bluuebunny/crossref_metadata_2025 huggingface dataset:
#2134 Very low protein integrated diet (sVLPD), without keto analogues, in patients with advanced chronic renal failure: clinical and economic benefits
Authors: Cecchi Sofia , Distante Silvio , Diluca Marina
Published: May 2024

Background and Aims

The integrated very low protein diet (sVLPD) has proven effective in slowing the progression of stage 5 chronic renal failure and in postponing the start of dialysis treatment (1)SVLPD with keto analogues is difficult to implement due to the high number of tablets to be taken (2), therefore, to increase compliance we decided to prescribe, in compliance with the guidelines of normal clinical practice, SVLPD (0.3 g/prot/day) integrated with only essential amino acid drugs without the use of keto analogues, in stage 5 patients and we have verified its effectiveness, safety and clinical and economic effects(3).

Method

129 patients were started on dietary therapy (middle age 75.2 ± 13.7, 60.5%male, all with hypertension, 40.3% with diabetes and 24.8% with heart disease) who were tested at the beginning of the observation, every 3 months and for 24 months, characterizing blood chemistry tests and body composition (with impedance analysis).

Results

During the 24-month observation period 91 patients (70.5%) were compliant with dietary therapy. Chronic kidney disease progression is slowed with average eGFR 11.6 ± 3.3 (compliant) vs. 9.3 ± 2.7 (no compliant) mL/min/1.73 m2, p < 0.001) Urea (mg/dL) 116.1 ± 31.7 (compliant) 174.2 ± 42.2 (no compliant) p < 0.002; and initiation of dialysis treatment (adjusted HR = 0.361, CI 0.200–0.650, p = 0.001) was delayed without evidence of malnutrition, in compliant versus noncompliant patients. Metabolic acidosis was well compensated in both groups with an improving trend in bicarbonate levels in compliant patients. Hemoglobin, uricemia, serum albumin, glycemia (downward trend NS), potassium, sodium, chlorium, calcium, magnesium, pH, lipids remained within normal values. Better blood pressure control was observed in compliant patients compared to non-compliant patients (SBP (mmHg) 136.9 ± 11.8 vs 150.1 ± 7 <0.01), DBP (mmHg) 75 ± 3.1 vs 79.4 ± 1 <0.001) During the observation, there were 24 deaths (13 patients older than 85 years), 20 peritoneal dialysis hospitalizations, 36 hemodialysis hospitalizations, 4 preventive living transplants and 15 renal functional recoveries with eGFR consistently >15 mL/min/ 1.73 m2. The months of dialysis avoided generated gross savings in terms of healthcare expenditure equal to EUR 3,076,470; the expenditure sustained by the Marche region for protein-free products (EUR 90 per patient per month) was EUR 158,358. As a result, the total net savings were EUR 2,918,112.

Conclusion

This non-interventional longitudinal observational study is part of standard clinical practice and suggests that VLPD supplemented with only essential amino acids is safe and effective and could be widely used to reduce the incidence of dialysis treatments, with a favorable economic impact on the National Health Service.
#1375 Association of NT-proBNP and kidney function progression in chronic kidney disease patients without heart failure
Authors: Lu Yi , Chen Junzhe , Lukwaro Andrew Fanuel , Fu Sha , Hou Fan Fan , Nie Sheng , Tang Ying
Published: May 2024

Background and Aims

Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is reported to be associated with higher risk of decline in kidney function. However, little evidence exists about the relationship between NT-proBNP and kidney function progression stratified by estimated glomerular filtration rate (eGFR) in chronic kidney disease (CKD) patients without heart failure. Therefore, we aim to investigate the association of NT-proBNP and CKD progression in different CKD stages for CKD patients without heart failure.

Method

A multicentric retrospective cohort study recruited 23860 patients diagnosed with CKD from China Renal Data System (CRDS) database. Eligible participants were classified into five groups according to eGFR. CKD progression was defined as a composite of an increase in serum creatinine ≥50% or a decrease in eGFR ≥40% from baseline or a need for kidney replacement therapy. A linear regression model evaluated the relationship between eGFR and NT-proBNP. Cox regression analysis assessed the association between NT-proBNP and CKD progression. We also performed restricted cubic spline (RCS) and threshold effect analysis to investigate non-linear relationships between NT-proBNP and CKD progression.

