bluuebunny/crossref_metadata_2025 huggingface dataset:
P0982PTEN-INDUCED KINASE 1 (PINK1) DEPLETION ALTERS MITOCHONDRIAL EFFICIENCY AND GLYCOLYSIS IN HUMAN PODOCYTES
Authors: Audzeyenka Irena , Rogacka Dorota , Piwkowska Agnieszka
Published: June 2020

Background and Aims

Podocytes are terminally differentiated cells, which constitute an inner layer of the renal filtration barrier. Podocytes are characterized by high metabolic activity, and their elevated energy requirements are met by maintaining the appropriate mitochondrial number and quality, which depend on mitochondrial biogenesis and mitophagy. Alteration of mitochondrial dynamics is linked to the development of insulin resistance and diabetes. The main goal of the research was to determine the role of mitophagy in podocytes bioenergetics and to elucidate the effects of hyperglycemia on mitochondrial dynamics.

Method

In order to inhibit mitophagy, we generated a human podocyte cell line stably expressing PINK1 shRNA through lentiviral transduction. Biochemical analyses were performed to assess the oxidative phosphorylation efficiency (by measurement of oxygen consumption rate; OCR) and glycolysis contribution to the total cell energy production (by measurement of extracellular acidification rate; ECAR) in the differentiated shPINK1 podocytes. The expression levels of mRNAs and proteins were evaluated in podocytes cultured in standard glucose (11 mM) and high glucose (30 mM) concentrations using real-time PCR and western blot. Intracellular mitochondrial network was visualized by MitoTrackertTM staining. The co-localization of proteins in podocytes was analysed by double immunofluorescence labelling and confocal microscopy.

Results

PINK1-deficiency resulted in the significant decrease of maximal respiration and spare respiratory capacity in podocytes (by 40% and 70%, respectively). Non-mitochondrial respiration was also decreased by 45% in shPINK1 cells. Interestingly, basal respiration and ATP production appeared similar in shPINK1 and control podocytes. PINK1 depletion increased glycolytic flux by 70%, in addition, the accompanying decline in glycolytic capacity and glycolytic reserve was observed (by 38% and 63%, respectively). Moreover, we observed accumulation of small and ring-shaped mitochondria in PINK1-deficient podocytes compared with the control cells.

We showed a decreased expression of PINK1 and Parkin (mRNA and protein) in normal human podocytes cultured in hyperglycemic medium, which was associated with an elevated levels of mitochondrial fission markers (DRP1, FIS1) and with a decreased levels of PGC1α and TFAM, which play a role in mitochondrial biogenesis and mtDNA replication.

Conclusion

In this research, we demonstrated a novel role of mitophagy in podocyte bioenergetics. Moreover, we showed that high glucose inhibits mitophagy and promotes mitochondrial fission leading to the accumulation of damaged mitochondria and podocyte injury, which underlies the pathogenesis of diabetic nephropathy.
P0990RENINAAV DOSE-DEPENDENTLY EXACERBATE ALBUMINURIA AND GLOMERULOSCLEROSIS, AND REDUCE GFR IN FEMALE UNINEPHRECTOMIZED DB/DB MICE
Authors: Østergaard Mette Viberg , Ida Rune , Pedersen Annemarie Aarup , Secher Thomas , Sembach Frederikke Emilie , Thrane Sebastian Tølbøl , Roostalu Urmas , Fosgerau Keld , Fink Lisbeth N , Vrang Niels
Published: June 2020

Background and Aims

Diabetic nephropathy (DN) is a long-term complication that occurs in ∼40% of diabetes patients and is a leading cause of end-stage renal disease. Despite recent emergence of SGLT2 inhibitors and GLP-1 receptor agonists for nephroprotection in diabetes patients, drug discovery has been halted by the lack of reliable rodent models exhibiting features of human DN. In a newly established mouse model of progressive DN, we investigate the effects of hypertension on kidney injury.

Method

Female db/db mice were uninephrectomized (UNx) at 8 weeks of age and injected i.v. with a Renin adeno-associated virus (AAV) construct at different doses to induce hypertension, while a LacZAAV construct was used as negative control. db/+ mice served as healthy controls. Hypertension was measured by tail cuff and glomerular filtration rate (GFR) transcutaneous recoding of FITC-sinistrin after i.v. bolus injection at 22 weeks of age. Urine ACR measured in spot urine samples collected before termination 24 weeks of age. Terminal kidney samples were collected for 3D image analyses, histopathological evaluation, and next generation sequencing for gene expression analyses.

Results

GFR measurements indicated hyperfiltration in all AAV-injected UNx db/db mice compared to db/+ mice, while ReninAAV tended to dose-dependently decrease GFR compared to LacZAAV in UNx db/db mice. Urine ACR was worsened by ReninAAV-induced hypertension compared to LacZAAV controls. Automized AI-based glomerulosclerosis scoring showed ReninAAV dose-dependent increases in glomerulosclerosis compared to LacZAAV controls. 3D kidney imaging demonstrated increased glomerular volume in LacZAAV UNx db/db mice compared to db/+ mice with no further effect in ReninAAV groups. RNA sequencing revealed upregulated gene expression markers of fibrogenesis (incl. Col1a1, Col3, Col4, Fn1, Lamc2 and Vim) and tubular injury markers (Ngal and Kim-1), as well as downregulation of proximal tubular markers (Megalin and Aqp1) in ReninAAV UNx db/db mice compare to LacZAAV controls.

