bluuebunny/crossref_metadata_2025 huggingface dataset:
SO044ALPHA LIPOIC ACID COMPARED TO SELENIUM IN MITOCHONDRIAL RESUSCITATION AND MI RNA-126 EXPRESSION IN HEMODIALYSIS PATIENTS
Authors: ElSharkawy Magdy , Al Kasaby Zainab , A. Elewa Hosny , Abdelrahman Maha
Published: June 2020

Background and Aims

anti-oxidants may decrease the risk of cardiovascular complications (CVC) in HD patients. We aimed to study antioxidant effect of Alpha lipoic acid and selenium on oxidative stress, endothelial repair, and mitochondrial functions in HD patients by evaluating the serum level of reactive oxygen species (ROS), miRNA-126, and CoQ10.

Method

60 individuals were enrolled and randomized into 3 groups, G1; 22 HD patients as control, G2; 20 HD patients received Selenium, and G3;18 HD patients received. Serum levels of ROS, CoQ10, and miRNA-126 were assessed at base line and after three months treatment for all patients.

Results

At baseline, all groups were matched regarding their demographic data and target parameters.

After three months, in G1; the serum level of ROS increased significantly (P < 0.05), CoQ10 didn't change significantly (P > 0.05), while the fold expression of miRNA-126 decreased significantly (P < 0.05). In G2,3; there were statistical significant changes in target parameters after the treatment, ROS level decreased significantly by 34%, and by 79%, CoQ10 mean levels increased significantly from 13.21 to 28.35, and from 13.46 to 36.43 ng/ml, mean fold expression of miRNA126, increased significantly by 6.94, and 10.54 folds, in Selenium and, Thiotacid groups respectively. The results showed that Thiotacid was better than Selenium in ROS level reduction, and CoQ10 level improvement, while no statistical significant difference between two drugs regarding miRNA126 level (P > 0.05).

Conclusion

Selenium and, Thiotacid reduce oxidative stress and also they enhancing the endothelial repairing, and improve mitochondrial functions and thus may reduce risk of CVC.
SO055PROBIOTIC BIO-THREE DECREASES SERUM PHOSPHATE LEVELS WITH INVOLVEMENT OF BACTERIA IN GUT MICROBIOMA IN HEMODIALYSIS PATIENTS: A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTOLLED STUDY
Authors: Ogawa Tetsuya , Hosoda Yumi , Horimoto Ai , Nishizawa Yoko , OMAE KIYOTSUGU , Nagano Nobuo
Published: June 2020

Background and Aims

Recent studies revealed that the importance of the gut microbioma in the development and progression of CKD. Dysbiosis of the intestinal microbiota increases uremic toxin, which damage the epithelial tight junctions and increase the permeability of the intestinal wall via endotoxemia and systemic inflammation. Some articles reported that probiotics reduced the uremic toxin and decreased inflammation biomarkers in CKD patients, while others reported no remarkable changes. Meanwhile, we have already reported that oral administration of Bifidobacterium longum in a gastro-resistant seamless capsule decreases serum phosphate levels in patients receiving haemodialysis. The aim of this study is to evaluate the efficacy of probiotics by changes of serum data, including inflammation and intestinal flora in patients receiving hemodialysis.

Method

A 6-month prospective, randomized, double-blind, placebo-controlled study was conducted at three hemodialysis centers. As probiotic therapy, of three-combination probiotics (Bio-Three) tablets, each containing 2 mg of lactomin (Streptococcus faecalis T-110), 10 mg of Clostridium butyricum TO-A, and 10 mg of Bacillus mesentericus TO-A, were used. The patients receiving hemodialysis were randomly assigned to the Bio-Three group (n=37) and the placebo group (n=36). In both the Bio-Three group and the placebo group, patients orally received 6 tablets 3 times daily. We evaluated the effect of probiotic on the ratio of CRP to albumin as an inflammatory biomarker, other serum data and gut microbioma before and 6 month after the start of treatment. The gut microbioma composition was analyzed by a 16s rRNA gene-based sequencing protocol.

Results

The ratio of CRP to albumin did not change before and after treatment in both groups. The serum phosphate levels in the Bio-Three group significantly decreased after 6-month treatment, while did not change in the placebo group. In a 16s rRNA gene-based sequencing protocol analysis, the ratio of Firmicutes, Actinomycetales and Neisseriaies significantly changed after 6 month treatment in the only probiotic group. Meanwhile, serum phosphate levels were positively correlated with the number of genus Haemephilus and gunus Neisseria in the only probiotic group. Furthermore, serum phosphate levels were negatively correlated with the number of genus Bifidobacterium in the only probiotic group.

Conclusion

In this study, three-combination probiotics did not decrease systemic inflammation in hemodialysis patients. Meanwhile, three-combination probiotics might decrease serum phosphate levels, and the specific bacteria in the gut microbioma might contribute to the decrease of serum phosphate levels.
SO057BETA-BLOCKERS ARE ASSOCIATED WITH REDUCED MORTALITY IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION AND ADVANCED CHRONIC KIDNEY DISEASE: COHORT STUDY
Authors: Fu Edouard L , Uijl Alicia , Dekker Friedo W , Lund Lars H , Savarese Gianluigi , Carrero Juan Jesus
Published: June 2020

Background and Aims

Beta-blockers reduce mortality and morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, patients with advanced chronic kidney disease (CKD) were underrepresented in landmark trials. We evaluated if beta-blockers are associated with improved survival in patients with HFrEF and advanced CKD.

Method

We identified 3906 persons with an ejection fraction <40% and advanced CKD (eGFR <30 mL/min/1.73m2) enrolled in the Swedish Heart Failure Registry during 2001-2016. The associations between beta-blocker use, 5-year all-cause mortality, and the composite of time to cardiovascular (CV) mortality/first HF hospitalization were assessed by multivariable Cox regression. Analyses were adjusted for 36 variables, including demographics, laboratory measures, comorbidities, medication use, medical procedures, and socioeconomic status. To assess consistency, the same analyses were performed in a positive control cohort of 12,673 patients with moderate CKD (eGFR <60-30 mL/min/1.73m2).

