KOREAN HEMODIALYSIS PATIENTS USING NEWLY DEVELOPED SEMI QUANTITATIVE FOOD FREQUENCY QUESTIONNAIRE(SEMI-FFQ)
Authors: Kim Jung-Hyun , Ryu Dong-Ryeol , Kim Hyun-Jung , Kyung Min-Sook
Published: June 2020

Background and Aims

Dietary intake patterns in hemodialysis (HD) patients in Korea are diverse and unique comparing with those of other countries. Hyperphosphatemia and hyperkalemia are closely related to intake of dietary phosphorus and potassium. Dietary intake of Korean HD patients was analyzed using newly developed semi-FFQ for Korean food in order to get the baseline data for improving a dietary management guide for Korean HD patients.

Method

We investigate the effects of consumed food on serum phosphorus and potassium levels of 128 HD patients(74 males and 54 females) in 6 tertiary referral hospitals using semi-FFQ consisting of 23 food meal items based on the Korean usual diets.

Results

The mean age was 59.7±11.6 years for males and 58.9± 9.3 years for females and the hemodialysis duration was 5.4±5.6 years for men and 5.4±3.9 years for women, respectively. Mean serum phosphorus level was 4.50±1.52 mg/dl and mean serum potassium level was 4.74±0.73 mEq/L. Hyperphosphatemia was found in 45.8% of the subjects, and hyperkalemia in 35.4%. Energy, protein and other nutrients intake were significantly lower than the recommended intakes for HD patients (p<0.05). Serum phosphorus levels showed positive correlation with intake of mixed grain meals (p<0.05). There was a significant difference in the daily intake frequency of cooked rice between males (2.5±0.76/day) and females (2.15±0.86/day)(p<0.001). The noodle intake frequency also showed a significant difference between males (0.09±0.14/day) and females (0.04±0.06/day) (p<0.001). Serum potassium level showed positive correlation with intake of potatoes, high-potassium vegetables & fruits and Kimchi (p<0.05). There was a significant gender difference in the daily intake frequency of Kimchi between males (1.28±0.11/day) and females (1.07±0.99/day)(p<0.05). In case of medium and high potassium vegetables & fruits, consumption was higher in females than in males (p<0.05). Intake of white rice showed negative correlation with serum potassium levels (p<0.05).

Conclusion

Intake of white rice meals rather than mixed grains meals is an important factor for maintaining normal serum phosphorus and potassium levels. Intake of potatoes, medium and high potassium vegetables & fruits is recommended to be reduced to less than three serving per week. Considering abundance of potassium and phosphorus in Korean food pattern, customized dietary management as well as medical treatment is essential in all HD patients.
P0945STUDY PROTOCOL: ADIPOSE TISSUE CONTENT OF N-3 POLYUNSATURATED FATTY ACIDS AND THE RISK OF CHRONIC KIDNEY DISEASE
Authors: Hashemi Bahram , Berg Schmidt Erik , Svensson My , Lundbye-Christensen Søren , Bork Christian , Hagstrup Christensen Jeppe
Published: June 2020

Background

Chronic kidney disease (CKD) is associated with life style diseases such as hypertension and type 2 diabetes. However the role of diet is not yet clearly defined for development of CKD.

Recent studies have shown that n-3 polyunsaturated fatty acids (PUFAs) may exert favourable effects on several processes that may inhibit the development and progression of CKD.

A gold standard biomarker for long-term intake and metabolism of n-3 PUFAs, is their content in adipose tissue; because these fatty acids are essential and not endogenously produced.

Aims

The primary aim of this study is to investigate the association of adipose tissue content of marine and plant-based n-3 PUFAs to the risk of incident CKD.

This study will also examine associations between the content of n-3 PUFAs in adipose tissue and the risk of main subtypes of CKD: Proteinuria with unknown cause, Hypertensive nephropathy, Glomerular diseases, Diabetic nephropathy and Chronic renal failure of unknown cause.

Method

In this case-cohort study based on data from the prospective Danish Diet, Cancer and Health cohort (DCH), information concerning diet and other lifestyle factors was obtained from 57,053 Danish men and women aged 50 to 65 years, using questionnaires and interviews. Anthropometric measurements were undertaken, and adipose tissue biopsies were taken from the buttocks of all participants at baseline.

The follow-up period was from December 1993 to September 2017. The outcome CKD is defined as having a diagnosis of one of the CKDs causes in the Danish National Patient Registry (DNPR). Cases of CKD will be identified and included together with a randomly drawn subcohort, representative for all participants of the cohort. Adipose tissue samples will be analyzed by gas chromatography in all incident CKD cases and in 5,000 randomly drawn participants from the whole cohort.

The outcome will be adjusted for age, sex, body mass index, physical activity, energy intake, alcohol consumption, fermented dairy products, education, smoking status, hormone replacement therapy and comorbidity.

The study is approved by the Danish National Committee on Health Research Ethics (N-20180074) and the Danish Data Protection Agency (2018-139).

Results

No results are available yet.

Conclusion

Our hypothesis is that the content of total n-3 PUFAs, as well as both marine and plant-based n-3 PUFAs, in adipose tissue is inversely associated with the risk of CKD and its subtypes.
P0948ASSOCIATION OF PHASE ANGLE WITH NUTRITION, MORTALITY, MAJOR ADVERSE CARDIOVASCULAR EVENTS AND SARCOPENIA IN MAINTENANCE HEMODIALYSIS PATIENTS
Authors: Bae Eunjin , Lee Tae Won , Jang Ha Nee , Cho Hyun Seop , Kim Hyun-Jung , Chang Se-Ho , Park Dong Jun
Published: June 2020

Background and Aims

Nutrition has been consistently important in end stage renal disease patients. However, it is difficult to obtain adequate nutritional status while avoiding fluid overload, hyperphosphatemia and hyperkalemia in hemodialysis patients. In addition, there is no golden standard for diagnosing protein energy wasting (PEW) in maintenance hemodialysis patients. We studied the clinical significance of phase angle using bioelectrical impedance analysis (BIA), one of the PEW diagnostic tools, to predict various clinical outcomes in maintenance hemodialysis patients.

