bluuebunny/crossref_metadata_2025 huggingface dataset:
#2803 ECG ABNORMALITIES AND MORTALITY IN HEMODIALYSIS PATIENTS
Authors: Kharsa Chloé , Chlawit Roy , Aoun Mabel
Published: June 2023

Background and Aims

Hemodialysis patients undergo electrocardiogram (ECG) testing for acute events or as a part of the regular workup. It is still unknown whether chronic ECG abnormalities could be considered as a prognostic factor in dialysis patients. This study aims to analyze the association between mortality and ECG abnormalities of the last two years of follow-up of hemodialysis patients.

Method

This is a retrospective study that included all patients treated with chronic hemodialysis in a single center between January 2002 and December 2021. Patients who had no ECG in their medical file during the last two years of follow-up were excluded. ECGs were interpreted by two physicians. Logistic regression analysis evaluated the association between ECG signs and mortality. The study was approved by the institutional ethics committee and was conducted in accordance with Helsinki Declaration.

Results

A total of 298 medical files were reviewed, 149 files included an ECG in the last two years of follow-up. Mean age of patients was 67.1 ±13.2 years, 64.4% were males, 54.4% had diabetes, 44.2% had documented coronary artery disease (CAD), 14.8% had chronic or paroxysmal atrial fibrillation. The median left ventricular ejection fraction (LVEF) was 60% [55.5, 64.5]. 55% percent died after a median follow-up of 47 [25, 87] months. Table 1 summarizes the ECG characteristics found among all patients. In the univariate analysis, age, CAD, LVEF, left axis deviation, large QRS, ST depression and first-degree AV block were significantly associated with mortality. After adjustment to age, dialysis vintage, sex, diabetes, CAD and LVEF, we found a significant association between all-cause death and left axis deviation (Table 2). The poor R wave progression was associated with increased sudden cardiac arrest after adjustment to age, dialysis vintage, sex, diabetes and CAD (OR = 2.65, 95%CI 1.01-6.94, p = 0.048).

Conclusion

This study showed that left axis deviation on ECG of patients treated with chronic hemodialysis is an independent factor associated with increased all-cause mortality after adjustment to demographic and medical factors. Poor R wave progression was associated with sudden cardiac arrest.
#2804 ALBUMINURIA IS ASSOCIATED WITH DECREASED SEVR AND ANKLE-BRACHIAL INDEX IN PATIENTS WITHOUT CKD
Authors: Piko Nejc , Bevc Sebastjan , Hojs Radovan , Naji Franjo , Petreski Tadej , Varda Luka , Ekart Robert
Published: June 2023

Background and Aims

Albuminuria signifies subclinical vascular damage in the kidneys and other organs and is associated with systemic endothelial dysfunction and increased future cardiovascular risk.

Subendocardial viability ratio (SEVR) is defined as diastolic to systolic pressure-time integral ratio and is a marker of subendocardial perfusion. Reduced SEVR has been uncovered in patients with chronic kidney disease (CKD) and simultaneous albuminuria. Albuminuria is also considered a risk factor for peripheral artery disease, especially in patients with additional atherosclerosis risk factors or diabetes mellitus. The aim of our study was to determine the impact of albuminuria on SEVR and ankle-brachial index (ABI) in patients without known CKD.

Method

We included 111 patients (73% male, mean age 64.2±9.3 years) that were hospitalized at our Cardiology department between 2016-2020 due to elective cardiac catheterization. Albuminuria was determined by urine albumin to creatinine ratio (UACR) from a random urine specimen. SEVR was determined by using applanation tonometry on radial artery (Sphygmocor, Atcor Medical, Australia). Ankle-brachial index (ABI) was measured by using an automated, non-invasive waveform analysis device (MESIÒ, Slovenia), mean ABI between the left and right side was used. Glomerular filtration rate was estimated (eGFR) by using the CKD-EPI 2009 creatinine equation. All the data were obtained prior to cardiac catheterization and only patients with eGFR ³60 ml/min/1.73 m2 were included. Statistical analysis was performed with the Statistical Package for Social Sciences version 22.0 (SPSS Inc, USA).

Results

Basic descriptive statistics, comorbidities, and medications are presented in Tables 1 and 2. Spearmann's correlation test showed significant correlation between UACR and SEVR (r = - 0.238; p = 0.017) and UACR and ABI (r = - 0.304; p = 0.003). Multiple regression analysis with SEVR as the dependent variable and waist-to-hip ratio, body mass index (BMI), arterial hypertension, diabetes, dyslipidemia, eGFR and UACR as independent variables, showed a significant association between UACR and SEVR (b = - 0.232; p = 0.029). The same model was used for ABI as the dependent variable, and a significant association was found only between UACR and ABI (b = - 0.232; p = 0.029).

Conclusion

Albuminuria is independently associated with decreased SEVR and ABI even in the absence of CKD.
#2818 UNIQUE SIGNATURES OF EXTRACELLULAR MATRIX REMODELING IN PATIENTS WITH LUPUS NEPHRITIS, FSGS, AND MCD: A PILOT STUDY
Authors: Sparding Nadja , Genovese Federica , Karsdal Morten A , Derner Ondrej , Neprasova Michaela , Frausova Doubravka , Kollar Marek , Hruskova Zdenka , Tesar Vladimir
Published: June 2023

Background and Aims

Glomerulonephritis is one of the most common causes of chronic kidney disease (CKD). Causes of glomerular diseases include lupus nephritis (LN), focal segmental glomerulonephritis (FSGS) and minimal change disease (MCD). The hallmark of CKD is renal fibrosis characterized by an imbalanced turnover of extracellular matrix (ECM) components and CKD is associated with increased inflammation. The aim for this study was to screen a biomarker panel based on extracellular matrix remodeling biomarkers as well as fibrotic activity and inflammation biomarkers. Additionally, to identify biomarkers that are differentially expressed in glomerular diseases compared to healthy and that are differently expressed between the different etiologies.