Results

The majority (89%) of individuals with HFrEF and advanced CKD received treatment with beta-blockers. Median (IQR) age was 81 (74-86) years, 36% were women and median eGFR was 26 (20-28) mL/min/173m2. During 5 years of follow-up, 2086 (53.4%) individuals had a subsequent HF hospitalization, and 2954 (75.6%) individuals died, of which 2089 (70.1%) due to cardiovascular causes. Beta-blocker use was associated with a significant reduction in 5-year all-cause mortality [adjusted hazard ratio (HR) 0.86; 95% confidence interval (CI) 0.76-0.96)] and CV mortality/HF hospitalization (HR 0.87; 95% CI 0.77-0.98). The magnitude of the associations between beta-blocker use and outcomes was similar to that observed for HFrEF patients with mild/moderate CKD, with adjusted HRs for all-cause mortality and CV mortality/HF hospitalization of 0.85 (95% CI 0.78-0.91) and 0.88 (95% CI 0.82-0.96), respectively.

Conclusion

Despite lack of trial evidence, the use of beta-blockers in patients with HFrEF and advanced CKD was high in routine Swedish care, and was independently associated with reduced mortality to the same degree as HFrEF with moderate CKD.
SO065TYPE OF EXERCISE INTERVENTION AND MUSCLE FUNCTIONS IN CHRONIC HEMODIALYSIS PATIENTS
Authors: Rogowski Łukasz , Dziubek Wioletta , Mariusz Kusztal , Bulinska Katarzyna , Gołębiowski Tomasz , Klinger Marian , Magdalena Krajewska , Wozniewski Marek
Published: June 2020

Background and Aims

Decreased exercise capacity due to muscle weakness and exercise intolerance reduces the ability to perform activities of daily living in patients with end-stage kidney disease. Data on exercise type in dialysis population and its muscle effects are scarce. We aimed to determine the impact of training type (strength, resistance and mixed) on cardiovascular performance, muscle function (strength-speed parameters, electrophysiological function of muscles) in patients on hemodialysis maintenance.

Method

Eighty six dialysis patients underwent claster randomisation and were assigned to an exercise intervention groups: A - controlled endurance training during haemodialysis using rotors (MOTOmed letto2), B - controlled force training (resistance), C - Tai Chi training on non dialysis days. Intervention lasted 6 months, 3 times a week (A, B) and 2 times a week (C) for 60 minutes. The outcome measures were spiroergometry (VO2/VO2max), strength of the lower limbs and electromyographic examination. Values at the baseline and 6 months later were compared.

Results

45 patients completed intervention period and were analysed. Mean age in group A was 64±12y (n-16), in B was 60,5±10y. (n-15) and in C – 68,5±9y. (n-14). Patients did not differ markedly between groups in term of sex, BMI, dialysis vintage and comorbidities.

After 6 months of training, VO2 and VO2max increased significantly only in group B (resistance training) Δ12.7 % for VO2 and 12.9% for VO2max but not in A and C group (Fig.1.). Regarding force torque of quadriceps (ΔPT) in isometric conditions the highest peak values were measured in group B (resistance training), namely increase by 13.6% (p=0.0004) in right (R) and 14% (p<0.0001) in left (L); in group A (endurance) 3.2% in R and 3.7% in L; in group C (Tai Chi group) by 7% (p<0.05) in R and 6.8% (p<0.05) in L. In terms of changes in electrophysiological function of right (QEMG_R) and left (QEMG_L) quadriceps, there were increases: for group A by 10.5% (p<0.0001) and 9.6% (p<0.05); B 9.7% (p=0.0002) and 20.1% (p=0.0001); for C by 4.5% and 6.2% for R and L, respectively (Fig.2).

In groups B and C significant increases in static force moments (Δ%PT) was associated with increases in electrophysiological action (Δ%QEMG), but in group A increase in EMG activity did not correspond with rise in muscle force (Fig.2).

Conclusion

Differences in muscle strength and functions were observed after 6 months of various type of exercise intervention in dialysis patients. Resistance training during dialysis showed the largest improvement in cardiorespiratory function and isometric leg muscle strength.
SO07118F-SODIUM FLUORIDE POSITRON EMISSION TOMOGRAPHY AND BONE HISTOMORPHOMETRY - COMPARISON BETWEEN ONLY BONE TURNOVER -BASED AND EXPERT EVALUATION -BASED CLASSIFICATION OF RENAL OSTEODYSTROPHY
Authors: Aaltonen Louise Caroline , Koivuviita Niina , Seppänen Marko , Burton Inari , Kröger Heikki , Metsarinne Kaj Peter
Published: June 2020

Background and Aims

The diagnosis and the differentiation of renal osteodystrophy (ROD) are challenging. Bone biopsy is the golden standard, but it is invasive and not available in every center.

Bone turnover rate is defined by bone formation rate and/or activation frequency. Adynamic bone disease is defined as low turnover bone with reduced osteoblast- and osteoclast activities. Hyperparahyreoid bone disease or osteitis fibrosa is defined as high turnover bone with osteoclast- and osteoblast activities and fibrosis.

18F- Sodium Fluoride positron emission tomography (18F-NaF PET) is a noninvasive imaging technique that allows assessment of regional bone turnover.