Method

We retrospectively enrolled patients who received hemodialysis for more than 3 months from 2016 to March 2019, excluding patients had active cancer, or died within 30 days, had no BIA data. We evaluated the factors related phase angle and the role of phase angle as predictors of all-cause mortality and major adverse cardiovascular events (MACE), sarcopenia.

Results

Of 191 patients, 63.4% were men, mean age was 64.2 ± 12.4 years, mean body mass index (BMI) was 23.8 ± 6.9 kg/m2, and the most common underlying disease were hypertension and diabetes mellitus. Lower phase angle group (phase angle ≤4°) patients had older age, higher portion of women, malnourished, and history of coronary artery disease (CAD) than higher phase angle group (phase angle >4°) patients. Phase was significantly related with nutritional parameters. During a median follow up of 16.7 months, 14.1% (n=27) patients experienced a MACE, 11.0% (n=21) patients died. In multivariate Cox analyses, lower phase angle, higher CRP level and history of CAD were significantly related with all-cause mortality even after adjustment for covariates. However, phase angle was not significantly associated with MACE and sarcopenia.

Conclusion

In maintenance hemodialysis patients, phase angle was significantly related to mortality as well as nutritional status, but MACE and sarcopenia were not. Clinicians should be careful to find and treat correctable factors with low phase angle and high CRP level in maintenance hemodialysis patients.
P0960HOME BASED RESISTANCE EXERCISE PROGRAM AND SARCOPENIA IN HEMODIALYSIS PATIENTS: IT IS A USEFUL INTERVENTION?
Authors: Esteve Simó Vicent , Junqué Jiménez Anna , Duarte Gallego Verónica , Tapia González Irati , Moreno Guzmán Fátima , Fulquet Nicolás Miquel , Pou Potau Mónica , Saurina Solé Anna , Ramírez de Arellano Serna Manel
Published: June 2020

Background and Aims

Sarcopenia is a skeletal muscle disorder associated with adverse outcomes including falls, physical disability and mortality particularly in hemodialysis (HD) patients. Currently, progressive resistance training exercise has been shown a proven method to treat and prevent sarcopenia. Nevertheless, these findings are poorly investigated in HD patients since exercise programs are not widespread.

The aim of our study was to assess the effect of a home-based resistance exercise program (HBREP) on muscular strength, functional capacity and body composition in our hemodialysis patients with sarcopenia according to the European Working Group on Sarcopenia in Older People criteria (EWGSOP2).

Method

A 12 weeks single-center prospective study. HD patients from our institution with EWGSOP2 sarcopenia diagnosis were enrolled in a HBREP. Demographical an anthropometrical data, main biochemical and nutritional parameters, hand grip (HG) muscular strength, functional capacity tests: Sit to stand to seat 5 (STS5); Short Physical Performance Battery (SPPB), gait speed (GS), as well as body composition determined by electrical bioimpedance (BIA) and sarcopenia severity were analized.

Results

18 HD patients with sarcopenia (71.4% severe) were included (4 drop out).78.6% men. Mean age 74.7 years and 53.3 months on HD. The main etiologies of ESRD were the HBP (21.4%) and DM (14.3%). Globally, a significant improvement was observed at the end of the study in relation to muscular strength (HG 19.9±6.1 vs 22.2±7.1 kg, p 0.001) and functional capacity tests (STS5 21.9±10.3 vs 17.2±9.9 sec, p 0.001; SPPB (6.9±2.3 vs 9.1±2.5 score, p 0.001 and GS 0.8±0.1 vs 0.9±0.2 m/s, p 0.015). Likewise, higher total skeletal muscle mass (SMM, 14.3±2.8 vs 14.5±2.9 kg) and SMM index (SMM/height2, 5.5±0.7 vs 5.7±0.9 Kg/m2 ) were found at the end of the study, although these differences were not significant. Finally, 2 patients (14.8%) reverse the EWGSOP2 sarcopenia criteria and 3 (21.4%) enhanced their severe sarcopenia. No relevant changes regarding anthropometrical data, main biochemical and nutritional parameters or dialysis adequacy were observed at the end of the study.

Conclusion

A home-based resistance exercise program improves muscular strength, functional capacity and body composition in our sarcopenic hemodialysis patients. With our results, home-based resistance exercise programs should be considered a key point in the prevention and treatment of skeletal muscle mass reduction due to sarcopenia in these patients. Further studies are mandatory to confirm our encouraging results.
P0983INHIBITION OF ATF3 BY RAF INHIBITOR GW5074 ON DIABETIC NEPHROPATHY
Authors: Han Jee Young , Cha Jin Joo , Kang Young Sun , Ghee Jung Yeon , Yoo Ji Ae , Cha Dae
Published: June 2020

Background and Aims

Activating Transcription Factor 3 (ATF3) is a stress-adaptive transcription factor, which has been suggested to be involved in maintaining glucose homeostasis. ATF3 respond rapidly to various stimuli like high glucose, fatty acids and oxidative stress, and is observed to either protective or detrimental effects in diabetic condition. Therefore to elucidate the exact role in diabetic nephropathy of ATF3, we investigated the role of ATF3 by inhibition with Raf-inhibitor GW5047 on diabetic mice model.

Method

ATF3 level was examined in the mouse podocytes and NRK cells with either overexpression or downregulation with ATF3. 8 week db/m and db/db mice as the model of diabetic mice were examined for the expression of ATF3 and were treated with GW5074, a Raf1 kinase inhibitor targeting the ATF3 intraperitoneally with a dose of 0.5mg/kg for 12 weeks.

