bluuebunny/crossref_metadata_2025 huggingface dataset:
MO434CHRONIC KIDNEY DISEASE AND ITS RELATIONSHIP WITH THE STATE OF THE INTESTINAL MICROBIOTA AND INDICATORS OF SYSTEMIC INFLAMMATION
Authors: Olimkhonova Komilakhon
Published: May 2021

Background and Aims

In view of the fact that the human microbiota varies depending on many factors, including comorbid pathology, it seems reasonable to investigate the gut microbiota in patients with chronic kidney disease and its likely relationship with markers of systemic inflammation.

To reveal the relationship between some biomarkers of inflammation with changes in the composition of the intestinal microbiota in patients with chronic kidney disease.

Method

The study included 85 patients with CKD C 2-4. The average age of the patients was 52 ± 4 years (48 men and 37 women). The control group consisted of 30 healthy volunteers aged 50 ± 3 years, 15 men and 15 women, comparable to the main group in terms of sex and age. Blood samples were taken using standard methods. GFR was assessed using the CKD-EPI formula (2011). In addition, biomarkers such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) were evaluated. Bacteriological examination of feces was carried out in the bacteriological laboratory.Markers of systemic inflammation were assessed based on an increase in the level of leukocytes (> 11 × 109 / L), C - reactive protein (> 5.0 mg / L) by immunoturbodimetric method, fibrinogen (> 4.0 g / L), as well as interleukin 6 by enzyme immunoassay. Differences between groups were considered statistically significant at p`0.05; correlation analysis was performed using Spearman's nonparametric rank correlation method.

Results

Analysis of fecal matter showed a deficiency of Bifidobacterium bacteria (<108 CFU) in the examined patients. In addition, the examined patients showed an increase in the number of Echerichia (> 108 CFU). According to the results of the study, in the group of CKD patients, the level of inflammatory markers was higher (CRP-55%, IL-6-60%, leukocytes 62%) than in the control group (CRP-45%, IL-6-40%, leukocytes 38% ).

In men, the IL-6 index was higher than in women. The results of the study demonstrated that in patients with CKD, an imbalance of the intestinal microbiota is combined with an increased level of CRP, IL-6, and leukocytes.

Conclusion

The study of markers responsible for pro-inflammatory effects in the body showed that indicators such as IL-6, CRP, fibrinogen showed a significant correlation with the composition of the microbiota in patients with CKD.
MO435MULTIMODAL IMAGING FOR MOLECULAR TISSUE ANALYSIS
Authors: Lellig Michaela , Brehmer Kai , Hohl Mathias , Speer Thimoteus , Schunk Stefan , Thiele Herbert , Jankowski Joachim , Jankowski Vera , Hermann Juliane
Published: May 2021

Background and Aims

MALDI mass spectrometric imaging (MALDI MSI) is a powerful histologic tool for the analysis of biomolecules in tissue samples. MALDI MSI measurements result in a high sensitivity and accuracy of spatial distribution of biomolecules in tissue samples. For more detailed analysis of MALDI MSI data and correlation between the molecular and microscopic levels, a combination of MALDI MSI data and histological staining is essential. By combining MALDI MSI data and histological data, much more information are obtained than by analyzing both methods individually. Therefore, MALDI MSI datasets and histological staining were fused to a 3D model presenting a biomolecule distribution of the whole organ and provides more information than a single tissue section. We have developed, established and validated an algorithm for an automatic registration of MALDI data with different histological image data for cross-process evaluation of multimodal datasets to create 3D models. This multimodal imaging approach simplifies and improves molecular analyses of tissue samples in clinical research and diagnosis.

Method

The datasets for fusion and creation of a 3D model consist of mass spectrometric data, histological and immunohistochemical staining methods. Histological tissue sections of a whole mouse kidney were prepared. For MALDI MSI data, organ sections were analyzed by using a Rapiflex mass-spectrometer.

Results

A mathematical registration was used to achieve a perfect superposition of the individual histological sections of mass spectrometric data. It is feasible to combine mass spectrometric data, histological and immunohistochemical datasets in high numbers and reconstruct the measured mouse kidney. By using different imaging methods, a variety of information about tissue structure as well as tissue changes and protein distributions can be obtained. The fusion of the data also offers a virtual incision of the organ from arbitrary angle and level. The algorithms are adapted to take the data fusion automatically offering a high-throughput approach for clinical diagnostics and the possibility to involved artificial intelligence in its interpretation in research.

Conclusion

A successful fusion of MALDI MSI data and different histological and immunohistochemical staining datasets of a whole organ is performed.
MO436PLASMA OXALATE VALUES IN PATIENTS WITH END-STAGE KIDNEY DISEASE
Authors: Metry Ella , Garrelfs Sander , Oosterveld Michiel , Neradova Aegida , Bijlsma Joost , Vaz Fred , Groothoff Jaap
Published: May 2021

Background and Aims

Patients with end-stage kidney disease (ESKD) are known to have higher plasma concentrations of metabolic waste products than healthy individuals. Patients with Primary Hyperoxaluria (PH), a rare congenital cause of ESKD, suffer from hepatic overproduction of the metabolic end product oxalate. Plasma oxalate (POx) levels are determined in the diagnostic and therapeutic work-up for PH. Remarkably, correct interpretation of these values is hampered by the absence of knowledge concerning POx levels in patients with ESKD due to common causes.

Method

In this observational study, we obtained POx values in patients with ESKD due to another cause than PH, to establish reference values in this patient group. We collected blood samples from 120 adults with eGFR < 15 mL/min/1.73 m2 who required maintenance hemodialysis or peritoneal dialysis at the Amsterdam UMC.

Results

While there was a wide variation in POx levels in patients with ESKD, the median was 50 umol/L and lowest values were twice the upper reference limit that applies to healthy individuals (6.7 umol/L).

