bluuebunny/crossref_metadata_2025 huggingface dataset:
MO477SERUM C-REACTIVE PROTEIN AND PROCALCITONIN LEVELS IN HEMODIALYSIS AND INTRADIALYTIC ALTERATIONS
Authors: Sonikian Makrouhi , Barbatsi Aggeliki , Karakou Eugenia , Chiras Theodoros , Skarakis Jacob , Sklapani Pagona , Trakas Nikolaos
Published: May 2021

Introduction

C-reactive protein (CRP) and procalcitonin (PCT) are widely used as markers of inflammation and infection in general population and in chronic hemodialysis (HD) as well. However, in dialysis (D) patients, serum CRP and PCT levels may be elevated even in the absence of inflammatory or infectious disease and diagnostic process is a challenge in such cases. We studied HD patients' laboratory profile concerning CRP and PCT.

Subjects and Methods

We studied 25 stable HD patients, M/F=22/3, aged 68(44-89) years, dialyzed thrice weekly for 55(6-274) months with a dialysate flow rate of 700 ml/min, with a residual daily diuresis less than 200 ml, Kt/V values of 1,44±0,3 and no signs of infection. Patients were classified in two groups. Group A included 10 patients on pre-dilution online hemodiafiltration (HDF). Group B consisted of 15 patients on conventional HD with low-flux polysulfone membrane. Twenty healthy subjects formed a control group C. Serum CRP and PCT levels were measured in duplicate in A and B groups before and at the end of mid-week dialysis sessions and also in C group.

Results

Pre-D serum CRP values in the total of patients were higher than those in healthy controls (10,89±19,29 vs 2,54±1,28 mg/L-p=0,004). Compared with group C, pre-D CRP values were higher only in B group (15,98±24,54 mg/L-p=0,001) but not in A group (4,09±3,33 mg/L-p=NS). There was a significant difference in pre-D serum CRP values between A and B groups (p=0,028). At the end of D session serum CRP values showed a tendency to increase in both groups A (5,16±4,81 mg/L) and B (17,00±27,00 mg/L) but differences were not significant.

Pre-D serum PCT values in the total of patients were higher than those in healthy controls (0,82±0,9 vs 0,29±0,55 ng/ml-p<0,001). Compared with group C, pre-D PCT values were higher in both A group (0,52±0,15 ng/ml-p<0,001) and B group (1,01±1,13 ng/ml-p=0,006). There was no significant difference in pre-D serum PCT values between A and B groups (p=0,261). At the end of D session serum PCT values decreased in A group (0,32±0,11 ng/ml-p<0,001) and increased in B group (1,12±1,21 ng/ml-p=0,014).

Conclusions

In patients on both conventional low-flux HD and online HDF pre-D serum CRP and PCT levels were higher than those in healthy subjects. Dialysis modality and membrane flux did not affect post-D serum CRP values, but post-PCT values decreased in online HDF. PCT usefulness might be limited in dialysis with high-flux membranes. Cut-off values have to be established for both markers to eliminate confusion in diagnosis of inflammatory and infectious diseases in hemodialyzed patients.
MO479BLOOD PRESSURE CONTROL AND OUTCOMES IN DIABETIC RENAL DISEASE : EVIDENCE FROM A TUNISIAN COHORT
Authors: Mariem Boukhtioua , Ikram Mami , Syrine Tlili , Hiba Ghabi , Jbali Hela , Ben Fatma Lilia , Zouaghi Karim , Ben Hmida Fethi
Published: May 2021

Background and Aims

Diabetic nephropathy (DN) is associated with a high incidence of cardiovascular morbidity and mortality. The relationship between hypertension and diabetic nephropathy is complex and blood pressure (BP) control is an important management strategy in the prevention of its onset and progression .The aim of this study was to determine whether blood pressure control delays the progression of DN and prevents macrovascular complications in patients with diabetes mellitus.

Method

Hypertension guidelines advocate treating systolic blood pressure to less than 130 mm Hg and diastolic blood pressure to less than 80 mmHg for patients with diabetes mellitus and overt nephropathy.The relationship between blood pressure and progression of nephropathy was studied in 120 diabetic and hypertensive patients with established diabetic nephropathy. We divided hypertensive patients with stage 1 to 3 CKD already treated with antihypertensive therapy into 2 groups: those with BP < 130/80 mmHg were designated as Group A (n=66) and those with BP> 130/80 as Group B (n=54). Serum creatinine level as well as urinary albumin excretion were measured at 3 months,6 months, one year,2 years and at last visit during follow-up.The GFR was calculated using the Modification of diet in renal disease formula.The kidney disease outcome was defined as time to end-stage renal disease. The cardiovascular outcome was defined as time to myocardial infarction, stroke,ischemic stroke, hospitalization for heart failure, or revascularization.

Results

During the mean follow up period of 33,8 ± 11,7 months, the primary end point of end-stage renal disease occured in 9 patients (7 patients in Group B versus 2 patients in groupe A) while 11 hypertensive patient experienced a cardiovascular event.  The decline rate in GFR was significantly more important in groupe B (p<0,05). However, little difference existed between the two groups in urinary albumin excretion. Blood pressure control was not associated with improved cardiovascular outcomes when comparing the two groups.

Conclusion

The results of our study indicate that an uncontrolled hypertension is associated with a rapid progression of kidney impairment in diabetic patients with overt nephropathy but no relationship with the incidence of cradiovascular events was seen in our population.
MO447PROTEIN ARGININE METHYLTRANSFERASE 3 INHIBITS RENAL INTERSTITIAL FIBROSIS THROUGH ENHANCING RENAL ASYMMETRIC DIMETHYLARGININE LEVELS
Authors: Yang Feng , Wu Ming , Ye Chaoyang
Published: May 2021

Background and Aims

Mammalian Protein Arginine Methyltransferase 3 (PRMT3) catalyzes the monomethylation and dimethylation of the Arginine residues of proteins. The role of PRMT3 in renal fibrosis is currently unknown. We aimed to study the role of PRMT3 in renal fibrosis and explored its underlining mechanisms.

