bluuebunny/crossref_metadata_2025 huggingface dataset:
#2161 Phosphodiesterase V inhibitor attenuates the fibrotic gene expression of human renal fibroblast derived from IgA nephropathy: an in-vitro study
Authors: Behera Manas Ranjan , Singh Mantabya , Rai Mohit , Kaul Anupma , Prasad Narayan , Bhadauria Dharmandr , Misra Durga Prasanna , Agarwal Vikas
Published: May 2024

Background and Aims

Renal fibrosis (RF) is the final common pathway that determines the progression of many glomerular disease including IgA nephropathy (IgAN). Till date there is no definite therapy available to retard RF. Being the key mediator of fibrosis, TGF-β is being targeted in many studies. Phosphodiesterase V inhibitor (PDE5i) is known to inhibit TGF-β but its role in RF is yet to be established. Hence, in the current in-vitro study we wish to establish the role of PDE5 inhibitor as an inhibitor of TGF-β and hence the RF.

Method

This is a pilot study to evaluate the efficacy of ‘Phosphodiesterase V inhibitor’ on TGFβ1 induced fibrosis on fibroblasts derived from biopsy specimen of IgA nephropathy patients. Renal fibroblasts were cultured from six IgA patients. The fibroblasts cells were treated with PDE5i inhibitor (tadalafil) (at different doses of 1 µm, 5 µm, 10 µm and 15 µm), both before and after stimulation with transforming growth factor beta-1 (TGF-b1) (at doses of 5 ng/ml, 10 ng/ml, 15 ng/ml and 20 ng/ml). Gene expression was studied by real-time polymerase chain reaction (RT-PCR) for messenger ribonucleic acid (mRNA) of pro-fibrotic genes Col1a1, Col1a2, FN1, CTGF, ASMA, TIMP1, and anti-fibrotic MMP2.

Objectives

Results

Our results shows that TGFβ significantly increased the expression of profibrotic gene (Col1a1, Col1a2, ASMA, CTGF, FN and TIMP1) at concentration of 10 ng/ml in the fibroblast cells derived from IgAN patients. Treatment of fibroblast cells with Tadalafil (PDE5 inhibitor) significantly decreased the pro-fibrotic gene mRNA expression (Col1a1, Col1a2, ASMA, CTGF, FN and TIMP1) with increased anti-fibrotic gene expression (MMP2) at the dose of 5 µm and 10 µm concentration in the fibroblast cells (Fig. 1).

Conclusion

This study may provide potential therapeutic target for prevention of renal fibrosis in IgAN patients. Till date PDE5 inhibitors were not used for IgAN. We found that, PDE5 inhibitor reduces the fibrosis in this in vitro study, this drug may be proposed as a potential therapy for IgAN.
#2424 Higher 24-hour urine sodium-to-potassium ratio is associated with worse renal outome
Authors: Zwager Charlotte , van Vliet Anne Myrthe , Vogt Liffert , Engberink Rik Olde
Published: May 2024

Background and Aims

Low sodium and high potassium intake are advised to control blood pressure and may improve long term cardiorenal outcomes. The optimal potassium intake for patients with chronic kidney disease remains to be defined. We investigated whether the 24-hour urine sodium-to-potassium ratio (Na/K-ratio), which incorporates estimates of both sodium and potassium intake, could predict long-term renal outcome.

Method

We selected adult outpatients of a Dutch tertiary hospital who collected at least one 24-hour urine collection with available sodium and potassium measurements between 1998-2023. Patients with a history of dialysis or kidney transplantation were excluded. We examined the need for persistent renal replacement therapy (RRT), defined as dialysis or kidney transplantation, using Cox regression. The association between the 24-hour urine Na/K-ratio and the estimated glomerular filtration rate (eGFR) slope was assessed using linear regression in patients who had ≥3 eGFR measurements available in ≥3 years. The linear regression analysis was adjusted for age, sex, baseline eGFR, diabetes mellitus and hypertension. In the Cox regression analysis, we additionally adjusted for the interaction between the 24-hour urine Na/K-ratio and baseline eGFR. Hypertension was defined as a clinical diagnosis or an office blood pressure ≥140/90 mmHg.

Results

We included 720 patients aged 50 ± 15 years, of whom 52% were male, 58% had hypertension and 31% diabetes mellitus. The baseline eGFR was 64 ± 34 ml/min/1.73 m2. The 24-hour urine Na/K ratio was 2.5 ± 1.2 in a median number of 1 (IQR = 1-2) urine collection. During a median follow-up of 11.2 (14.0) years, 29% of patients needed RRT. In 575 patients with sufficient eGFR measurements (mean 12 ± 8 measurements per subject) the median annual eGFR decline was 1.51 (IQR = 0.49-3.98) ml/min/1.73 m2.

Every unit increase in the 24-hour urine Na/K-ratio was associated with a 19% higher risk for persistent RRT need (HR 1.19, 95% CI 1.03-1.39; p = 0.02) and an additional 0.44 ml/min/1.73 m2 (95% CI −0.83, −0.04; p = 0.03) decline in eGFR.

Conclusion

This study suggests that higher 24-hour urine Na/K-ratio is associated with faster kidney function decline and the need for RRT, independent of hypertension, in a selected group of outpatients.
#1553 Effects of proteinuria on muscle oxygenation and microvascular reactivity in patients with pre-dialysis CKD: a post-hoc analysis
Authors: Theodorakopoulou Marieta P , Zafeiridis Andreas , Dipla Konstantina , Faitatzidou Danai , Koutlas Aggelos , Iatridi Fotini , Karagiannidis Artemios , Stamatiou Anastasia , Doumas Michael , Papagianni Aikaterini , Sarafidis Pantelis
Published: May 2024

Background and Aims

Vascular dysfunction is a hallmark of CKD. Previous studies showed an impaired microvascular reactivity in the skeletal muscles, which deteriorates in advanced CKD stages. This analysis aims to examine the impact of proteinuria on skeletal muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with pre-dialysis CKD.