Conclusion

This study shows that POx levels of 50 umol/L are not necessarily suggestive for PH which contradicts the current literature. This study could lead to a paradigm shift in the diagnostic and therapeutic work-up for patients with ESKD.
MO588DECREASED IL-15 PRODUCTION INDUCED BY HYPERPHOSPHATEMIA AS A POSSIBLE MECHANISM OF AGED-RELATED SARCOPENIA*
Authors: Alcalde-Estévez Elena , Asenjo-Bueno Ana , Olmos Gemma , Rodríguez-Puyol Diego , López-Ongil Susana , Ruiz-Torres Maria Piedad
Published: May 2021

Background and Aims

The loss of muscle mass and function, termed sarcopenia, is an aging-related condition associated to some important diseases such as chronic kidney disease (CKD). Hyperphosphatemia has been related to both pathologies. A chronic subclinical inflammation and a dysregulated immune system function are associated to aging affecting to multiple pathways in the skeletal muscle, and this fact has been linked to the development of sarcopenia. Interleukin-15 (IL-15) is a skeletal muscle-derived cytokine which promotes muscle regeneration. The aim of this work was to analyze the role of hyperphosphatemia on the IL-15 production of the skeletal muscle and its implication in aging-related sarcopenia.

Method

Cultured C2C12 myoblasts were used for in vitro experiments. Cells were treated with 10 mM beta-glycerophosphate (BGP) as a phosphate donor for 2, 4, 6, 8 and 24 hours. IL-15 mRNA levels were assessed by RT-qPCR. Three groups of C57BL6 male mice were used for the in vivo studies: 5-months-old mice (young), 24-month-old mice fed with a standard diet containing 0.6 % of phosphate (old) and 24-month-old mice fed with a hypophosphatemic diet, containing a 0.2% of phosphate (old+lowPi), for the last three months before sacrifice. Muscle force was measured by a grip test. Serum phosphate levels were analyzed with a commercial kit. Quadriceps muscle samples were collected to evaluate in them the IL-15 mRNA expression by RT-qPCR.

Results

C2C12 cells treated with BGP show a significant decrease in the IL-15 mRNA expression. On the other hand, in vivo studies showed that old mice had an increase in serum phosphate concentration and a reduction in forelimb strength and muscle mass, compared to young mice. Old animals fed with the hypophosphatemic diet displayed lower levels of phosphate serum linked to an improvement in the muscle mass and function. IL-15 expression of quadriceps muscle was reduced in old mice compared to young mice, whereas those values were increased in old mice fed with the low phosphate diet. Furthermore, there was a negative correlation between IL-15 expression levels and serum phosphate concentrations and a positive correlation between IL-15 and forelimb strength and muscle mass, suggesting that a decreased IL-15 expression affects muscle function.

Conclusion

High extracellular phosphate concentrations decrease IL-15 mRNA expression in myoblasts, and it is correlated with low IL-15 mRNA expression in the quadriceps muscle isolated from old mice. This reduction was associated to a decreased muscular strength and muscle mass, whereas the dietary restriction of phosphate improved these features. These results point to a role of hyperphosphatemia in the impaired immune system function, disrupting the skeletal muscle function, and this could be involved in aging and CKD-related sarcopenia.
MO603PREVALENCE AND PROGNOSTIC SIGNIFICANCE OF MALNUTRITION IN DIALYSIS PATIENTS UNDERGOING ENDOVASCULAR THERAPY FOR PERIPHERAL ARTERY DISEASE
Authors: Lin Ting-Yun , Hung Szu-Chun
Published: May 2021

Background and Aims

Malnutrition often coexists with inflammation and atherosclerosis and is associated with adverse clinical outcomes in dialysis patients. However, both prevalence and prognostic significance of preexisting malnutrition in dialysis patients with peripheral artery disease (PAD) referred for endovascular therapy are not well known.

Method

A prospective cohort of 395 dialysis patients undergoing endovascular therapy for PAD between 2005 and 2019 was studied. Nutritional status was assessed at admission by using the Controlling Nutritional Status (CONUT) score, a simple tool incorporating serum albumin concentration, total peripheral lymphocyte count, and total cholesterol concentration. Patients were divided into 4 groups based on the CONUT score: normal nutrition (0–1), mild malnutrition (2–4), moderate malnutrition (5–8), and severe malnutrition (9–12). We examined the associations between malnutrition and all-cause mortality as well as major adverse limb events (MALE) and major adverse cardiovascular events (MACE) using Cox proportional hazards models.

Results

According to the CONUT score, 40.8% patients were moderately or severely malnourished. During a median follow-up of 2.1 years, 218 (55.2%) patients died, 211 (53.4%) patients had MALE, and MACE occurred in 135 (34.2%) patients. Severely malnourished patients, as compared to patients with normal nutritional status, had significantly increased risk for all-cause death (adjusted hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.56 to 9.12) and in particular non-cardiovascular death (adjusted HR, 7.20; 95% CI, 3.22 to 16.08) and MALE (adjusted HR, 2.42; 95% CI, 1.23 to 4.74) but not MACE (adjusted HR, 1.81; 95% CI, 0.74 to 4.40). Similar results were found when the CONUT score was analyzed as a continuous variable.

Conclusion

Malnutrition is common and is strongly associated with increased all-cause mortality and MALE among dialysis patients with PAD requiring endovascular therapy. Clinical trials are needed to evaluate whether nutritional interventions improve outcomes for dialysis patients with PAD.
MO604DIFFERENCES IN THE EXTRACELLULAR BODY WATER/TOTAL BODY WATER (EBW/TBW) IN HEMODIALYSIS AND CHRONIC KIDNEY DISEASE PATIENTS. RELATIONSHIP WITH NUTRITIONAL PARAMETERS
Authors: Barril Guillermina , Nogueira Ángel , Alvarez Graciela , Sapiencia David , Andres Natalia , Giorgi Martin , Nuñez Almudena , Romasco Paula
Published: May 2021

Background and Aims

Knowing the hydration status of CKD patients is one of the basic objectives in CKD patients considering the Ratio of EBW(TBW) as indicator of them.