Method

The study included 79 healthy controls (age (median years): 35, sex (%women): 51), 48 patients with LN (age: 39, sex: 63), 13 patients with FSGS (age: 44, sex: 23), and 14 patients with MCD (age: 51, sex: 47). The following biomarkers were measured in serum and/or urine samples from all 154 subjects:

• Interstitial matrix remodeling biomarkers; formation of collagen type III (PRO-C3) and VI (PRO-C6), and degradation of collagen type III (C3M).

• Basement membrane remodeling biomarkers; MMP-mediated degradation of collagen type IV (C4M, C4G, TUM), laminin (LG1M) and perlecan (LG3).

• Two biomarkers of fibrotic activity; acetylated N-terminal of alpha-smooth muscle actin (αSMA) and transforming growth factor β (TGF-β).

• An inflammation biomarker of calprotectin (CPa9-HNE) reflecting neutrophil activity.

Results

Overall, all three diseases showed the same trend of change (either no change, increase or decrease compared to healthy controls) in biomarker levels. There was a significant increase of PRO-C3, PRO-C6, TUM, LG1M, αSMA, and CPa9-HNE in serum, and a significant decrease of C3M and C4M serum in patients compared to heathy controls. Four of the biomarkers were differently expressed between the different etiologies. In serum, C4G levels were significantly higher LN and MCD compared to FSGS, LG1M levels were significantly higher in LN compared to MCD, and CPa9-HNE levels were significantly higher in MCD compared to LN (all, P<0.05). In urine, TUM levels were significantly higher in LN compared to FSGS and MCD (P<0.05).

Conclusion

The data presented in this study indicate that both biomarkers of interstitial matrix and basement membrane remodeling as well as biomarkers of fibrotic activity and inflammation reflect the changes that take place during development of glomerular diseases. Some of these markers may be able to distinguish etiologies including the hardly differentiated diseases FSGS and MCD. This needs to be tested in larger studies.
#2827 RISK FACTORS FOR VENOUS AND ARTERIAL THROMBOEMBOLIC COMPLICATIONS IN NEPHROTIC SYNDROME: A COHORT STUDY
Authors: Kelddal Sarah , Tofig Bawer , Hvas Anne-Mette , Grove Erik , Christiansen Christian Fynbo , Birn Henrik
Published: June 2023

Background and Aims

Venous thromboembolic events (VTE) and arterial thromboembolic events (ATE) are serious complications of nephrotic syndrome (NS). Studies are needed to identify patients at high risk for VTE and ATE. We aimed to describe patient-related risk factors for VTE and ATE in a mixed population of nephrotic patients.

Method

This multicentre cohort study included adult NS patients with plasma albumin <30 g/l and urine albumin-creatinine ratio (uACR) >2,200 mg/g, who were hospitalized or followed at an outpatient clinic in the Central Denmark Region between 2014-2018. Using computerized data extraction from medical files, patients were identified and followed until dialysis, transplantation, or end of study. We recorded comorbidities, family history, renal parameters and, histological diagnosis at index time as well as, renal parameters and medication at the time of VTE/ATE event. Categorical and continues data were compared using a risk difference and mean difference respectively. The incidence of event is presented as incidence rate.

Results

Among 531 included patients, 22 patients had their first VTE and 46 their first ATE within the first observation year (median time to event VTE 0.8 vs. ATE 0.9 years). Incidence rates were 11 per 1000 person-years (95% CI: 7-17) for VTE and 24 (95% CI: 18-32) for ATE. Plasma-albumin levels (27 g/l) were identical in the VTE and ATE group at event time, but eGFR was lower (Table 1), and uACR was higher in the ATE group (median uACR; VTE 1055 mg/g vs. ATE 2752 mg/g). Hypercholesterolemia was more prevalent among patients with VTE, and they were more often on corticosteroids than patients with ATE. Diabetes, hypertension, and heart failure was more prevalent at baseline in patients with ATE resulting in an increased CHADS-VASC score. Mortality was higher among patients with ATE (83%) than VTE patients (32%).

Conclusion

Patients with NS have a high risk of VTE and ATE. Corticosteroid use was more common among patients with VTE than ATE. ATE was associated with a higher uACR, higher CHADS2-VASC score, and increased mortality compared to patients with VTE.
#2885 DYNAMICS OF URINARY SYNDROME IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS DEPENDING ON THE USE OF ANTICOAGULANT
Authors: Abduvakhitova Asalya
Published: June 2023

Background and Aims

to study the dynamics of urinary syndrome in patients with chronic glomerulonephritis (CGN) against the background of the use of rivoroxaban.

Method

108 patients with chronic glomerulonephritis (CGN), on the background of 3-month basic therapy with the inclusion of with anticoagulant rivaroxaban 55 patients and without anticoagulant 53 patient. Initially and after 3 months, the composition of the urinary sediment was assessed.

Results

Patients with CGN had significant proteinuria (3.23±0.12g/l versus 0.01±0.004 control group (CG), p<0.001), hematuria (42.58±2.10 erythrocytes in the field of vision, against 0.75±0.25 cells in the field of vision, p<0.001), leukocyturia (38.25±0.80 leukocytes in the field of vision, against 1.70±0.24 cells in the field of view in CG, p<0.001) and cylindruria (38.11±1.04 cylinders in the field of view, versus 0.10±0.07 cylinders in the field of view in CG, p<0.001). Albuminuria contributed to an increase in the specific gravity of urine (1021.64±0.44 g/l versus 1017.45±0.65g/l in CG, p<0.001). By the end of the hospitalization period, there was a significant improvement in urinary syndrome: the relative dynamics of urinary syndrome indicators was more than 30%. Thus, the degree of proteinuria decreased to 1.98± 0.10 g/l (p<0.001 the reliability of the difference with the initial data), hematuria – to 26.38±1.43 cells in the field of vision (p<0.001), leukocyturia – to 22.04±0.88 cells in the field of vision (p<0.001), cylindruria – to 25.45±0.79 cylinders in the field of view (p<0.001). Against the background of a decrease in proteinuria and diuretic therapy, there was a decrease in the specific density of urine by 0.73% (up to 1014.15 ± 0.45g/l, reliability with baseline data - p <0.001).