The aim was to assess how well bone turnover –based classification of ROD correlates with the classification determined by an expert histomorphometrist (HK), and how these correlate with 18F-NaF PET analysis

Method

A total of 24 dialysis patients underwent a 18F-NaF PET scan. Fluoride activity was measured at the anterior iliac crest and in the lumbar region. An iliac crest bone biopsy was obtained within 4 weeks from the PET-scan. The diagnosis of bone histomorphometry was determined based on turnover-mineralization-volume (TMV) classification. Firstly, bone turnover was assessed using bone formation rate and activation frequency. Secondly, also other histomorphometric parameters (eg. osteoid volume, osteoid surface, resorption surface, mineralized surface, osteoblast and osteoclast surfaces and peritrabecular fibrosis) were also taking into account for classification of ROD by a histomorphometrist.

Results

Based on bone turnover parameters only, 12% of the patients had high turnover and 64% low turnover. When the diagnosis of renal osteodystrophy was made by a histomorphometrist, 40% had hyperparathyreoid bone/osteitis fibrosa and 24% adynamic bone disease or ostemalasia.

18F-NaF PET´s sensitivity to recognize hyperparathyreoid bone disease was 80% end specificity 100% (cut-of value 0.055).18F-NaF PET´s sensitivity to recognize adynamic bone disease was 100% and specificity 61% (cut-of value of fluoride-activity 0.038)

Conclusion

18F-NaF PET works well as a diagnostic tool, when the diagnosis of ROD is based on the histopathological evaluation. It remains unknown how variations in normal bone turnover rate can be detected in CKD patients by 18F-NaF PET and if treatment decisions of ROD can be made only based on bone turnover.
SO072INCIDENCE OF FRACTURES BEFORE AND AFTER DIALYSIS INITIATION AMONG INCIDENT DIALYSIS PATIENTS
Authors: Iseri Ken , Carrero Juan Jesus , Evans Marie , Felländer-Tsai Li , Berg Hans , Runesson Björn , Stenvinkel Peter , Lindholm Bengt , Qureshi Abdul Rashid Tony
Published: June 2020

Background and Aims

The incidence of fractures is markedly higher in dialysis patients than in pre-dialysis patients, but it is not clear to what extent the initiation of dialysis as such is associated with accelerated fracture incidence or if fracture rates are already increasing prior to dialysis start among incident dialysis patients. Here we investigated the temporal pattern of occurrence of a first major osteoporotic fracture (MOF) among incident dialysis patients in the pre-dialysis period and in the period following dialysis initiation.

Method

We analyzed data from Swedish Renal Registry (SRR) and identified 9041 incident dialysis patients (2005 -2015; age 67 years, 67% men). We identified all first MOF (MOFfirst) in hip, spine, humerus and forearm during 12 months before and after dialysis initiation. Using flexible parametric hazard models and Fine-Gray analysis accounting for competing risk of death and renal transplantation, we estimated adjusted fracture incidence rates and predictors of MOFfirst.

Results

During the whole follow-up period, there were 361 fractures including 196 hip fractures. The crude incidence rate of MOFfirst (n=157) before dialysis initiation was 17/1000 patient-years and after initiation of dialysis the incidence rate of MOFfirst increased to 24/1000 patient-years. Overall the adjusted MOFfirst incidence rates increased from 6 months before initiation of dialysis, fluctuated, and stabilized at a higher rate than that of the baseline rate after 12 months. The adjusted hip fracture rate rose steeply 3 months before dialysis initiation, declined 3 months after dialysis initiation, fluctuated, and then became stabilized. On the contrary, the adjusted incidence rates of other fractures, i.e., non-hip fractures, appeared to be stable all the time, before as well as after initiation of dialysis. Female gender, higher age and previous history of MOF had a negative impact on fracture incidence rates before and after dialysis initiation.

Conclusion

We conclude that the incidence of MOFfirst is increasing already from 6 months prior to dialysis initiation among incident dialysis patients, and that there is a further increase following dialysis initiation. For hip fracture, which was the most common MOF, the temporal pattern of incidence rates was compressed to a high risk period lasting from 3 months before to 3 months after dialysis initiation, underlining the need of increased attention to prevent hip fractures in incident dialysis patients during this critical period.
SO073IRON-RELATED PARAMETERS AND ANTI-ANAEMIC THERAPY IN HAEMODIALYSIS PATIENTS TREATED WITH SUCROFERRIC OXYHYDROXIDE: A 1-YEAR RETROSPECTIVE EUROPEAN CLINICAL DATABASE (EUCLID) ANALYSIS
Authors: Carey-George Jayne , Gurevich Konstantin , Ramos Sanchez Rosa , Chazot Charles , Ferreira Anibal , Di Benedetto Attilio , Feuersenger Astrid , Wolf Melanie , Arens Hans-Juergen , Walpen Sebastian , Stuard Stefano
Published: June 2020

Background and Aims

This retrospective analysis of data from the European Clinical Database (EuCliD®) evaluated changes in iron-related parameters and use of concomitant anti-anaemic therapies in European haemodialysis (HD) patients treated with sucroferric oxyhydroxide (SFOH). Previous Phase 3 clinical studies and non-clinical studies have indicated that there is minimal iron absorption from SFOH. This study aimed to evaluate the changes in iron-related parameters among patients treated with SFOH in the real-world setting.

Method

De-identified patient data were extracted from a clinical database (EuCliD®) for adult HD patients newly prescribed SFOH routinely for up to 1 year (1 Jan 2015–1 Jan 2019). Levels of serum ferritin, transferrin saturation (TSAT) and haemoglobin were compared between baseline (BL; 3-month period before starting SFOH) and each quarterly period in the year after starting SFOH treatment (Q1–Q4). Proportions of patients receiving intravenous (IV) iron and erythropoiesis-stimulating agent (ESA) therapies, in addition to their mean weekly doses, during each quarter were recorded.