Method

66 patients with CKD stage 2-4 were included in this post-hoc analysis; 24-h urine samples were used for evaluation of proteinuria. Continuous measurement of muscle oxygenation [tissue saturation index (TSI%)] via near-infrared-spectroscopy at rest, during occlusion-reperfusion and during a 3-min handgrip exercise (at 35% of maximal-voluntary-contraction).

Results

The study groups were similar in terms of age (proteinuric vs nonproteinuric: 68.4 ± 10.6 vs 67.2 ± 10.8; p = 0.676), eGFR (41.3 ± 18.9 vs 46.3 ± 14.8; p = 0.248) and BMI (28.4 ± 4.9 vs 28.1 ± 4.8; p = 0.803). Resting muscle oxygenation did not differ between study groups (proteinuric vs nonproteinuric: 63.35 ± 4.09 vs 62.34 ± 3.21; p = 0.280). During occlusion, proteinuric CKD patients had marginally lower TSI occlusion magnitude (25.77 ± 7.87 vs 29.95 ± 10.34; p = 0.074) but no difference in occlusion slope (−0.09 ± .03 vs -.10 ± .04; p = 0.134). During reperfusion, the TSI reperfusion slopes were significantly lower in proteinuric CKD (slope to max 1.03 ± .45 vs 1.39 ± 0.69; p = 0.035 and 10-sec slope: 1.34 ± .63 vs 1.92 ± .75; p = 0.002); hyperemic response was numerically lower in proteinuric CKD (7.13 ± 4.27 vs 8.89 ± 4.68; p = 0.131). Finally, during exercise no differences were detected in the average muscle oxygenation between-group (10.76 ± 6.05 vs 10.65 ± 5.39; p = 0.943).

Conclusion

Although no differences in resting muscle oxygenation were detected, CKD patients with proteinuria showed more impaired skeletal muscle oxidative capacity (as suggested by lower TSI magnidute during occlusion), and miscrovascular reactivity during reperfusion.
#985 Disease outcomes of chronic kidney disease: a Phenome-wide association study
Authors: Chunyang Li , Yang Wanyi , Zeng Xiaoxi
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) is one of the prevalent diseases worldwide leading to increasing global disease burden, however, comprehensive studies of the subsequently developed disease outcomes are lacking. We aimed to explore the associations between CKD and a broad range of following disease conditions.

Method

Polygenic risk score (PRS) of 347308 white participants in UK Biobank were calculated using PLINK1.9 software with summing of risk alleles weighted by the effect sizes of. Genome-wide association study (GWAS) summary statistical data of CKD from CKDGen consortium was utilized as base data. The phenome codes of disease outcomes were derived from the primary and secondary diagnoses of ICD-10 and ICD-9 codes in the HSE records in the U.K. Biobank. Then, the association between genetically predicted eGFR and following disease outcomes were evaluated using logistic regression adjusting for age (continuous variables), sex (male/female), assessment cancer (category variables), and the first 10 genetic principal components (PCs) (continuous variables). PRS of eGFR was scaled to a unit reflecting one SD (equals to 1) decrease of PRS. We applied the Bonferroni correction (P threshold = 0.05/665 phecodes = 7.52 × 10−5) to correct for multiple testing.

Results

Totally, 261,254 SNPs (pruned by r2 < 0.1 within the 250 kb region, P < 0.4) from base data were retained for PRS calculation. Our PheWas identified that one standard deviation (SD) increase in the PRS of CKD significantly associated with chronic renal failure (OR = 1.16, 95% CI: 1.14-1.18, P = 2.01 × 10−66), essential (primary) hypertension (OR = 1.05, 95% CI: 1.04-1.06, P = 2.12 × 10−29), hypertensive renal disease (OR = 1.22, 95% CI: 1.16-1.29, P = 3.81 × 10−14), gout (OR = 1.09, 95% CI: 1.07-1.12, P = 6.57 × 10−13), intestinal malabsorption (OR = 1.12, 95% CI: 1.08-1.16, P = 6.71 × 10−9), acute renal failure (OR = 1.05, 95% CI: 1.03-1.07, P = 2.08 × 10−8), disorders of lipoprotein metabolism and other lipidaemias (OR = 1.03, 95% CI: 1.01-1.04, P = 9.11 × 10−7), non-insulin-dependent diabetes mellitus (OR = 1.03, 95% CI: 1.02-1.04, P = 3.11 × 10−6), obesity (OR = 1.03, 95% CI: 1.02-1.05, P = 3.13 × 10−6), unspecified renal failure (OR = 1.11, 95% CI: 1.06-1.16, P = 1.18 × 10−5), chronic ischaemic heart disease (OR = 1.03, 95% CI: 1.01-1.04, P = 1.52 × 10−5).

Conclusion

Increased risk of CKD significantly associated with a series of subsequent conditions, providing evidence for prevention of following diseases in patients with CKD.
#960 Trends in eGFR and ultra-processed food intake in relationship to income among United States adults
Authors: Leonberg Kristin E , Maski Manish , Scott Tammy , Naumova Elena N
Published: May 2024

Background and Aims

Ultra-processed foods (UPF) are formulations of ingredients that are mostly of exclusive industrial use and may contain additives like artificial colors, flavors, or stabilizers. The sale and consumption of these foods has been increasing despite their associations with increased risk for several non-communicable diseases including chronic kidney disease. Ultra-processed foods are widely accessible, more shelf-stable and convenient while tending to be more affordable and lower in nutritional quality. The aim of this study was to evaluate trends in kidney function and UPF intake and temporal effect of income among United States (US) adults.