Conclusion

Rivaroxaban is an effective oral anticoagulant, the long–term use of which as part of the basic therapy of patients with CGN is safe, well tolerated and pathogenetically justified. The inclusion of rivaroxaban in the basic therapy of patients with CGN is associated with the achievement of more favorable values of proteinuria, hematuria and leukocyturia by the end of the 3rd month of therapy.
#2886 THE COURSE OF OSTEODYSTROPHY IN PATIENTS WITH STAGE 5 CHRONIC KIDNEY DISEASE RECEIVING PROGRAMMED HEMODIALYSIS
Authors: Mirzaeva Barno , Daminov Botir
Published: June 2023

Background and Aims

In a normal physiological state, there are many regulatory molecules that act as inhibitors of mineral formation to prevent the spread of tissue hardening. In patients with CKD, the levels or functions of these inhibitors may be abnormal, which in turn may predispose to or enhance ectopic calcification. to increase the effectiveness of early diagnosis of demineralization of the bone skeleton in patients with stage V chronic kidney disease receiving hemodialysis.

Method

The study included 94 CKD patients receiving hemodialysis for 15 months. The average age of the patients was 42.13±12.16 years. Etiologically, the cohort of patients included in the study was diverse, with a significant predominance of chronic glomerulonephritis as the cause of CKD in 72 patients, chronic pyelonephritis in 22 patients occupied the second place among the causes of CKD, the remaining causes occurred with a single frequency. Anemia was diagnosed in 71 patients. The observation lasted 12 months. Pathological changes in phosphorus-calcium metabolism and secondary hyperparathyroidism in patients were associated with a significant decrease in bone mineral density, it was shown both for the bodies of the lumbar vertebrae and for the femoral neck, the significance of the difference from the control group for absolute values of mineral density and relative deviation.

Results

In dynamics for 6 months in the general cohort of patients, there was a significant increase in the absolute mineral density of the femoral neck by 11.38%, p<0.01 the reliability of the difference with the baseline data, and a decrease in the degree of deviation of the mineral density index from the age norm -3.13%, p<0.05 for the bodies of the lumbar vertebrae and -4.01%, p<0.01 for the femoral neck, which confirms the effectiveness of osteoporosis therapy. In the present study, in 45 patients 37.5% at the time of inclusion in the study in the bodies of the lumbar vertebrae, the T-index was higher than -2.5 SD, in respect of the femoral neck – in all patients, the T was lower than 2.5 ST. The study of bone mineral density in patients with HCBP, the decrease of which reflects the syndrome of renal osteodystrophy, developing in response to secondary hyperparathyroidism, against the background of osteoporosis therapy.

Conclusion

In patients with CKD, against the background of programmed hemodialysis, there is a decrease in bone mineral density (1.93 times the bodies of the lumbar vertebrae and 2.83 times the femoral neck). The use of calcium carbonate, biphosphonate and vitamin D3 contributes to an increase in the mineral density of the femoral neck by 8.64% (p<0.05). The introduction of sevelamer hydrochloride into the therapy regimen increases the effectiveness of therapy and increases the mineral density of the bodies of the lumbar vertebrae by 5.96% (p< 0.05) and the femoral neck by 14.04% (p<0.05).
#2913 BLOODSTREAM INFECTIONS IN CHRONIC HEMODIALYSIS PATIENTS: CHARACTERISTICS AND OUTCOMES
Authors: Pravda Miri Schamroth , Maor Yasmin , Brodsky Konstantin , Katkov Anna , Cernes Relu , Pravda Nili Schamroth , Tocut Milena , Soroksky Arie , Feldman Leonid
Published: June 2023

Background and Aims

Bloodstream Infections (BSI) are a major cause of death and hospitalization among hemodialysis (HD) patients. In recent years several preventive measures were introduced to reduce BSI in HD patients. Despite these various strategies, the rate of BSI in HD remains high. The aim of the present study was to explore factors associated with BSI in a contemporary cohort of HD patients at a public teaching hospital dialysis center.

Method

This was a retrospective cohort study of HD patients with a BSI in the years 2014 to 2018. The cohort included patients aged ≥ 18 years treated with chronic HD for at least three months. The primary outcome was the occurrence of BSI. We examined the clinical characteristics of the patients, causative pathogens, and mortality.

Results

The study involved 251 chronic HD patients. The mean age was 68.5±13.4 years, 69.9% were male. The most frequent cause of end-stage renal disease was diabetes (46.7% of patients). The mean time from initiation of HD was 34.8±40.8 months and the follow up period was 25.2±15.9 months. During the observation period, 44 patients (17.5%) developed 54 BSI events, while 9 of them (3.6% of the whole cohort) developed recurrent BSI events. Gram-negative microorganisms caused 46.3% of all BSI events. 31.4% of these BSI were caused by resistant bacteria. In multivariate logistic regression analysis, factors that increased the risk of mortality were BSI events (OR 2.566, p = 0.035), patients' age (OR 1.068, p<0.001), diabetes (OR 1.019, p = 0.001).