Results

The cohort included 1,096 patients with recorded SFOH prescriptions (mean age: 60.6 years; 65.8% male). There were small, but significant increases in ferritin from BL to Q1–Q4 (P<0.05 for all periods vs BL). There were also increases in TSAT (P<0.05 at Q1 and Q2 vs BL) and haemoglobin (P<0.001 at Q1 and Q3 vs BL) (Table). During the 1-year SFOH treatment period, the proportion of patients receiving IV iron therapy decreased (P<0.05 at Q2 and Q3 vs BL) and there was a significant reduction in the mean weekly dose of IV iron administered (P<0.05 at Q2 and Q3 vs BL). The use of ESA therapy also declined (P<0.05 at Q3 and Q4) and there was a significant decrease in the mean weekly dose of ESA during the 1-year SFOH follow-up period (P<0.05 for all periods vs BL).

Conclusion

This real-world study showed that SFOH treatment in routine clinical practice for up to 1 year was associated with small increases in iron-related parameters and decreases in the use and mean dose of concomitant anti-anaemic therapies in European HD patients. The results from this study indicate that SFOH treatment may be associated with the reduction in concomitant IV iron and ESA use in HD patients, in line with previous findings from the Phase 3 study.
SO077A PROSPECTIVE RANDOMIZED STUDY ON PRE-EMPTIVE IMMUNOSUPPRESSIVE TREATMENT IN LUPUS NEPHRITIS PATIENTS WITH ASYMPTOMATIC SEROLOGICAL REACTIVATION
Authors: Yap Desmond , Tang Colin Siu On , Chung Ho Yin , Chan Julia , Lo Joseph M W , So Benjamin Y F , Chan Daniel Tak Mao
Published: June 2020

Background and Aims

The optimal management for asymptomatic serological reactivation (ASR) in lupus nephritis (LN) patients remains undefined. Our previous retrospective study suggested that pre-emptive treatment with moderate increase of immunosuppression may reduce subsequent clinical flares.

Method

This prospective study randomized LN patients with ASR (defined as >2-fold increase of anti-dsDNA to >100 IU/mL, with or without change in complement level, and absence of clinical lupus exacerbation) to receive pre-emptive treatment (‘Pre-emptive’ group) or unchanged management (‘Control’ group). Pre-emptive treatment included increasing prednisolone dose to 0.5 mg/kg/D, and the dose of mycophenolate to 1g/D or azathioprine to 75 mg/D, then tapered over 12-16 weeks back to the original dosages.

Results

Thirty-four patients were randomized (17 in each group). Pre-emptive group showed lower anti-dsDNA and higher C3 levels after 12 weeks compared with Controls (90.3±58.3 IU/mL vs. 153.8±92.9 IU/mL, and 98.7±33.4 mg/dL vs. 81.8±26.2 mg/dL, respectively; p<0.001 for both) (Figure 1). Pre-emptive group showed significantly lower incidence rates of all clinical flares and renal flares during subsequent 9 months of follow-up compared with Controls (11.7% vs 47.1%, p=0.01; and 0% vs 17.7%, p=0.03; respectively). Mean time-to-flare was 6.4±4.2 months and 5.2±3.4 months in Pre-emptive and Control groups respectively (p=0.77). There was no clinically significant adverse event.

Conclusion

Our results suggest that pre-emptive moderate increase of immunosuppressive treatment reduces the risk of disease flare in LN patients with ASR and is well tolerated.
SO081LITHIUM EXPOSURE AND OCCURENCE OF CHRONIC KIDNEY DISEASE IN THE IRISH HEALTH SYSTEM: A COHORT STUDY
Authors: Behan Mark , Browne Leonard , Austin Stack
Published: June 2020

Background and Aims

Lithium is implicated as a causative factor in the development and progression of chronic kidney disease (CKD). Few studies have assessed the independent impact of plasma levels and duration of lithium therapy on CKD progression. We examined the influence of lithium on CKD progression in the Irish health system.

Method

We utilised data from the Irish Kidney Disease Surveillance System (IKDSS) to explore associations of lithium levels and duration of exposure with kidney function in a regional cohort. A retrospective cohort study was conducted between 1999 to 2014 from the Midwest Region. All adult patients with lithium levels were identified and followed longitudinally. Kidney function was assessed at baseline and longitudinally using serum creatinine and estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI. Patients with < 2 lithium values, missing data on creatinine were excluded. The index date was the date of the first lithium blood test. Toxicity from lithium was defined as levels >1.2mmol/L as per NICE guidelines while duration of treatment was calculated based on patient –years of exposure as determined by positive blood lithium levels. Relationships between baseline kidney function, lithium levels, duration of exposure and each patients most recent eGFR value on follow up were assessed using multiple linear regression

Results

We identified 1,978 patients exposed to lithium from 1999-2014, mean age was 47.4 (15.6), 45.1% were men, eGFR [median (IQR)] at baseline was 84.4 (32.1) ml/min1.73m and the median duration of exposure was 3.0 years (IQR=4 years). Frequency of lithium testing increased from 1.77 in 1999 to 2.66 in 2014. In multiple linear regression, the final eGFR on follow-up was significantly lower in older patients (-0.48 ml/min/1.73m per year increase in age), P<0.001; in patients with elevated baseline lithium levels (-2.18 ml/min1.73m lower per unit increase), P<0.05, with long duration of exposure (-1.42 ml/min/1.73m lower for each year on lithium), P<0.001, and for patients with low GFR at baseline (P<0.001). Together these variables explained 58% of the variation in the final model.

Conclusion

Both the magnitude of and the duration of lithium exposure are both independently associated with CKD progression among lithium users in the Irish health system. Higher baseline lithium values had a more deleterious impact on kidney function. Continued efforts should be expended in minimising the risks of lithium induced nephrotoxicity through switching to alternatives and dose reduction when over possible.