Results

In a linear regression model, NT-proBNP was negatively correlated with eGFR in CKD patients. Each decrease of 15 ml/min/1.73 m2 in eGFR was associated with 1.06-fold, 1.50-fold, 1.52-fold, 1.94-fold, 3.37-fold higher levels of log (NT-proBNP) in CKD patients with stage 1-2, 3a, 3b, 4 and 5 respectively. In the multivariable Cox hazard model, elevated NT-proBNP was associated with a greater risk of kidney function progression, particularly among CKD stage 3 patients (stage 3a: HR, 1.42, 95% CI, 1.32-1.53; stage 3b: HR, 1.43, 95% CI, 1.32-1.54), with P-interaction≤0.001. However, the correlation of NT-proBNP and CKD progression had no statistical significance among CKD patients with stages 4-5 after sensitivity analyses. RCS and two-segment Cox regression model showed reversed L-shaped non-linear relationships between NT-proBNP and CKD progression in CKD patients with stages 1-4, with the inflection point at 250 pg/mL, 750 pg/mL, 653 pg/mL, 526 pg/mL, but not in stage 5 (Figure).

Conclusion

NT-proBNP may be a reliable biomarker to predict CKD progression in stages 1-3 CKD (mainly for stage 3) without heart failure. This helps clinicians predict a decline in kidney function early and set the threshold for therapy. However, the predictive role of NT-proBNP in in advanced CKD patients is insignificant.
#2422 Iohexol plasma clearance measurement protocol standardization—a consensus of the European Kidney Function Consortium
Authors: Ebert Natalie , Schaeffner Elke , Seegmiller Jesse C , van Londen Marco , Bökenkamp Arend , Cavalier Etienne , Delanaye Pierre , Derain-Dubourg Laurence , Eriksen Bjørn O , Pálsson Runólfur , Shafi Tariq , White Christine A
Published: May 2024

Background and Aims

International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the adoption of mGFR determination in both clinical and research settings.

Method

The European Kidney Function Consortium (EKFC) convened an international group of mGFR experts. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using one-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, widely available, and can be assayed at a central laboratory. Other commonly used non-radio labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected as it requires no timed urine collections. A one-compartment model was preferred to a two compartment model as it requires fewer samples. The resulting recommendations were based on published evidence complemented by expert opinion.

Results

Recommendations include practical advice for patients and health professionals, preparation, administration and safety aspects of iohexol, laboratory analysis, blood sample collection and sample timing for both multiple and single sample protocols, description of the mGFR mathematical calculations as well as implementation strategies (Fig.). EKFC will provide materials such as patient information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation.

Conclusion

Members of the EKFC have evaluated the evidence and formulated recommendations that include all aspects of iohexol plasma clearance measurement using a one compartment model.

*Author list on behalf of the European Kidney Function Consortium (EKFC).
#2025 Associations of obesity, sarcopenia, and sarcopenic obesity with chronic kidney disease development in the elderly population
Authors: Park Jung Tak , Joo Young Su , Han Seung Hyeok , Yoo Tae-Hyun , Kang Shin-Wook
Published: May 2024

Background and Aims

Previous studies indicate that sarcopenia and obesity increase the risk of chronic kidney disease (CKD) in middle-aged populations. Despite noting reverse epidemiology for cardiovascular disease in the elderly, the relationship between sarcopenic obesity and CKD incidence in older populations is insufficiently explored. This study aims to assess whether obesity modifies the association between sarcopenia and CKD development in elderly adults with preserved kidney function.

Method

Elderly individuals aged over 65 with preserved kidney function among UK Biobank participants were examined. Participants with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² or albuminuria were excluded. The individuals were categorized based on the presence of sarcopenia and obesity, with sarcopenia defined as hand grip strength <27 kg in males and <16 kg in females. Obesity was defined as having a BMI of 30 kg/m² or higher, and sarcopenic obesity was identified in those with concomitant obesity and sarcopenia. The development of CKD was determined using ICD-10 codes in claim and death register records.