Method

Sham or Unilateral Ureter Obstruction (UUO) operation was performed in Prmt3 wild-type (WT), heterozygous (Het) and homozygous (Homo) mutant mice, which were sacrificed at day 14. A single dose of aristolochic acid (5mg/kg) was injected in WT or HE mice, which was sacrificed at day 42.

Results

A strong interstitial fibrosis was observed in WT UUO mice as shown by Masson staining, and heterozygous or homozygous deletion of Prmt3 gene further enhanced interstitial fibrosis in mouse kidneys. The expression of collagen-I in mouse kidneys were analyzed by Western blotting. UUO operation increased the expression of collagen-I in WT mouse kidneys, which were further increased by genetic deletion of Prmt3 gene in a dose-dependent manner. A mild renal interstitial fibrosis was observed in AAN mice, which was enhanced by heterozygous deletion of Prmt3 gene. Western blot analysis showed that aristolochic acid increased the expression of collagen-I in WT mice, which was further increased in Prmt3 Het mutant mice. Mechanismly, asymmetric dimethylarginine levels were elevated in UUO or AAN mouse kidneys as compared with its controls as shown by immnohistochemistry staining or ELISA. Renal ADMA levels were not elevated in Prmt3 mutant UUO or AAN mice. Moreover, renal injection of ADMA in UUO kidneys blocked the enhanced renal interstitial fibrosis in Prmt3 Het mutant mice as shown by Masson staining and Western blot analysis of collagen-I.

Conclusion

Prmt3 inhibits renal interstitial fibrosis through enhancing renal ADMA levels.
MO612THE ROLE OF MECHANICAL MUSCLE POWER IN PHYSICAL DYSFUNCTION: A MODEL FOR TAILORING RESISTANCE-BASED REHABILITATION IN CHRONIC KIDNEY DISEASE
Authors: Wilkinson Thomas , Gore Eleanor , Palmer Jared , Baker Luke , Watson Emma , Smith Alice
Published: May 2021

Background and Aims

Individuals living with CKD are characterised by adverse changes in physical function. Knowledge of the factors that mediate impairments in physical functioning is crucial for developing effective interventions that preserve mobility and future independence. Mechanical muscle power describes the rate of performing work and is the product of muscular force and velocity of contraction. Muscle power has been shown to have stronger associations with functional limitations and mortality than sarcopenia in older adults. In CKD, the role of mechanical muscle power is poorly understood and is overlooked as a target in many rehabilitation programmes, often at the expense of muscle mass or strength. The aims of this study were to 1) explore the prevalence of low absolute mechanical power, low relative mechanical power, and low specific mechanical power in CKD; and 2) investigate the association of mechanical power with the ability to complete activities of daily living and physical performance.

Method

Mechanical muscle power (relative, allometric, specific) was calculated using the sit-to-stand-5 (STS5) test as per previously validated equations. Legs lean mass was derived from regional analyses conducted using bioelectrical impedance analysis (BIA). Physical performance was assessed using two objective tests: usual gait speed and the ‘time-up-and-go’ (TUAG) test. Self-reported activities of daily living (ADLs) were assessed via the Duke Activity Status Index (DASI). Balance and postural stability (postural sway and velocity) was assessed using a FysioMeter. Sex-specific tertiles were used to determine low, medium and high levels of relative STS power and its main components.

Results

102 participants with non-dialysis CKD were included (mean age: 62.0 (±14.1) years, n=49 males (48%), mean eGFR: 38.0 (±21.5) ml.min.1.73m2). The mean estimated relative power was 3.1 (±1.5) W.kg in females and 3.3 (±1.3) W.kg in males. Low relative power was found in 35/102 (34%) patients. Relative power was a significant independent predictor of self-reported ADLs (via the DASI) (B=.413, P=.004), and performance on the TUAG (B=-.719, P<.001) and gait speed (B=.404, P=.003) tests. Skeletal muscle mass was not associated with the DASI or any of the objective function tests

Conclusion

Patients presenting with low muscle power would benefit from participation in appropriate interventions designed to improve the physiological components accounting for low relative muscle power. Assessment of power can be used to tailor renal rehabilitation programmes as shown in Figure 1. Incorporation of power-based training, a novel type of strength training, designed by manipulating traditional strength training variables and primarily movement velocity and training intensity may present the best strategy for improving physical function in CKD.
MO613EFFECT OF 12 WEEK TRAINIG ON PHYSICAL ACTIVITY ON PATIENT ON A LOW PROTEIN DIET
Authors: Saipova Durdona
Published: May 2021

Background and Aims

Symptoms such as fatigue, muscle weakness and impaired nutritional status are common in CKD and lead to decreased exercise tolerance.

The aim of the study was to study the effect of 12-week training on physical activity in patients with pre-dialysis stages of CKD on a low-protein diet.

Method

The study included 119 patients with CKD C3 and C4 stages. Clinical data included anthropometric data: body mass index (BMI), mid-thigh circumference and mid-shoulder circumference, laboratory data: urea, creatinine, electrolytes, albumin, total protein, hemoglobin. All patients underwent instrumental research methods: ECG, EchoCG, cardiopulmonary stress test. The patients included in the study were offered three dietary options - with a low protein content (0.6 g / kg / day;) and a limited protein content (0.6-0.8 g / kg / day;), and low protein diet with keto analogs (1 tab / 5 kg body weight / day). The physical exercise program was designed for independent home use and included cardiovascular exercises (primarily walking, morning exercises) and strength training exercises with dumbbells 1 and 3 kg. The training frequency was at least 3 times a week and had a duration of at least 20–30 minutes. The patients kept exercise diaries, which were reviewed by the doctor at each subsequent visit. The training exercise was adjusted depending on the self-perception of the patients; if necessary, the training time was increased to 60 minutes.