Funding

This study is funded by the Health Research Board and the Midwest Research and Education Foundation (MKid).
SO085CIRCULATING PCSK9 LEVEL PREDICTS RISK OF CARDIOVASCULAR EVENTS AND DEATH IN HEMODIALYSIS PATIENTS
Authors: Hwang Hyeon Seok , Kim Jin Sug , Kim Yang-Gyun , Lee So-Young , Ahn Shin Young , Lee Hong Joo , Lee Dong-Young , Lee Sang ho , Moon Ju-Young , Jeong Kyung Hwan
Published: June 2020

Background and Aims

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for prevention of cardiovascular (CV) events. However, the clinical significance of circulating PCSK9 is unclear in hemodialysis (HD) patients.

Method

A total of 353 HD patients were prospectively enrolled from June 2016 to May 2018 in a K-cohort. Plasma PCSK9 level was measured at the time of study enrollment. Patients were classified into three groups based on PCSK9 tertile. The primary endpoint was defined as composite of CV event and death from any cause.

Results

Plasma PCSK9 level was positively correlated with total cholesterol level in patients with statin treatment. However, PCSK9 was not related to plasma inflammatory (high-sensitivity C-reactive peptide, monocyte chemoattractant protein-1, interleukin-6) or calcification-related markers (osteoprotegerin and receptor activator of nuclear factor kappa-Β ligand). Multivariate linear regression analysis revealed that baseline statin treatment and serum glucose, albumin, and total cholesterol were independent determinants of circulating PCSK9 levels. In Cox-regression analysis, PCSK9 tertile 3 was associated with a 1.99-fold risk for composite events (95% CI, 1.08–3.66), and it was associated with a 2.26-fold risk for CV events (95% CI, 1.11–4.62) after adjustment for multiple variables. PCSK9 tertile 3 provides additional prognostic power to predict composite events in subgroups with higher levels of high-sensitivity C-reactive peptide and LDL.

Conclusion

In conclusion, higher circulating PCSK9 level independently predicted CV events and death in HD patients. These results suggest the importance of future studies regarding the effect of PCSK9 inhibition on reduction of CV events.
SO086SNF472 CONSISTENTLY SLOWS PROGRESSION OF CORONARY CALCIFICATION IN PATIENTS ON HEMODIALYSIS: SUBGROUP ANALYSIS OF THE CALIPSO STUDY
Authors: Raggi Paolo , Bellasi Antonio , Bushinsky David , Bover Jordi , Rodriguez Mariano , Ketteler Markus , Sinha Smeeta , Garg Rekha , Padgett Claire , Perelló Joan , Gold Alex , Chertow Glenn
Published: June 2020

Background and Aims

In the CaLIPSO study, SNF472 significantly attenuated progression of coronary artery calcium (CAC) volume score compared with placebo. This pre-specified analysis examined the effect of SNF472 on CAC progression in key subgroups of patients in CaLIPSO.

Method

Patients with a CAC Agatston score of 100 to 3500 at baseline were randomized to SNF472 300 mg (n=92), SNF472 600 mg (n=91), or placebo (n=91), infused during hemodialysis (HD) thrice weekly for 52 weeks. Patients received standard of care therapy, including phosphate binders and calcimimetics as determined by investigator. The primary endpoint (change in log CAC volume score from baseline to week 52 in the combined dose groups vs placebo) was analyzed for patients who received SNF472 or placebo and had an evaluable CT scan post-randomization (modified ITT population). Sensitivity analysis was also performed for the per protocol population of patients that met entry criteria, received 80% of scheduled treatment, completed the study procedures, and had both a baseline and week 52 evaluable CT scan. The analysis plan pre-specified key subgroups: age, sex, diabetes, dialysis vintage, and arteriosclerotic cardiovascular disease (ASCVD), as well as baseline use of non-calcium phosphate binders, calcium-based phosphate binders, calcimimetics, activated vitamin D, warfarin, or statins.

Results

Demographics and disease characteristics were similar across the treatment groups. Age (mean±SD) at baseline was 63.6±8.9 years and 39% of the patients were female; 62% had diabetes and 41% had prior ASCVD. Median dialysis vintage was 42.4 months; 33% had received hemodialysis for ≥5 years. Concomitant medications at baseline were: non-calcium phosphate binders, 62%; calcium-based phosphate binders, 28%; calcimimetics, 31%; activated vitamin D, 51%; warfarin, 8%; and statins, 64%. CAC volume progression was 11% for the combined dose groups and 20% for placebo (p=0.016). Treatment differences for CAC volume score progression from baseline to week 52 were similar across the subgroups (FIGURE). All interaction p-values were non-significant, and comparisons favored SNF472 vs placebo in each subgroup for both the modified ITT and per protocol population.

Conclusion

SNF472 treatment for 52 weeks attenuated CAC progression compared with placebo in all subgroups of the CaLIPSO study. These results support the potential benefit of SNF472 across a broad population of patients with cardiovascular calcification. Future studies are needed to determine the effects of SNF472 on cardiovascular events in patients receiving HD.
SO087RISK OF INTRADIALYTIC HYPOTENSION BY DAY OF THE WEEK IN MAINTENANCE HEMODIALYSIS
Authors: Correa Simon , Guerra-Torres Xavier E , Waikar Sushrut S , Mc Causland Finnian R
Published: June 2020

Background and Aims

Intradialytic hypotension (IDH) affects up to 50% of maintenance hemodialysis (HD) patients and is associated with a higher risk of cardiovascular (CV) events and mortality. CV events are more common on the days of dialysis and are most pronounced following the longer interdialytic interval. We wished to investigate if the rates of IDH differed according to dialysis day.