Results

A total of 62,735 individuals were assessed, with a mean age of 66.9 ± 1.5 years and 44.3% being male. Sarcopenia was identified in 8,648 individuals (13.8%), while obesity was present in 13,075 individuals (20.8%), resulting in a 3.29% prevalence of sarcopenic obesity. Over a median follow-up of 13.3 years (770,179 person-years), 5,567 participants (8.9%) developed CKD. A significant interaction between sarcopenia and obesity was observed for CKD development (P < 0.001). Incident CKD rates were 7.8% in non-obese without sarcopenia, 9.5% in obese without sarcopenia, 11.7% in non-obese with sarcopenia, and 14.7% in obese with sarcopenia. Compared to the non-obese without sarcopenia group, hazard ratios (HRs) and 95% confidence intervals (CIs) were 1.26 (1.16-1.37) in the obese without sarcopenia group, 1.55 (1.45-1.65) in the non-obese with sarcopenia group, and 2.02 (1.80-2.27) in the obese with sarcopenia group. After adjusting for confounding factors, the risk of CKD development in the obese without sarcopenia group was comparable to the non-obese without sarcopenia group (HR, 1.07, 95% CI, 0.99-1.15). However, elevated risk persisted in participants with sarcopenia and was most accentuated in those with sarcopenic obesity (non-obese with sarcopenia; HR, 95% CI, 1.22 [1.11-1.34]; obese with sarcopenia, 1.32 [1.15-1.50]).

Conclusion

Sarcopenia, not obesity, was significantly associated with an increased risk of chronic kidney disease (CKD) development in elderly individuals, with sarcopenic obesity showing the highest risk elevation for incident CKD in this group.
#1913 Long-term trends of blood pressure and blood glucose in patients with chronic kidney disease in South Korea, 1998-2021
Authors: Kim Dae Kyu , Kim Hyun Kyu , Lee Jeong-Yeun , Yoon Soo-Young , Kim Jin Sug , Jeong Kyung Hwan , Hwang Hyeon Seok
Published: May 2024

Background and Aims

Uncontrolled hypertension and elevated blood glucose are established risk factors for the progression of chronic kidney disease (CKD) and its complications. The long-term trends in these CKD risk factors, including the coronavirus 2019 (COVID-19) pandemic, have not been thoroughly studied in South Korea.

Method

We used data from Korea National Health and Nutrition Examination Survey, which nationally representative survey in South Korea. Data from Korean adults from 1998 to 2021 were obtained. We defined CKD as the participant's estimated glomerular filtration rate being <60 mL/min/1.73 m², one-time spot proteinuria of ≥1+. The evaluated risk factors for CKD included uncontrolled blood pressure and blood glucose, defined as a mean systolic blood pressure ≥120 mmHg and a glycated hemoglobin (HbA1c) level ≥6.5%. We examined the trend in the prevalence of uncontrolled hypertension and blood glucose, conducting subgroup analysis based on socioeconomic and behavioral factors.

Results

The trend among a total of 4,648 CKD patients with uncontrolled hypertension gradually decreased or remained steady from 1998 to 2019, however, there was an increase observed in COVID-19 pandemic period from 2019 to 2021 (1998-2005, 75.5% [95% confidence interval (CI) 71.5–79.5]; 2016–2019, 63.6% [95% CI 60.5–66.7]; 2021, 69.4% [95% CI 63.6–75.1]; and β diff, 0.65; 95% CI 0.30 to 1.00). Moreover, in the subgroup analysis of the prevalence of uncontrolled hypertension in CKD, almost all subgroups increased during the pandemic, except for older patients (age ≥ 65)

However, the overall trend difference in the prevalence of uncontrolled blood glucose among a total of 1,848 CKD patients with diabetes did not show significant changes (β diff, 2.80; 95% CI −0.11-5.71) between the periods before and during the COVID-19 pandemic.

Conclusion

During the COVID-19 pandemic, uncontrolled hypertension had a more significant impact on CKD patients than uncontrolled blood glucose, with an increase in the prevalence of uncontrolled hypertension. It is estimated that additional attention and policies for uncontrolled hypertension with CKD patients may be needed during periods of medical vulnerability, such as the COVID-19 pandemic.
#986 Sarcopenia and chronic kidney disease among adults over 45 years old: findings from CHARLS
Authors: Liu Fang , Jiamin Yuan
Published: May 2024

Background and Aims

Little is known about the association between sarcopenia and chronic kidney disease (CKD) among Chinese adults older than 45. The present study sought to investigate the relationship between sarcopenia and CKD based on a large, nationally representative survey.