Method

We used dietary intake data collected with 24-hour dietary recalls from 35160 US adults across 8 cycles of the National Health and Nutrition Examination Survey (NHANES) (from 2003-2004 to 2017-2018 cycles) to categorize intake using the Nova processed food classification system. Poisson regression models were used to assess the 15-year trends in populations at risk for kidney function decline (measured by estimated glomerular filtration rate [eGFR]) and higher percentage of calories from UPF (PC-UPF) consumed along with the temporal effect of income in select subpopulations and adjusted for age and gender and non-linear effects of income and age).

Results

Over the past 15 years eGFR, PC-UPF, and self-reported income continue to increase among US adults. However, the associations between eGFR, PC-UPF and income are quite complex, vary by subpopulation and non-linearly depend on age. Specifically, among Black adults adjusted for age (age2) and gender, eGFR was the lowest (85 mL/min/1.73 m2, 95% CI: 84.9, 85.0 mL/min/1.73 m2) among those with the lowest ($2,500) and highest ($125,000) income (p = 0.0000000579 for a quadratic term of income), respectively. Hispanic and Mexican Americans also have similar pattern eGFR with the lowest and highest income though the eGFR is consistently higher than White and Black Americans. Across cycles, White Americans with the lowest income ($2,500) have the highest PC-UPF (range: 57-62%, p <2e-16; mean: 59.4%, 95% CI: 59.3, 59.6%) while Black Americans with the lowest ($2,500) and highest income ($125,000) have the highest PC-UPF (range: 53-58%, p <2e-16; mean: 54.8%, 95% CI: 54.3, 55.4%). Income levels does not predict PC-UPF among Mexican Americans. Overall, the PC-UPF is steadily increasing in all population subgroups.

Conclusion

Among Non-White US adults, higher eGFR was associated with higher income until reaching a group-specific threshold when the relationship reversed. We observed a similar threshold pattern in the association between PC-UPF and income among Black and Hispanic Americans. These complex non-linear relationships between eGFR, PC-UPF and income are driven in part by age-related association and warrant further exploration.
#908 The effect of obesity and fat distribution on estimated glomerular filtration rate (eGFR): A Mendelian randomization and image data analysis study
Authors: Ene Patrik , Eriksson Svensson Maria K , Strand Robin , Kullberg Joel , Ahlström Håkan , Lind Lars
Published: May 2024

Background and Aims

Obesity is intimately linked to the initiation and progression of chronic kidney disease, but questions on causality still remain. The diagnosis of chronic kidney disease is often based solely on creatinine- and/or cystatin C-based estimated glomerular filtration rate (eGFR), but both these endogenous biomarkers are also known to be related to body composition. This study aims to further investigate how obesity causally affects eGFR, derived from both biomarkers.

Method

Methods used were: Traditional cross-sectional analyses and magnetic resonance imaging data analyses performed in the POEM study (502 subjects, all aged 50 years), and two-sample Mendelian randomization using already published summary data. Outcome variables for all analyses were eGFR indexed to body surface area, based on creatinine and cystatin C, respectively. In both the traditional cross-sectional and the Mendelian randomization analyses body mass index and waist circumference were used as exposure variables. In the image data analyses, eGFR was regressed nonparametically on fat content and tissue volume for each 3D voxel. Results were visualized as a correlation “imiomics” map.

Results

Results from the POEM study showed in an adjusted model a negative correlation between cystatin C calculated eGFR and both body mass index [beta = −0.190 (95% CI: −0.280 to −0.100)] and waist circumference [beta = −0.160 (95% CI: −0.250 to −0.060)]. In contrast, a positive association was found for eGFR when using creatinine levels [beta = 0.120 (95% CI: 0.030 to 0.210) for body mass index; beta = 0.160 (95% CI: 0.070 to 0.260) for waist circumference].

This pattern was repeated in the image data analysis, which was visualized in the imiomics map: both visceral and subcutaneous adipose tissue were negatively correlated to eGFR based on cystatin C but positively correlated to eGFR based on creatinine (Fig. 1).

Mendelian randomization implied a negative causal effect of obesity-related measures on cystatin C-based eGFR, with statistically significant estimates for both body mass index [beta = −0.031 (95% CI: −0.037 to −0.026)] and waist circumference [beta = −0.038 (95% CI: −0.045 to −0.031)]. No statistically significant effects was found on creatinine-based eGFR (Fig. 2).

Conclusion

This study indicates a causal negative effect of obesity on cystatin C-based eGFR, but not on eGFR calculated from creatinine. This discrepancy is further highlighted by analyses of adipose tissue from magnetic resonance imaging. These findings thus warrant further research on the impact of using the endogenous biomarkers creatinine and cystatin C to estimate renal function when assessing the link between obesity and chronic kidney disease.
#2124 Accuracy and interferences in the T50 test: assessing the reliability of a novel diagnostic tool
Authors: Xu Joyce , Falconnet Didier , van den Berkmortel Tarah , De la Rosa Sandra , Linder Vincent , de Jonge Robert , Pasch Andreas , Vervloet Marc , Hamer Henrike
Published: May 2024

Background and Aims

A novel blood-based in vitro diagnostic test determines the calcification propensity in patients, e.g. chronic kidney disease (CKD) patients. This assay is known as the ‘T50 test’ and is based on the one-half maximal transition time (T50; minutes) of calciprotein particle 1 (CPP1) to calciprotein particle 2 (CPP2) in serum (Fig. 1). Numerous studies have associated a lower T50 with cardiovascular and all-cause mortality in chronic kidney disease (CKD) patients at stages 3, 4 and 5, kidney transplant recipients, and in the general population. To date, the T50 test has been performed at a single site (Calciscon AG, Biel, Switzerland). The aim of this study was to determine the accuracy of the T50 test. Additionally, the effect of haemolysis, hyperbilirubinemia and lipidemia interferences on the T50 was studied and compared to the manufacturer's claims.