Method

We examined data from adult patients undergoing in-center thrice-weekly maintenance HD (N= 975 patients/n=59,004 sessions from a large dialysis organization [LDO] and N=1,838 patients/n=64,407 sessions from the Hemodialysis [HEMO] Study). We fit random effects logistic regression models to determine the association of day of HD (Mon/Tue [HD1]; Wed/Thu [HD2]; Fri/Sat [HD3]) with various definitions of IDH. Models were adjusted for age, sex, race, Kt/V, membrane flux, heart failure, peripheral vascular disease, diabetes, access type (catheter vs. fistula vs. graft), pre-dialysis blood urea nitrogen, ultrafiltration rate, pre-HD systolic blood pressure (SBP). IDH definitions included Nadir90 (nadir intra-HD SBP <90mmHg), Nadir90/100 (nadir intra-HD SBP <90mmHg if pre-HD SBP <160mmHg or <100mmHg if pre-HD SBP ≥160mmHg), Fall20 (pre-SBP minus nadir SBP ≥20mmHg) and Fall30 (pre-SBP minus nadir SBP ≥30mmHg).

Results

Mean age was 60 years, 44% were female and 38% were black in the LDO cohort, while mean age was 58 years, 56% were female and 63% were black in HEMO. Nadir90 occurred in 15% of LDO and 11% of HEMO sessions; Nadir90/100 occurred in 18% of LDO and 14% of HEMO sessions; Fall20 occurred in 76% of LDO and 68% of HEMO sessions; Fall30 occurred in 60% of LDO and 50% of HEMO sessions. Overall, a monotonic increase in the risk of IDH was observed for HD2 and HD3 compared with HD1 for all IDH definitions in both cohorts (see Table and Figure).

Conclusion

We observed a consistent monotonic increase in the risk of IDH for HD2 and HD3, compared with HD1 in two separate cohorts of maintenance HD patients. Potential explanations may relate to progressive reduction in post-HD weight during the dialytic week, or perhaps more aggressive ultrafiltration in advance of the longer interval. Further research to determine the underling mechanisms is necessary to guide practicing nephrologists when individualizing the HD prescription.
SO088BURDEN OF VALVULAR HEART DISEASE IN HAEMODIALYSIS RECIPIENTS
Authors: Elewa Mohamed , Jayanti Anu
Published: June 2020

Background and Aims

Valvular heart disease (VHD) is highly prevalent in maintenance haemodialysis patients. This high prevalence is associated with poor outcomes and higher mortality [Samad et al., Journal of the American Heart Association, 6 (10), (2017)]. Previous large studies found VHD prevalence between 14% and 16% among prevalent haemodialysis patients [2018 USRDS Annual Data Report | Vol 2] [Hickson et al., Journal of the American College of Cardiology, 67(10), (2016)]. KDIGO consensus group identified several evidence gaps where research is necessary in order to improve our understanding of diagnosis and management of VHD in this population [Marwick et al., Kidney international, 96 (4), (2019)]. The aim of our study is to assess the burden of VHD in a large cohort of haemodialysis recipients in one center in the United Kingdom (UK).

Method

This is a retrospective cross-sectional evaluation of valvular heart disease in prevalent haemodialysis patients. Prevalent haemodialysis recipients were defined as patients established on haemodialysis for ≥ 3 months. Echocardiographic data was collected for all patients. Patients were considered to have VHD if they had significant aortic (AVD) or mitral valve disease (MVD) based on standard echocardiographic criteria. These valvular diseases are classified as mild, moderate or severe. Here, we report some descriptive statistics from our data.

Results

The study group includes 544 prevalent haemodialysis patients. Mean age was 62 years (SD 15.28), 40% females and 60% were males. Median dialysis vintage was 1.9 years (IQR 1, 3.2) [Range: 0.2, 10.2]. 14 % of patients received home-based hemodialysis and 86% received in-center dialysis. 30% of patients were actively awaiting a transplant. A total of 1155 echocardiography studies were reviewed. Of the 425 patients who had an echocardiogram; 34% (n=143) had evidence of VHD as defined above. Significant AVD was identified in 18% of patients (n=78). The dominant lesion was aortic regurgitation in 11%, and aortic stenosis in 7% of patients. 20% of patients (n=85) had significant MVD with mitral valve stenosis in 0.7% of patients (n=3) and mitral regurgitation in 18% of patients. 5% of patients had cardiothoracic intervention (n=21) for valvular heart disease, which included aortic valve replacement (n=9), transcatheter aortic valve implantation (TAVI) (n=9), and mitral valve replacement (n=3).

Conclusion

We found that at least one third (34%) of patients in this cohort had significant VHD- higher than the previously published figures. The numbers are likely to be higher, if echocardiogram information was available for all patients in the study. Timely echocardiographic studies and follow-up imaging for those with established disease are essential to identify patients with significant VHD, in order to establish impact of disease on both dialysis delivery and patient symptoms.
SO089THE EVOLUTION OF THE RENAL FUNCTION IN A COHORT OF ITALIAN PATIENTS WITH ADPKD: AN ANALYSIS BY THE JOINT MODEL
Authors: Galliani Marco , Vitaliano Elio , Chicca Silvana , Paone Antonio , Di Lullo Luca , Tosti Maria Elena , Mele Alfonso , Calvaruso Luca , D'Arrigo Graziella , Tripepi Giovanni Luigi , Zoccali Carmine
Published: June 2020

Background and Aims

The natural history of ADPKD has been defined in numerous studies in various countries and in various genetic and environmental contexts but the problem has not yet been studied in sufficiently large studies in the Italian population. We have studied the evolution of ADPKD in a cohort of 445 incident patients enrolled in a time span between 2012 and 2016 in 28 nephrological centers in 3 regions of central Italy. The main demographic and clinical characteristics of this cohort are reported below.

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Method

The analysis was carried out on a sample of 296 patients with at least 2 creatinine measurements prior to ESKD and with eGFR at onset ≥45 ml/min/1.73m2. The median follow-up was 15 years (range 1-42 years). The analysis of the data was carried out with the Joint model, an approach that allows the simultaneous modeling of longitudinal (repeated over time) and time to event ESKD or GFR<45 ml/min/1.73m2 data. This approach produces two sub-models: a longitudinal model (mixed linear model, sub-model A in the table) and a time to event model (Cox model, survival sub-model B in the Table). The two models are mutually associated through an analytical structure that quantifies the relationship between the variables of interest.