Conclusion

ReninAAV-induced hypertension in female UNx db/db mice accelerates kidney injury in uninephrectomized db/db mice and aggravates GFR, albuminuria and glomerulosclerosis in parallel with increased expression of genes associated with tubular injury renal fibrosis. Together, these data confirm that ReninAAV UNx db/db mice is a reliable model of DN with features of late stage human disease.
P0997BLUEBERRY JUICE IMPROVED THE METABOLIC PROFILE IN A PREDIABETIC RAT MODEL INDUCED BY A HYPERCALORIC DIET WITHOUT RENOPROTECTION
Authors: Alves André , Preguiça Inês , Barbosa Adelaide , Vieira Pedro , Martins Diana , Nunes Sara , D. Viana Sofia , Reis Flávio
Published: June 2020

Background and Aims

Blueberries (BB), due to their enriched content in polyphenolics and in other compounds with potential cytoprotective properties, have been associated with beneficial effects in distinct cardiometabolic conditions. The goal of this study was to evaluate the metabolic and renal effects of long-term blueberry juice (BJ) treatment in a rat model of prediabetes induced by a hypercaloric diet.

Method

Prediabetes was developed in adult male Wistar rats through the ingestion of high-sucrose (35% HSu) and high-fat (60% HF) diets during 23 wks (HSuHF animals, n=16). After 9 weeks, half of the former rats received BJ orally (25g/kg BW, HSuHF+BJ group). Control animals (n=8) received standard diet during the entire protocol. Glycemic, lipidic and insulinemic profiles were evaluated throughout the protocol, as well as gut microbiota composition, gut barrier permeability, endotoxemia (LPS) and inflammation (hs-CRP). Renal function was assessed by using serum and urinary measures of creatinine, uric acid and blood urea nitrogen and calculating the glomerular filtration rate (GFR). Histological characterization of the kidney was performed by H&E and lipid deposition by Oil Red O staining and quantification of triglycerides. Serum and renal tissue inflammatory markers were evaluated by Elisa (hs-CRP) and by RT-qPCR and/or WB (IL-6, TNF-α, iNOS, MMP2, TLR-4 and RAGE). The study was approved by the local animal welfare body (Ref: 9-2018). Values are presented as means ± S.E.M. and possible differences evaluated by ANOVA/post-hoc tests.

Results

While no major changes between groups were found for gut microbiota, gut barrier and endotoxemia/inflammation, BJ treatment was able to ameliorate hypercaloric diet-induced glucose intolerance, insulin insensitivity and plasma hypertriglyceridemia. In addition, in the HSuHF+BJ rats there was a trend to alleviate the reduction of GFR found in the HSuHF animals, as well as some early glomerular lesions, including mesangial expansion and basal membrane thickening. However, this nutraceutical intervention was unable to halt or slow down glomerular crescent-like lesions, renal lipidosis and the overexpression of renal IL-6 found in the HSuHF-treated animals.

Conclusion

Despite the metabolic improvement viewed by the amelioration of glucose intolerance, insulin insensitivity and hypertriglyceridemia, in this rat model of prediabetes a nutraceutical intervention with BJ presented very modest renoprotective effects.

Acknowledgements: FEDER, COMPETE and FCT (CENTRO-01-0145-FEDER-000012-HealthyAging2020, UID/NEU/04539/2013, UID/NEU/04539/2019, POCI-01-0145-FEDER-007440, POCI-01-0145-FEDER-031712, PTDC/SAU-NUT/31712/2017 and SFRH/BD/109017/2015), as well as COAPE and MIRTILUSA.
P1007CHANGES IN METABOLIC SYNDROME COMPONENTS AND RISK OF END STAGE RENAL DISEASE: A NATIONWIDE COHORT STUDY
Authors: Koh Eun Sil , Chae Yura , Chung Sungjin , Kwon Hyuk Sang
Published: June 2020

Background and Aims

Few studies have investigated the impact of a change in metabolic syndrome (MetS) components on clinical renal outcomes in the general population.

Method

Using nationally representative data from the Korean National Health Insurance System, 13,310,924 subjects who underwent two health examinations over 2 years and were free from end-stage renal disease (ESRD) from 2009 to 2012 were followed to the end of 2016. The subjects were divided into four groups according to the change in MetS components between the two visits over 2 years: no MetS (–/–), post-MetS (–/+), pre-MetS (+/–), and both MetS (+/+).

Results

After a median follow up of 5.11 years, 18,582 incident ESRD cases were identified. In the multivariate adjusted model, the hazard ratio (HR) and 95% confidence interval (CI) for the development of ESRD in the both-MetS (+/+) group compared with the no-MetS (–/–) group was 5.65 (95% CI, 5.42–5.89), which was independent of age, sex, and baseline estimated glomerular filtration rate. Additionally, the HR for the pre-MetS (+/-) group versus the no-MetS (–/–) group was 2.28 (2.15–2.42). In subgroup analysis according to renal function, the impact of a change in MetS on the incidence of ESRD was more pronounced in individuals with advanced renal dysfunction. Subjects with resolved MetS components had a decreased risk of ESRD, but not as low as those that never had MetS components.

Conclusion

This provides evidence supporting the strategy of modulating MetS in the general population to prevent the development of ESRD.
P1015IMPACT OF DIABETIC DISEASE ON IPTH LEVELS IN DIALYSIS PATIENTS
Authors: Guinsburg Adrian , Berbessi Juan Carlos , Caseiro Mauro , Stuard Stefano
Published: June 2020

Background and Aims

Mineral bone disease in dialysis patients is an important predictor of morbimortality.iPTH levels had been previously associated with different parameters, but not clearly to diabetic disease (DBT). We aim to analyze relationship between DBT and iPTH levels in a large cohort of dialysis patients from Fresenius Medical Care LatinAmerica (FMC LA).

Method

Prevalent dialysis patients (more than 90 days on renal replacement therapy) by November 2019 in FMC LA dialysis units (Argentina, Brasil, Chile, Colombia, Ecuador, Perú) were included into the dataset. We obtained demographic, treatment and laboratory data by November 2019. Patients were identified as DBT when DBT was informed as etiology of renal disease or any DBT related ICD10 code was recorded as comorbid condition into the database. Use of insulin, calcitriol, paricalcitol and cinacalcet was also obtained.To evaluate association between DBT and iPTH level, Student t test for independent samples was used. Kruskal-Wallis and Mann-Whitney tests were also performed as confirmatory non-parametric tests for iPTH. Categorical variables were compared using Chi Square test. Linear regression was used to predict iPTH and analyze association with DBT. All procedures were performed on IBM SPSS Statistics© 21.