Aim

Determine the cut-off point of the EBW/TBW ratio using Bioimpedance in patients with global CKD and divided into advanced CKD and hemodialysis (HD) as a hydration marker in relation to MIS scale (malnutrition inflammation score), cut-off point 5.

Method

We value 199 CKD patients by setting the EBW/TBW cut-off points using Inbody S10 multifrequency bioimpedance with global ROC curve and for advanced CKD (ACKD) and HD analyzing differences according to age ranges (<65,65,1-75 and >75 years) and differences in nutritional parameters (visceral proteins, MIS scale and body composition).

Results

We have evaluated 199 patients with ACKD, 143 male and 56 female, 74 in CKD xage72.27 ?11.98years and 125 in HD, xage 70.76 ?12.73 years. Overall EBW / TBW ratio: AUC 0.657, p0.006, cut-off point 0.3965 60% sensitivity, 64% specificity. Advanced CKD: AUC 0.648, p0.071, cutoff point 0.397, 64% sensitivity, 61% specificity. HD: AUC 0.706, p0.012, cutoff point 0.391, 71% sensitivity, 63% specificity. The results in relation to age strata and MIS with 5 as the cut-off point in the table. No greater hydration in men than in women overall.

The nutrition-inflammation parameters according to the cut-off point are different: Advanced CKD: age 0.001, albumin 0.024, prealbumin 0.013, trasferrin 0.078, CRP 0.432. HD: albumin 0.014, prealbumin 0.001, transferrin 0.939, lymphocytes 0.030, CRP 0.342, age 0.000.

Conclusion

1. We have found slightly higher cut-off points between ACKD and hemodialysis in the assessed sample. 2. The EBW / TBW ratio appears higher in patients > 65 years in both ACKD and HD, in contrast to what is observed in the healthy population. 3. A greater malnutrition appairs in a greater hyperhydration in HD and ACKD.
MO589PLASMA CONCENTRATIONS OF TRIMETHYLAMINE N-OXIDE, AND ITS DIETARY DETERMINANTS ARE ASSOCIATED WITH INCREASED RISK OF GRAFT FAILURE
Authors: Flores-Guerrero Jose L , C.J. Osté Maryse , Baraldi Paula B , Connelly Margery A , Garcia Erwin , Navis Gerjan , Bakker Stephan , Dullaart Robin P F
Published: May 2021

Background and Aims

Due to the critical shortage of kidneys for transplantation, the identification of modifiable factors related to graft failure is highly desirable. The role of trimethylamine-N-oxide (TMAO) in graft failure remains undetermined. Here we aimed to investigate the clinical utility of TMAO and its dietary determinants for graft failure prediction in renal transplant recipients (RTRs).

Method

We included 448 RTRs who participated in the TransplantLines Cohort Study. Cox proportional-hazards regression analyses were performed to study the association of plasma TMAO with graft failure. Net Benefit, a decision analysis method, was performed to evaluate the clinical utility of TMAO and dietary information in the prediction of graft failure.

Results

Among RTRs (age 52.7 ± 13.1 years; 53% males), baseline median TMAO was 5.6 (3.0–10.2) µmol/L. In multivariable regression analysis, the most important dietary determinants of TMAO were egg intake (Std. β = 0.10 [95%CI, 0.01;0.19]; P=0.03), fiber intake (Std. β = -0.13 [95%CI, -0.22, -0.05]; P =0.002), and fish and seafood intake (Std. β = 0.11 [95%CI, 0.02,0.20]; P=0.01). After a median follow-up of 5.3 (4.5–6.0) years, graft failure was observed in 58 subjects. TMAO was associated with increased risk of graft failure, independent of age, sex, BMI, blood pressure, lipids, albuminuria and eGFR (Hazard Ratio per 1-SD increase of TMAO, 1.62 (95% confidence interval (CI): 1.22; 2.14, P<0.001). A TMAO and dietary enhanced prediction model offered approximately double Net Benefit compared to a previously reported, validated prediction model for future graft failure, allowing the detection of 21 RTRs per 100 RTRs tested with no false positives versus 10 RTRs respectively.

Conclusion

A predictive model for graft failure, enriched with TMAO and its dietary determinants yielded a higher Net Benefit compared with an already validated model. This study suggests that TMAO and its dietary determinants are associated with an increased risk of graft failure and that it is clinically meaningful.
MO607THE EFFECT OF VITAMINE E ON OXIDATIVE STRESS AND CARDIOVASCULAR COMPLICATIONS IN HEMODIALYSIS PATIENTS
Authors: Azouaou toualbi Leila , Arab Medina , Toualbi Chahine , Abderrezak Khelfi , Chader Henni , Benoui Abdelghani , Seba Atmane
Published: May 2021

Background and Aims

Oxidative stress represents a risk factor for cardiovascular complications . The aim of the work is to evaluate the effectiveness of vitamin E on cardiovascular complications in hemodialysis patients.

Method

a study including 420 patients on hemodialysis and 360 controls. Treatment with Vit E at a rate of 300 mg / day for 2 years. All patients benefited from a blood sample of oxidative stress markers as well as paraclinical explorations in search of cardiovascular complications.