Method

The China Health and Retirement Longitudinal Study (CHARLS) provided data for the study in four waves in 2011, 2013, 2015, and 2018. Based on the Asia Working Group for Sarcopenia 2019 (AWGS 2019) criteria, sarcopenia and possible sarcopenia were defined. CKD was defined as eGFR less than 60 mL/min/1.73 m2, calculated according to the CKD Epidemiology Collaboration (CKD-EPI) equation, or self-reported CKD. Logistic regression models were conducted to analyze the cross-sectional relationship between sarcopenia and CKD. Cox proportional hazards regression models were used to examine the effect of sarcopenia on CKD. Stratified analyses were used to assess the association between sarcopenia status and CKD in various subgroups.

Results

Totally, 12323 participants over 45 years old (48.2% males; mean age 59.3 ± 9.5 years) were enrolled in a cross-sectional study in 2011, and further 10445 individuals were followed up in 2013, 2015 and 2018. The prevalence of CKD was 8.4% (1040/12323) in general populations, 7.2% (556/7703) in individuals without sarcopenia, 10.1% (380/3760) in adults with possible sarcopenia, and 12.1% (104/860) in individuals with sarcopenia, respectively. In cross-sectional study, possible sarcopenia [OR (95% CI): 1.236 (1.069-1.430)] was significantly associated with CKD (P < 0.01). While sarcopenia was not significantly associated with CKD. 783 cases (7.5%) with incident CKD events were identified during the 7 years of follow-up. In subgroup analyses, the incidence of CKD was 1.855 (95% CI 1.176-2.928) in the sarcopenia group compared with non-sarcopenia group among the female participants. The sarcopenia group (HR: 1.639, 95% CI 1.099-2.443) was independently associated with a higher incidence of CKD among non-smokers. Low muscle mass alone was not significantly associated with an increased risk of incident CKD (P > 0.05).

Conclusion

In our cross-sectional analysis, possible sarcopenia determined by AWGS2019 criteria was associated with a higher prevalence of CKD. In our longitudinal study, sarcopenia assessed using AWGS2019 criteria was associated with a higher risk of CKD in Chinese women over 45 years old or non-smokers.
#2514 Clinical impact of the CKD-EPI 2021 versus the CKD-EPI 2012 formula on GFR estimation and CKD prevalence: results from a Dutch routine-care cohort
Authors: Veltkamp Denise Mj , Rookmaaker Maarten B , Verhaar Marianne , van Solinge Wouter W , Haitjema Saskia , Vernooij Robin Wm
Published: May 2024

Background and Aims

Quantifying the kidney function is crucial for diagnosing and monitoring kidney disorders in clinical practice. Recently, the CKD-EPI 2021 formula was developed for estimating glomerular filtration rate (eGFR), excluding the ethnicity variable. In this study, we aimed to analyze the impact in a Dutch routine-care cohort of introducing the new serum creatinine-based CKD-EPI 2021 formula on glomerular kidney function estimation and the prevalence of chronic kidney disease (CKD), compared to the now used CKD-EPI 2012 formula.

Method

All patients of 18 years and older of whom serum creatinine was measured between January 2013 and December 2023 at the University Medical Center Utrecht in the Netherlands, were included. Differences in the eGFR measured with the CKD-EPI 2012 formula and the new CKD-EPI 2021 formula were defined as median difference, stratified by gender, age categories, and CKD stages.

Results

251.960 patients with 2.312.313 serum creatinine measurements were included in our analysis. Our findings indicate that the CKD-EPI 2021 formula results in a higher eGFR compared to the CKD-EPI 2012 formula (median +3.6 (Inter quartile range (IQR) 2.4 to 4.5) ml/min/1.73 m2 in men, and median +3.1 (IQR 2.0 to 4.0) ml/min/1.73 m2 in women). In total, 21.1% of the patients with CKD stage 2-5 according to the CKD-EPI 2012 formula were classified as having a better CKD stage using the new CKD-EPI 2021 formula; 26.1%, 20.5%, and 15.1% of the patients classified as having CKD stage 3A, 3B, and 4 were classified as having CKD stage 2, 3A, and 3B, respectively (Table 1).