Results

A total of 31,709 prevalent patients were included. DBT prevalence was 29.7%. Main differences found between DBT and non-DBT patients are shown in table 1:

Linear regression model to predict iPTH showed variables associated with increase in iPTH: Ca, P, K, use of calcitriol, use of cinacalcet; while others were associated with decrease in iPTH: age, dialyzate Ca, Hb, glucose, albumin, use of calcium carbonate as supplementation and DBT (table 2):

Conclusion

In our population diabetic patients were older, showed higher male prevalence and higher rate of catheter use. Kt/V, Ca and P serum levels were slightly lower than non-diabetic, but not clinically significant.Remarkable differences in laboratory were higher glucose and lower K and alb in DBT. While these differences were expected and already known and well described, lower iPTH in DBT is not.Diabetic disease affects iPTH level independently from other factors increasing the risk for hypoparathyroidism. Those findings should be analyzed to determine if DBT should be considered as a different group when targeting in mineral bone disease or P-binder prescription.
P1028EFFECTS OF CANAGLIFLOZIN ON MAJOR ADVERSE CARDIOVASCULAR OUTCOMES IN PATIENTS WITH DIFFERENT BASELINE LEVELS OF TYPE 2 DIABETES MELLITUS DISEASE SEVERITY: RESULTS FROM THE CANVAS PROGRAM
Authors: Young Tamara , Li Jing-wei , Kang Amy , Heerspink Hiddo , Hockham Carinna , Arnott Clare , Neuen Brendon , Zoungas Sophia , Mahaffey Kenneth W , Perkovic Vlado , De Zeeuw Dick , Fulcher Gregory , Neal Bruce , Jardine Meg
Published: June 2020

Background and Aims

Patient with type 2 diabetes mellitus (T2DM) included in trials of sodium-glucose cotransporter 2 inhibitors are heterogeneous in terms of disease severity. We assessed the effects of canagliflozin compared to placebo on cardiovascular and renal outcomes in the CANVAS program according to severity of T2DM as indicated by intensity of treatment, duration of diabetes and glycaemic control.

Method

We compared effects on major adverse cardiovascular events ([MACE], defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) according to three indicators of T2DM severity at study baseline: number of oral glucose lowering treatments or insulin therapy (0-1, 2, 3+, insulin), duration of diabetes (<10, 10-16, >16 years) and HbA1c (<7.0, 7.0-7.5, 7.5-8.0, 8.0-8.5, 8.5-9, >9.0%). We also assessed effects on other pre-specified cardiovascular outcomes, and an adjudicated composite of end-stage kidney disease, renal death or sustained 40% decline in estimated glomerular filtration rate. We assessed for constancy of hazard ratios across subgroups by fitting an interaction term that tested for linear trend.

Results

Of 10,142 participants in the CANVAS Program, 1011 experienced a MACE during a mean follow-up of 3.6 years. Event rates for MACE were higher in those with longer duration of diabetes and higher HbA1c at baseline. The effect of canagliflozin on MACE in the overall population (HR 0.86, 95 % CI 0.75-0.97) was consistent irrespective of the number of glucose lowering treatments (p=0.509), duration of diabetes (p=0.174) and baseline HbA1c (p =0.314). Effects were also consistent across different levels of T2DM disease severity for all other outcomes studied.

Conclusion

Higher event rates were observed in those with longer disease duration and higher HbA1c. The proportional risk reductions achieved with canagliflozin were comparable regardless of diabetes duration, number of therapies or HbA1C at baseline.
P1029SAFETY AND EFFICACY OF LONG-TERM ADMINISTRATION OF DPP-4 INHIBITORS IN PATIENTS WITH NEW ONSET DIABETES AFTER KIDNEY TRANSPLANTATION
Authors: Mpratsiakou Adamantia , Papasotiriou Marios , Tsiotsios Konstantinos , Ntrinias Theodoros , Papachristou Evangelos , Goumenos Dimitrios
Published: June 2020

Background and Aims

New onset diabetes (NODAT) is a common complication after kidney transplantation. The available treatment options in this patient population have limitations due to reduced renal function, possible interactions with immunosuppressive drugs and side effects such as hypoglycemic events. The aim of this study was to investigate the long term safety and efficacy profile of dipeptidyl peptidase-IV (DDP-4 inhibitors) administration in renal transplant recipients with NODAT.

Method

The study included 12 patients treated with DPP-IV inhibitors monotherapy as well as 5 patients receiving insulin monotherapy as initial treatment immediately after NODAT diagnosis. All patients were monitored at every scheduled outpatient visit and for 12 months after diagnosis by measuring glycosylated hemoglobin (HbA1c), serum creatinine (eGFR calculation with CKD-EPI formula), plasma immunosuppressive trough levels, serum lipids, blood pressure, and body weight. The mean values of the aforementioned parameters for the last six months of follow up were compared to the ones at diagnosis.

Results

Patients receiving DPP-IV inhibitors were treated with either linagliptin (4 patients), sitagliptin (4 patients), vildagliptin (2 patients) or halogliptin (2 patients). These patients had a mean age of 59.4 ± 12 years, a mean HbA1c of 6.6% and a mean fasting glucose of 114.5 mg/dl at diagnosis. The mean HbA1c the last 6 months of one year of follow up after initiation of treatment, decreased to 6.1% (p=0.03). Renal function remained stable (mean eGFR from 58.8 to 61.7 ml/min/1.73m2, p=ns) while plasma tacrolimus levels did not appear to be affected (from 6.2 to 5.5 ng/dl, p=ns). Patients received a slightly reduced mean dose of tacrolimus during the last six months of follow up in comparison to the one at initiation of treatment (from 2.9 to 2.6 mg/24h, p=ns). No significant difference was shown in serum total, LDL, and HDL cholesterol before and after treatment, nevertheless, triglyceride levels were significantly reduced (from 214.4 to 174.9 mg/dl, p=0.0039). A decrease in body weight was observed (from 79.9 to 77.9 kg, p=ns) which was however not statistically significant. Finally, achieving the goal of lowering HbA1c levels was better in patients treated with DPP-IV inhibitors than in those treated with insulin (6.1% vs 7.1%, respectively, p=0.01).