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Results

The average eGFR decline in the entire population was -2.13 ml/min/1.73m2/year. In males the decline in GFR was significantly higher than in females (M: -2.63 ml/min/1.73m2; in F -1.74 ml/min/1.73m2/year, p <0.005) while it was not significant differences are observed for the different age groups considered separately in the two sexes (p = 0.158 in the M; p = 0.625 in the F).

In the longitudinal model the age at diagnosis >30 years and the presence of hypertension were significantly associated with an accelerated decline in GFR and patients older than 50 years exhibited a reduction by 35 ml/min/1.73m2 greater than those younger than 30 years. In the survival model the GFR trend and sex were associated with the risk of renal survival. For each incremental baseline unit of GFR the risk for ESKD decreased by 16% (HR: 0.84) and in females the risk was about one third compared to males (HR: 0.31).

Conclusion

This study, the first to apply the joint model in the analysis of the evolution of renal function in ADPKD and the first in a sizeable cohort in Italy, provides important information on the progression of polycystic kidney disease in an incident series of Italian patients with ADPKD.
SO092REDUCED QUALITY OF LIFE IN ADPKD PATIENTS WITH CKD STAGE 1-3: THE CYSTIC I QUALITY OF LIFE STUDY
Authors: Winterbottom Jean , Simms Roslyn , Ong Albert
Published: June 2020

Background and Aims

ADPKD is the most common inherited kidney disease in man, a major cause of end-stage renal disease and is a significant medical and economic burden across Europe. However the impact of this major disease on the quality of life of patients with preserved kidney function has not been systematically explored.

Method

The CYSTic 1 study was an academic prospective study designed to study the natural history of ADPKD, the impact of the disease on individual patients and the health economic costs on care systems across Europe in adult patients with preserved kidney function (eGFR ≥30 mls/min). Around 400 patients were recruited from 6 expert centres across Europe (Belgium, France, Italy, Netherlands, Spain, UK) with baseline clinical data recorded including HR-QOL (Health-Related Quality of Life) incorporating a Kidney Disease QOL short form (KDQOL-SF v1.3 questionnaire), renal MRI for TKV (Total Kidney Volume) and DNA for genotyping. Here we report initial results based on baseline HR-QOL data in the UK patients.

Results

Detailed analysis was conducted on 76 patients recruited from a single centre (UK) whose mean age was 43 years, 53.9% were female with a mean eGFR-EPI of 69ml/min/1.73m2 and mean height-adjusted TKV (Ht-TKV) of 664ml/m. The cohort was subdivided by groups based on eGFR stage (I, II, III), Ht-TKV (<>750ml/m) and genotype (PKD1 v PKD2/NMD) and correlated with HR-QOL scores. As expected, age, hypertension and Ht-TKV were significantly associated with eGFR stage. Of interest, flank pain was more frequently reported in patients with smaller kidneys (Ht-TKV<750) and patients with PKD1 more likely to be hypertensive. All QOL scores (SF36) were significantly lower in patients with progressively lower eGFR except for emotional well-being whereas Symptom/problem (p=0.043) and Sleep (p=0.021) (KDQOL-SF1.3) were significantly worse in patients with lower kidney function. SF36 scores for Physical functioning (p=0.001), General health (p=0.026) and physical component summary (PCS) (P=0.019) decreased in patients with more advanced disease defined by larger kidneys (ht-TKV>750).

Conclusion

In ADPKD patients with stage 1-3 chronic kidney disease (CKD), stepwise lower QOL scores were consistently found and significantly associated with decreasing eGFR. A notable reported item was disturbed sleep. Unexpectedly, patients with smaller kidneys reported significantly more flank pain. PKD1 patients and those with large kidneys were more likely to be hypertensive. Our results suggest that the impact of ADPKD on patients with stage 1-3 CKD is underestimated. Future work will investigate possible national differences and the relationship of HR-QOL with markers of disease within the entire cohort.
MO020EFFICACY AND SAFETY OF THE LONG-ACTING C5 INHIBITOR RAVULIZUMAB IN PATIENTS WITH POSTPARTUM ATYPICAL HAEMOLYTIC URAEMIC SYNDROME
Authors: Gäckler Anja , Dobronravov Vladimir , La Manna Gaetano , Denker Andrew , Liu Peng , Schoenermarck Ulf , Vinogradova Maria , Yoon Sung-Soo , Praga Manuel
Published: June 2020

Background and Aims

Atypical haemolytic uraemic syndrome (aHUS) triggered by pregnancy is a rare and under-recognised disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor built on eculizumab, with a maintenance dosing interval of 8 weeks, is efficacious in treating aHUS. In this analysis, we report outcomes in a subgroup of patients with postpartum-aHUS enrolled in the 311 study.

Method

This was a global, phase 3, single-arm, multicentre trial evaluating the efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete thrombotic microangiopathy (TMA) response (simultaneous platelet count normalisation [≥150 x 109/L], lactate dehydrogenase [LDH] normalisation [≤246 U/L] and ≥25% improvement in serum creatinine at 2 separate assessments ≥28 days apart) through the 183-day initial evaluation period. Additional efficacy endpoints were: time to complete TMA response, haematological normalisation (platelet count and LDH), dialysis requirement status, and change in eGFR.

Results

Eight patients with postpartum-aHUS (mean age 36 [±8] years) were diagnosed within 12 days of delivery. Seven patients were white and one was Asian. Six patients (75%) had received plasma exchange/infusion before ravulizumab therapy; five (63%) were on dialysis. Complete TMA response was achieved in 7/8 patients (87.5%) in a median time of 32 days. Haematological normalisation was observed in all patients. By Day 29, all five patients on dialysis at baseline had discontinued dialysis, and by Day 183 all eight patients had improved CKD stage (defined based on eGFR value) by ≥1 category. Three possible treatment-related adverse events (non-serious) were noted in two patients (arthralgia and nasopharyngitis; urinary tract infection). All patients survived and no meningococcal infections occurred.