Results

In cultured mouse podocytes and NRK cells, high glucose and angiotensin II markedly increased ATF3 expression. Gene Expressions of NOX4, MCP-1 and NF-kB were augmented by ATF3, and were attenuated by ATF3 siRNA. In db/db mice, plasma ATF3 level was not different from control db/m, however the urinary ATF3 excretion was significantly higher. Treatment of GW5074 decreased urinary ATF3 excretion. After 12 week treatment, serum creatinine level was significantly lower in the treatment db/db group, with less systemic oxidative stress. There were no significant differences in body weight, whereas the food intake was decreased in GW5047 group. Overall lipid profile or HOMA-IR, HbA1c level was not different from each group. Serum adiponectin were otherwise increased in GW5074 group. Urinary excretion of albumin at 2 month of treatment decreased with urinary nephrin excretion. Trend of increased gene expression of JNK, p-38, smad2, ERK which was downregulated by GW5074 was noted.

Conclusion

These findings suggest that in diabetic condition, the activation of ATF3 is associated pathogenesis of diabetic nephropathy and targeting ATF3 may have a protective role in the disease progression.
P0986NO/CGMP PATHWAY MODULATES GLUCOSE UPTAKE VIA REGULATION OF SIRT1 DEACETYLASE EXPRESSION AND ACTIVITY IN PODOCYTES EXPOSED TO HIGH GLUCOSE CONCENTRATIONS
Authors: Rogacka Dorota , Audzeyenka Irena , Piwkowska Agnieszka
Published: June 2020

Background and Aims

Glomerular podocytes have become the aim of the extensive research in diabetes because of their importance in the development of diabetic nephropathy. High glucose concentration affects podocyte metabolism and function leading to the development of insulin resistance. Moreover, it decreases deacetylase SIRT1 protein amount and activity, leading to abolition of insulin effect on glucose uptake into the cells. The aim of our study was to examine the involvement of NO/cGMP pathway in the regulation of sirtuin 1 (SIRT1) protein expression and activity in podocytes, in the context of high-glucose induced insulin resistance. This work was supported by grant from the National Science Centre (2016/23/B/NZ4/03448).

Method

Experiments were performed in primary rat podocytes cultured with normal (NG, 11.1 mM) or high (HG, 30 mM) glucose concentrations for 5 days. RT-PCR and immunodetection methods were used to detect mRNA and protein expressions. Glucose uptake was measured by the addition of 1 µCi/well of 2-deoxy-(1,2-3H)-D-glucose uptake diluted in non-radioactive dglucose (50 µM final concentration) with or without 300 nM insulin. SIRT1 activity was determined with a SIRT1 Fluorometric Kit according to the manufacturer’s instructions. SIRT1 expression was modified by transfection with SIRT1 siRNA. To examine the effect of NO/cGMP pathway activity on SIRT1, cells were incubated in the presence of SNAP, a mimetic of nitric oxide synthase activity (NOS), and 8-Br-cGMP, protein kinase G (PKG) activator. We also used L-NAME – NOS inhibitor, and Rp-8-Br-cGMPs, PKG inhibitor.

Results

SIRT1 protein expression and activity were decreased in podocytes exposed to high glucose concentrations. We showed that in the presence of SNAP and 8-Br-cGMP, SIRT1 protein amount and activity were increased, leading also to enhancement of basal and insulin-dependent glucose uptake. In podocytes, transfected with SIRT1 siRNA, treatment with NO/cGMP pathway activators SNAP or 8-Br-cGMP increased glucose uptake. NO/cGMP pathway inhibitors exerted opposite effects on SIRT1 protein level and activity as well as on glucose uptake. Insulin action on glucose uptake into podocytes cultivated in the presence of normal glucose concentrations was abolished after NO/cGMP pathway inhibition.

Conclusion

We found that impairment of insulin effect on glucose uptake in HG-exposed podocytes, which was associated with SIRT1 downregulation, may be prevented by NO-dependent signaling modulation.
P0987MIR-181A IMPROVED RENAL INFLAMMATION VIA TARGETING TNF-Α IN DIABETIC NEPHROPATHY
Authors: Liu Dan , Liu Bicheng
Published: June 2020

Background and Aims

Recent studies have revealed that miR-181a is involved in various inflammation associated diseases, however, its participation in pathogenesis of diabetic nephropathy (DN) remains unclear. Hence, we investigated the involvement of miR-181a in the pathogenesis of DN patients and in animal model.

Method

miR-181a level was measured in the kidney of DN patients and DN mice model (db/db mice) by RT-PCR. To investigate the interaction of miR-181 a with the 3’-UTR of potential target transcripts, Luciferase reporter assays were performed. miR-181a-GFP-AAV and miR-181a inhibitor was generated to over-express or downregulate miR-181a in the kidney of db/db mice respectively. The expression of target gene and inflammatory proteins were measured in the kidney of our animal model.

Results

In DN patients and DN mice, a significant decrease in miR-181a levels in kidney were revealed by Expression analyses performed. Overexpression of miR-181a reduced proinflammatory genes (TNF-ɑ, IL-1β, and IL-18 ) expression, whereas suppression of miR-181a worsened these changes. Furthermore, there was a negative linear correlation between miR-181a and TNF-ɑ, IL-1β, and IL-18 expression levels in the kidney from DN patients. Luciferase assays revealed TNF-ɑ as a direct target of miR-181a.

Conclusion

Our data emphasized on the anti-inflammatory actions of miR-181a via targeting TNF-ɑ in the context of renal inflammation in DN. Hence, miR-181a could be served as a potential therapeutic options for controlling renal inflammation in DN.
P0993GYMNEMA SYLVESTRE EXTRACT ATTENUATE THE PATHOLOGICAL PROGESSION OF DIABETIC NEPHROPATHY IN RATS
Authors: Rajput Sumit
Published: June 2020

Background and Aims

Diabetic nephropathy is not only a common and severe microvascular complication of diabetes mellitus but also the leading cause of renal failure. Aqueous extract of leaves of Gymnema sylvestre (ALGS) has been reported to cause reversible increases in intracellular calcium, hypolipidemic activity and insulin secretion in mouse and human β cells with type 2 diabetes.