Conclusion

Administration of DPP-IV inhibitors appears to be a safe and effective option for the treatment of NODAT in renal transplant recipients with the benefit of avoiding hypoglycemic episodes and possibly better diabetes control than with insulin therapy.
P1031CHADS2 AND CHAD2DS2-VASC SCORES IN THE PREDICTION OF PERIPHERAL ARTERIAL DISEASE IN DIABETIC PATIENTS
Authors: Chen Yi-Hsin
Published: June 2020

Background and Aims

Peripheral arterial disease (PAD) is more often seen in diabetic patients, accounting for 25-30%. Diabetic patients suffered more lower limb amputations in Unites States as high as 60% and patients with PAD suffer higher risk for amputations. We want to use CHADS2 and CHA2DS2-VASc scores to predict the risk of PAD in diabetic patients.

Method

We analysed data from the Taiwan National Health Insurance Research Database between January 1st, 2002 and December 31st, 2009. A total of 5,6732 diabetic patients were selected as the study cohort. The CHADS2 score and CHA2DS2-VASc score were calculated for each patient.

Results

During the follow-up period, 228 (0.4%) patients experienced new-onset PAD. The rate of PAD increased from 0.3% (CHADS2 score 1-2) to 1.4% (CHADS2 score 4-6) (p<0.001). The rate of PAD increased from 0.2% (CHA2DS2-VASc score 1-3) to 3.5% (CHADS2 score 7-9) (p<0.001). According to a multivariate analysis, the hazard ratio of each point increment in the CHADS2 score for predicting PAOD was 1.67 (p<0.001), CHA2DS2-VASc score was 2.03(p<0.001).

Conclusion

The CHADS2 and CHA2DS2-VASc scores are useful predictors of new-onset PAD in diabetic patients.
P1045MISALIGNED EXPECTATIONS ON INTEGRATIVE MEDICAL SERVICE FOR DIABETES AND DIABETIC KIDNEY DISEASE: A COMPARATIVE FOCUS GROUP SERIES OF PATIENTS AND PHYSICIANS
Authors: CHAN Kam Wa , Lee Pak Wing , Leung Crystal Pui Sha , Chan Gary Chi Wang , Chan Loretta Yuk Ying , Leung Joseph Chi Kam , Lam Tai Pong , Lai Kar Neng , Tang Sydney
Published: June 2020

Background and Aims

Difference of perspective between patients and physicians over integrative medicine (IM) research and service provision remains unclear despite significant use worldwide. We sought to explore the barriers and recommendations regarding IM service among diabetes and diabetic kidney disease (DKD) patients and physicians.

Method

A 10-group, 50-participant semi-structured focus group interview series was conducted. Twenty-one patients with diverse severity of disease, comorbidities and education levels; and 29 physicians (14 western medicine (WM) and 15 Chinese medicine (CM)) with diverse clinical experience, academic background and affiliation were purposively sampled from private and public clinics. The perspectives were qualitatively analysed by constant comparative method with grounded theory approach.

Results

Seven subthemes regarding barriers towards IM service were identified including finance, service access, advice from medical professionals, uncertainty of service quality, uncertainty of CM effect, difficulty in understanding CM epistemology and access to medical records. Patients underreported the use of CM due to the concern over neutrality of medical advice among physicians. Practical issues including inconvenience of access to service, frequent follow-up, use of decoction and long-term financial burden were identified as key obstacles among patients. Regarding research design, WM physicians emphasized standardization and reproducibility while CM physicians emphasized personalization. Some CM-related outcome measurements were suggested as abstract and non-communicable. Both WM and CM physicians acknowledged the discordance in epistemology should be addressed by pragmatic approach.

Conclusion

Further assessment on IM should be pragmatic to balance between standardisation, reproducibility and real-world practice. Evidence-based IM programs and research should merge with existing infrastructure.
P1071WITHIN-PATIENT RELATIONSHIPS BETWEEN ULTRAFILTRATION AND FLUID GAINS IN HAEMODIALYSIS PATIENTS
Authors: Nguyen Mai , Corbett Richard , Duncan Neill , Ashby Damien
Published: June 2020

Background and Aims

Despite the now-widespread use of haemodialysis treatment, optimal fluid management in long-term dialysis patients remains challenging. Whilst the between-patient factors affecting target weight and ultrafiltration have been well studied, little is known regarding the within-patient factors affecting these relationships.

Method

Dialysis data for a group of stable haemodialysis patients, from 4 dialysis units, were analysed over a period of one year. All weights and volumes are expressed as percentage of target weight.

Results

From 100 patients (aged 28–89, mean 65.4, 54% male) observed over a year, complete data were available for 15530 dialysis sessions, and 13027 combinations of dialysis session plus the following inter-dialytic interval.

Mean arterial pressure dropped by 3.5(+/-14.6)mmHg during dialysis, with a significant correlation (p<0.05) between pressure drop and ultrafiltration volume in 26 patients (mean R=0.09, mean regression gradient 3.2).

In 87 patients, inter-dialytic fluid gain correlated strongly (p<0.05) with the previous dialysis session’s ultrafiltration volume (mean R=0.37, mean regression gradient 0.20) suggesting a significant role of ultrafiltration volume in driving subsequent fluid intake behaviour (thirst).