Conclusion

We noted an increased prevalence of gram-negative pathogens in the etiology of BSI in HD patients. Our findings highlight the need to be aware of local epidemiology in order to implement appropriate preventative measures and tailor empiric antibiotic therapy.
#2974 SERUM CHEMOKINE CC-MOTIF LIGAND 17 IS A PREDICTIVE MARKER OF SEVERE COVID-19 IN HAEMODIALYSIS PATIENTS
Authors: Beppu Hiroko , Fukuda Tatsuya , Otsubo Naoya , Kawanishi Tomoko , Ogawa Toshie , Abe Yasutomo , Endo Mariko , Hanawa Tomohide , Sugita Chise , Hatakeyama Shuji , Yamada Tetsuya , Wakai Sachiko
Published: June 2023

Background and Aims

Maintenance haemodailaysis (HD) patients are at higher risk for severe coronavirus disease 2019 (COVID-19). Because of a limited number of facilities that can provide inpatient treatment for COVID-19 and HD, it is important to identify HD patients who are at high risk for severe COVID-19. For mild to moderate COVID-19 patients, chemokine CC-motif ligand 17 (CCL17) was reported to be a predictive marker for severe COVID-19; however, the validity of CCL17 among HD patients is unknown.

Method

This retrospective observational study enrolled 107 HD patients with mild or moderate COVID-19 at hospitalisation (mean age 70.1 ± 15.1 years; 71.0% male). Receiver operating characteristic and logistic regression analyses were used to examine the predictive validity of indices for severe COVID-19 which is defined as partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio <300 or SpO2 <94%. Multi-variate logistic regression models were used to investigate the association of CCL17 level with the development of severe COVID-19. Furthermore, to evaluate the degree of improvement in predicting performance in the pre-existing model with the addition of CCL17 compared to the pre-existing model, we calculated net reclassification improvement (NRI) and the integrated discrimination improvement (IDI).

Results

During hospitalisation, 32 patients developed severe COVID-19. Serum CCL17 collected at admission exhibited a higher area under the curve value (0.818) compared with that of other indicators including LDH and C-reactive protein for the prediction of severe COVID-19. The optimal cut-off value for CCL17 was 150.5 pg/ml. A multi-variate logistic analysis revealed that CCL17 (above 150.5 pg/ml) was significantly associated with severe COVID-19 (Odds ratio, 0.063; 95% Confidence interval [CI], 0.017–0.227; P < 0.001) even after adjustment for covariates. The addition of the CCL17 to a model consisting of vaccination status, albumin, blood urea nitrogen, C-reacting protein and lactate dehydrogenase, that are variables incorporated in multivariate logistic model, significantly improved classification performance for severe COVID-19 using the NRI (1.16, 95% CI: 0.82–1.50, P < 0.001) and IDI (0.18, 95% CI: 0.09–0.26, P < 0.001).

Conclusion

CCL17 levels in HD patients with mild or moderate COVID-19 predict risk of developing severe COVID-19.
#2996 EARLY DECLINES IN KIDNEY FUNCTION AND ADVERSE OUTCOMES IN YOUNG ADULTS
Authors: Hussain Junayd , Grubic Nicholas , Akbari Ayub , Canney Mark , Elliott Meghan , Ravani Pietro , Tanuseputro Peter , Clark Edward , Hundemer Gregory , Ramsay Tim , Tangri Navdeep , Knoll Greg , Sood Manish
Published: June 2023

Background and Aims

Whether early eGFR declines (eGFR below age-expected values) in younger adults are associated with adverse outcomes is unknown. We aim to estimate the association of an early eGFR decline with adverse outcomes by age group (18-39, 40-49, 50-65 years).

Methods

We included 8.9 million adults (aged 18-65) with ≥1 eGFR value using linked healthcare datasets in Ontario from January 2008-March 2020. The association of eGFR categories from <60 to >120 mL/min/1.73 m2 and adverse outcomes (death, cardiovascular outcomes, end-stage kidney disease) was examined using adjusted Cox models. Comparisons were relative to age normalized measured GFR categories (100-110 mL/min for 18-39, 90-100 mL/min for 40-49, 80-90 mL/min for 50-65).

Results

The mean age, eGFR and median follow up were 41 years, 104 mL/min and 9.2 years, respectively. 17.3%, 18.9%, and 17.7% had an eGFR below normal for ages 18-39, 40-49, and 50-65, respectively. The risk of an adverse event increased in a stepwise manner with eGFR values below the referent and occurred at higher eGFR values in those 18 to 39 [eGFR 70-80, age 18-39: incidence 4.37 events per 1000 person-years[p-y], HR 1.54(1.46-1.61); age 40-49: incidence 9.78 per 1000 p-y, HR 1.18(1.15-1.21); age 50-65: incidence 24.0 per 1000 p-y, HR 1.11(1.10-1.12)] (see Figure 1). Results persisted for each outcome individually, and after using repeated eGFR, using a common referent, and adjusting for multiple covariates.

Conclusion

Young adults (18-39) with an early eGFR decline were at a higher risk of adverse events and this occurred at higher eGFR levels relative to middle-aged and older adults.
#3001 PREVALENCE OF IMPLANTABLE CARDIAC DEVICES IN A COHORT OF PATIENTS WITH CHRONIC KIDNEY FAILURE: A MULTICENTER CROSS-SECTIONAL STUDY
Authors: Sabiu Gianmarco , Reseghetti Elia , Conti Costanza , Fattizzo Vincezo , Miglio Roberta , Airaghi Cristina , Caruso Sabrina , Heidempergher Marco , Gallieni Maurizio
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) increases the risk of arrhythmic events and sudden cardiac death. For preventive purposes, the use of cardiac implantable electronic devices (CIEDs), including pacemakers (PMs), implantable cardiac defibrillators (ICDs), pacemakers for cardiac resynchronization therapy (CRTs), and loop recorders, can be used. However, in the absence of large epidemiological studies, whether the use of CIEDs in hemodialysis patients is associated with a lower mortality benefit than in pre-dialysis patients remains controversial. In this cross-sectional study, we evaluate the prevalence of CIEDs in a cohort of patients with CKD.