The present study aimed to investigate the antidiabetic and renoprotective effects of ALGS in a rat model of type 2 diabetic mellitus.

Method

Male Sprague-Dawley rats with type 2 diabetes induced by a high-fat diet (HFD)/streptozotocin (STZ) were treated with ALGS at dosages of 0.5% and 1% (w/w) daily for 4 weeks. At the end of the experimental period, body weight, serum glucose levels, insulin levels, and kidney function were assessed. Furthermore, antioxidant enzyme and lipid peroxide levels were determined in the kidney with histopathological examination Molecular mechanism underlying the functioning of ALGS, mouse glomerular mesangial cells (MES-13) treated with high glucose (HG, 25 mM glucose) were chosen as a model for an examination of the signal transduction pathway of ALGS.

Results

The results revealed that ALGS improved diabetic kidney injury by reducing blood glucose, serum creatinine, and blood urea nitrogen levels and enhanced antioxidant enzyme activities in kidney tissue. Treatment with ALGS significantly reduced the malondialdehyde and 8-hydroxy-2-deoxyguanosine levels and increased serum insulin levels; expression of renal superoxide dismutase, catalase, and glutathione peroxidase activities; and glutathione content. Histological studies have also demonstrated that ALGS treatment inhibited the dilation of Bowman's capsule, which confirmed its renoprotective action in diabetes. In addition, treatment with ALGS attenuated 25 mM HG-induced suppressed nuclear factor erythroid 2-related factor 2 and antioxidant enzyme expression in MES-13 cells.

Conclusion

The results of present study reveal that ALGS extract could be useful intervention in the treatment of diabetes mellitus and, through antioxidative pathways.
P0994PROTECTIVE EFFECTS OF CATECHIN ON GENE EXPRESSION OF GLUCOSE METABOLISM IN STREPTOZOTOCIN-INDUCED DAIBETIC NEPHROPATHY IN RATS
Authors: SHIN BYUNG CHUL , CHUNG JONG HOON , Kim Hyun Lee
Published: June 2020

Background and Aims

Diabetes patients continue to increase worldwide, and persistent hyperglycemia could induce diverse complications, such as diabetic nephropathy. The purpose of this study was to investigate the transcriptoms of liver, muscle and adipose tissue to observe the effects of catechin on glucose metabolism in diabetic nephropathy rats.

Method

The experimental group was divided into control group, diabetic nephropathy (DN) group and DN + catechin group. The control and diabetic groups received tap water as drinking water and the DN + catechin group received tap water containing 0.1% catechin as drinking water for 12 weeks. After 12 weeks, blood glucose, BUN and creatinine levels were measured in the blood and transcriptomes were examined in liver, soleus muscle and visceral fat. The gene expression levels of glucose metabolism-related enzymes, lipid metabolism-related enzymes and insulin signaling pathway-related proteins were compared between each experimental group.

Results

Fasting blood glucose in the diabetic + catechin group was decreased by 8%, 13%, 15% and 18% at 2, 4, 8 and 12 weeks, respectively, compared to the diabetic group. After 12 weeks, serum BUN levels in the DN + catechin group decreased by 35% and serum creatinine levels by 33%, respectively, compared to the DN group. Glucose metabolism-related genes in the DN group were decreased in liver Gck, Pdp2 and Phkb mRNA levels, and Aldob mRNA levels in soleus muscle were decreased. In DN group, expression of Pfkm, Eno3 and Pgam2 in visceral fat were increased and Aldob and Pklr expression was decreased. Hepatic Gck, Pdk4 and Phkb mRNA levels were increased in the DN + catechin group compared to the DN group.

Conclusion

Catechin has the effect of improving diabetic nephropathy, which is thought to be the result of increased expression of liver glucose metabolism related enzymes and proteins related to insulin signal transduction pathways. Further study is needed to elucidate the mechanism of action on catechin gene expression and its usefulness as a functional substance.
P0995EVALUATION OF ANTIDIABETIC, ANTIOXIDANT AND NEPHROPROTECTIVE ACTIVITY OF FLAVONOID RICH FRACTION OF HYBANTHUS ENNEASPERMUS IN DIABETIC RATS: IN-SILICO MOLECULAR DOCKING STUDIES FOR SOD, CATALASE, GPX, XANTHINE OXIDASE AND NF-KB
Authors: Patel Dinesh Kumar
Published: June 2020

Background and Aims

Diabetes mellitus is a chronic metabolic disease affected a wide range of population all over the world and leads to development of secondary complications. Enzymes play key role in the development of secondary complication.

Method

The flavonoid rich fraction was prepared using ethyl acetate. Oral glucose tolerance test normoglycemic effect of flavonoid rich fraction of Hybanthus enneaspermus (EHE) was evaluated at a dose of 45 and 90 mg/kg, p.o. Further effect of EHE on blood glucose, body weight, enzymes such as super oxide dismutase (SOD), catalase and thiobarbituric acid reactive substances (TBARS) and lipid parameters were estimated out at 45 and 90 mg/kg p.o. per day for 21 days in streptozotocin-induced type-2 diabetic rats. Molecular docking technique was also performed against Super Oxide Dismutase (SOD), Catalase, Glutathione Peroxidase (Gpx), xanthine oxidase and nuclear factor kappa B (NF-κB) for selected phytoconstituents.

Results

EHE contain significant amount of phenolic, tannin, flavonoid and saponin. EHE significantly decreased blood glucose level in diabetic rats. All the tested lipid parameters and enzyme level of SOD, Catalase and Gpx were significantly restored to the normal level in the EHE treated rats. Moreover, there was a significant increase in the body weight in the EHE treated rats. Docking study showed the best binding affinity and interaction of phytoconstituents with xanthine oxidase and NF-κB signified their role in kidney disorders.