Method

The T50 was measured using T50 test kits and according to the protocol of Calciscon AG using an automatic pipetting machine (EVOware Freedom, Tecan) and a nephelometer (NEPHELOstar, BMG). Patient serum samples were spiked with haemoglobin, bilirubin, or lipids (triglyceride) for the interference analysis. In total, three dilution series with interferences and four additional non-spiked patient serum samples were included (n = 32). The T50 of all samples were measured at two laboratory sites: Amsterdam UMC (Amsterdam, The Netherlands) and Calciscon AG. Data were statistically analysed for accuracy using the Passing Bablok regression and the Bland Altman plot. Interference was established with deviations >10% in T50 compared to the control sample.

Results

The measurements of all samples at both sites were similar with a mean bias of 0.24% (±4.84%) and a great agreement was found (slope = 1.012; 95% CI [0.931 to 1.107]) (Table 1). Interference was observed at higher levels of haemoglobin and triglyceride with concentrations of at least 0.1 g/dL and 1124.8 mg/dL, respectively. The triglyceride interference is in agreement with the manufacturer's claim (>1000 mg/dL) in contrary to haemoglobin (>0.3 g/dL). No interference was detected for bilirubin with concentrations up to 59.8 mg/dL.

Conclusion

The accuracy of the T50 test was high with nearly identical T50 results between two laboratory sites. Furthermore, no interference was observed within usual clinical ranges of haemoglobin, bilirubin, and lipid levels. Interference was present at extremely high values only.
#336 Early detection of vascular access complication in pediatric CKD hemodialysis patients
Authors: Sallam Dina E
Published: May 2024

Background and Aims

Vascular access (VA) dysfunction is a major clinical complication in the hemodialysis (HD) population and has a direct effect on dialysis outcome. Where in patients undergoing HD, neointimal hyperplasia results in vascular stenosis and subsequent thrombosis, which lead to vascular access failure. Interleukin-10 (IL-10), hs CRP, and tumor necrosis factor- (TNF–α) are inflammatory markers which are proved to be involved in the process neointimal hyperplasia & subsequent complications.

We aimed to evaluate the value of these inflammatory markers in early detection of arterio-venous fistula (AVF) failure, in pediatric patients on regular HD, together with the clinical & radiological diagnoses, for proper intervention for correcting AVF failure according to guidelines.

Method

It was an prospective cohort study, where we included 59 pediatric chronic kidney disease patients’ stage 5, on regular HD (CKD5d), who were following up regularly with us for 1 year. Patients with nonfunctioning AVFs due to complications as thrombus occluding fistula, infections, or large aneurysm, were excluded from the beginning of the study.

Monitoring of VA by pre-cannulation physical examination was performed to detect the physical signs of dysfunction, at least once per month according to KDOQI guidelines. Venous pressure (VP) and trans-membrane pressure (TMP) were recorded at each HD session, to detect any abnormalities and to record the pressure changes with the appearance of any AVF complications. Doppler ultrasound (DUS) was performed routinely every 3 months for all HD patients, & at the time of development AVF complications. Blood samples for measuring IL10, TNF, hs CRP were collected from the patients every 2 weeks for 12 months, prior to HD sessions, where we included the most recent samples prior to, and at the time of development complications, which were clinically and radiologically confirmed.

Results

The mean (±SD) age of our patients was 13.97 (±2.65) years, where we had 39 (56.5%) males, and 30 (43.5%) females, with a median (IQR) HD duration of 4.0 (5.0) years.

On assessing the AVF complications, 33 patients (55.9%) had experienced complications, where thrombosis was the most common reported one (17 patients, 28.8%), followed by aneurysm formation in 14 patients (23.7%), while 6 patients (10%) had stenosed AVF, early VA failure in 2 patients (3.4%),1 patient (1.7%) had pseudoaneurysm, and another patient (1.7%) had perivascular hematoma.

Mean serum levels of Hs-CRP, TNF-α, IL-10 were elevated at timing of early development of complication, in comparison to their baseline levels, meanwhile serum IL10, and TNF alpha were significantly higher among patients who developed AVF stenosis. The baseline hs-CRP had related positively with AVF diameter at the time of the development of the complications.

Conclusion

The inflammatory markers have no clinically applied role in early detection of AVF abnormalities, therefore, physical examination and DUS are deemed sufficient.
#1443 Bone and mineral metabolism in patients with nephropathic cystinosis as a function of age and eGFR
Authors: Lahring Johannes , Leifheit-Nestler Maren , Herzig Nadine , Oh Jun , Büscher Anja , Thumfart Julia , Weber Lutz T , Arbeiter Klaus , Acham-Roschitz Birgit , Tönshoff Burkhard , Hohenfellner Katharina , Haffner Dieter
Published: May 2024

Background and Aims

Cystinosis-associated metabolic bone disease (CMBD) is a major challenge in the treatment of patients with infantile nephropathic cystinosis (NC). Study data are limited due to small case numbers, lack of adults or patients on renal replacement therapy and/or inadequate assessment of bone health.

