bluuebunny/crossref_metadata_2025_split huggingface dataset:
#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

Abstract

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

Abstract

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

Abstract

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 &lt; 0.1 within the 250 kb region, P &lt; 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

Abstract

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 &lt;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 &lt;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

Abstract

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

Abstract

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 &gt;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 (&gt;1000 mg/dL) in contrary to haemoglobin (&gt;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

Abstract

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

Abstract

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.