Conclusion

EHE has very impressive profile as an antidiabetic, antioxidant and nephroprotective activity via enzymes modulation and it may prove to be effective treatment for kidney disorders in hyperglycemia.
P1003STUDY DESIGN OF THE ROTATION FOR OPTIMAL TARGETING OF ALBUMINURIA AND TREATMENT EVALUATION (ROTATE-3): A ROTATION STUDY OF DIFFERENT ALBUMINURIA LOWERING DRUGS CLASSES TO STUDY INDIVIDUAL DRUG RESPONSE IN DIABETIC AND NON-DIABETIC CKD
Authors: Provenzano Michele , Puchades Montesa Maria Jesãºs , De Nicola Luca , D'Marco Luis , Garofalo Carlo , Sasso Ferdinando Carlo , Acierno Carlo , Panizo Gonzalez Nayara , Romero-Parra Maria , Sen Taha , Gagliardi Ida , Hoyo-Garcia Rafael , Andreucci Michele , Lambers Heerspink Hiddo , Gorriz Jose Luis
Published: June 2020

Background and Aims

Patients with diabetic kidney disease show a wide variability in their response to established and new treatments. SGLT2 inhibitors have also shown to slow the progression of kidney disease. Some studies have also shown kidney benefits for Mineralocorticoid Receptor Antagonists (MRA). A large outcome trial with the MRA finerenone is currently ongoing to assess effects of this MRA on major kidney outcomes. The individual trials will solve the issue whether a patient may have benefit from an SGLT2 inhibitor or MRA, but they do not address the key question which of the two or their combination is better to reduce albuminuria for each individual patient. Therefore, we designed the ROTATE-3 trial is designed to investigate the individual albuminuria response to MRA (eplerenone), SGLT2 inhibitor (dapagliflozin) or the combination.

Method

ROTATE-3 is a randomized, prospective, open label, multicentre, crossover trial with a total duration of 28 (to 42) weeks [EudraCT number: 2017-004641-25]. Patients with or without type 2 diabetes, ≥18 years and elevated albuminuria (100-3500 mg/24 hour) already receiving a stable (same dose at least 4 weeks) maximum tolerated dose of an ACE-inhibitor or Angiotensin Receptor Blocker will be enrolled.Patients receive in random order 4 weeks of treatment with the eplerenone 50 mg/day, dapagliflozin 10 mg/day or combination of both drugs with a 4-weeks wash-out period in between. After the last treatment period patients will proceed to a 4-weeks wash-out period. The primary study outcome is the correlation in albuminuria response to eplerenone and dapagliflozin for which 46 patients provides 80% power to detect a Pearson correlation coefficient of 0.4 between the log transformed albuminuria response to eplerenone and dapagliflozin. Blood is collected for clinical chemistry every two weeks during each treatment period. Patients are requested to collect one 24-hour urine sample at start and at end of each treatment period. Home blood pressure is monitored every 2 days.

Results

As of January 1st 2020 the study has enrolled 13 patients. It is anticipated that recruitment will be completed by December 2020 with study completion in August 2021.

Conclusion

The results of the ROTATE-3 study will provide more insight in the individual albuminuria lowering response to potentially two new treatment options for patients with CKD and may help to implement personalized medicine in diabetic kidney disease.Study sponsored by University Medical Center Groningen. The Netherlands.
P1011ATHE SGTL-2 INHIBITORS DECREASE THE MORTALITY AND PROGRESSION OF CHRONIC KIDNEY DISEASE (CKD) IN TYPE 2 DIABETES PATIENTES. SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE
Authors: Cabrera Sebastian , Torres Ruben , Elgueta Leticia , Segovia Erico , Sanhueza Maria Eugenia , Boltansky Andres , Alvo Miriam
Published: June 2020

Background and Aims

Diabetic nephropathy is one of the main causes of chronic kidney disease (CKD) in the world. In the past years new studies using SGLT-2 inhibitors in diabetic patients have shown benefit in both mortality and progression of CKD. However, these works show heterogeneity between studies regarding the severity of CKD of patients included. All above complicates the interpretation of the benefits of SGLT-2 inhibitors.

Method

We did a systematic search of the literature in PUBMED, EMBASE, Cochrane CENTRAL trials database and in references of the selected studies. Terms used for the search were Canaglifozin, Dapaglifozin, Ertuglifozin, Empaglifozin, diabetes, mortality and CKD. Search included studies in all languages. We selected only randomized and controlled studies that reported mortality and relevant renal outcomes (doubling serum creatinine or decrease in eGFR> 40%, need for renal replacement or renal death). We included studies until September 30, 2019. For the meta-analysis, a Mantel-Haenszel model of random effects was used. The software Review Manager, Version 5.3 The Cochrane Collaboration, 2014 was used.

Results

We obtained results from 142 studies, fifteen studies met the selected criteria, but only four reported mortality and renal outcomes (EMPA-REG, CANVAS, CREDENCE AND DECLARE-TIMI 58). A total of 38,721 patients (SGTL2 inhibitors n = 21,264 and control n = 17,457) were included for the analysis. The EMPA-REG study used Empaglifozin, the CANVAS and CREDENCE studies used Canaglifozin and the DECLARE-TIMI 58 used Dapaglifozin. All studies were funded by pharmaceutical laboratories.The average age range of the studies was between 62 to 67 years. The percentage of patients with eGFR <60ml/min were 26%, 20%, 60% and 7% for the EMPA-REG, CANVAS, CREDENCE and DECLARE-TIMI 58 studies respectively.Mortality was lower in patients who used SGTL2 inhibitors OR 0.86 (CI 0.80-0.94) Figure 1. Renal outcomes were also lower in patients who used SGTL-2 inhibitors OR 0.69 (CI 0.60-0.78) Figure 2. We assessed whether the effect was related to the severity of the CKD taking out the work with patients with more severe CKD (CREDENCE study), the effect on mortality did not change OR 0.87 (CI 0.80-0.95) as well as renal outcome OR 0.66 (CI 0.52- 0.83).