Method

We investigated markers for CMBD in all age groups (1-44 years; 61% children) and CKD stages 1-5D/T in the largest NC cohort to date with 103 German and Austrian NC patients. Skeletal comorbidity and concentrations of fibroblast growth factor 23 (FGF23), the osteoblast marker bone-specific alkaline phosphatase (BAP), the bone remodeling inhibitor sclerostin, the osteoclast marker tartrate-resistant acid phosphatase 5b (TRAP5b), the soluble receptor activator of nuclear factor kappa B ligand (sRANKL), osteoprotegerin (OPG) and the sRANKL/OPG ratio as surrogates for the regulation of osteoclastogenesis by osteoblasts were determined by ELISA, converted into age- and sex-specific z-scores and compared as a function of eGFR. Multivariable regression analyses were used to identify specific influencing factors associated with biochemical and clinical findings in pre-transplant NC patients.

Results

Skeletal complications occurred in two-thirds of patients, with the risk being five times higher in adults than in children. Pediatric and adult NC patients with CKD stages 1-4 showed hypophosphatemia and hypocalcemia associated with suppressed FGF23 and PTH levels and elevated BAP concentrations. This was associated with age, eGFR and treatment with phosphate and active vitamin D, suggesting more vigorous treatment of Fanconi syndrome in pre-transplant patients. As indicated by the increased TRAP5b and decreased sRANKL/OPG ratio, osteoclast activity was increased despite counterregulation by osteoblasts, which in conjunction with increased sclerostin activity may have contributed to the progressive bone loss and skeletal comorbidity in our patient cohort.

Conclusion

Bone health in NC progressively deteriorates with age, largely due to persistent rickets/osteomalacia associated with inadequate treatment of Fanconi syndrome and increased osteoclast activity despite osteoblast counterregulation via OPG/RANKL. Our data suggest that a primary osteoclast defect in NC promotes increased bone resorption, limiting maximal bone mass and leading to progressive bone loss and increased skeletal comorbidity.
#2049 Prognosis of decreased renal function in patients with arterial hypertension
Authors: Boiko Olha , Rodionova Viktoriia
Published: May 2024

Background and Aims

Chronic kidney disease and hypertension are closely related in cause and effect. As the glomerular filtration rate decreases, the frequency and severity of arterial hypertension increases. In addition, the risk of morbidity and mortality from cardiovascular diseases increases significantly with comorbidity of arterial hypertension and chronic kidney disease. The purpose of this study was to identify predictors of a decrease in GFR below 60 ml/min in patients with arterial hypertension.

Method

The cross-sectional study included 43 patients with arterial hypertension (average age 56.7 (10.6) years). Exclusion criteria were age over 80 years, primary kidney disease, diabetes mellitus, cancer, heart failure, stage III arterial hypertension. All patients underwent determination of cystatin C in the blood, the composition of the body was studied using the bioimpedance method and 24-hour blood pressure monitoring. To identify predictors of kidney damage, we used regression analysis with ROC curve estimation using MedCalc software.

Results

The optimal value (cut-off point) of the content of total adipose tissue, which allows the most accurate prediction of a decrease in GFR < 60 ml/min in patients with hypertension, was 26.1% (sensitivity −100%, specificity—77.8%), and the content of total muscle tissue—35.9% (sensitivity −100%, specificity—44.4%). The optimal value (cut-off point) of cystatin C was 1.13 (sensitivity −100%, specificity—53.9%), AUC—0.73 (0.46; 0.92). At the same time, when this predictor was included once in multiple logistic regression, the statistical significance decreased (p = 0.5). Among individual predictors of decreased renal function, indicators of 24-hour blood pressure monitoring were studied. The optimal value (cut-off point) of the ambulatory arterial stiffness index, which allows the most accurate prediction of a decrease in GFR < 60 ml/min in patients with arterial hypertension, was 0.36 (sensitivity −100%, specificity—71.4%), an indicator of an increase in the rate of increase in diastolic blood pressure. blood pressure—0.27%, AUC 0.74 (0.48; 0.91)) and the rate of increase in nighttime decrease in systolic blood pressure—8.1%, AUC 0.71 (0.47; 0.89).

Conclusion

Increase in total adipose tissue > 26.1%, decrease in total lean tissue <35.9%, increase in ambulatory arterial stiffness index >0.36, increase in rate of increase in diastolic blood pressure >0.27%, and increased nocturnal decrease in systolic blood pressure > 8.1% were identified as significant predictors of a decrease in GFR below 60 ml/min in hypertension.
#723 The impact of kidney function on arterial stiffness in COVID-19 survivors: an analysis from CARTESIAN Study
Authors: Moriconi Diego , Mayer Christopher , Boutouyrie Pierre , Bruno Rosa Maria
Published: May 2024

Background and Aims

SARS-CoV-2 pandemic has been linked to an increased incidence of cardiovascular events, potentially due to accelerated vascular aging [1]. Conversely, impaired kidney function is known to contribute to the pathogenesis of heightened arterial stiffness, independent of traditional cardiovascular risk factors [2]. This study aimed to assess the impact of COVID-19 on arterial stiffness among a cohort of survivors of the first pandemic wave, with varying degrees of infection severity. The assessment was conducted at 6 ± 3 (T1) and 12 ± 3 months (T2) post-infection, with the population stratified based on kidney function.

Method

the CARTESIAN study, a large international multicenter cohort study, was designed to assess the long-term effects of COVID-19 on vascular aging.

A total of 938 subjects were stratified into three groups based on their estimated glomerular filtration rate (eGFR) percentiles using the CKD-EPI_2021 equation: 1) >75th percentile, 2) 75th-25th percentile, and 3) <25th percentile, respectively. The same population was further categorized based on the severity of COVID-19 into three groups: 1) patients who were not hospitalized (No-Hosp), 2) subjects requiring hospitalization in a medical unit (Hosp), or 3) those in an intensive care unit (ICU). Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). A hierarchical repeated measures mixed model analysis was conducted to compare cf-PWV across these groups (>75th, 75th-25th, and <25th groups, respectively).