Results

The study grouped together 780 cases. We find that there is a significant relationship between cardiovascular complications and Advanced Oxidation Protein Product (AOPP), Low Density Oxidized Lipoprotein (LDLox), Malondialdehydes (MDA) and Gluthations), we did not find any correlation with nitrogen monoxide (NO) and myeloperoxidases (MPO) .Concerning gluthations (IU / ml ) we observe that the mean values clearly increased after treatment (P-value <0.05) . The mean value of MDA µmol / l significantly decreased after treatment .we note that the cardiovascular complications have decreased (11.03% versus 16.04%) with the decrease in certain markers of oxidative stress. (p > 0.05)

Conclusion

Regarding cardiovascular complications, we have certainly noticed a drop in their frequency after treatment with vit E without the difference being significant.
MO609PREVALENCE OF MALNUTRITION AND INFLAMMATION IN NONDIALYZED PATIENTS WITH CHRONIC KIDNEY DISEASE: A CLINICAL STUDY
Authors: Parry Manzoor , Jeelani Hamad
Published: May 2021

Background and Aims

The prevalence of chronic kidney disease (CKD) in India varies from 0.16–0.78%. The reported incidence of malnutrition in CKD patients is 37–84%. There is a paucity of data on the quantification of malnutrition and inflammation in undialyzed patients of CKD from north east of India. This study analyzed the prevalence and causes of malnutrition and inflammation in patients with CKD before the initiation of dialysis treatment.

Method

This study was conducted from May 2017 to May 2019 in the department of nephrology Guahati medical college hospital. Assessment of nutritional and inflammatory status was carried out in patients with CKD before initiation of dialysis. Serum albumin; body mass index (BMI); triceps skin fold thickness (TST); mid-arm muscle circumference (MAMC); and subjective global assessment (SGA) scoring were used for assessment of nutritional parameters. Serum C-reactive protein; serum albumin and serum ferritin level were used to assess the inflammatory status in these patients.

Results

A total of 528 (male:female= 359:169) patients with CKD participated in this study. Diabetic Nephropathy (35%) was the most common; followed by; hypertension (23%) and chronic glomerulonephritis (20 %). The evidence of malnutrition was noted in 344 (65%). The mean age of patients with malnutrition was 52.8±12.45 years with a male predominance (68%). On the basis of SGA score; malnutrition was noted in 344 patients (mild moderate [36%]; severe; [30%]); remaining (34%) were well nourished. Thus; evidence of Malnutrition was noted in 65% of patients with CKD.). Serum total protein & albumin were higher in the non-malnourished patients in comparison to malnourished (5.83±1.0 vs 5.31±1.12 p<0.05; 3.65±0.7 vs 2.62±0.74) The inflammatory markers (serum ferritin & C reactive protein) were elevated significantly in patients with malnutrition in comparison to those without malnutrition (308.15±60.18 mg/dL vs. 251.64±63.14 mg/dL; p < 0.001; 77% vs. 50%; p < 0.01).

Conclusion

Malnutrition and inflammation are common in patients with CKD before the commencement of dialysis. This indicates that an emphasis should be placed on the assessment and prevention or correction of malnutrition and inflammatory burden in these patients with CKD.
MO595FREQUENCY OF INTAKE OF DIETARY FIBER SOURCES NOT ASSOCIATED WITH HYPERKALEMIA IN HEMODIALYS PATIENTS IN A MULTICENTER STUDY
Authors: Dos Santos Rafaela G , Malinovski Juliana , Scatone Natália , De Oliveira Jorgiane , Sczip Andrea , Moraes Jyana , Vieira Marcos , NERBASS FABIANA
Published: May 2021

Background and Aims

Patients undergoing hemodialysis (HD) treatment usually have a low intake of food groups rich in dietary fiber to avoid hyperkalemia. However, dietary potassium is not associated with serum potassium or hyperkalemia in recent studies, and higher intake of fiber food groups such as fruits and vegetables is associated with lower mortality and other complications in HD populations. This multicenter cross-sectional study aimed to investigate the frequency of intake of dietary fiber sources, its determinants, and the relationship with hyperkalemia in HD patients.

Method

Prevalent HD patients from four dialysis clinics in Southern Brazil were invited to participate (at least 80% of eligible patients from each clinic). Patients were interviewed by the researchers and answered a food frequency questionnaire (FFQ) with the main dietary fiber sources (fruits, vegetables, legumes, whole grains cereals and seeds) with seven frequency possibilities (from never to more than twice a day). To estimate the weekly frequency of intake, answers were transformed into a score. Every score point corresponded to one time per week (ex.: score 7 = seven times per week). The sum of the five scores was calculated to determine the total score. Demographical and laboratory data were obtained from medical records. Univariate analysis was used to assess total score associations, and the variables with P<0.20 were included in the regression analysis model.

Results

305 HD patients were included (male: 51%; age: 52.2 ± 14.7 years old; HD vintage: 46 (19 – 82) months; hyperkalemia: 29%). Median (interquartile) FFQ scores were: fruits: 6 (2-14); vegetables: 6 (3-10); legumes: 3 (1-7); whole-grain: 0 (0-1) and seeds: 0 (0-0). Total score was 19 (14-28) and correlated with age (r=0.15; P=0.01), HD vintage (r=-0.22; P=<0.001) and body mass index (BMI) (r=0.15; P=0.007). Patients with diabetes had a higher total score (22 (15-31) versus 18 (13-27) P=0.03). Only the vegetables score correlated with serum potassium (r=0.17; P=0.03) and no difference was found between dietary fiber food groups scores and total score with hyperkalemia. The linear regression analysis model also included gender and education (years at school) (all with P<0.20 in the univariate analysis). The independent predictors of dietary fiber total score were age (OR=0.1 (95%IC 0.01-0.20);P=0.04), HD vintage (month) (OR=-0.03 (95%IC -0.06 - -0.01);P=0.02) and years at school (OR=0.27 (95%IC 0.85-0.46);P=0.005).

Conclusion

The usual frequency of intake of fiber sources was low, and its independent determinants were age, HD vintage and education. The lack of association with hyperkalemia suggests that other dietary sources and clinical factors should be considered to manage hyperkalemia in this population.
MO450ANEMIC PATIENTS WITH ELEVATED RED CELL DISTRIBUTION WIDTH (RDW) ARE LIKELY TO HAVE FASTER FUTURE CKD PROGRESSION
Authors: Tanaka Hiroshi
Published: May 2021

Background and Aims

Elevation in red cell distribution width (RDW), a marker of size variance in red blood cells, recently has been reported to predict future cardiovascular event. RDW elevation has also been reported to be associated with faster CKD progression. It is not known whether the elevation of RDW is merely a sequela of, or truly a predictor of, the decline in kidney function.