Conclusion

The SGTL-2 inhibitors decrease mortality and improve renal outcomes in patients with diabetic nephropathy. These benefits remain in patients with less severe CKD.
P1019CANAGLIFLOZIN AND RISK OF SKIN AND SOFT TISSUE INFECTIONS IN PEOPLE WITH DIABETES MELLITUS AND KIDNEY DISEASE - A POST-HOC ANALYSIS OF THE CREDENCE TRIAL
Authors: Kang Amy , Smyth Brendan , Neuen Brendon , Lambers Heerspink Hiddo , Di Tanna Gian Luca , Neal Bruce , Zhang Hong , Hockham Carinna , Agarwal Rajiv , Bakris George , Charytan David M , De Zeeuw Dick , Greene Tom , Levin Adeera , Pollock Carol , Wheeler David , Zinman Bernard , Mahaffey Kenneth W , Perkovic Vlado , Jardine Meg
Published: June 2020

Background and Aims

The skin’s hypertonic microenvironment has a hypothesized protective antimicrobial function that may be disrupted by SGLT2i. The association between sodium glucose cotransporter inhibitors (SGLT2i) and genital mycotic infections is well established, but it is not known if these agents increase the risk of other skin and soft tissue infections (SSTI). We aimed to describe SSTI in the CREDENCE trial, and determine whether canagliflozin affects the risk of skin and soft tissue infections (SSTIs) overall and in subgroups.

Method

We performed a post-hoc analysis of the CREDENCE trial that randomised people with type 2 diabetes and albuminuric stage 2 and 3 chronic kidney disease to either canagliflozin 100mg daily or placebo. Infections reported as adverse events were assessed by two blinded authors following predetermined criteria for SSTI with discrepancies resolved by consensus. We analysed the risks of SSTIs in the on-treatment population as the more conservative approach, with a sensitivity analysis conducted in the intention-to-treat population. Univariable time-to first-event regression models were assessed.

Results

Overall 373/4397 (8.5%) participants experienced 478 events comprising 252 bacterial skin infections (including 2 episodes of necrotising fasciitis), 94 fungal skin infections, 109 other skin infections and 23 soft tissue infections. Of these, 136/478 (28%) were serious. Drug was continued in 290/373 (78%) of first events, with similar frequency of subsequent events between groups (31/133 (23%) and 33/157 (21%) for those continuing canagliflozin and placebo respectively). In both cases of necrotising fasciitis, drug was withdrawn and the participants recovered.Canagliflozin did not increase the risk of SSTI (HR 0.85 [95% Confidence Interval (CI) 0.69-1.04] p=0.11) (Figure 1). Results were similar in the intention-to-treat population (HR 0.88 [95% CI 0.73-1.07] p=0.20), in analyses confined to serious SSTI (HR 0.83 [95% CI 0.58-1.21] p=0.33), and in the predefined subgroups.

Conclusion

Although other studies suggest that SGLT2i may reduce the sodium content of the skin, we found that canagliflozin does not increase the risk of skin and soft tissue infections, overall or in any subgroup, in people with type 2 diabetes mellitus and albuminuric chronic kidney disease.
P1021MARKERS OF “METABOLIC MEMORY” AND KIDNEY GRAFT FUNCTION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION
Authors: Larina Irina , Severina Anastasia , Shamhalova Minara , Shestakova Marina , Nikankina Larisa , Artemova Ekaterina , Egorova Darya , Musaeva Gulya , Dmitriev Ilya , Pinchuk Aleksey , Kaabak Michael
Published: June 2020

Background and Aims

To evaluate the relationship between oxidative stress markers and advanced glycation end products receptor (RAGE) with kidney graft function and complications of end-stage renal disease (ESRD) in patients with type 1 diabetes mellitus (T1DM), who reached stable euglycemia after simultaneous pancreas-kidney transplantation (SPKT).

Method

The study included 27 patients with T1DM duration for 21 [19; 28] years, diabetic nephropathy (DN) duration 7,0 [5,5; 13,5] years and duration of renal replacement therapy (dialysis) for 2 [1; 4] years after successful SPKT. The posttransplantation period at the time of inclusion was 61 [20; 90] months. Assessment included examination of oxidative stress markers (3-nitrothyrosine (3-NT), superoxide dismutase (SOD) and RAGE, analysis of the main kidney transplant dysfunction markers (KIM-1, NGAL, podocin, IL-18) and state of carbohydrate metabolism with monitoring for 1 year. All patients received three-component immunosuppressive therapy.

Results

SPKT allowed to achieve stable euglycemia (HbA1c 5.5 [5.1; 5.9] %, 5.5 [5.3; 5.7] % and С-peptide 2,9 [2,1; 3,6] ng/ml, 2,6 [2,0; 3,4] ng/ml at baseline and after 1 year of follow – up, respectively) and the restoration of graft function to the rate of estimated glomerular filtration rate (eGFR) CKD-EPI stage C2, albuminuria stage A1 of chronic kidney disease (CKD). However, 22% of patients experienced an increase of albumin-to-creatinine ratio to A2 at different times after surgical treatment. There was a statistically significant increase in SOD level (p=0.0005) and RAGE level (p=0.011) after 12 months of observation. Significant correlations of kidney transplant function parameters with “metabolic memory" markers (oxidative stress and RAGE) were also found: RAGE & creatinine (R=0.50, p=0.02), RAGE & KIM-1 (R=0.43, p=0.047), 3-NT& eGFR (R= - 0.40, p=0.046), IL-18 & SOD baseline (R=0.43, p=0.047). Attention is drawn to the correlations of RAGE & HbA1c+12 month (R=0.47, p=0.01), podocin with HbA1c (R=-0.46, p=0.03), which may probably reflect the direct influence of carbohydrate metabolism compensation to the kidney graft condition and also the correlation of SOD baseline & RAGE +12 month (R= - 0.70, p=0.0008), which may demonstrate the relative influence of components of "metabolic memory”.