Results

The 1 group 24% of patients received a diet with a low protein content, the second group consisted of 40% of patients, the third group consisted of 37% of patients receiving a diet with a limited protein content. The male to female ratio, mean glomerular filtration rate, daily proteinuria and BMI did not differ significantly between groups. In the dynamics of 12 weeks of training, an increase in the mid-thigh and upper arm circumference was recorded. The study of physical activity of patients with different types of diet showed that in patients of the 1st group, even with a low nutritional status in the dynamics of 12 weeks of training, there was an improvement in such physical indicators as the circumference of the mid-thigh and upper arm, and also a slight improvement in the BMD. When comparing the groups of patients who received and did not receive ketoanologs (groups 2 and 3, respectively), physical training for 12 weeks instilled a significant improvement in indicators such as mid-arm circumference and maximum oxygen consumption(peak VO2). However, in the group receiving keto analogs, there was a significantly greater improvement in maximum oxygen consumption (peak VO2).

Conclusion

Regular dosed exercise has a positive effect on physical fitness in CKD patients on a low-protein diet. Correction of nutrition with keto analogs improves the cardiorespiratory status of patients.
MO616GAIT SPEED AND BODY COMPOSITION IN HAEMODIALYSIS PATIENTS
Authors: Cancho Castellano Barbara , López Arnaldo Cristina , Rodriguez Sabillon Jorge Alberto , Aragón Lara Rafael , Álvarez López Álvaro , Diaz Campillejo Rosa Maria , Valladares Alcobendas Julián , Martín Hidalgo Barquero María Victoria , Ruiz Calero Cendrero Rosa María , Robles Perez-Monteoliva Nicolas-Roberto
Published: May 2021

Background and Aims

Gait speed is a predictor of disability, mobility limitation and mortality. Buchner et al. the first to observe a non-linear relationship between leg strength and normal gait speed. This relationship was explained as small changes in physiological capacity. The objective of this study is to assess the relationship between gait speed and body composition in haemodialysis.

Method

Cross-sectional study in 40 subjects with CKD in hospital haemodialysis, 70.5±13.03 years, 62.5% male. 40% Diabetic Nephropathy, 10% Glomerulopathies, 7.5% Nephroangiosclerosis, 2.5% Chronic Tubule-Interstitial Nephropathies, 32.5% Unknown, 2.5% Others. 35% arteriovenous fistula, 10% arteriovenous graft, 55% central venous catheter. Haemodialysis type: 40% High Flux, 45% Online postdilutional Haemodiafiltration, 10% Acetate Free Biofiltration. Gait seed was measured on the middle day of the week, predialysis.

Body composition was estimated by monofrecuency bioimpedance measurement (50 KHz) on the middle day of the week, posthemodiálisis.

Statistical analysis was performed with SPSS 13.0.

Results

Average gait speed 0.6±0.38 m/s, median 0.65 (IQR 0.18) m/s, range (0, 1.23) m/s. The prevalence of a gait speed less than or equal to 0.8 m/s was 67.5%, while 32.5% of the patients presented a gait speed less than or equal to 0.8 m/s. Gait speed was lower among diabetics (0.77±0.3 vs 0.46±0.39, p=0.0074). A positive and significant correlation was observed between gait speed and phase angle. No correlation was observed between gait speed and body fat. A positive linear relationship or dependence was observed between gait speed and muscle mass and cell mass. In relation to body water, a negative linear relationship is observed with the EW/IW ratio. Table 1.

Conclusion

There is a dependent relationship between gait speed and diabetes in haemodialysis patients. The decrease of the phase angle, the increase of the ratio EW/IW changes with the decrease the cell mass index are inversely related to the gait speed in haemodialysis patients. These items and the gait speed, which provide information on the state of vulnerability of the patient, could be markers of frailty.
MO617EFFECTS OF 12 WEEK PHYSICAL EXERCISES ON ECHO-GEOMETRIC PARAMETERS IN PATIENTS WITH CKD
Authors: Saipova Durdona
Published: May 2021

Background and Aims

Structural and functional changes in the cardiovascular system in patients with chronic kidney disease (CKD) will lead to decreased exercise tolerance, decreased quality of life, and, ultimately, premature death.

The aim of this study was to study morphometric changes in the left ventricle of the heart depending on the direction of therapeutic physical training.

Method

The study involved 60 patients with CKD stage C3. The average age of the patients was 54.2 ± 3.40 years. The average level of GFR for the sample as a whole was 79.1 ± 9.4 ml / min / 1.73 m2. The control group (CG) consisted of 20 people (10 men and 10 women) comparable to the main group in terms of gender and age. The examination of patients included a general examination, assessment of complaints, collection of anamnestic data, anthropometry with calculation of BMI cardiopulmonary stress test, echocardiography.

According to the data of the cardiopulmonary stress test, 3 groups were formed on the basis of the predominant manifestation of any physical quality in the course of therapeutic training: group 1 (n = 20) - with a respiratory orientation of the training process; 2nd group (n = 20) - with a focus on cardio loads; 3rd group (n = 20) - development of predominantly endurance.