Method

A hospital-wide study with all the laboratory data for a period of 4 years and 2 months was conducted. All the adult patients in whom an eGFR slope was obtained over 731 days or more with haemoglobin (Hb) measurements of at least twice over 731 days or more were included. Hb and RDW values were classified according to the timing of measurement: first-year measurements during the period vs last-year values. The effects of Hb and RDW on the annual decline in eGFR (mL/min/1.73m2/year) were analyzed. Statistical analysis was performed with R 3.6.0 on Ubuntu.

Results

A total of 4,611 patients (M:F = 2124:2487, age 18-105 (median 68) years) were included. The first-month Hb and RDW were 7.5 − 20.2 (median 13.6) g/dL and 10.5 − 34.6 (median 12.6). eGFR was 3.4 − 195 (median 69.3) mL/min/1.73m2. Patients with the highest tertile in the first-year RDW had significantly faster decline in eGFR than the rest (-1.74 vs -1.51, P=0.04), while patients with the highest tertile in the last-year RDW had virtually identical eGFR decline compared with the rest. Patients with higher RDW (>=median) and lower Hb (< median) had significantly faster decline in eGFR than the rest (-1.84±4.11 vs -1.47±2.95, P =0.002).

Conclusion

Anemic patients with elevated RDW are likely to have faster CKD progression in the future.
MO451GUANIDINYLATED APOLIPOPROTEIN C3 (APOC3) A NOVEL PLAYER IN CKD AND CKD-ASSOCIATED CARDIOVASCULAR DISEASES
Authors: Schunk Stefan , Hermann Juliane , Sarah Triem , Lellig Michaela , Hahm Eunsil , Boor Peter , Reiser Jochen , Jankowski Joachim , Fliser Danilo , Jankowski Vera , Speer Thimoteus
Published: May 2021

Background and Aims

Cardiovascular diseases (CVD) and chronic kidney diseases (CKD) are highly prevalent in Western populations and account for a substantial proportion of mortality. We found that apolipoprotein C-3 (ApoC3), a constituent of triglyceride-rich lipoproteins, induces alternative NLRP3 inflammasome activation in human monocytes and thus causes sterile inflammation. The aim of the present study was to screen ApoC3 for the presence of posttranslational protein modifications and to assess its relevance in vitro, in vivo, as well as in a prospective cohort of CKD patients.

Method

ApoC3 was subjected to proteomic analysis. The proinflammatory properties of ApoC3 were assessed in human monocytes and in humanized mice. Moreover, posttranslationally modified ApoC3 was quantified in prospective cohort of 543 patients with various etiologies of CKD and linked to kidney and cardiovascular outcomes.

Results

We identified posttranslational guanidinylation of lysine residues of ApoC3 (gApoC3) in patients after acute myocardial infarction and in patients with CKD. gApoC3 accumulates in kidneys and hearts after injury as determined by 2D-proteomic analyses. In human monocytes, guanidinylation enhanced the binding of ApoC3 to the cell surface and exerted substantially stronger pro-inflammatory effects as compared native ApoC3. In humanized mice, gApoC3 strongly induced kidney fibrosis and abolished the regeneration after vascular injury. In a prospective clinical trial of 543 patients, higher gApoC3 blood levels as determined by mass spectrometry were associated with increased mortality as well as cardiovascular and renal events during a long-term follow-up.

Conclusion

The present study provides evidence from preclinical models and a prospective clinical trial that gApoC3 plays an important role in the development of organ injury in patients with CKD, myocardial infarction and other clinical conditions. The clinical study represents one of the largest trials, in which the association of a specific PTM and clinically relevant outcomes was assessed. These findings highlight gApoC3 as a pathophysiologically relevant factor in development of organ dysfunction.
MO454A NEW AKI TO CKD PROGRESSION IN VIVO EXPERIMENTAL MODEL
Authors: Massaro Giampiero A , Mercado-Hernandez Joana , Fuentes-Calvo Isabel , Sancho Martinez Sandra M , Quiros Yaremi , Martinez Salgado Carlos , Lopez-Hernandez Francisco J
Published: May 2021

Background and Aims

Chronic kidney disease (CKD) represents an enormous problem for healthcare systems. It is estimated that in USA more than 37 million people suffer from this disease. Risk factors include hypertension, diabetes mellitus, older age, proteinuria and previous episodes of acute kidney injury (AKI). Indeed, several studies have shown that AKI increases the risk of CKD, independently of other risk factors, especially when the episode is severe or recurrent. Under these circumstances, maladaptive responses may occur leading to structural and functional abnormalities. Renal fibrosis is the hallmark for maladaptive repair and is considered the final common outcome of progressive kidney disease. We hypothesized that after multiple renal insults, the mechanisms of adaptive repair could be less effective generating a progressive accumulation of extracellular matrix and a progressive deterioration of kidney function.

Method

We used 8 weeks old male Wistar rats and we analyse their evolution during 9 months. Animals were subdivided into 4 experimental groups: Control group: SHAM operated rats, saline solution, i.p.; “CDDP5-I/R60-I/R60” group: 5 mg/kg cisplatin i.p., after renal function normalization, 60-minute ischemia-reperfusion (I/R60) on left kidney, and 2 weeks later 60-minute ischemia-reperfusion (I/R60) on right kidney; “5/6 RMR” group: 5/6 renal mass reduction; “UNX” group: nephrectomy. Blood and urine were collected at: day 0 (basal); day 4 (AKI development); day 8 (normalized renal function after AKI and induction of renal ischemia); day 9 (1 day after ischemia); day 13, day 20 and monthly thereafter. Renal function was analyzed by sCr, creatinine clearance, blood urea nitrogen and proteinuria determination using colorimetric methods. Tissue samples were stained with Masson´s trichrome and Sirius Red at days 13, 20, 56, 165 and 270 and renal fibrosis was quantified using Image J program.