Unsurprisingly, more fluid was gained over longer inter-dialytic intervals: mean(sd) weight at the start of dialysis was 103.2(1.0)% after a 3-day gap and 102.5(1.0)% after a 2-day gap, with this difference being significant (p<0.05) in 87 patients. However, fluid gain was non-linear, diminishing during longer inter-dialytic intervals: mean(sd) daily inter-dialytic fluid gain was 1.13(0.38)% during the 3-day gap vs 1.21(0.53)% during the 2-day gap (p<0.05 in 36 patients), implying that at least a third of patients consume less fluid during the 3rd post-dialysis day.

Conclusion

Inter-dialytic fluid gain is strongly dependent on ultrafiltration during the previous dialysis session, and diminishes during the inter-dialytic interval. Large ultrafiltration volumes, which have historically been perceived as the inevitable result of large fluid intakes, are actually a cause of thirst and large fluid intakes in haemodialysis patients. These data, derived from within-patient analyses, strongly challenge our conventional understanding of dialytic fluid management.
P1076HEMODYNAMIC TOLERANCE TO INTERMITTENT DIALYSIS IN CRITICALLY ILL PATIENTS: THE CLINICAL JUDGMENT OF HIPERVOLEMIA IS ABLE TO PREDICATIT?
Authors: Melo Erica , Silveira Marcelo , Dutra Fábio , Baptista Ana , Miranda Filipe , Nascimento Carolina , Coelho Fernanda , Teixeira Maurício , Gomes Marcel , Souza Sérgio , Benigno Paulo , Messeder Octavio , Farias Augusto , Caldas Juliana , Passos Rogério
Published: June 2020

Background and Aims

Evaluation and management of fluid balance are a key challenge in caring for the critically ill requiring renal replacement therapy. As intradialytic hypotension is a common complication and can be associated ultrafiltration rate. Usually the nephrologist and critical care physician have relied in their subjective clinical judgment and clinical data to calculate ultrafiltration. The aim of this study was to assess the prediction of clinical judgment of fluid overload and other clinical and dialysis data as predictors of hemodynamic tolerance to intermittent dialysis.

Method

This prospective observational single-center study was performed in critically ill patients with acute kidney injury undergoing intermittent hemodialysis. Before hemodialysis, clinical judgement of Hypervolemia from nephrologists and intensivists were assessed and posterior-anterior views of chest-X-rays done within three hour before of beginning of dialysis were collected for measurement of vascular pedicle width (VPW). Factors predicting intradialytic hypotension were identified by multiple logistic regression analysis.

Results

248 AKI patients requiring intermittent dialysis were considered eligible. The clinician judgement of hypervolemia was not different between hypotensive and non hypotensive sessions. Multiple logistic regression showed that the size of VPW was independently associated with the development of hypotension during IHD session. A VPW value of > 70 mm had an 86.1 % sensitivity, 55 % specificity for identifying non hypotensive sessions with an area under the curve (AUC) = 0.81, 95 % CI 0.75–0.84, p < 0.001.

Conclusion

Clinical judgment of hypervolemia and other clinical and demographic variables that are used by nephrologists and critical care physicians at bedside did not predict hypotensive hemodialysis sessions. The high predictive ability of VPW measurement can help physicians to avoid inductive and deductive thinking and may assist critical thinking.
P1084LONG TERM EVALUATION OF THE EXPANDED HEMODIALYSIS (HDX) ON DIALYSIS ADEQUACY, ANEMIA AND QUALITY OF LIFE
Authors: Gernone Giuseppe , Partipilo Francesca , Detomaso Francesco , Pepe Vito , Pietanza Stefania , Mitrotti Adele
Published: June 2020

Background and Aims

The High-Flux (HF) dialyzer in standard hemodialysis (HD) allow the removal of a wider spectrum of uremic toxin. However, the HD can remove mostly low molecular weight solutes while the HDF can remove solutes around 15kDa, so-called Middle Molecules (MM), improving morbidity and mortality by exchange volumes >23L per session. The new medium cut-off (MCO) filter Theranova® is designed to expand the removal of toxins up to 45kDa in HD compared to HF membranes (HemoDialysis eXpanded, HDx) even with conventional blood flows and without exchange fluid infusion. The aim of this study is to evaluate the performance of HDx and its impact on anemia and quality of life (QoL) in haemodialysis patients.

Method

11 stable HDs patients were enrolled (M/F 8/3, age 70.8±9) with Qb ≤300 ml/min in a 12 months observational case-control study. Each patient was evaluated first with HF filter (T0) and then in HDx for 12 months (T12). At T0-T6-T12 were evaluated: urea, phosphate (P), beta2-microglobulin (B2m), myoglobin (Myo), free light-chains k and λ (FLC- K and FLC- λ), C-Reactive Protein (CRP), hemoglobin (Hb) and albumin as well. Furthermore Kt/V, dose of EPO, ERI and SF-36 questionnaire were evaluated at the beginning and end of observation. We treat HD patients accordingly to the KDIGO Guideline for Anemia in CKD. The values have been reported as mean ±SD.

Results

HDx (Qb = 275 ± 41 ml/min, TT 215 ± 21 m) shows a significant increase in KT/V (T0 1,33 ± 0,19; T12 1,57 ± 0,16; p = 0.001) with relevant RR of: Urea 73.5%; P 58.4%; B2m 66,1 % (p< 0.05); Myo 55,1% (p< 0.05); FLC-k 64.1 % (p< 0.05); FLC-λ 59.9% (p< 0.05). There is a significant reduction at 12months for PCR (Tab.1). HDx reduced ERI [T0 10.1 ± 11.2; T6 4.1 ± 5.3 (p <0.05); T12 6±9.8] and EPO dose [T0 8182 ± 9141; T6 3545 ± 4547 (p <0.05); T12 5273±8912], keeping the Hb unchanged. QoL is significantly improved (ISF: T0 27.3 ± 10.1; T12 40.2 ± 8.4 p = 0.0001) (ISM: T0 43.8 ± 14.2; T12 51.1 ± 9.8 p = 0.001).