Method

The study includes patients with CIEDs with estimated GFR <45 ml/min/1.73 m2 from two hospitals in Milan, divided into two groups based on treatment with conservative therapy (IRC stage IIIb-V) or hemodialysis.

Results

Of the 499 patients enrolled, 268 had CKD stage IIIb-V, and 231 were in hemodialysis (Table 1).

Among CRT carriers, the prevalence in the CKD IIIb-V group is significantly higher than in the hemodialysis group (4.09% vs 0.86%; p = 0.025) (Figure 1), even if among the hemodialysis patients the prevalence of patients with previous stroke and hypertension was significantly higher (Table 1).

Furthermore, in multiple logistic regressions, hemodialysis was a variable independently correlated with reduced use of CRTs (OR 0.27; 95% CI = 0.01-0.96; p 0.04), while the other devices (individually and cumulatively) correlated positively only with age and previous myocardial infarction (MI) (Table 2).

Conclusion

The reduced prevalence of CRT in hemodialysis patients is probably related to the shorter life expectancy and the higher rate of related complications, such as the increased risk of infectious complications and/or stenosis of the central venous vessels. Further studies are needed to evaluate the impact of these devices on the cardiac mortality of hemodialysis patients and the associated complication rate.
#3041 DNAJB9 POSITIVE PRIMARY FIBRILLARY GLOMERULONEPHRITIS: TREATMENT WITH CORTICOSTEROID PULSES EXPERIENCE
Authors: Oleas Diana
Published: June 2023

Background and Aims

Fibrillary glomerulonephritis (FGN) is a rare histological pattern. Electron microscopy is needed for diagnostic confirmation where predominantly mesangial fibrils are observed. To support the diagnosis; DNAJB9 is a biomarker that is 100% sensitive and 100% specific for FGN. To date, there is no defined therapeutic approach. Various immunosuppressants have been implemented to treat FGN showing poor renal response and approximately 50% progression to chronic kidney disease.

Method

Ambispective observational study. A protocol based on a bibliographic review was developed. The protocol included an induction therapy with methylprednisolone pulses (MTP), 500 mg a day for three days. Followed by oral prednisone at a dose of one mg/kg with an individual titration period considering the clinical evolution. Demographic, clinical, and pathological variables were extracted from the electronic health record.

Results

Case 1. Seventy-eight-year-old female. History of arterial hypertension (HT) treated with an angiotensin-converting enzyme inhibitor (ACEi). She debuted with a nephrotic syndrome characterized by proteinuria of 15 grams/day, hypoalbuminemia, and altered kidney function with creatinine (Cr) of 2.7 mg/dL. Secondary causes were rule out. The kidney biopsy showed mesangial expansion with mesangial deposition of IgG and C3 on the immunofluorescence. Congo red was negative. Positivity for DNAJB9 was observed. The electron microscopy (EM) showed 20-nanometer fibrils in the mesangium. The patient was initiated on the treatment protocol with a subsequent reduction of prednisone over a period of 24 weeks. Complete remission, defined as proteinuria <0.5g/day and reduction > 50% of Cr was achieved after 20 weeks of treatment. Case 2. Forty-seven-year-old female with a history of hypertension treated with ACEi. The patient presented with proteinuria 3.5g/d with a normal kidney function. Secondary causes were rule out. The kidney biopsy showed mesangial thickening with IgG, C3, C1q, Kappa, and lambda positivity on immunofluorescence. Congo red was negative. DNAJB9 was positive. An electron microscopy study showed randomly arranged mesangial fibrils. The treatment protocol was started. Prednisone was titrated over a period of 20 weeks. Partial remission was observed, defined by >50% reduction of proteinuria. Kidney function remained preserved.

Conclusion

Induction treatment based on steroid pulses followed by prednisone titration in patients with FGN with predominantly mesangial compromise was associated with a substantial reduction of proteinuria and stabilization of kidney function.
#3042 AMBULATORY BLOOD PRESSURE LEVELS AFFECT THE ASSOCIATION OF INTRADIALYTIC HYPERTENSION WITH ADVERSE CARDIOVASCULAR EVENTS IN HEMODIALYSIS PATIENTS
Authors: Iatridi Foteini , Theodorakopoulou Marieta , Georgiou Areti , Karpetas Antonios , Pella Eva , Tsouchnikas Ioannis , Giamalis Panagiotis , Papagianni Aikaterini , Sarafidis Pantelis
Published: June 2023

Background and Aims

Patients with intradialytic hypertension (IDH) display also higher ambulatory blood pressure (BP) levels during the whole 44-h interdialytic interval compared to patients without the phenomenon. Sustained high 44-h ambulatory BP levels is a potential risk factor for cardiovascular events and mortality in these individuals. The aim of this study is to evaluate the influence of elevated 44-h BP levels on the high cardiovascular risk of individuals with IDH.

Method

A total of 242 hemodialysis patients with valid 48-h ABPM with Mobil-O-Graph-NG had an extended follow up for a median of 57.8 months. IDH was defined as: rise in SBP greater or equal to 10 mmHg from pre- to post-dialysis and post-dialysis SBP greater or equal to 150 mmHg. The primary end-point was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, resuscitation after cardiac arrest, hospitalization for heart failure, coronary or peripheral revascularization procedure. The secondary endpoint was cardiovascular mortality.