Conclusion

SPKT as the way to achieve compensation of carbohydrate metabolism remains just one of factors of stable kidney graft function. The results of analysis of “metabolic memory” markers could indicate not only their direct contribution to the persistence of metabolic consequences of DM and DN, but also their possible participation in the development of recurrent nephropathy.
P1039BARIATRIC SURGERY AND RISKS OF RENAL DISEASES, CARDIOVASCULAR DISEASES AND MORTALITY AMONG PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Wong Carlos , Wu Tingting , Wong Simon , Law Betty , Grieve Eleanor , Wu Olivia , Lam Cindy
Published: June 2020

Background and Aims

To measure and compare the risks of end-stage renal diseases (ESRD), cardiovascular diseases (CVD), all-cause mortality between obese type 2 diabetes mellitus (T2DM) patients with and without bariatric surgery.

Method

A retrospective population-based cohort of 1,690 obese T2DM patients who were free of ESRD and CVD were assembled based on 2006-2017 Hospital Authority database. One-to-five propensity-score matching was used to balance baseline covariates between patients in bariatric surgery and control groups. Incidence rates (IR) of stage 4/5 chronic renal diseases, ESRD, CVD and all-cause mortality events for two groups were calculated. Hazard ratios (HR) for stage 4/5 chronic renal diseases, ESRD, CVD events were assessed using Cox proportional hazard models. Changes in estimated glomerular filtration rate (eGFR), and urine albumin-creatinine ratio (UACR) were measured up to 60 months.

Results

Over a mean follow-up period of 34 months with 863 person-years, cumulative incidences of mortality, stage 4/5 chronic kidney diseases, ESRD and CVD for surgical patients were 0, 0.050, 0.017, and 0.036, respectively. Surgical patients had reduced IR of all-cause mortality, stage 4/5 chronic kidney diseases, ESRD and CVD (IR=0, 1.784, 0.587 and 1.321 per 100 person-years, respectively) than control patients (IR=1.954, 2.028, 0.914 and 2.814 per 100 person-years, respectively). Surgery group had a significant reduction in risk of CVD events (HR=0.464, P=0.015), and no occurrence of mortality events. However, the IR of stage 4/5 chronic kidney diseases and ESRD of the two groups were not significantly different. Surgical patients had significantly higher eGFR within 12 months, and had significantly lower until 48 months.

Conclusion

Among obese T2DM patients, bariatric surgery lowered the risk of CVD and mortality, and was beneficial towards the kidney outcomes of eGFR up to 36 months.
P1060USING ARTIFICIAL INTELLIGENCE TO PREDICT HOME THERAPY CANDIDATES
Authors: Yu Jerry , Long Andrew , Hanson Maria , Ellis Aleetha , Macarthur Michael , Chatoth Dinesh , Turk Joseph , Buck Michael , Usvyat Len A , Kossmann Robert J , Maddux Franklin
Published: June 2020

Background and Aims

There are many benefits for performing dialysis at home including more flexibility and more frequent treatments. A possible barrier to election of home therapy (HT) by in-center patients is a lack of adequate HT education. To aid efficient education efforts, a predictive model was developed to help identify patients who are more likely to switch from in-center and succeed on HT.

Method

We developed a model using machine learning to predict which patients who are treated in-center without prior HT history are most likely to switch to HT in the next 90 days and stay on HT for at least 90 days. Training data was extracted from 2016–2019 for approximately 300,000 patients. We randomly sampled one in-center treatment date per patient and determined if the patient would switch and succeed on HT. The input features consisted of treatment vitals, laboratories, absence history, comprehensive assessments, facility information, county-level housing, and patient characteristics. Patients were excluded if they had less than 30 days on dialysis due to lack of data. A machine learning model (XGBoost classifier) was deployed monthly in a pilot with a team of HT educators to investigate the model’s utility for identifying HT candidates.

Results

There were approximately 1,200 patients starting a home therapy per month in a large dialysis provider, with approximately one-third being in-center patients. The prevalence of switching and succeeding to HT in this population was 2.54%. The predictive model achieved an area under the curve of 0.87, sensitivity of 0.77, and a specificity of 0.80 on a hold-out test dataset. The pilot was successfully executed for several months and two major lessons were learned: 1) some patients who reappeared on each month’s list should be removed from the list after expressing no interest in HT, and 2) a data collection mechanism should be put in place to capture the reasons why patients are not interested in HT.

Conclusion

This quality-improvement initiative demonstrates that predictive modeling can be used to identify patients likely to switch and succeed on home therapy. Integration of the model in existing workflows requires creating a feedback loop which can help improve future worklists.
P1061ACID-BASE MODELLING AND TREND IN CENTRAL VENOUS OXYGEN SATURATION IN HEMODIALYSIS
Authors: Mauro Pietribiasi , Leypoldt John (Ken) , Waniewski Jacek
Published: June 2020

Background and Aims

Central venous oxygen saturation (sO2cv) is commonly used as a proxy of cardiac output in non-uremic populations. Recently, the decrease in sO2cv commonly observed in many hemodialysis (HD) sessions was correlated with ultrafiltration volume (UFV) and was suspected to be linked with a treatment-induced decrease in cardiac output (Zhang et al, NDT 2018). High variability in sO2cv has also been associated with all-cause mortality in this group of patients (Zhang et al, Blood Purif 2019). We adapted a comprehensive mathematical model of whole body oxygen (O2) and carbon dioxide (CO2) biochemistry, storage and transport and applied it to simulate the changes in sO2cv during bicarbonate hemodialysis to test their connection with changes in CO.

Method

The original model of biochemistry and transport of base excess, CO2 and O2 was originally developed by Rees and Andreassen (Crit Rev Biomed Eng 2005), and describes in detail the chemical and respiratory mechanisms that regulate the biochemical status in different physiological compartments of the patients’ body (venous blood, arterial blood, tissue cells, interstitial fluid). The model was modified to include the effect of the HD treatment on these systems, allowing to calculate the variations in venous and arterial sO2. Treatment perturbations included the removal via ultrafiltration of interstitial fluid and plasma volume (and consequent hemoconcentration), and infusion of bicarbonate. Simulation experiments of 4h HD sessions were carried out with bicarbonate dialysate concentration = 35 mmol/L and dialysance = 198 mL/min, and various ultrafiltration volumes (UFV); CO was assumed to decrease by 2% for each 1% change in blood volume. The initial biochemical status of the patient was defined assuming 20 mEq/L bicarbonate concentration, 7.4 pH, and 97% oxygen saturation in the arterial compartment, resulting in initial sO2cv equal to 66.6%. Both artero-venous and veno-venous access were simulated.