Conclusion

HDx effectively removes uremic toxins up to 45kDa, even with Qb <300 ml/min, without reducing serum albumin and with interesting results on inflammation. Reduction of ERI and improvement of QoL are encouraging and suggest the use of HDx even in patients who cannot benefit from convective techniques because of vascular access or intolerance to high volumes of exchange.
P1095USE OF CYTOKINE ADSORBING MEMBRANES IN PATIENTS WITH ACUTE RENAL FAILURE IN INTENSIVE CARE UNITS
Authors: Jakopin Eva , Hren Martin , Knehtl Masa , Dvorsak Benjamin , Hojs Nina , Zorman Tadej , Stropnik Galuf Tina , Sinkovic Andreja , Svensek Franci , Borovsak Zvonko , Wagner Kovacec Jozica , Ekart Robert , Hojs Radovan , Bevc Sebastjan
Published: June 2020

Background and Aims

Use of cytokine adsorbents has been proposed as a novel therapeutic approach in sepsis management. Our aim was to evaluate laboratory markers, clinical parameters and SOFA (Sequential Organ Failure Assessment) score in patients who were treated with cytokine adsorbing membrane (CytoSorb®, CytoSorbents Corp. New Jersey, USA) and continuous veno-venous haemodialysis.

Method

We included adult patients with septic shock and acute renal failure. We retrospectively collected laboratory results (leukocytes, thrombocytes, C-reactive protein, procalcitonin, lactate, urea, creatinine, bilirubin, PaO2), clinical parameters (mean arterial pressure (MAP), FiO2, residual diuresis), SOFA score and vasopressor use at the beginning and at the end of the procedure.

Results

We included 69 patients, 51 men, aged 56.6 ± 15 years. 51 patients had 1 procedure, 14 patients had 2 procedures, 3 patients had 3 procedures and 1 patient had 4 procedures. Median time from admission to initiation of procedure was 47 hours, median treatment time was 23.6 hours.

We discovered significant improvement in procalcitonin (35.36 ± 37.33 ng/mL vs. 24.25 ± 31.18 ng/mL; p<0.001), creatinine (345.06 ± 174.65 μmol/L vs. 233.11 ± 108.82 μmol/L; p<0.0001), SOFA score (14.20 ± 2.64 vs. 12.69 ± 3.52; p<0.001) and FiO2 (48.17 ± 21.17 % vs. 44.63 ± 21.45 %; p=0.020).

Patients with more than 1 procedure showed statistically significant reduction in lactate level (5.40 ± 4.74 mmol/L vs. 2.46 ± 1.74 mmol/L; p=0.010) and vasopressin dose (1.26 ± 1.61 vs. 0.88 ± 3.2 IU/h; p=0.022).

Conclusion

We observed potential beneficial effect of adsorptive membrane use in septic patients. According to our results two or more procedures were associated with improved laboratory markers and lower vasopressor requirement.
P1099EVALUATION OF THE DEPURATION OF SOLUTES IN THE MIDDLE TO HIGH MOLECULAR WEIGHT RANGE WITH DIFFERENT TECHNIQUES OF HAEMODIALYSIS
Authors: Cancho Castellano Barbara , Diaz Campillejo Rosa , López Arnaldo Cristina , Valladares Alcobendas Julián , Ruiz Calero Cendrero Rosa María , Martín Hidalgo Barquero Maria Victoria , López Gómez Juan M , García Yun Purificación , Olivera Azevedo Lilia , García de Vinuesa Calvo Elena , Robles-Perez Nicolas-Roberto
Published: June 2020

Background and Aims

Haemodialysis is the most commoly used replacement therapy for chronic kidney disease. We are looking for new solutions to remove solutes in the middle to high molecular weight range. Our objective is to evaluate and compare the purification of small and middle to high molecular weight between 15-45 KDa with Haemodyafiltration On Line postdilutional (HDF-OL-post) technique, Haemodialysis High-Flux (HD-HF) and Haemodialysis Expanded (HDx) using specific high permeability membranes: in the first two techniques polyphenylene membranes (1.7m2) and in the HDx technique cut point membranes PAEs/PVP (1.7 m2).

Method

10 chronic prevalent patients on haemodialysis, older than 18 years, without diuresis and stable, 60% males. Mean age 65.3±17.47 years. Time in HD, mean 49.5 months. Etiologies: 20% NAE, 30% ND, 10 % Glomerulopathies, 40% unaffiliated. Vascular Accesses: 50% FAVn, 20% FAVp, 30% CVC-T. They were evaluated for three consecutive weeks with analytics in the intermediate session, modifying the technique and the membrane, keeping the dialysis patient stable. Post-dialysis concentrations of solutes in the middle to high molecular weight range were corrected in relation to haemoconcentration. A comparison of the reduction percentages (RP%) of various molecules was performed. The possible normal distribution was studied in the continuous variables with the Shapiro-Wilk test and the comparison of means using the t-Student or Wilconson test as the most appropriate. SPSS statistical program 17.0.

Results

No serious adverse events or allergies were recorded. The comparative results between the three techniques are shown in the figure 1.

Conclusion

The mean reduction of medium molecules (β2-microglobulin, cystatin-C) was not lower in HDx compared to HDF-OL-post. From 20 KDa there is no greater capacity to reduce solutes in HDx in our sample than in the other techniques. Between the three techniques, the HDF-Ol-post is the one that shows a higher percentage of mean reduction of α1-acid glycoprotein and albumin.
P1103A RANDOMIZED CONTROLLED STUDY ON THE DIALYZERS WITH CELLULOSE TRIACETATE MEMBRANE AND WITH POLYSULFONE MEMBRANE FOR MAINTENANCE HEMODIALYSIS PATIENTS
Authors: Chen Zhang , Yun Yang , Liu Nai-quan , Zhou Guang-yu , Li De-tian
Published: June 2020

Background and Aims

With the continuous development and optimization of dialysis membrane materials, polysulfone (PS) as the third generation of dialysis membrane has replaced cellulose triacetate (CTA) and dominated the market because of its better biocompatibility. However, we found that the hypersensitivity to PS could be remitted by the application of CTA in clinical practice. Objective to compare the differences in toxin removal, hematological change and biocompatibility in maintenance hemodialysis (MHD) patients using CTA dialyzer and PS dialyzer.