Results

Of all groups of patients with CKD, the LVMM indicator reached the highest values in men in group 2 (with a cardio-load orientation of the treatment-training process), as well as in women in group 3 (predominantly endurance development). It is this orientation of the training process that has the greatest effect on the increase in the mass of the left ventricular myocardium in patients with CKD. The 2nd group of patients with CKD stage CKD had the highest values of LVTD in diastole both among men and women. In addition, men in this group had the highest RTI per systole. In patients of the 2nd group, undergoing mainly cardio load, the change concerned a slightly more pronounced increase in the wall thickness of the left ventricle.

In the 3rd group of patients with CKD stages C3, both men and women had the maximum values of TMV in diastole, as well as LVTD in systole. Types of physiotherapy exercises with a predominance of endurance in physical exertion are distinguished by the most pronounced signs of left ventricular myocardial hypertrophy.

Conclusion

The present study has shown that patients with pre-dialysis CKD have decreased maximal and submaximal exercise tolerance. Analysis of the data obtained made it possible to reveal the peculiarities of adaptation of the cardiovascular system of patients with CKD stages CKD to a specific type of therapeutic training and to determine the quantitative values of echocardiographic parameters in patients with CKD.
MO123USE OF RIVAROXABAN VERSUS WARFARIN IN PATIENTS WITH ATRIAL FIBRILLATION AND ADVANCED CHRONIC KIDNEY DISEASE*
Authors: Abdullaev Sherzod , Igamberdieva Rano , Sharapov Olimkhon
Published: May 2021

Background and Aims

Patients with chronic kidney disease (CKD) develop bleeding and thromboembolic tendencies, so the indication for the use of anticoagulants for atrial fibrillation (AF) is difficult. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are the main complications. In recent years, new oral anticoagulants (rivaroxaban) have been developed and have shown superiority over classic anti-vitamin K anticoagulants in preventing the risk of stroke, systemic embolism and bleeding.

Aim is to evaluate the safety parameters of rivaroxaban in patients with stage 4 chronic kidney disease (CKD) or a transient sustained decrease in glomerular filtration rate (GFR) to 15–29 ml/min/1,73 m2 in the presence of atrial fibrillation (AF).

Method

Multicenter prospective randomized study that included patients from cardiology departments in 2019. Of 5448 hospitalized patients, 109 (2%) patients with AF and CKD stage 4 or a sustained decrease in GFR to 15-29 ml/min/1.73 m2 were randomized in a 2:1 ratio to rivaroxaban 15 mg/day (n=73) or warfarin (n=36). Primary endpoint: development of large, small and small clinically significant bleeding according to the BARC (Bleeding Academic Research Consortium) and ISTH (International Society on Thrombosis and Hemostasis) scales. The average follow-up period is 12 months.

Results

Patients taking warfarin were significantly more likely to develop minor bleeding according to BARC scales (n=26 (72.2%) versus n=31 (42.4%), p<0.01) and ISTH (n=22 (61.1%) versus n=27 (36.9%), p<0.01) and all clinically significant (minor clinically significant and major) bleeding according to the ISTH scale [n=10 (27.7%) versus n=8 (10.9%), p=0.03]. The number of readmissions was 32 (43.8% of patients) in the rivaroxaban group, 17 (47.2% of patients) in the warfarin group (p=0.57), of which 12 (37.5%) and 7 (41.1%) (in the rivaroxaban and warfarin groups, respectively) - for urgent reasons (p=0.96). A significant improvement in the dynamics of creatinine levels, GFR (according to CKD-EPI) in the rivaroxaban group was revealed.

Conclusion

The study provides evidence of a favorable safety profile for rivaroxaban compared with warfarin in patients with AF and advanced CKD.
MO222DO WE OFTEN THINK OF MULTIPLE MYELOMA AS THE CAUSE OF KIDNEY DISEASE?
Authors: Pešić Snezana , Grujic Nevena , Stopić Bojan , Janković Aleksandar , Markovic Katarina , Damjanovic Tatjana , Naumovic Radomir
Published: May 2021

Background and Aims

Kidney disease is a common complication in patients with multiple myeloma and other plasma cell dyscrasias. This disease can be manifested by various kidney disorders, which can evolve as either an acute or chronic disorder. Cast nephropathy is the most common cause of severe acute kidney injury (AKI) in patients with multiple myeloma. Among newly diagnosed patients, 20 to 50 % have AKI or cronic kidney disease (CKD) at the time of diagnosis. Treatment of acute renal failure consists of good supportive care and anti-myeloma therapy. Introduction of novel agents has considerably improved outcome in patients with multiple myeloma and renal failure. The aim of this study was to identify the most common risk factors (RF) for mortality in patients with MM and renal failure.

Method

The study included 22 patients ( mean years 67 ± 12 years, 12 men). Who followed two years. We analyzed routine laboratory tests, Bence Jones protein, urinary protein excretion, and creatinine clearance. Plain radiography for the evaluation of skeleton lesions were performed for all patients.

Results

Overall two years mortality of patients with MM was 38.1% with no significant difference regard to patients' age and gender. About 33% of patients required renal replacement therapy and 19% remained on a chronic dialysis treatment program. Renal biopsy was performed in 9.1% of patients (1 - FSGS, 1 - LCCD, light chain deposition disease). Bone marrow transplant (stem cell transplant) was performed in 9.1% of patients. Of the associated comorbidities, 19% had DM, 81% had hypertension, CVD 52.4%. Osteolytic changes at the time of diagnosis were present in 52.4%. In older patients, kappa chains have been identified to a much more extent. Survival is significantly lower in dialysis dependent patients with a two-year survival of 30%. Binary logistic regression revealed that platelet decrease (OR = 0.982< CI 0.961–1.003< p = 0.09) and increase of IgA significantly influenced mortality (OR = 103,867< CI 0.459–23567.201< p = 0.09) can be considered as potential predictors of mortality. Comorbidity DM, HTA, CVD were not the predictors for mortality in patients with MM