Results

The addition of several AKI episodes induces a progressive accumulation of extracellular matrix. In addition, the “CDDP5-I/R60-I/R60” group presented an initial reduction in renal function that remained stable in the last 6 months of the study. On the contrary, we observed a spontaneous and progressive decline of kidney function in the “5/6 RMR” group, which nevertheless presented a significant lower degree of interstitial fibrosis than the “CDDP5-I/R60-I/R60” group.

Conclusion

We have generated a new in vivo experimental model of AKI to CKD transition combining nephrotoxic and ischemic AKI. We demonstrate that after recurrent episodes of AKI, kidneys show progressive interstitial fibrosis which however does not correlate with a progressive decline of renal function.
MO460ASSOCIATION BETWEEN CARBAMYLATED ALBUMIN, GUT MICROBIOTA AND THEIR DERIVED METABOLITES IN CHRONIC KIDNEY DISEASE
Authors: Steenbeke Mieke , Valkenburg Sophie , Van Biesen Wim , Delanghe Joris , Speeckaert Marijn , Glorieux Griet
Published: May 2021

Background and Aims

Chronic kidney disease (CKD) is characterized by gut dysbiosis. We recently demonstrated a decrease of short-chain fatty acid (SCFA) producing bacterial species with the progression of CKD. Besides, levels of protein-bound uremic toxins (PBUTs) and post-translational modifications of protein are increased in CKD, both are risk factors for accelerated cardiovascular morbidity and mortality. The link between the gut-kidney axis and protein carbamylation is unclear. The aim of the study was to explore the relation between carbamylated albumin, estimated by the albumin symmetry factor, and plasma levels of PBUTs, fecal levels of SCFAs (ongoing), and the abundance of related gut microbiota in different stages of CKD (1-5).

Method

The study cohort includes 103 non-dialyzed CKD patients (stages 1-5). Serum proteins were detected by capillary electrophoresis and UV absorbance at 214 nm with the symmetry factor as a marker of albumin carbamylation [the lower the symmetry factor, the more carbamylated albumin].

The quantification of PBUTs and SCFAs in plasma and fecal samples, respectively, using validated UPLC methods.

Results

The Pearson correlation coefficient (r) shows a positive correlation between the albumin symmetry factor and the estimated glomerular filtration rate (eGFR) (r=0.3025; p=0.0019).

The albumin symmetry factor correlates positively with the abundance of Butyricicoccus spp. (r= 0.3211; p=0.0009), Faecalibacterium prausnitzii (r=0.2765; p=0.0047) and Roseburia spp. (r=0.2527; p=0.0100) and negatively with the PBUTs, p-cresyl sulfate (pCS) (r=-0.2819; p=0.0039), p-cresyl glucuronide (pCG) (r=-0.2819; p=0.0039) and indoxyl sulfate (IxS) (r=-0.2650; p=0.0068).

Conclusion

The decreased abundance of SCFA producing gut bacteria with the progression of CKD can evoke unfavorable conditions in the gut. This can contribute to increased plasma levels of PBUTs potentially (indirectly) playing a role in albumin carbamylation. It will be further explored whether fecal levels of SCFAs are affected in parallel and could be potential targets to restore gut dysbiosis and uremia.
MO462TIME-TRAJECTORIES OF RENAL FUNCTION AND OUTCOMES IN ELDERLY INDIVIDUALS WITH CKD OF VARIOUS ETIOLOGY
Authors: Zicarelli Mariateresa , Comi Alessandro , Patella Gemma , Cianfrone Paola , Coppolino Giuseppe , Comi Nicolino , Fuiano Giorgio , Bolignano Davide , Andreucci Michele
Published: May 2021

Background and Aims

Despite hypertension ranks among the leading causes of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the so-called “nephrosclerosis” (NS), on CKD progression towards end-stage kidney disease (ESKD) is often unpredictable, particularly in older populations. We run a prospective, observational study to define renal function patterns and outcomes in elderly individuals with or without NS-related CKD.

Method

304 elderly patients with already established CKD (mean age 69±4 y; mean eGFR 44.2±19.6 mL/min/1.73 m2; male= 64.1%), followed in our outpatients’ clinic were categorized according to the etiology of CKD. NS was defined as the presence of CKD associated with long-term essential hypertension, hypertensive retinopathy, left ventricular hypertrophy and minimal proteinuria. Time-trajectories in eGFR (CKD-Epi) were computed over a 4-year follow-up. In addition, we analysed the occurrence of a composite outcome of doubling of serum creatinine, eGFR reduction≥ 25% and/or ESKD needing dialysis or kidney transplantation.

Results

CKD was secondary to nephrosclerosis (CKD-NS) in 220 (72.3%) patients. Among the remaining 84 (27.7%), glomerular/diabetic diseases were the most frequent cause of CKD (47.6%). In the whole cohort, the average estimated annual GFR slope was of 1.8 mL/min/1.73 m2. eGFR decline was slower in CKD-NS as compared with the one of others (1.4 vs. 3.4 mL/min/1.73 m2; p<0.001. Figure 1). The composite renal outcome during follow-up (median 36 mo.; range 6-48) occurred less frequently among elderly with CKD-NS (16/204 vs 14/70; p=0.01 Crude HR 0.43, 95%CI 0.22-0.85) and was associated at logistic analyses with etiology of CKD, serum total cholesterol, serum LDL cholesterol levels and glycemia (p ranging from 0.01 to 0.04).