Method

A total of 20 MHD patients treated in the Second Blood Purification Center of Shengjing Hospital from June 2017 to September 2017 were enrolled in this study. They were randomly divided into group CTA and group PS (n=10/each group). They were treated with regular hemodialysis of 4 hours/time and 3 times/week for one month. The clearances of creatinine (CR), blood urea nitrogen (BUN) and serum phosphorus (P), the changes of hemoglobin (Hb), platelet (PLT) and white blood cell (WBC), and the differences of C-reactive protein (CRP), IgE, complement 3 (C3), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were compared between group CTA and group PS.

Results

Age (t=-0.735, P=0.465), gender (c2 =2.410, P=0.120), dialysis age (t=0.336, P=0.738) and primary diseases (c2 =3.817, P=0.701) had no statistical differences between the two groups. Before the hemodialysis with CTA dialyzer and PS dialyzer, there were no statistical differences in all of the parameters between the two groups (P>0.05). After application of CTA dialyzer and PS dialyzer for one month, ①there were no statistical differences in CR, BUN and P, nor in the changes of the above indicators between the two groups (P>0.05); ② there was a statistical difference in Hb change between the two groups (t=-2.282, P=0.027), with better improvement of anemia in group CTA; ③ there was a statistical difference in PLT (t=2.947, P=0.005) between the two groups, with slighter change in group CTA than in group PS (t= 2.219, P=0.031); ④there were no statistical significances in WBC, VCAM-1, ICAM-1, IgE, CRP and C3 between the two groups (P>0.05).

Conclusion

①There were no significant difference in the clearances of small molecule toxins between CTA dialyzer and PS dialyzer. ② CTA was better than PS in the improvement of anemia. ③ The effect on PLT was less in group CTA than in group PS. ④ There were no significant differences in biocompatibility between CTA dialyzer and PS dialyzer.
P1104THE ROLE OF THERAPEUTIC PLASMA EXCHANGE COMBINED WITH HEMODIALYSIS IN MANAGEMENT OF POISONING AND INTOXICATION
Authors: VanSickle Judith
Published: June 2020

Background and Aims

Background: Poisonings, intoxications, and drug overdoses are common occurrences and rapid lowering of the toxin level is key of all effective therapies. Therapeutic plasma exchange (TPE) has several unique characteristics that allow it to be a potentially effective therapy in rapidly achieving this goal with large molecular weight, protein-bound molecules that have a small volume of distribution. Ibuprofen is a commonly used anti-inflammatory, antipyretic, and analgesic drug. The number of reported ibuprofen overdoses (IO) has increased. Although the vast majority of IOs are not consequential, large ingestion can cause severe metabolic acidosis (MA) resulting in multi-organ failure and death. TPE has been reported as solo intervention in IO, however frequently with remaining renal dysfunction. We report two cases of massive IO that responded well to prompt combined TPE with continuous renal replacement therapy (CRRT).

Method

Literature and chart review of cases of IO in our institute treated with TPE+CRRT.

Results

Case 1: A 17 year old male presented to the Emergency Department (ED) following intentional IO in coma with serum pH of 7.09, cardiorespiratory failure and acute kidney injury (AKI). Urine drug screen was positive for only ibuprofen. He reportedly took 1381 mg/kg. Supportive care was unsuccessful, therefore TPE+CRRT was soon initiated. After two days of treatment the patient was able to be extubated, maintained normal cardiovascular status and renal function. The patient fully recovered.

Case 2: A 17 year old female presented to the ED following intentional IO with serum pH of 6.9, cardiorespiratory failure, AKI, arrhythmia and bilateral leg compartment syndrome. Urine drug screen was positive for ibuprofen. The estimated ibuprofen exposure was above 2000 mg/kg. The initial ibuprofen serum plasma level was 330 µg/mL (therapeutic range is 10-50 µg/mL). Initial Supportive care was unsuccessful and TPE+CRRT was immediately started. Plasma ibuprofen level was normal after the 3rd TPE+CRRT. The patient fully recovered.

Conclusion

Intentional IO may result in major morbidity and mortality. TPE is more efficient in removing drugs with a high protein binding and/or a low volume of distribution, such as ibuprofen. In settings of massive overdose, hemodialysis may provide additional removal of unbound portion, as well corrects acidosis and allows provision of optimal nutrition. Combined TPE+CRRT is beneficial and may facilitate recovery. To our knowledge this is the first pediatric report of severe IO successfully treated with combined therapy.
P1107CENTRALIZED CONTROL OF HEMODIALYSIS PROCEDURES AND CORRECTION OF CKD COMPLICATIONS WITH BI TOOLS
Authors: Galchenkov Aleksei , Malkoch Andrey , Novitskiy Vladimir , Parfenov Vadim
Published: June 2020

Background and Aims

Life expectancy of patients with terminal stage of chronic kidney disease depends on the quality of dialysis therapy and timely and adequate correction of dialysis complications. The goal of this work is to improve the treatment quality for dialysis patients in a setting of multi-facility hospital by employing of Business intelligence (BI) tools for centralized control of diagnostic and treatment process.

Method

We have created a system for centralized control of patients’ condition, using Microsoft Power BI platform. This system allows to analyze the process of hemodialysis procedure as well as treatment of hypertension, anemia and mineral bone disorder. The system generates various reports that may include parameters of a specific patient, single clinic, or multi-facility hospital for the period from arbitrary date to the day, previous to the report generation date.

The effect of system usage was assessed on 288 patients from 30 hemodialysis facilities of “Nefrosovet” private organization, for the period of 6 month.