Results

5 patients with and 197 without were included in this prospective analysis. Cumulative freedom from the primary and secondary endpoint was significantly lower for patients with IDH (logrank-p = 0.019), while freedom from the secondary endpoint did not differ significantly between the two groups (logrank-p = 0.321). Patients with IDH presented a significantly higher risk for the composite endpoint (HR = 1.651, 95%CI[1.083, 2.516]), without, however, showing a significant difference in the risk for cardiovascular mortality (HR = 1.320, 95%CI[0.762, 2.288]). After adjustment for 44-h SBP, the association of IDH with the primary endpoint slightly attenuated, while the association with the secondary outcome had no significant changes (HR = 1.421, 95%CI[0.906, 2.228] and HR = 1.270, 95%CI[0.708, 2.276], for primary and secondary outcome respectively).

Conclusion

IDH is associated with higher risk for adverse cardiovascular outcomes. High ambulatory BP during the interdialytic interval contributes to the excess cardiovascular risk observed in this population.
#3056 IMPACT OF ALBUMIN BINDING FUNCTION ON PHARMACOKINETICS AND PHARMACODYNAMICS OF FUROSEMIDE
Authors: Klinkmann Gerd , Klammt Sebastian , Reuter Daniel , Mitzner Steffen
Published: June 2023

Background and Aims

Albumin binding of furosemide forms the basis for its transport to the kidney and subsequent tubular secretion, which is a prerequisite for the effect of furosemide. Accordingly, high albumin concentrations should result in higher efficacy of furosemide. However, study results on the combination of furosemide in conjunction with albumin and on the efficacy of furosemide in hypoalbuminemia did not confirm this hypothesis. The aim of this study was to determine the efficacy of furosemide not only in relation to concentration, but also to take albumin function into account.

Method

In a prospective and non-interventional clinical observational trial, blood and urine samples from 50 intensive care patients receiving continuous intravenous furosemide therapy were evaluated. Albumin binding capacity (ABiC) determination allowed conclusions to be drawn about the binding site-specific loading state of albumin by quantifying the unbound fraction of the fluorescent marker dansylsarcosine. In addition, assessment of the total concentration of furosemide in plasma and urine as well as the concentration of free furosemide fraction in plasma was performed by HPLC-MS. The efficacy of furosemide was evaluated by the ratio of urine excretion to fluid intake.

Results

In patients with an ABiC ≥ 60% free furosemide fraction was significantly lower compared to patients with a lower ABiC (p < 0.001), urinary furosemide concentration was higher (p = 0.136), and a significantly higher proportion of infused furosemide was excreted renally (p = 0.010). ABiC was positively correlated (r = 0.908, p = 0.017) with the increase in urine excretion to fluid input ratio after initiation of furosemide therapy.

Conclusion

ABiC could serve as a marker for individual response to furosemide and could be used to generate patient-specific therapeutic regimens. In view of the relatively low number of patients in this study, the relationship between furosemide efficacy and albumin function should be investigated in larger studies in the future.
#3065 INVESTIGATION OF NOTCH PATHWAY ACTIVATION AND ITS RELATION TO GREMLIN IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Authors: Tejedor Lucia , González Laura Núñez , Marquez-Exposito Laura , Cordido Adrian , Marchant Vanessa , Basantes Pamela Estefanía , Diez Raul Rodrigues , Tejera Antonio , Rayego-Mateos Sandra , Sanz Ana Belen , Ortiz Alberto , Gonzalez Miguel Angel Garcia , Ruiz-Ortega Marta
Published: June 2023

Background and Aims

Activation of the NOTCH signalling pathway has been described in several progressive kidney diseases. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disease caused by PKD1 or PKD2 mutations, which codify for the Polycystin-1 and Polycystin-2 proteins, respectively. ADPKD prevalence is among 1:800 and 1:1000 of live births and is characterized by fluid-filled renal cysts. During this process the production of chemokines, cytokines and growth factors by epithelial cells, interstitial fibroblasts and inflammatory cells, such as macrophages, increases, leading to end-stage renal disease (ESRD). GREMLIN has been proposed GREMLIN as an important mediator of chronic kidney disease in preclinical studies. In addition, urinary levels of GREMLIN may be a biomarker in any renal disease. However, there are no studies on GREMLIN in polycystic kidney disease.

Method

We have done the studies in an orthologous murine model of polycystic kidney disease (Pkd1cond/cond;Tam-Cre−/+) where we investigated the role of GREMLIN and its related mechanisms (its receptor VEGFR2 and the Notch signalling pathway) in different stages of renal cystic progression. The polycystic phenotype was induced in lactating mice by administering tamoxifen to the mother on postnatal days 10 and 11, causing a deletion in Pkd1 gene. Studies were performed considering different sacrifice points: at 18, 30 and 45 days. Furthermore, in urine and renal tissue from ADPKD patients, we studied the expression of GREMLIM.

Results

We have been able to see how in Pkd1−/+ mutant mice, grem-1 renal expression (that encoding GREMLIN protein), was increased from 18 days, with a significant increase at 30 days. This increase was associated with progressive cysts expansion and detriment in renal function measured by BUN. These results were confirmed at the protein level by western blot. Immunohistochemistry revealed positive GREMLIM staining since pre-cystic tubuloepithelial cells, which remained elevated in the tubules at later times. Positive GREMLIN expression was observed in biopsy samples of cysts from ADPKD patients as well as GREMLIN protein presence in urine samples. In the polycystic model, GREMLIN induction was correlated with VEGFR2 activation in the same tubular segments. Cyst formation was associated with activation of the NOTCH pathway, characterized by NOTCH1 and NOTCH3 activation.