Conclusion

Despite being highly prevalent in the elderly, NS is associated with a more favorable renal disease course as compared with other conditions. Therapeutic efforts to delay CKD progression in older populations should go beyond just optimizing blood pressure control and focus more on concomitant diseases.
MO463EVIDENCE OF MICROALBUMINURIA AND ESTIMATED GLOMERULAR FILTRATION RATE DECLINE AS CHRONIC KIDNEY DISEASE RISKS IN NON-ALCOHOLIC FATTY LIVER DISEASE PATIENTS: META-ANALYSIS OF COHORT STUDIES
Authors: Putra Boby Pratama , Putra Felix Nugraha
Published: May 2021

Background and Aims

Recent evidences showed an association between NAFLD and extrahepatic manifestations such as chronic kidney disease (CKD) although the result is still inconclusive. This study aims to measure the association of microalbuminuria and estimated glomerular filtration rate (eGFR) decline as CKD risks in NAFLD patients.

Method

Comprehensive searching using predefined queries was done through online databases Pubmed, EMBASE, ScienceDirect, and The Cochrane Library to include all relevant literature until November 2020. We included all cohort studies of NAFLD patients diagnosed by ultrasonography (USG), commutated tomography (CT), or scoring system fatty liver index (FLI) that reports microalbuminuria and eGFR decline below 60 ml/min/1.73m2. Bias risk was assessed by The Newcastle-Ottawa Scale for cohort studies. Analysis of this study was performed to provide pooled hazard ratio (HR) with 95% confidence interval (CI) using random-effect heterogeneity test.

Results

We included 10 cohort studies met our criteria. Analysis of 6 NAFLD cohort studies diagnosed by USG is significantly associated with eGFR decline (pooled HR = 1.54, 95% CI 1.13 to 2.11, p=0.006, I2=88%), while NAFLD patients diagnosed by FLI also showed significant association with eGFR decline (pooled HR = 1.58, 95% CI 1.52 to 1.64, p<0.0001, I2=0%), thus overall analysis combined with CT diagnostic modalities showed significant association between NAFLD and eGFR decline (pooled HR=1.53 95%CI 1.29-1.80 p<0.00001 I2=82%). Microalbuminuria risk is significantly increased in NAFLD patients (pooled HR = 1.93, 95% CI 1.39 to 2.67, p<0.0001, I2=0%). Surprisingly, NAFLD patients whose increased gamma-glutamyltransferase (GGT) has higher eGFR decline risk (pooled HR = 1.73, 95% CI 1.02 to 2.92, p=0.04, I2=78%).

Conclusion

Microalbuminuria and eGFR decline are associated as CKD risks in NAFLD patients. However, further studies are still needed to establish the causality.
MO464TWO-YEARS CHANGES IN ABPM, CARDIAC AND RENAL PARAMETERS PREDICT CARDIOVASCULAR OUTCOME OF PATIENTS WITH CKD AND HYPERTENSION
Authors: Bussalino Elisabetta , Ravera Maura , Mallia Laura , Minutolo Roberto , Vettoretti Simone , Paoletti Ernesto
Published: May 2021

Background and Aims

Changes over time in eGFR and albuminuria provide better accuracy than baseline values for end-stage risk prediction in CKD patients, whereas no studies have evaluated the impact of changes in renal, cardiac, and BP parameters on cardiovascular (CV) outcome.

Methods

We prospectively evaluated 249 hypertensive CKD patients with available baseline and 2-year echocardiography and ambulatory blood pressure monitoring (ABPM). Outcome was a composite of death or any non fatal CV event. Predictors of outcome were tested by multivariable regression analysis. The accuracy of prediction models that included baseline and 2-year changes (Δ) in cardiac, renal and BP parameters was assessed by ROC analysis.

Results

During a follow-up period of 71 months, 69 CKD patients (28%) experienced a major CV event or died. By multivariable Cox regression analysis baseline nighttime pulse pressure (PP) (HR 1.01, 95% CI 1.00 to 1.04), left ventricular mass (LVMi) (HR 1.03, 95% CI 1.02 to 1.04), ejection fraction (EF) (HR 0.96, 95% CI 0.90 to 0.97), Δ nighttime PP (HR 1.04, 95% CI 1.01 to 1.07), Δ LVMi (HR 1.02, 95% CI 1.00 to 1.04), and ΔEF (0.93, 95% CI 0.89-0.97) were associated with outcome. A model that includes 2-year changes in LVMi, EF, proteinuria, and nighttime PP was more accurate than a model that only evaluated baseline values (Δc-statistic 0.08, 95% CI 0.02 to 0.13, P=0.006; net reclassification improvement -NRI- 0.24, P= < 0.0001).

Conclusion

Estimation of 2-year changes in renal, cardiac, and BP parameters improve the predictive accuracy of adverse CV outcome in CKD patients followed in tertiary care.
MO465PROGNOSTIC IMPLICATION OF URINARY POTASSIUM EXCRETION IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Mori Daisuke , Tamai Shinjiro , Tokuchi Maho , Inoue Natsumi , Kawai Hideaki , Shimada Naoyuki , Nomi Hiroki , Haga Ryota , Nagatoya Katsuyuki , Yamauchi Atsushi
Published: May 2021

Background and Aims

Plasma potassium levels are impacted by decreased kidney function and are known to be associated with increased mortality, adverse cardiovascular events and adverse kidney events. However, the prognostic implication of urinary potassium is unclear.

Method

We conducted an observational study of 1102 patients with chronic kidney disease (CKD) who were hospitalized between 2010 and 2018. The expected primary outcomes were all-cause mortality, adverse cardiovascular events and CKD progression. CKD progression was defined as a 30% increase in serum creatinine, the initiation of maintenance dialysis or the need for kidney transplantation. The Cox proportional hazards model was used to analyse the association between urinary potassium excretion and adverse clinical outcomes after adjustment for potential confounders.