Results

The model predicted a negative linear trend for sO2cv with variable slope depending on UFV, as shown in the table:

The trend in sO2cv was directly proportional to the decrease in CO during HD and inversely proportional to UFV. In case of constant CO, the simulated sO2cv would actually increase during the session. Although the type of vascular access determined changes in other simulated quantities, partial pressures of CO2 and O2 and oxygen saturation in both arterial and venous blood were practically unchanged.

Conclusion

Our model confirmed the correlation between the trend in sO2cv and UFV already highlighted in previous works. Moreover, it showed that the decrease in cardiac output is a major determinant of the decrease in sO2cv during the HD session. The developed mathematical model may provide physiological insights in the development of new technologies to monitor changes in cardiac performance during HD.
P1064HEPARIN-FREE DIALYSIS: A PHASE II PILOT STUDY USING ASYMMETRIC TRIACETATE (ATA) CELLULOSE DIALYZERS
Authors: Meijers Björn , Vandenbosch Ines , Bammens Bert , De Vusser Katrien , Van Craenenbroeck Amaryllis , Claes Kathleen , Evenepoel Pieter
Published: June 2020

Background and Aims

Not all dialysis patients tolerate heparin anticoagulation. Heparin should be avoided in patients at high risk of bleeding. Strategies include saline infusion, citrate-containing dialysate, regional citrate anticoagulation and heparin-coated membranes. We recently studied the combination of a heparin-coated membrane and citrate-containing dialysate, with a success rate of 94% . Although this combination resulted in low rates of clotting, heparin-coated membranes are not ubiquitously available. The quest for easy to perform, safe and affordable heparin-free dialysis is on. Asymmetric cellulose triacetate (ATA) dialyzers have a low degree of platelet contact activation and might be an alternative to heparin-coated dialyzers.

Method

We performed a phase II pilot study in maintenance dialysis patients. The ‘Strategies for Asymmetrical Triacetate dialyzer heparin-Free Effective hemodialysis (SAFE study)’ was a two-arm open-label cross-over study. In Arm 1, patients were dialyzed using a 1.9 m2 ATA membrane (Solacea™-19H, Nipro Corp., Japan) in combination with citrate (1 mM) containing dialysate. In Arm 2, patients were dialyzed with the same 1.9 m2 ATA membrane, in combination with high volume predilution hemodiafiltration. The primary endpoint was the success rate to complete 4 hours of hemodialysis without preterm clotting.

Results

We scheduled 240 dialysis sessions (120 per arm) in twenty patients. Ten patients were randomized to start in Arm 1, the others to Arm 2. All patients crossed to the other arm halfway the study. 232 (96.7%) study treatments were delivered. Overall, 23 clotting events occurred, 7 in Arm 1 and 16 in Arm 2. Success rate in Arm 1 (ATA + citrate containing dialysate) was 90.8 / 94.0 % (intention to treat/ as treated). Success rate in Arm 2 (ATA + predilution HDF) was 83.3 / 86.2 % (intention to treat/ as treated). Therapy survival was borderline significantly better in Arm 1(Mantel-Cox log rank P = 0.05).

Conclusion

Asymmetric cellulose triacetate (ATA) dialyzers have a low clotting propensity. In combination with citrate-containing dialysate, asymmetric cellulose triacetate (ATA) may be a suitable alternative to heparin-coated membranes for systemic heparin-free hemodialysis.
P1065EXTRACORPOREAL CYTOKINE ADSORPTION IN PATIENTS WITH AKI AND SEPTIC SHOCK AFTER CARDIAC SURGERY
Authors: Boss Kristina , Jahn Michael , Wendt Daniel , Demircioglu Ender , Thielmann Matthias , Ruhparwar Arjang , Kribben Andreas , Tyczynski Bartosz
Published: June 2020

Background and Aims

Extracorporeal cytokine adsorption is a new option in septic shock as an additional measure to prevent severe cytokinaemia. The purpose of this study was to investigate the effects of extracorporeal cytokine adsorption on hemodynamics in patients with acute kidney injury (AKI) and septic shock after cardiac surgery.

Method

In this retrospective study 64 patients with AKI and septic shock after cardiac surgery were investigated for the effect of extracorporeal cytokine adsorption by CytoSorb® columns on hemodynamics. In all patients CytoSorb®-treatment was applied in addition to continuous renal replacement therapy (CRRT) with citrate anticoagulation. A paired t-test has been performed to determine statistical significance.

Results

Before treatment, the mean noradrenalin dose to reach a mean arterial pressure (MAP) > 65 mmHg was 0.49 µg/kg bw/min, the mean adrenalin dose was 0.1 µg/kg bw/min. 24 h after treatment, significantly reduced catecholamine doses were necessary to maintain a MAP > 65 mmHg (0.23 µg/kg bw/min noradrenalin; p***< 0.0002 and 0.06 µg/kg bw/min adrenalin; p* < 0.02). The mean SOFA-score for these patients with AKI and septic shock 24 h before CytoSorb®- treatment was 16.6 points. The mean predicted in-hospital mortality rate based on this SOFA-score of 16.6 points was 77 % while the all-cause mortality rate of the patients in this study was 59.4 %.

Conclusion

In patients with AKI and septic shock after cardiac surgery, 24 h after extracorporeal cytokine adsorption by CytoSorb® the catecholamine dose required to maintain a MAP > 65 mmHg was halved. Additionally, observed in-hospital mortality was lower than SOFA-score predicted mortality.