Conclusion

Thus, we can suggest that GREMLIN expression may be an important mediator of renal damage progression in ADPKD and this protein would act through the Notch pathway.
#3101 LOW CIRCULATING LEVELS OF CARDIO-REGULATORY MIRNAS PREDICT WORSE OUTCOMES IN HEMODIALYSIS PATIENTS
Authors: Zicarelli Mariateresa , Greco Marta , Presta Pierangela , Duni Anila , Vita Caterina , Pappas Efthymios , Mirabelli Maria , Lakkas Lampros , Naka Katerina , Brunetti Antonio , Foti Daniela , Andreucci Michele , Coppolino Giuseppe , Ntounousi Evangelia , Bolignano Davide
Published: June 2023

Background and Aims

Patients with end stage renal disease (ESKD) on hemodialysis (HD) have a high risk of cardiovascular (CV) events, this being mostly related to the presence of uraemic cardiomyopathy. A deregulation in the expression of various microRNAs (miRNAs: non-coding RNAs that regulate post-transcriptional gene expression) has previously been implied in pathological cardiac remodelling. Nevertheless, scarce evidence has accrued so far on a possible significance in CV morbidity and mortality in HD patients, in relationship with the presence of uremic cardiomyopathy.

Method

We run a pilot, prospective, multicentre cohort study involving 74 ESKD patients undergoing chronic HD from 3 different hospitals in Italy and Greece. HD patients underwent a thorough clinical, laboratory and echocardiography assessment and were then prospectively followed for 24 months or until the occurrence of a composite endpoint of (CV and all-cause) mortality or non-fatal CV events. Through a systematic review of the literature, we identified a small panel of miRNAs (30a-5p, 23a-3p,451a and let7d-5p), which levels are known to be altered in either major CV disorders and kidney failure. miRNAs were then measured in the blood of HD patients and in a small group of matched healthy controls.

Results

miRNAs 23a-3p (p<0.0001), 451a (p = 0.001), 30a-5p (p = 0.003) and let7d-5p (p <0.0001) were all reduced in HD patients as compared with controls. Significant correlations were found between miRNAs and indexes of cardiac dysfunction such as Vmax, TAPSE and E/E’, as well as with some other laboratory parameters such as uric acid, sodium, potassium, HDL and CRP. During follow-up, 30/74 patients (40.5%) reached the composite endpoint. In these individuals, all miRNAs but let7d-5p were significantly reduced at baseline (p<0.0001). As showed by multivariate Cox-regression analyses, miRNAs 23a-3p, 451a, 30a-5p were all predictors of the composite endpoint (HR ranging from 0.943 to 0.995; p = 0.05 to 0.02) and Kaplan-Meier analyses confirmed a faster progression to the endpoint in subjects with miRNAs levels below an optimal ROC-derived cut-off value (p ranging from 0.001 to <0.0001; crude HRs 7.95 to 8.61; Figure 1).

Conclusion

Our study demonstrated that the evaluation of a very small panel of circulating miRNAs (30-5p, 23a–3p and 451a) may impart important prognostic information in chronic HD patients with respect to mortality and CV risk. Although the biological meaning of their deregulation remains unanswered, these preliminary findings may set the stage for larger investigation to generalize their usefulness as biomarkers, as well as possible therapeutic targets.
#3122 30-DAY COMPLICATIONS IN PERITONEAL DIALYSIS CATHETERS INSERTED PERCUTANEOUSLY VERSUS SURGICALLY IN A SECOND LEVEL HOSPITAL IN MERIDA, YUCATAN, MEXICO
Authors: Tapia Leticia , Álvarez Naomi
Published: June 2023

Background and Aims

Peritoneal dialysis (PD) catheter insertion technique has an impact on the health outcomes and technical success in PD. The percutaneous technique allows for a bedside, minimally invasive and faster insertion without the need of using an operating room and general anesthesia. In 2021, Agarwal et. al reported that percutaneous insertion was associated with a 64% relative risk reduction (RRR) of early exit site infection and a 48% RRR of early peritonitis with no difference in terms of mechanical complications compared to the surgical technique [1]. The aim of our study was to describe the frequency of mechanical and infectious complications within the first 30 days of PD catheter insertion between the percutaneous and surgical technique.

Method

We conducted a descriptive and prospective study in our Hospital from January 1st to December 31st, 2022. Patients who were candidates for renal replacement therapy with PD and who had no previous history of abdominal surgery or only minor abdominal surgery, underwent percutaneous insertion of PD catheter by a nephrologist with a bedside blind technique, whereas patients with previous abdominal surgery underwent surgical insertion with a mini laparotomy. Informed consent and preoperative blood tests were obtained before the procedure in both techniques. Patient preparation for the percutaneous insertion included fasting the night before, colonic enema and the placement of a urinary catheter, patients received antimicrobial prophylaxis as well as analgesia and light sedation. Mechanical and infectious complications within the first 30 days after insertion of double cuff Tenckhoff catheters were registered.

Results

During the study period, 155 PD catheter insertions took place in our hospital, the majority of insertions were surgical (53.5% versus 46.4%) and happened in women (60.6%). The mean age of the population was 51.5 years and 70.3% of the participants were diabetic. Exit-site infection was significantly more frequent in the surgically placed PD catheters (10% versus 1%, p = 0.02), there was a tendency for more mechanical dysfunction in the surgical technique versus the percutaneous technique (14.4% versus 5.5%, p = 0.07) and transfer to hemodialysis was more frequent in the surgical insertion group (10.8% versus 1.3%, p = 0.01). There was no difference between peritonitis in both groups and the frequency of uncomplicated PD catheters (catheter survival without any complication) was similar in both techniques.