Conclusion

Multiple myeloma associated with high mortality rate and kidney disease. High percentage of patients required renal replacement therapy (33%) and 19% remained on a chronic dialysis treatment program. Among the estimated parameters, the risk factors for mortality were significant decrease of platelet (p = 0.09) and increase IgA (p = 0.09). Survival is significantly lower in in dialysis dependent patients with a two-year survival of 30%.
MO224VCAM-1 LEVELS ASSOCIATED WITH ALBUMINURIA IN MULTIBACILLARY LEPROSY
Authors: Donadello Tessarolo Louise , Cavalcante Meneses Gdayllon , Freire Bezerra Gabriela , Bezerra da Silva Junior Geraldo , De Francesco Daher Elizabeth , Costa Martins Alice Maria
Published: May 2021

Background and Aims

Leprosy may present important renal and endothelial abnormalities, and this can worse patients’ prognosis. However, renal and vascular involvement in these patients has been poor investigated. The aim of this study was to investigate if higher systemic endothelial biomarkers levels are associated with renal abnormalities and clinical aspects of leprosy.

Method

This is a cross-sectional study with leprosy patients before initiation of multidrug therapy enrolled in January 2017 to December 2018 in Fortaleza, northeast Brazil. Leprosy-associated clinical and epidemiological data were collected. Two groups were constructed: Paucibacillary (PB) and Multibacillary (MB) for comparisons. Serum and urine samples were obtained for laboratory analysis. In urine the following parameters were evaluated: creatinine, proteinuria and albuminuria. In serum the endothelial biomarkers were evaluated: VCAM-1 and ICAM-1, using ELISA assay.

Results

A total of 101 leprosy patients were included, with mean age of 48±15 years, and 71 (70%) were male. The multibacillary form occurred in 81 cases (80%), where 22 had a Virchowian form. VCAM-1 was elevated in MB group and was correlated with the bacteriological index (skin smear) (r = 0.372, p <0.01), duration of disease symptoms (r = 0.234, p = 0.04), and number of skin lesions ( r = 0.331, p <0.001). Moreover, in MB patients who presented albuminuria >15 mg/g of creatinine, VCAM-1 showed a significant correlation (r = 0.341, p <0.05) with increased albuminuria and improve the correlation with number of skin lesions (r = 0.653, p=0.003).

Conclusion

Multibacillary leprosy patients present high systemic levels of VCAM-1, associated with leprosy clinical features and increased albuminuria, an important marker of kidney disease progression. Further prospective studies are necessary to establish a cause-effect relation and evaluate the preventive role of these biomarkers, aiming to improve clinical care.
MO230A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED STUDY OF ATRASENTAN IN PATIENTS WITH IGA NEPHROPATHY (THE ALIGN STUDY)
Authors: Lambers Heerspink Hiddo , Kohan Donald , Lafayette Richard , Levin Adeera , Zhang Hong , Glicklich Aland , Camargo Marianne , King Andrew , Barratt Jonathan
Published: May 2021

Background and Aims

IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally and an important cause of chronic kidney disease (CKD). Up to 40% of IgAN patients are at risk of progressing to end-stage kidney disease (ESKD) and proteinuria is the strongest predictor of progression. There are no approved therapies for IgAN, leaving an important need for new strategies to lower proteinuria and preserve kidney function in high-risk patients.

Endothelin A (ETA) receptor activation drives proteinuria, along with kidney inflammation and fibrosis. Atrasentan, a potent and selective ETA antagonist, has been studied extensively in >5,000 patients with type 2 diabetes and kidney disease (DKD), demonstrating clinically significant and sustained reductions in proteinuria when administered on top of a maximum tolerated dose of RAS inhibitor (RASi). In a global Phase 3 outcome study in DKD (SONAR), atrasentan demonstrated a 35% reduced risk of the primary composite outcome of doubling of serum creatinine or end stage kidney disease (95% CI: 0.49, 0.88; P = 0.005). The most common adverse event was fluid retention.

Selective ETA blockade represents a promising approach to reduce proteinuria and preserve kidney function in high risk IgAN patients.

This is a presentation of a global, phase 3, double-blind, placebo-controlled trial to determine the effect of atrasentan in IgAN patients at high risk of kidney function loss.

Method

Approximately 320 patients across North America, South America, Europe, and Asia-Pacific with biopsy-proven IgAN will be randomized to receive 0.75 mg atrasentan or placebo daily for 132 weeks. Patients will continue receiving a maximally tolerated and stable dose of a RAS inhibitor as standard of care. The study will also include patients that are unable to tolerate RAS inhibitor therapy. Additional eligibility criteria include urine protein creatinine ratio (UPCR) ≥1 g/g and eGFR ≥30 mL/min/1.73 m2. Participants will have study assessments over two and a half years with options for remote study visits using telemedicine and home health visits. The primary objective is to evaluate the effect of atrasentan versus placebo on proteinuria at Week 24. Secondary objectives include evaluating the change from baseline in eGFR, safety, and tolerability, and quality of life.

Results

N/A

Conclusion

N/A
MO231INFECTIVE ENDOCARDITIS IN CHRONIC KIDNEY DISEASE: CLINICAL AND OUTCOME’S FEATURES
Authors: Harzallah Amel , Chargui Soumaya , Hajji Mariem , Barbouch Samia , Ounissi Mondher , Gorsane Imen , Ben Hamida Fethi
Published: May 2021

Background and Aims

Infective endocarditis complicating chronic kidney disease is associated with high morbidity and mortality among this population particularly exposed to bacteremia.The aim of our study was to study the clinical and evolutionary features of infective endocarditis among patients with chronic renal failure.