Results

in the cross-section analysis (T1) <25th group exhibited higher age, increased cardiovascular risk factors, and higher prevalence of severe COVID-19 compared to the >75th group. Using hierarchical linear modeling, the <25th exhibited higher cf-PWV than the >75th group, even after adjusting for both all the random and fixed variables, included the three COVID-19 group (+0.51 m/s, p = 0.013).

In longitudinal analysis, globally, no substantial changes were found in the cf-PWV between T1 and T2, remained significantly higher in the <25th group compared to the >75th group (p = 0.003), in a linear mixed model adjusted for all the random and fixed variables. Interestingly, a significant interaction between eGFR groups* COVID-19 groups was found in repeated measures analysis (p = 0.039). In particular, within ICU group, we found a significant increase of cf-PWV between 6- and 12-months in <25th group, from 8.64 [7.59-9.31] to 9.41 [8.89-10.41] m/s, p = 0.021) (Fig. 1).

Conclusion

the findings suggest that individuals with both lower eGFR and a history of severe COVID-19 may be at a heightened risk of accelerated arterial aging. Understanding these dynamics is crucial for targeted interventions to mitigate long-term cardiovascular consequences in COVID-19 survivors with kidney disease.
#780 “In vivo” difference in ultrafiltration coefficient between two same membrane dialyzers: bigger surface area accounts for better dialysis outcomes?
Authors: Villa-Valdés Miguel , Nava-Chávez Coraima Claudia , Vega Almudena , Verde Eduardo , Vaca Marco , Bascuñana Arturo , Macías Nicolás , Goicoechea Marian
Published: May 2024

Background and Aims

Ultrafiltration coefficient (KUF) is a measure of dialyzer permeability to water, given by manufacturers, and expressed in milliliters/hour/mmHg of pressure gradient. Most dialyzers used at this moment are classified as high-flow as having a KUF >20 mL/h/mmHg. KUF value of a dialyzer is an “in vitro” measure which does not correlate with “in vivo” measure, stated to be 5-30% less than theoretical KUF. According to this statement, we wanted to study differences between theoretical and real KUF of two dialyzers with the same membrane composition and different surface area. For this task, we chose 2 dialyzers of usual use in our dialysis unit: FX CorDiax 1000 and FX CorDiax 80 (®FMC). These dialyzers have a main difference in Surface area: 2.3 and 1.8 m2, respectively, and have a theoretical KUF of 76 and 64 mL/h/mmHg. Also, both dialyzers differ in intern diameter (210 vs 185 µm).

Method

A prospective, not randomized trial was conducted. Inclusion criteria were patients in chronic dialysis at our center, in postdilutional online hemodiafiltration with a FX1000 dialyzer. All patients were informed and accepted freely signing an informed consentment. On 2 consecutive weeks, the intermediate dialysis session of the week was performed in a DBB-EXA dialysis monitor (®Nikkiso), first with a FX CorDiax 1000 and next week with a FX CorDiax 80, with habitual patient dialysis parameters (240 minutes). Blood tests were taken previous and after the session to evaluate clearance differences between both filters. During the session, pressure and flow data was recorded, with an “in vivo” KUF measurement given by the monitor.

Results

Dialysis sessions were performed in 12 patients who met inclusion criteria. Data results are shown in Table 1. Significant differences between FX CorDiax 1000 and FX CorDiax 80 were observed in prefilter pressure (p 0.008), convective volume (p 0.034), prolactin reduction ratio (p 0.012), “in vivo” KUF/ “in vitro” KUF ratio (p 0.002). “In vivo” KUF graphic given by the monitor showed a logarithmic function curve, with a stabilization between the 2nd and 3rd hour of the session.

Conclusion

In our study, measurement of “in vivo” KUF by Nikkiso monitor showed a slow decrease after 2nd hour of session, probably related with protein cake of membrane pores. “In vivo” KUF measure was approximately a 40-45% of theoretical value given by manufacturer. The “in vivo” KUF/ “in vitro” KUF ratio was higher for the smaller dialyzer, which probably means a higher optimization of its surface area with usual dialysis sessions.

Convective volume and prolactin reduction ratio, as parameters of dialysis efficacy, are higher in the dialyzer with higher surface area and inner intern diameter.
#949 Factor XIIa inhibitory antibody does not provide sufficient anticoagulation in ex vivo hemodialysis
Authors: de Laval Philip , Nilsson Bo , Ekdahl Kristina Nilsson , Fellström Bengt , Soveri Inga
Published: May 2024

Background and Aims

Unfractionated heparin (UFH) and low molecular-weight heparin (LMWH) are the most commonly used anticoagulants in haemodialysis (HD). While effective in preventing clotting, they are also associated with complications including increased risk of bleeding and heparin induced thrombocytopenia. The contact activation system is commonly assumed to be the main trigger of coagulation during HD, through autoactivation of factor (F)XII upon contact with the dialyser. FXII deficient individuals do not have an increased risk of bleeding which makes activated FXII (FXIIa) an attractive drug target as it has the potential to inhibit clotting without disrupting haemostasis. The aim of the study was to evaluate the efficacy of CSL312, a monoclonal, humanized IgG4 antibody against activated FXII (FXIIa), in preventing intradialytic coagulation.

Method

An ex vivo haemodialysisis model was used to test the efficacy of CSL312 as an anticoagulant. CSL312 (400 µg/mL) was compared to standard doses of UFH, LMWH and citrate anticoagulation. The antibody was provided by CSL Limited. Anticoagulant-free haemodialysisis was used as control. Whole-blood was collected from 12 healthy adult donors in blood-transfer bags containing citrate to prevent clotting before dialysis. Each donor provided blood for two HD-sessions, using different anticoagulants. The blood was dialyzed for one hour through paediatric polysulfone high-flux dialysers. Right before the start of HD, calcium was added to reverse the anticoagulant effect of citrate, except in the citrate group. Blood was sampled before and at 5, 15, 30 and 60 minutes after HD start. To quantify the activity of the contact system, the concentrations of enzyme-inhibitor complexes of antithrombin (AT) or C1-inhibitor (C1INH) in conjunction with FXIIa, FXIa, kallikrein, MASP-1, MASP-2 and thrombin were measured in plasma using enzyme-linked immunosorbent assays.