Conclusion

This is the first prospective analysis of a C5 inhibitor in postpartum-aHUS. Treatment with ravulizumab resulted in rapidly improved haematological and renal outcomes with no unexpected adverse events identified when administered at 8-weekly dosing intervals through intravenous infusion.
MO022URINARY PHOSPHATE/UREA RATIO, A NEW TOOL TO EVALUATE ADHERENCE TO PHOSPHATE DIETARY INTERVENTIONS IN CKD PATIENTS
Authors: Pendon-Ruiz de Mier M Victoria , Santamaria Rafael , Rodelo-Haad Cristian , Muñoz-Castañeda Juan R , Membrives Cristina , Lopez-Baltanas Rodrigo , Lopez-Zamorano M Dolores , Martin-Malo Alejandro , Caravaca Francisco , Soriano Cabrera Sagrario , Rodriguez Mariano
Published: June 2020

Background and Aims

In chronic kidney disease (CKD) patients, phosphate (P) restriction is crucial for the control of mineral metabolism. Many reports indicate that P intake doesnot correlate with 24-hour phosphaturia. Different sources of P (organic or inorganic) have different intestinal absorption rates. Different proportions of organic and inorganic P in diet might be the reason for the lack of correlation between phosphorus intake and phosphaturia. Therefore, we aimed to evaluate if the source of dietary P rather than the total amount of P ingested determines total phosphaturia and it was accessed to what extent inorganic P intake modifies phosphaturia

Method

A 3-day dietary survey was performed in 71 stages G2-3 CKD patients with metabolic syndrome to estimate the amount and source of P in the diet. Blood and 24-hour urine-samples were collected. Total phosphaturia, fractional excretion of P (FeP%), urinary P/eGFR ratio (mg/day/GFR that reflects the urine P excretion relative to renal function), P/creatinine ratio, urinary urea /Cr ratio, and urinary P/urea ratio (that reflects daily intestinal absorption of P relative to the amount of proteins absorbed and metabolized) were evaluated. P/urea ratio was categorized into tertiles and contrasted in terms of the other variables analyzed (T1=<0.027 mg/mg, T2=0.027-0.033 mg/mg, T3= >0.033 mg/mg). Statistics were performed using R 3.6.2, RStudio, Tidyverse, and tableone v0.10.0 packages.

Results

Patients` age was 61±9 years, and eGFR was 68±21 ml/min/1.73m2. Estimated P intake was 869±289 mg/day. According to sources, P intake was 64% from animal sources, 22% from vegetable sources, and 14% from inorganic P. Total P intake did not correlate with urinary P (r=0.18, p=0.12), urinary P/eGFR (r=-0.32, p=0.79), or FeP (r=-0.08, p=0.48). Figure 1 shows that patients ingesting more P have a greater intake of inorganic P. There was a correlation between P intake and P/Urea ratio (p=0.008). Patients in the upper urinary P/urea tertile showed the highest daily P intake (p=0.04), and inorganic P (p=0.03). These patients from tertile 3 also showed the highest amount of urinary P excretion (p=0.04).

Conclusion

Urinary P/urea reflects the total P intake and, more importantly, provides information about the amount of inorganic P. Therefore, the P/urea ratio may be used to guide the appropriate nutritional advice for CKD patients.
MO024WHAT IS THE BEST PREDICTABLE LIPID SUBFRACTION FOR CARDIOVASCULAR OUTCOMES AND ALL-CAUSE MORTALITY IN PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE?
Authors: Kim Yaerim , Yoon Jeongsoo , Paek Jin Hyuk , Park Woo Yeong , Jin Kyubok , Han Seungyeup , Joo Kwon Wook , Kim Dong Ki
Published: June 2020

Background and Aims

Dyslipidemia is an essential parameter for the prediction of cardiovascular disease (CVD). We aimed to investigate the most valuable subfraction of lipid for predicting CVD in patients with chronic kidney disease (CKD).

Method

We retrospectively reviewed the National Health Insurance Service database for people who received nationwide health screening in 2009. All subjects exposed with lipid-lowering agent before screening were excluded. The population was divided as control, early CKD (eGFR 45-60 ml/min/m2), and advanced CKD (eGFR <45 ml/min/m2) by estimated glomerular filtration rate. Each subfraction of lipid profile, including LDL, TG, HDL, and TG/HDL, was categorized by decile, and the reference was the fifth decile. The end-point of the study was major adverse cardiovascular events (MACCE). The hazard ration (HR) of MACCE was calculated using Cox regression models after adjustment of multiple covariates.

Results

A total of 3,634,915 examiners were included in this study, with 66,810 (1.8%) and 404,315 (11.1%) in advanced and early CKD, respectively. For all populations, LDL, TG, HDL, and TG/HDL showed a linear relationship to MACCE. Except HDL, all subfraction showed positive correlation with the risk for MACCE: adjusted HR (aHR) in tenth decile, 1.45 (1.42-1.49) in LDL; 1.25 (1.22-1.28) in TG; 1.30 (1.27-1.33) in TG/HDL; 0.88 (0.85-0.90) in HDL. Although these patterns were similar in TG, HDL, and TG/HDL for all-cause mortality, only LDL showed different pattern for the two outcomes. In the subgroup analysis using LDL, according to the renal function, the significance for the outcomes and a linear pattern was decreased in the advanced CKD group. For the TG/HDL, although the significance was deceased, the linear pattern has maintained in the advanced CKD group (Fig 1).

Conclusion

The pattern and significance of lipid subfraction were different according to the grade of renal function. Thus, TG/HDL should be additionally considered with LDL as a target variable in patients with advanced CKD.