Method

It is a retrospective and descriptive study including patients with chronic kidney disease hospitalized in our department, whom presented an infective endocarditis confirmed by modified DUKE criteria

Results

13 patients were included aged meanly of 42.69 years [27-63 years] with a sex-ratio of 0.85. Twelve were in end stage renal disease with an average duration of dialysis of 52 months [1-180 months] and in stage 5 in one case. At the time of diagnosis, vascular access was fistula in one case and a central venous catheter in 11 cases. The catheter was simple in 3 cases and tunnelled in eight cases. The circumstances of discovery were fever in 12 cases associated with an alteration of the general state with asthenia in 10 cases. Low blood pressure was present in seven cases. At biology, the mean hemoglobin level was 8.28 g/dl [6.1-10.8 g/dl]. Leukocytosis was noted in 8 cases. Mean albuminemia was 30.61g/l [24-41g/l]. Albuminemia below 35 g/l was objectified in 6 cases. Major causative organisms were Staphylococcus species in 10 cases. Trans-thoracic echography shows vegetation in 11 cases with an average size of 17.4 mm [6-37 mm] and aortic annular abscess in 2 cases. Antibiotherapy was conducted in all cases. Complications were frequent, including congestive heart failure in 2 cases, secondary septic localisations in 3 cases, hemoptysis in one case and valve perforation in 2 cases. Five patients underwent surgery after a mean delay of 32.75 days [6-47 days]. Death occurred in 8 cases.

Conclusion

Infective endocarditis is severe during chronic kidney failure and more frequent among patients on dialysis by catheter. It is associated with high morbidity and mortality. Management of central venous catheter must be enhanced. Treatment must be early to improve the prognosis of this complication.
MO232BORTEZOMIB INDUCED PERIPHERAL AND CENTRAL NEUROPATHY : ABOUT 3 CASE REPORTS
Authors: Houli Rawnak , Barbouche Samia , Mariem Hajji , Sakay Amira , Badrouchi Samarra , Nadia Cherni , Ben Hmida Fethi
Published: May 2021

Background and Aims

Bortezomib is a proteasome inhibitor, whose efficacy in the treatment of multiple myeloma has been proven over the last years. However, its side effects may cause concern for patients as well as physicians. We focused in this study on Bortezomib-induced neuropathy, one of the most frequent complications. We present 2 cases of peripheral sensory neuropathy and one intriguing case of central neurological manifestation, all caused by Bortezomib administration.

Case 1

A 62-year-old man, with a history of diabetes and hypertension, was diagnosed with multiple myeloma in 2019. He received 2 cycles of Bortezamib (2,5 mg), Dexamethasone , and Cyclophosphamide. Each cycle included 4 doses of Bortezomib, and the cycles were 21 days apart. At the end of the second cycle the patient developed posterior cord syndrome with balance disorder and lower extremities paresthesia. Axonal sensitivo-motor polyneuropathy was confirmed by electromyography. A pharmacology investigation was conducted, and the symptoms were attributed to Bortezomib toxicity. Evolution was favourable after change in protocol to Revlimide. No recurrence was noted.

Case 2

A 64-year-old man with no prior history was diagnosed with multiple myeloma in 2020. She received a protocol of 4 cycles, 21 days apart, of Bortezomib (2.1 mg) ,Dexamethasone and Thalidomide . Three weeks after the first cycle, the patient presented with confusion, gait disturbance and four-limb pyramidal deficiency syndrome. Electromyography showed axonal sensitivo-motor polyneuropathy .In the absence of other causes, Bortezomib toxicity was suspected and the patient underwent an emergency epurative hemodialysis session, after which symptoms completely disappeared. Bortezomib doses were then reduced. The evolution was favourable.

Case 3

A 50-year-old woman was diagnosed with multiple myeloma in 2018 with Randall's disease and quadri-pyramidal syndrome. She was put on 4 courses of Bortezomib 2.4mg Cyclophosphamide and Dexamethasone, 21 days apart. After 2 coursess, she presented a generalized tonic-clonic seizure preceded by headache, dizziness and followed by speech disturbances. Biological screening for metabolic disorders and toxins was unremarkable. Cerebral MRI showed no abnormalities. Doses of Bortezomib were reduced during the following course. We then witnessed an improvement in speech and no recurrence of seizures.

Conclusion

Bortezomib induced neuropathy is a serious and debilitating complication to which physicians must pay special attention. This side effect can be managed by dose reduction or change of molecules. Outcomes are often favourable.
MO235EFFECT OF OMEGA-3 POLYUNSATURATED FATTY ACID SUPPLEMENTATION ON GLYSEMIC CONTROL AND RENAL FUNCTION IN TYPE 2 DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Usta Mehmet , Ersoy Alpaslan , Ersoy Canan , Ayar Yavuz , Goksel Gultekin , Saka Karagoz İsminur
Published: May 2021

Background and Aims

The aim of this study was to evaluate the short-term effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation on glycemic control and renal function in type 2 diabetic patients with chronic kidney disease.

Method

Twenty-five diabetic patients received medication containing 2 g/day n-3 PUFA orally in addition to standard treatments. Their estimated glomerular filtration rates (eGFR) were <80 mL/min/1.73 m2. Biochemical values were evaluated before and 3 months after treatment.

Results

After three months of supplementation, the changes in serum creatinine, uric acid, eGFR and urinary albumin excretion levels did not reach statistical significance. There was no difference between serum glucose, HbA1C and lipid profile values before and after the n-3 PUFA supplementation in patients. Only serum albumin significantly increased from 4.10±0.26 to 4.28±0.31 g/dL (p=0.016), and systolic blood pressure decreased from 121.4±14.5 to 116.6±14.9 mmHg (p=0.001).