Results

At baseline, 66% of the patients were men, with a median age of 72 years (interquartile range or IQR, 64–79 years); 61% of the patients were diabetic, and 54% of them were hypertensive. The median values for estimated glomerular filtration rate (eGFR) was 12 mL/min/1.73m2 (IQR, 8–18), serum potassium 4.5 mmol/L (IQR, 4.1–5.1) and urinary potassium/creatinine ratio (UK/Cr) 27 mmol/gCr (IQR, 20–38). Over a median follow-up period of 2.6 years (IQR 0.2–4.5), the number of all-cause deaths was 87. There were 171 cases of cardiovascular events and 860 cases of CKD progression. After adjusting for the eGFR, serum potassium level, proteinuria, renin–angiotensin system inhibitors, diuretics and other potential confounders, UK/Cr was found to be neither significantly associated with all-cause mortality nor with adverse cardiovascular events. However, a low UK/Cr was associated with an increased risk of CKD progression (adjusted hazard ratio [95% confidence interval] for the first, second and third quartiles, compared with the fourth quartile, were as follows: 2.09 [1.43-3.06], 1.33 [0.96-1.86] and 1.05 [0.75-1.46])

Conclusion

A low UK/Cr might be an independent risk factor for poor renal outcome.
MO466A NOVEL PREDICTION MARKER OF 10-YEAR RISK AND LIFETIME RISK OF RECURRENT CARDIOVASCULAR EVENTS IN PATIENTS WITH CKD AND DIABETES MELLITUS
Authors: Gembillo Guido , Cernaro Valeria , Siligato Rossella , Giuffrida Alfio Edoardo , Labbozzetta Vincenzo , Satta Ersilia , Santoro Domenico
Published: May 2021

Background and Aims

Chronic kidney disease (CKD) is one of the most prevalent complication of Diabetes Mellitus and patients with both diseases are more exposed to atherosclerosis injury and premature death from cardiovascular disease (CVD).

CVD is worsened by inflammation, oxidative stress, lipid accumulation and high-density lipoprotein cholesterol (HDL) reduction: patients with altered lipid metabolism more often present monocyte profile changes, with an altered pro-inflammatory phenotype leading to a significant risk of plaque formation and atherosclerosis. The alteration of the balance between monocyte and HDL, represented by the Monocyte/HDL ratio (MHR), is an easy way to evaluate the inflammatory status and to study appropriate strategies to treat high-risk patients.

Method

We evaluated 150 consecutive diabetic patients with CKD hospitalized in the Unit of Nephrology and Dialysis of the Policlinic G. Martino of Messina, Italy, with a history of CVD. We used the SMART-REACH SCORE, a model created to estimate life expectancy without recurrent cardiovascular events for individuals with a history of CVD. We performed a retrospective analysis of the MHR status of our patients to study its correlations with the 10-year risk and lifetime risk for myocardial infarction, stroke or vascular death, recurrent CVD events and free life-expectancy if standard care is provided.

Results

In the entire cohort of patients, MHR appeared to be positively correlated with ten-year risk (ρ=0.469; P <0.0001) (Figure 1) and lifetime risk of myocardial infarction, stroke, or CV death (ρ=0.428; P <0.0001) (Figure 2). Furthermore, patients with higher MHR levels had a significantly smaller number of years of CVD-free life expectancy (ρ=-0.364; P <0.0001) (Figure 3).

Conclusion

MHR can represent a valid tool to predict the recurrence of CVD in CKD patients with diabetes. This easy-to-perform marker of oxidative stress and CVD risk can be used alone or in a multiple biomarker panel, improving the stratification and management of patients with comorbidities and risk of life- threatening conditions.
MO467SINGLE NEPHRON GFR AND GLOMERULAR HYDROSTATIC PRESSURE IN JAPANESE HEALTHY SUBJECTS
Authors: Nobayashi Hiroki , Kanzaki Go , Sasaki Takaya , Oba Rina , Okabayashi Yusuke , Haruhara Kotaro , Koike Kentaro , Kobayashi Akimitsu , Yamamoto Izumi , Nobuo Tsuboi , Yokoo Takashi
Published: May 2021

Background and Aims

Hemodynamic abnormalities such as intraglomerular hypertension and glomerular hyperfiltration associated with the nephron loss are deeply involved in renal damage progression. Recent studies in humans have described a new method to calculate single nephron GFR (SNGFR), which is defined as GFR divided by the estimated total number of non-sclerosed glomeruli. We have previously shown that a higher SNGFR, which indicates glomerular hyperfiltration, is associated with CKD risk factors. However, it is still unknown that the hemodynamic changes in humans within the glomerulus in response to SNGFR. In the present study, we analysed the renal microcirculatory dynamics with SNGFR in healthy individuals without CKD.

Method

We retrospectively identified 51 living kidney donors who underwent enhanced computed tomography and kidney biopsy at the time of donation from January 2007 till December 2020. Nglom was calculated as the cortical volume of both kidneys assessed on computed tomography times the 1-hour posttransplant renal biopsy-determined glomerular density. SNGFR was calculated by dividing GFR (calculated from the corrected creatinine clearance) by the non-sclerosed Nglom. Glomerular hydrostatic pressure (Pglom) and afferent / efferent arteriolar pressure were calculated from the Gomez / Ohm's formula.

Results

Age was 57.0 ± 10.4 years, mean blood pressure was 88.7 ± 13.2 mmHg, GFR was 73.3 ± 16.7 mL/min, and Nglom was 807,774 ± 401,0352 / kidney. SNGFR was significantly associated with renal blood flow and Pglom (p for trend = 0.02, and 0.02, respectively), but not with age, mean blood pressure, renal plasma flow, filtration fraction, afferent / efferent arteriolar pressure (Table1).

Conclusion

Our results showed that the increase in SNGFR is associated with elevated Pglom, indicating that glomerular hyperfiltration may lead to intraglomerular hypertension.