Results

Using CSL312 to inhibit FXIIa protease activity (n = 5), clotting occurred in all tests (at 30, 31, 36, 49 and 50 minutes) with a mean clotting time of 39.2 minutes compared to 17 and 30 minutes using no anticoagulation (n = 2). No clotting was evident with other anticoagulants. Using CSL312, the plasma concentration of FXIIa-C1INH at 15 minutes was significantly higher than at baseline (mean 26.2 (SD 9.08) vs mean 17.6 (SD 10.6) µg/mL, p = 0.011).

Conclusion

FXIIa inhibition using a monoclonal antibody does not provide sufficient anticoagulation during HD. This suggests that the contact system may not be solely responsible for clotting during HD.
#1562 Longitudinal changes in quality of life—a comparison between institutional hemodialysis, home-hemodialysis and peritoneal dialysis
Authors: Rydell Helena , Caldinelli Aurora , Chesnaye Nicholas , Evans Marie
Published: May 2024

Background and Aims

Quality of life is an important factor for patients when planning for future dialysis care and for some individuals, it might be even more important than a prolonged life. Knowledge about differences between dialysis modalities is essential for patients making informed decisions. Most previous research on differences in quality of life between dialysis modalities have been cross-sectional and subjected to selection bias; few large contemporary studies have investigated the changes in quality of life between the three dialysis modalities; institutional hemodialysis (IHD), home hemodialysis (HHD) and peritoneal dialysis. The aim of the present study was to compare longitudinal changes in health-related physical and mental quality of life between patients on IHD, PD, and HHD.

Method

Patients on dialysis with at least two Research and Development 36 (RAND-36) questionnaires between 2017-2021 in the Swedish Renal Registry (SRR) were eligible for inclusion. Information on dialysis modality, patient characteristics and medication were obtained from the SRR and other national registries. Patients were followed for three years and remained in their designated dialysis modality in the analysis until end of the follow-up (intention-to-treat). Changes in physical (PCS) and mental (MCS) component summary score were analyzed in adjusted linear mixed models and joint models where informative censoring due to mortality and kidney transplantation was considered.

Results

930 patients (IHD 714, HHD 88, PD 128), were followed for 1.8 years (IQR 1.0–2.1). Patients on HHD were younger, had lower Charlson comorbidity index (CCI) and higher serum albumin compared with IHD and PD (Table 1). At baseline, patients on IHD had a mean PCS 30.7 (95% CI 29.9–31.4) and MCS 45.6 (95% CI 44.7–46.5). The unadjusted PCS at baseline was higher in HHD patients (4.5 [95% CI 2.2–6.9]) and PD patients (2.5 [95% CI 0.5–4.5]) compared with patients on IHD but showed no difference in the adjusted models. Both unadjusted and adjusted MCS was similar at baseline. The PCS declined over time in all modalities; faster for patients on PD compared with IHD (−1.2 per year [95% CI −2.1 – −0.3]; Fig. 1). MCS decreased similarly for both PD and IHD over time, while patients on HHD had an improving MCS (1.5 per year [95% CI 0.1–2.8]) compared with patients on IHD (Fig. 2).

Conclusion

There are differences in the development of physical and mental quality of life over time for patients on different dialysis modalities. The dialysis modality with the overall most positive development was HHD. Offering HHD to more patients could potentially improve the quality-of-life for patients on dialysis.
#1498 Higher body mass index in patients with diabetes mellitus and hemodialysis associated with a better survival in contrast to peritoneal dialysis
Authors: Afghahi Hanri , Nasic Salmir , Wãrme Anna , Peters Björn
Published: May 2024

Background and Aims

The association between Body Mass Index (BMI) and the risk of mortality in patients with end stage renal diseases and dialysis treatment is debated. The aim of this study was to assess the association between BMI and the risk of all-cause mortality in patients with diabetes mellitus (DM) on maintenance hemo- (HD) versus peritoneal dialysis (PD).

Method

We used the data from Swedish Renal Registry (SRR) which included 3235 patients with diabetes mellitus on dialysis treatment (2452 on HD and 783 on PD). The follow-up period was 3.9 ± 3.5 years and patients who switched from PD to HD, or vice versa, during the study period were excluded. The patients were divided in six groups by mean value of BMI according to classification of BMI by WHO. The relationships between mean value of BMI and mortality were examined by time-dependent Cox models to estimate hazard ratios (HR) and 95% confidence intervals (CI) in univariate and multivariate analyses, with adjustment for demographics, laboratory findings and comorbidities. The group with BMI 18.5<BMI≤25.0 kg/m2 was used as a reference group.

Results

During the follow-up period 1688 (53%) deaths occurred (1275 on HD, 413 on PD). The mean value of BMI was 27 ± 6 kg/m2 in HD and 26 ± 5 kg/m2 in PD. In the multivariate analyses, patients on HD with a low BMI≤18.5 kg/m2 had a higher risk for all-cause mortality (HR1.94, CI 1.47-2.54; p < 0.01) compared to the reference group. However, HD-patients with a higher BMI 25.1-30.0 kg/m2 (HR 0.84, CI 0.73-0.96; p < 0.01), 30.1-35 kg/m2 (HR 0.66, CI 0.55-0.78; p < 0.01), and 35.1-40.0 kg/m2 (HR 0.65, CI 0.49-0.85; p < 0.01) had a significantly decreased risk of all-cause mortality compared to the reference group. In multivariate analyses, patients on PD, BMI groups of 25.1-30 kg/m2 (HR 0.86, CI 0.67-1.09), 30.1-35 kg/m2 (HR0.94, CI 0.67-1.31), and 35.1-40 kg/m2 (HR 0.93, CI 0.48-1.77) were not-significantly associated with a risk of mortality.