Conclusion

Short-term n-3 PUFA supplementation did not affect renal function and glycemic control in patients with type 2 diabetes with chronic kidney disease.
MO237A SERUM COMPLEMENT ABNORMALITY REVEALED BY THROMBOTIC MICROANGIOPATHY DURING INTERFERON TREATMENT OF MULTIPLE SCLEROSIS
Authors: Rihem Dahmane , Sanda Mrabet , Raja Boukadida , Yosra Guedri , Asma Fradu , Wissal Sahtout , Awatef Azzabi , Narjess Ben aicha , Dorsaf Zellama , Abdellatif Achour
Published: May 2021

Background and Aims

Multiple sclerosis (MS) is a chronic and potentially disabling disease of the central nervous system and is the leading cause of non-traumatic neurological disability in young adults. Beta interferons (IFN-β) are the most-widely prescribed medications for this disease. Despite good overall long-term safety data with prolonged use of this group of drugs, they can rarely cause serious and sometimes life threatening adverse effects. We report a case of thrombotic microangiopathy (TMA) in a patient treated with IFN-β-1a for 03 years. The serum complement study revealed a decrease in Factor I.

Method

Case report

Results

A 28-year-old man was diagnosed with relapsing remitting multiple sclerosis in 2007. Subcutaneous IFNβ-1a 44 μg was commenced three times a week in 2017. He had not had a relapse since 2012. In July 2020, he was admitted to intensive care unit for a status epilepticus associated with severe arterial hypertension and then transferred to our department for management of malignant arterial hypertension with acute renal failure.On examination, he did not present any neurological disorder but had very unbalanced blood pressure under triple therapy. Biology had shown an hemoglobin at 9, 7 g / dl; no thrombocytopenia with a collapsed haptoglobin, very high LDH with absence of schizocytes, positive non-specific ANCA and proteinuria at 7g/24hour.

The renal puncture biopsy showed chronic vascular and glomerular TMA with IgG and fibrinogen deposits. The course was marked by the rapid deterioration of renal function. The patient received flash corticosteroid therapy 10 mg / kg IV for 3 consecutive days switched to oral corticosteroid therapy 0.5 mg / kg / day and received supportive treatment including plasma exchange and hemodialysis. He was discharged after a prolonged admission.

At follow-up 6 months later, he had not regained kidney function and remained on hemodialysis and was still taking 3 antihypertensive treatments. A follow-up immunological workup showed a decrease in Factor I: 26,83 mg/l (32,3-87,5).

The patient was diagnosed with drug-induced TMA favored by complement abnormality. Treatment with Eculizimab is under discussion.

Conclusion

IFN-β are main therapies for relapsing remitting multiple sclerosis. Serious complications are relatively rare and IFN-βs are generally considered to be safe. Nevertheless, rare serious and/or life-threatening side effects have been reported such as TMA. This can, as in our patient, be favored by an abnormality of the serum complement. Thus, a study on serum complement would be recommended before IFN-β prescription.
MO136RELATIONSHIP BETWEEN UPCR AND EGFR IN C3 GLOMERULOPATHY
Authors: Nester Carla , Breheny Patrick , Hall Monica , Charney Alan , Lefkowitz Martin , Trapani Angelo , Wang Yaqin , Smith Richard
Published: May 2021

Background and Aims

Considerable knowledge gaps exist in our understanding of the natural history of C3 glomerulopathy (C3G). Disease rarity, multiple nomenclature changes, and the inclusion of dissimilar cases in historical cohorts have precluded retrospective studies to define the natural course of C3G and identify risks for progression to kidney failure (end stage renal disease/ESRD). In the present analysis, we focus on C3G patients with native kidneys and examine the relationship between reductions in UPCR and disease progression as indicated by changes in eGFR.

Method

Patients included in this study were consented and enrolled in the University of Iowa C3G ReCom Registry, which was created in 2013. Beginning in 2017, complement activity and renal function data were collected prospectively at approximately 6-month intervals to define the natural history of C3G. Analyses were performed across 1-year periods of time (“spans”). To be included in a span, a patient had to meet the following criteria at the start of the 1-year period: native C3G, eGFR ≥30 mL/min/1.73 m2, UPCR ≥1 g/g and ≥12 years of age. An individual patient could be included in more than one span.

Results

Analyses were performed using 34 one-year spans for 24 patients who met inclusion criteria at the beginning of the 1-year span. Baseline characteristics for the 34 spans were: male, 59%; mean age, 22.7 years; mean eGFR, 83.1 ml/min/1.73m2; mean UPCR, 2.86 g/g; mean plasma C3, 75.1 mg/dL.

Similar analyses using only the first 1-year span for each of the 24 patients produced results that were consistent with those generated using all 1-year spans. Limitations of this study include its small sample size and data variability due to its observational nature.

Conclusion

The findings of this observational study support the premise that reductions in proteinuria are associated with a more stable eGFR in native kidney C3G. Regression analyses using UPCR as a continuous variable demonstrate the relationship between reduction in UPCR and preservation of eGFR. This association was also observed using both change in eGFR by UPCR reduction subgroup and UPCR-eGFR categorical analyses.
MO141ACUTE KIDNEY INJURY AS A RISK FACTOR FOR MORTALITY IN ONCOLOGICAL PATIENTS RECEIVING CHECK-POINT INHIBITORS
Authors: García Carro Clara , Bolufer Mónica , Bury Roxana , CAstañeda Zaira , Muñoz Eva , Felip Enriqueta , Lorente David , Carreras Maria Jose , Gabaldon Alejandra , Agraz Irene , Seron Micas Daniel , Soler María José
Published: May 2021

Background and Aims

Checkpoint inhibitors (CPI) have drastically improved metastatic cancer outcomes. However, immunotherapy is associated to multiple toxicities, including acute renal injury (AKI). Data about CPI related AKI are limited. Our aim was to determine risk factors for CPI related AKI, as well as its clinical characteristics and its impact on mortality in patients undergoing immunotherapy.