Conclusion

The introduction of the CKD-EPI 2021 formula would have significant implications for kidney function estimation in the Dutch clinical setting. It is crucial to consider these differences when interpreting kidney function data and making clinical decisions, especially given the potential impact on diagnosing CKD and dosing medication.
#1433 Geographical variation in chronic kidney disease: a nationwide cohort study in Denmark
Authors: Slot Matilde , Kristiansen Nina Sahlertz , Bertelsen Michael , Jensen Simon Kok , Nørgaard Mette , Thomsen Reimar , Birn Henrik , Heide-Jørgensen Uffe , Christiansen Christian Fynbo
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) represents a significant and growing global health challenge, especially among aging populations. Despite declines in mortality from other non-communicable diseases, CKD-related mortality has remained stable, underscoring the need for enhanced management strategies. Primary care physicians play a crucial role in early detection and appropriate intervention. Understanding geographical variation in CKD prevalence and incidence is essential for clinicians and policy makers, informing the development of targeted interventions and resource allocation strategies. This study investigates CKD in Denmark, assessing variations in prevalence and incidence across rural and urban areas.

Method

This nationwide cohort study included all Danish residents aged ≥18 years as of January 1, 2019. Patients with CKD were identified using measurements of eGFR from the Register of Laboratory results for Research. CKD was defined according to KDIGO as at least two reported outpatient eGFR <60 ml/min/1.73 m2 at least 90 days apart. Population characteristics, CKD prevalence and CKD incidence were analyzed by urbanicity of residence municipality (capital, large city, provincial, sub-rural and rural municipalities). Two different models were used to estimate incidence rates; a crude model and a model using propensity score weighting for standardization, accounting for age and sex.

Results

The study included 4,466,041 Danish residents. There was variation in population characteristics and CKD incidence between urban and rural areas such as CKD prevalence, hypertension, diabetes, and Charlson Comorbidity Index. The crude model showed geographical differences in CKD incidence rates varying between 7.4 and 12.8 per 1,000 person-years in large city municipalities and rural municipalities, respectively. The standardized model showed less variation, with incidence rates ranging from 9.2 to 10.5 cases of CKD per 1,000 person years.

Conclusion

The study illuminates geographical variations in CKD prevalence and incidence across Danish rural and urban municipalities. After standardization for age and sex, there was only minor variation in incidence rates of CKD, suggesting that variation could largely be explained by differences in demographic, highlighting the need for targeted interventions accounting for diverse population characteristics in different geographic regions.
#2175 Sodium-glucose cotransporter 2 (SGLT2) inhibitors-induced erythropoiesis and cardiovascular events in chronic kidney patients
Authors: Vidas Maria De San Miguel Marques , López Paula , Briales Paula Sanchez , Sanchez Ana , Illazquez María Victoria López , Portolés Jose Maria
Published: May 2024

Background and Aims

Prior research has established that in chronic kidney disease (CKD), elevating hemoglobin (Hb) levels above 11.5 g/dl correlates with heightened thromboembolic event risks and increased mortality. Similar findings are seen in heart failure patients with Hb levels exceeding 13 g/dl, following treatment with erythropoiesis-stimulating agents. Sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently raise Hb levels in CKD patients, both anemic and non-anemic.

This study aims to evaluate the consequences of Hb level elevation due to SGLT2 inhibitors beyond the safe threshold in CKD patients and to investigate its association with cardiovascular (CV) events.

Method

A retrospective observational study was conducted from January 2016 to December 2021, focusing on CKD patients treated with SGLT2 inhibitors. Patients receiving erythropoiesis-stimulating agents or undergoing renal replacement therapy were excluded. We assessed the impact of Hb level changes on atheroembolic events, blood pressure variations, and mortality, while considering demographic data, red blood cell parameters, and renal function indicators. Patients receiving iron treatment were excluded to ensure accurate ferrokinetic parameter assessment.