Conclusion

In patients with diabetes mellitus on maintenance hemodialysis underweight (BMI≤18.5 kg/m2) was associated with an increased risk of all-cause mortality; however overweight (BMI 25.1-30.0 kg/m2), class 1 obesity (BMI 30.1-35.0 kg/m2) and class 2 obesity (BMI 35.1-40.0 kg/m2) were associated with better survival. In contrast, in patients with diabetes mellitus on maintenance peritoneal dialysis no association between BMI and risk of all-cause mortality was found.
#861 Intradialytic oxygen saturation in chronic hemodialysis patients—results from a large U.S. population
Authors: Ban Andrea Nandorine , Wang Lin-Chun , Ye Xiaoling (Janice) , Filardi Vincent , Soni Mitesh , Scott Shawn , Singh Kanti , Waguespack Peter , Kotanko Peter , Zhang Hanjie
Published: May 2024

Background and Aims

The study of intradialytic oxygen saturation (SO2) in hemodialysis (HD) patients is a significant yet under-explored area. This study's objective was to evaluate the epidemiological aspects of SO2 during HD. 

Method

SO2 levels during HD were measured using the Crit-Line Monitor (CLM; Fresenius Medical Care North America, Waltham, MA), a device certified by the US Food and Drug Administration (FDA) for the measurement of hematocrit and SO2 in the extracorporeal circuit. CLM measurements were recorded at 10-second intervals and transmitted into Amazon Web Services (AWS) via Apache KAFKA, a real time streaming software. Apache KAFKA was rolled out in phased approach, started early 2021. We extracted CLM data between January 14, 2021, and July 30, 2023.

CLM values with the following characteristics were deemed implausible and hence, excluded: SO2 ≤ 0 or ≥99.9; hematocrit < 15% or >60%. We computed basic statistics of SO2 for every HD session. We then excluded the sessions with the standard deviation of SO2 < 0.1%, an interquartile range of zero, and sessions with less than 360 SO2 measurements (i.e., less than 60 minutes of recording).

Results

We collected data from over 5.6 million HD sessions. After data cleaning, we retained 4.9 million HD sessions from 72,656 patients treated in 727 dialysis clinics across the US. The average duration of a session was 204.5 (±42.8) minutes. Per HD session, on average 1,227 (±257) SO2 measurements were recorded. The distribution of the number of SO2 measurements per HD session is shown in Fig. 1A. The mean of the session-level average SO2 was 88% (±15%). The distribution of session-level average SO2 is shown in Fig. 1B. The bimodal distribution of SO2 is attributed to the use of arterio-venous and central venous vascular accesses, respectively. 

Conclusion

We collected and analysed a substantial dataset of intradialytic SO2 in a large US HD population. These data provide a rich source for future research into SO2 and its clinical correlates. Exploring intradialytic SO2 in depth will offer valuable insights to improve patient care and optimize treatment procedures.
#2155 Evaluating the health-related quality of life of patients undergoing haemodialysis: highlights from a multicentric nationwide study
Authors: Martínez-Vaquera Shaira , Sorribes Mª Paz , Sánchez Christian Israel Alfaro , Martínez-Sánchez Teresa , Porras Jonathan , de León Ignacio Ponce , Martínez-Pérez Oscar , Díaz-Cuervo Helena , Cuervo Jesús , Macário Fernando
Published: May 2024

Background and Aims

Haemodialysis (HD) represents the most common renal replacement therapy for end-stage renal disease worldwide. Despite recent advances in HD the health-related quality of life (HRQoL) should be monitored in conjunction with clinical variables to optimize a comprehensive treatment.

Method

From June to July 2022, all patients from 47 clinics were included. Among other key relevant clinical variables, HRQoL was assessed by using the Kidney Disease Quality of Life Short Form (KDQOL-SF™ 1.3).It`s generic part is summarised in the physical component summary (PCS) and mental component summary (MCS). The specific part evaluates 11 domains: symptom/problem list; effects of kidney disease on daily life; burden of kidney disease; work status; cognitive function; quality of social interactions; sexual function; sleep; social support; dialysis staff encouragement; and patient satisfaction. All scores range from 0 (worst) to 100 (best). To ensure comparability of results, mean ± SD values are outlined, even though non-parametric tests were used to test associations.

Results

A total of 3,595 patients (67.3% male) completed the KDQOL (out of 4259 HD patients treated during study period). Most of them (67.18%) were over 60yo of age, and 65.67% had a severe comorbidity index score. In addition, 50.54% had a native AV fistula and only 3.92% were incident HD. PCS scores reported were higher in over 75yo (47.68 ± 10.63) rather than normative population (40.16 ± 11.62), indicating an overall good physical function. However, MCS values (33.17 ± 9.36) were indicative of substantial impact. Gender differences were noted across almost all disease-specific and generic domains (all p < 0.05). Severe comorbidity scores were associated with lower scores in certain renal specific domains and MCS. Finally, incident HD patients reported lower satisfaction and poorer perceived overall health (p-values = 0.001).

Conclusion

Although PCS scores reported were reasonable, a remarkable impact on mental health was found. Moreover, a differential impact of patient's HRQoL was captured based on gender and other variables highlighting the need of individualised evaluation and management of HD patients.