Method

All patients under CPI at our center between March 2018 and May 2019, and with a follow up until April 2020, were included. Demographical, clinical data and laboratory results were collected. AKI was defined according to KDIGO guidelines. We performed a logistic regression model to identify independent risk factors for AKI and actuarial survival analysis to establish risk factors for mortality in this population.

Results

759 patients were included, with a median age of 64 years. 59% were men and baseline median creatinine was 0.80 mg/dL. Most frequent malignance was lung cancer and 56% were receiving PD1. 15.5% developed AKI during the follow-up. Age and baseline kidney function were identified as independent risk factors for AKI related ICI. At the end of follow-up, 52.3% patients had died. Type of cancer (not melanoma, lung or urogenital malignance), type of CPI (not CTLA4, PD-1, PD-L1 or their combination) and the presence of an episode of AKI were identified as risk factors for mortality.

Conclusion

15.5% of patients under immunotherapy presented AKI. A single AKI episode was identified as an independent risk factor for mortality in these patients and age and baseline renal function were risks factors for the development of AKI.
MO124THE SINGLE-CELL TRANSCRIPTOMIC OF HUMAN IDIOPATHIC MEMBRANOUS NEPHROPATHY*
Authors: Zhong Yong , Zhou Qiaoling
Published: May 2021

Background and Aims

Idiopathic membranous nephropathy (IMN) is an organ-specific autoimmune disease of the kidney glomerulus. Although substantial advances have been made in the understanding of the molecular bases of IMN in the last 10 years, there remain largely unanswered questions.

Method

To define the transcriptomic landscape at the single-cell resolution, we analyzed kidney samples from 6 patients with idiopathic membranous nephropathy (IMN) and 2 healthy control subjects using single-cell RNA sequencing.

Results

Based on transcriptional expression patterns, we identified all previously described cell types in the kidney. Also, we identified a novel population of the epithelial cell which is mainly from IMN patients. GO enrichment analysis showed that DEGs were enriched in the regulation of apoptosis and type I interferon signaling pathway in mesangial cells, while DEGs were enriched in the regulation of programmed cell death, and various cytokine-mediated signaling pathway in endothelial cells and the regulation of protein modification in pericytes. KEGG enrichment analysis revealed that DEGs were mainly associated with the IL-17 signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway as well as MAPK signaling pathway in endothelial cells as well as pericytes DEGs of proximal tubules cells (PT) and PCs between IMN and control subjects were both enriched in IL-17 signaling, TNF signaling, NOD-like receptor signaling. Moreover, the cell-cell crosstalk highlighted the extensive communication of mesangial cells, which infers great importance in IMN. IMN with massive proteinuria displayed elevated genes participating in the inflammatory signaling pathways that may be involved in the pathogenesis of the progression of IMN.

Conclusion

Overall, we applied single-cell RNA sequencing to IMN to uncover intercellular interactions, elucidate key pathways underlying the pathogenesis, and identify novel therapeutic targets of IMN.
MO147ASSOCIATION OF CHA2DS2-VASC SCORE WITH CAROTID-FEMORAL PULSE WAVE VELOCITY IN CHRONIC KIDNEY DISEASE PATIENTS
Authors: Vodošek Hojs Nina , Ekart Robert , Bevc Sebastjan , Piko Nejc , Hojs Radovan
Published: May 2021

Background and Aims

Chronic kidney disease (CKD) patients suffer from high cardiovascular morbidity and mortality. Arterial stiffness is an important parameter for the evaluation of cardiovascular risk. Carotid-femoral pulse wave velocity (cfPWV) is the gold standard measure for the assessment of arterial stiffness. CHA2DS2-VASc score was originally used to predict cerebral infarction in patients with atrial fibrillation (AF). However, it is also useful in predicting outcome in different cardiovascular conditions, independent of the presence of AF. Therefore, the aim of our research was to assess the association of CHA2DS2-VASc score with cfPWV in CKD patients.

Method

Eighty-seven non-dialysis CKD patients from our outpatient clinic were included. At the time of inclusion, medical history data and standard blood results were collected, CHA2DS2-VASc score was calculated, cfPWV measurements (SphygmoCor System) were done. Correlation between CHA2DS2-VASc score and cfPWV was assessed. Multiple regression analysis with cfPWV as dependent and CHA2DS2-VASc score, eGFR, urinary albumin/creatinine, haemoglobin, high sensitivity CRP, serum calcium, phosphate and intact PTH as independent variables was performed. Additionally, patients were divided into two groups according to median value of CHA2DS2-VASc score (group 1: CHA2DS2-VASc score ≤2, group 2: CHA2DS2-VASc score >2). Data of both groups were compared by t-test or Mann-Whitney test.

Results

CHA2DS2-VASc score correlated with cfPWV (r=0.380, p=0.001). In multiple regression analysis only CHA2DS2-VASc score was significantly associated with cfPWV (p=0.001). Data of both groups of patients divided according to median value of CHA2DS2-VASc score are presented in table 1. cfPWV was significantly higher in group 2 (13.40±3.50 vs 10.46±2.93, p=0.001). Groups of patients also differed significantly in age, presence of diabetes, eGFR and serum phosphate.

Conclusion

CHA2DS2-VASc score is associated with cfPWV in CKD patients. Patients with a higher CHA2DS2-VASc score have stiffer arteries.