Results

The study included 79 CKD patients, predominantly male (76%) and primarily with type 2 diabetes mellitus (T2DM) as the CKD cause (67%). Average follow-up post-SGLT2 inhibitor initiation was 3.5 years (SD 1.4, 0.7-6.7 years). Hb levels increased mainly in the first six months of treatment, with an average increase of 0.7 g/dl/year from baseline (p < 0.01). Ferritin levels slightly decreased (p 0.002), while the transferrin saturation index remained stable. Baseline estimated glomerular filtration rate (eGFR) did not influence Hb increase. Various responses to SGLT2 inhibitors were noted based on baseline Hb levels.

No significant association was found between elevated Hb levels (>16.0 g/dl) and increased atheroembolic events, mortality, or blood pressure changes. However, patients with Hb levels >13.0 g/dl experienced more CV events compared to those maintaining Hb ≤13.0 g/dl, though not statistically significant (0% vs 17.5%: p 0.30).

Conclusion

SGLT2 inhibitor treatment led to a significant Hb increase unless baseline levels were above 16.0 g/dl. Importantly, elevating Hb levels above 13.0 g/dl appears to be linked with a higher incidence of cardiovascular (CV) events, suggesting a potential risk associated with such an increase in Hb levels in this patient population. This finding underscores the necessity for further research to confirm this correlation and to delineate the safe therapeutic window for Hb levels in CKD patients treated with SGLT2 inhibitors.
#2595 Evolution of hemoglobin and serum uric acid levels after SGLT2i initiation in patients with and without diabetic nephropathy
Authors: Coca Armando , Moultamis Aya , Ardura Paula , Manrique María Martínez , Da Silva Ana Luisa Martins , Santana Henar , Cobo Kenia , Merizalde Carlos , Acosta-Ochoa Isabel , Mendiluce Alicia
Published: May 2024

Background and Aims

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are glucose-lowering drugs that inhibit glucose reabsorption in the proximal tubule, enhancing urinary glucose excretion. SGLT2i exhibit significant cardio- and renoprotective effects due to their capacity to increase diuresis and weight loss and reduce intraglomerular and blood pressure. Moreover, recent studies have described the potential of SGLT2i to improve additional cardiovascular risk factors, such as anemia or hyperuricemia. In this study, we aimed to describe the evolution of hemoglobin (Hb) and serum uric acid (SUA) levels in CKD patients with and without diabetic nephropathy before and after the initiation of SGLT2i therapy.

Method

CKD patients with and without diabetic nephropathy that were followed in the outpatient clinic of a tertiary referral academic hospital during January 2020 to September 2023 and that started SGLT2i therapy during that period were randomly recruited in the study. Patient characteristics, CKD staging, and levels of Hb and SUA before and after SGLT2i initiation were compared between groups. Hb and SUA levels were averaged considering all available laboratory controls during the last 12 months before treatment initiation and any available controls after treatment start.

Results

Demographic and clinical characteristics of enrolled patients are summarized in Fig. 1. Subjects with diabetic nephropathy were significantly older, more commonly hypertensive, presented worse kidney function, had received SGLT2i for a lengthier time and had lower hemoglobin values. We observed no change in hemoglobin levels after the initiation of SGLT2i in our sample, independently of diabetic nephropathy status or CKD stage (Fig. 2A, C). In contrast, SUA levels decreased significantly both in patients with and without diabetic nephropathy (Fig. 2B). This effect was observed across all the spectrum of CKD in our sample (Fig. 2D).

Conclusion

In our sample, SGLT2i initiation was associated with a significant decrease in SUA levels, both in patients with and without diabetic nephropathy and independently of CKD stage, which may help to explain its cardio- and nephroprotective effects. No change in Hb levels was observed, possibly due to a low prevalence of anaemia in our sample.
#1986 Incidence of renal anemia among patients with atrial fibrillation and chronic kidney disease stage IIIb-V
Authors: Igamberdieva Ranokhon , Abdullaev Sherzod
Published: May 2024

Background and Aims

According to the QICKD study, the prevalence of anemia in stage IIIb-V chronic kidney disease (CKD) is 22%. The incidence of renal anemia ranges from 8.4% in patients with stage I CKD to 83.7% in patients with stage V CKD. In patients on program hemodialysis, anemia develops in 94.5% of cases. The problem is associated with an increased risk of unfavorable outcome of CKD, therefore, the study of aspects of anemia among patients receiving anticoagulant therapy with atrial fibrillation (AF) and CKD remains the most relevant today. The purpose of the study is to study the prevalence of renal anemia among patients with AF and CKD stages IIIb-V.