Results

Before deployment of the system, target value of Kt/V (1.4) was reached or exceeded in 49% of hemodialysis procedures, median duration of hemodialysis procedure was 227±18 minutes (mean total duration per week - 683 minutes). As the result of usage of centralized control and prescription correction system, target values of Kt/V was reached or exceeded in 65% of hemodialysis procedures, median duration of hemodialysis procedure increased to 238±11 minutes (mean total duration per week - 714 minutes). Before the start of the study, hypotensive episodes were registered in 34% of hemodialysis procedures, and hypertensive episodes were registered in 22% of hemodialysis procedures. As the result of centralized control of hemodialysis procedures, number of procedures with hypotensive episodes reduced to 28%, and number of procedures with hypertensive episodes reduced to 17%. Number of patients with blood hemoglobin value in target range of 100-120 g/l, increased from 1617 patients (56%) to 2051 patients (71%). Number of patients with blood ferritin value in target range of values, increased from 1013 patients (35%) to 1386 patients (48%). Number of patients with TSAT value in target range of values, increased from 873 patients (30%) to 1097 patients (38%). We have also noticed an increase in number of patients with target values of calcium and phosphorus metabolism parameters: calcium corrected for albumin – from 1992 (69%) to 2165 (75%) patients, phosphorus – from 693 (24%) to 982 (34%) patients, intact parathyroid hormone (iPTH) – from 635 (22%) to 837 (29%) patients.

Conclusion

The usage of BI based centralized patients’ condition control system allows to improve adequacy of dialysis therapy and quality of CKD complications correction in dialysis patients.
P1115MEDICAL WASTE MANAGEMENT - HOW INDUSTRY CAN HELP US TO PROTECT ENVIRONMENT AND MONEY
Authors: Zawierucha Jacek , Prystacki Tomasz , Marcinkowski Wojciech , Malyszko Jolanta
Published: June 2020

Background and Aims

The global climate change and its consequences force us to remodel our processes and rethink current model of providing the HD treatments. One of the crucial point, which have massive impact on the environment and the economy is the waste management. Every HD session produces above 1 kg of medical waste, which should be properly stored and destroyed. Well thought out processes and our choices can improve dialysis unit budget as well as decrease CO2 emission produced during the waste incineration.

The aim of the study was was assessment of weight the different dialysers used during HD treatments and consequences of choice different types of filters.

Method

The weight of dialyser is the most crucial component of the medical waste produced during dialysis session. The authors checked the weight of different dialysers regularly used in dialysis centers in Poland. The Kern CM 320-IN scale was used for the measurement. The measurement accuracy was 0,1 g.

Also the filling volume of each dialyser has been taken into consideration.

Results

The dialysers were divided into four groups depending on the surface. 1,4m2 in group one, 1,5-1,6m2 in group two, 1.7-1,8m2 in group three and finally 2,0-2,2m2 in the group four. FX class dialysers were lightest in every group. The heaviest ones were Polyflux dialysers. Difference between the lightest and heaviest dialysers was about 95 g. Also the filling volume was lowest in FX class dialysers and the highest in case of Elisio dialysers. The difference was 20 ml.

Conclusion

The weight of different dialysis sets available on the market significantly differs. The decision-makers should take into account this fact as the additional quality feature. In extreme cases the weight difference reaches 95 g. In yearly perspective, the usage of the lighter dialysis set can cause the 17 millions kilograms decrease of medical waste and significant savings.

On the other hand modern HD machines like Fresenius 6008 machine, due to the dialysis set emptying function additionally decrease the mass of the medical waste about 150 g per one HD session, independently on the dialyser used.
P1121TOTAL PLASMA EXCHANGE (TPE) AND CITRATE CRRT IN A LOW-WEIGHT PEDIATRIC PATIENT WITH MACROPHAGE ACTIVATION SYNDROME (MAS): FEASIBILITY AND COMPLEXITIES OF BOTH TREATMENTS
Authors: Sagliocchi Alessandra , Ricci Davide , Caramelli Fabio , Mancini Elena
Published: June 2020

Background and Aims

Low-weight extracorporeal pediatric dialysis treatments remain a challenge due to their clinical and technical complexity.

Apart from some metabolic congenital disorders, the usual indications for CRRT in early pediatric patients and newborns are the same as for adults with acute kidney injury (AKI). But the implementation of TPE is still in the anecdotal stage.

Method

Clinical case: a 7-month female infant, weighing 5.7kg, in the neonatal intensive care unit with fever, lymphadenopathy, hepatosplenomegaly, pancytopenia, hyperferritinemia, hypertriglyceridemia, was diagnosed as having macrophage activation syndrome (MAS). She developed AKI and acute respiratory distress syndrome (ARDS), due to sepsis. Because of oliguria, ruling out administration of drugs and parental nutrition, and fluid overload (more than 20% of her body-weight), CRRT was started.

Results

CRRT lasted 22 days in continuous venovenous hemodiafiltration (CVVHDF), with regional citrate anticoagulation (Table 1). Mean filter patency: 26±17h. 43% of treatments were interrupted after CVC failure, 21% after clinical procedures, 7% after filter coagulation. There was in this case no citrate accumulation and satisfactory metabolic and electrolyte control were obtained (Figure 1).

After treatment of MAS failed with both i.v. immunoglobulins and corticosteroids, we considered TPE as a rescue therapy for the disease, even though we could not find a similar experience reported in the literature in such a small infant. We performed 3 TPE sessions, with heparin anticoagulation (Table 1), non-consecutively, with CRRT in between.

Conclusion

The treatments were well tolerated, resulting in a large decrease in triglycerides and ferritin (MAS index, Figure 2).

Despite the death of the patient after ARDS worsened, we showed that even in a small critically ill infant, complex depurative treatments such as total plasma exchange are feasible. Highly skilled nephrologists and dialysis nurses are mandatory for treatment management.