Conclusion

Bedside PD catheter insertion by the nephrologist using a percutaneous technique can be an easy, timely, safe and adequate procedure with comparable success to the surgical insertion. It may have the advantage of more efficient control of infectious and mechanical complications and what is more, this approach could reduce the cost of kidney failure treatment as it allows for the use of minimal material and human resources.
#3153 HEMOPERFUSION WITH CYTOSORB AND RENAL REPLACEMENT THERAPY IN PATIENTS WITH ACUTE KIDNEY INJURY IN THE INTENSIVE CARE UNIT
Authors: Kobal Barbara , Korošec Tea , Jakopin Eva , Svenšek Franc , Bevc Sebastjan , Hojs Radovan , Ekart Robert
Published: June 2023

Background and Aims

Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious clinical disorder in the intensive care unit (ICU), occurring in a substantial proportion of critically ill patients. The aim of our single centre retrospective observational study was to analyse the outcomes of patients admitted to a non-surgical ICU and treated with RRT and with/without continuous hemoperfusion with Cytosorb.

Method

One hundred critically ill patients (mean age, 64.3 years; 69 men) admitted to the ICU and requiring RRT for AKI were analysed. Patient demographics, concomitant diseases, type of RRT, and survival were obtained from the medical record. APACHE II and Sofa Scores on admission were calculated. 30-day mortality was assessed using Kaplan-Meyer or Cox proportional hazards models.

Results

Reasons for ICU admission were acute respiratory failure (39%), cardiopulmonary resuscitation (14%), shock (13%), acute coronary syndrome (9%), sepsis (3%), acute pancreatitis (3%), and other (19%). Prior comorbidities were hypertension (70%), diabetes (43%), heart failure (32%), chronic kidney disease (CKD) (30%), coronary artery disease (CAD) (27%), chronic obstructive pulmonary disease (COPD) (15%), malignancies (12%). Eighty-six patients were treated with continuous RRT (CRRT) and 14 with intermittent hemodialysis (IHD). Twenty-four (24%) of patients treated with CRRT were also treated with hemoperfusion with Cytosorb. Using an independent-samples T test, we compared the two groups of patients with respect to the use of Cytosorb (Table 1). 30-day mortality was 82% in all patients and 87.5% in patients treated with CRRT and Cytosorb. Among concomitant diseases, only patients with previous heart failure had worse survival (p = 0.032), previous CKD, CAD, COPD, malignancy had no statistically significant impact. We found no statistically significant differences in 30-day mortality between patients treated with CRRT+Cytosorb and patients treated with CRRT or IHD alone. Multivariate Cox proportional hazard regression showed that of all the variables in the statistical model (age, sex, body mass index, previous diabetes, C-reactive protein, lactate, procalcitonin, serum creatinine, mean arterial pressure, APACHE II, ultrafiltration between CRRT), only lactate levels on admission (p = 0.002; 95%CI 1.08-1.38) were significant predictor of survival.

Conclusion

The use of hemoperfusion with Cytosorb in ICU patients with AKI did not reduce 30-day mortality. Patients with prior heart failure had a worse outcome. Serum lactate levels at ICU admission were an independent highly prognostic factor for death within 30 days of admission.
#3161 CLINICAL EFFICACY AND OPTIMAL REGIMEN OF BNT162B2 VACCINE IN CHRONIC DIALYSIS PATIENTS
Authors: Hagai Keren Cohen , Hornik-Lurie Tzipi , Einbinder Yael , Nacasch Naomi , Grupper Ayelet , Wand Ori , Shashar Moshe , Benchetrit Sydney
Published: June 2023

Background and Aims

Highly effective vaccines against severe acute respiratory syndrome virus 2 (SARS-CoV-2) have been developed and administered worldwide. Protection from coronavirus disease 2019 (COVID-19), however, is not absolute, and optimal vaccination regimens need to be established. Concerns regarding breakthrough COVID-19 disease in vaccinated patients are increasing, as vaccine efficacy appears to gradually decline in the months following vaccination. The emergence of highly infective variants, escalates these issues. This study assessed the clinical efficacy of the BNT162b2 vaccine and all-cause mortality among dialysis patients receiving varying numbers of vaccine doses.

Method

This study was conducted using the electronic database of Clalit Health Services in Israel. Patients receiving chronic hemodialysis or peritoneal dialysis during COVID-19 pandemic were included in the analysis. The control group consisted of age-and sex-matched individuals, in a 4:1 ratio to the dialysis group. The study included the pre- and post-vaccination periods.

Results

A total of 14,230 people were included; 2,846 on chronic dialysis and 11,384 controls. Mean age was 66.2±14.3 years (range 18-97). Before the vaccine was available in Israel, 223 dialysis patients were infected with SARS-CoV2. Their mortality rate was 18.4% compared to 10.8% among uninfected, unvaccinated patients in the same period (p = 0.001). On post-vaccination period, we compared the clinical efficacy of a fourth dose to patients who received only 3 doses of BNT162b2 vaccine. SARS-CoV-2 infection rates, hospitalizations due to severe COVID-19, COVID-19–related mortality and all-cause mortality rates were lower among chronic dialysis patients who received a fourth dose of vaccine as compared to those who received only 3 doses (after adjusting for age, sex and comorbidities). Despite lower mortality rates observed with the Omicron variant, an additional booster dose was associated with reduced COVID-19–related mortality (1.7% vs. 3.8%, p = 0.04, HR 0.44 (95% CI 0.2–0.98) in patients who received 4 doses compared to 3 doses.

Conclusion

As seen in the general population, and with previous vaccine boosters, the fourth dose of the BNT162b2 vaccine reduced rates of severe COVID-19 hospitalization and mortality among chronic dialysis patients. This study strengthens the recommendation to administer a fourth booster dose of vaccine to dialysis patients. Further studies are needed to establish the exact dose and schedule of the COVID-19 vaccine in the vulnerable population patients on chronic maintenance dialysis.