Method

794 patients were admitted to the cardiology department with a diagnosis of AF and late stages of CKD—IIIb (glomerular filtration rate (GFR) 45–30 ml/min/1.73 m2), IV (GFR 29–15 ml/min/1.73 m2), V (GFR <15 ml/min/1.73 m2), for the first identified sustained decrease in glomerular filtration rate (FISD in GFR) of less than 45 ml/min/1.73 m2. The classification of renal anemia was carried out according to the recommendations of the World Health Organization.

Results

Renal anemia was diagnosed in 505 (63%) patients with AF and GFR less than 45 ml/min/1.73 m2. In total, among patients with CKD stage IIIb, anemia was detected in 207 (59%) patients, with CKD stage IV—in 110 (89%), with CKD stage V—in 43 (97%), with FISD in GFR—in 145 (51%). A mild degree of anemia (hemoglobin (Hb) in men 110-129 g/l, in women 110-119 g/l) was diagnosed in 39% of patients, with CKD stage IIIb in 85 (24%) patients, with CKD stage IV in 28 (22%) patients, with CKD stage V in 9 (20%) patients, with FISD in GFR in 75 (26%) patients. A moderate degree of anemia (Hb 81-109 g/l) was detected in 47.3% of cases, with CKD stage IIIb in 86 (25%) patients, with CKD stage IV in 60 (48%) patients, with CKD stage V in 29 (66%) patients, with FISD in GFR in 64 (23%) patients. Severe anemia (Hb 81-109 g/l) was detected in 47.3% of patients, with CKD stage IIIb in 36 (10%) patients, with CKD stage IV in 22 (19%) patients, with CKD stage V in 5 (11%) patients, with FISD in GFR in 6 (2%) patients.

Conclusion

Every fourth patient in the cardiology department with AF and GFR <45 ml/min/1.73 m2 was diagnosed with renal anemia, and its prevalence increases with a decrease in GFR. The above results indicate that a more careful selection of anticoagulant therapy is recommended for this patient population due to the high risk of progression of renal anemia in this cohort of patients.
#170 Vasoconstriction Inhibiting Factor: An endogenous inhibitor of vascular calcification as calcimimetic of calcium-sensing receptor
Authors: de la Puente Secades Sofia , Mikolajetz Dustin , Gayrard Nathalie , Jankowski Vera , Alghamdi Khaleda , Ciscart Angel Argiles , Schurgers Leon , Ward Donald , Jankowski Joachim , Orth-Alampour Setareh
Published: May 2024

Background and Aims

Patients with chronic kidney disease (CKD), have an increased risk of cardiovascular disease due to the massively accelerated calcification they develop. Vascular calcification is a highly regulated process mediated by different inducers and inhibitors. Recently, the peptide ‘vasoconstriction inhibiting factor’ (VIF) was isolated from bovine adrenal glands and has been described as an inhibitor of the angiotensin II-induced vasoconstriction. Angiotensin II inhibits calcium deposition, but VIF effect on vascular calcification is still unknown. In the present study, VIF has been characterised on vascular calcification assays.

Method

The effect of VIF was analysed in vitro in human aortic smooth muscle cells (hAoSMC) and ex vivo in rat aortic rings, both cultivated under high phosphate concentrations. VIF was also studied in vivo in rats treated with vitamin D and nicotine (calcification model).

Results

VIF inhibits calcium deposition in all the models studied. Furthermore, in hAoSMC VIF reduces the production of ROS and the initiation of diverse cascades in the cells, like activation of inflammatory cytokines and MAPK kinases, which in turn trigger the expression of various genes involved in the development of vascular calcification. Furthermore, in presence of VIF the population of apoptotic cells, directly linked to vascular calcification, is decreased. Calcium-sensing receptor (CaSR) has been found as VIF binding partner, pointing to VIF as a new calcimimetic of this receptor, that inhibits vascular calcification by increasing the production of carboxylated Matrix Gla Proteins (cMGP).

Conclusion

In conclusion, VIF is a new potent endogenous inhibitor of vascular calcification acting as a calcimimetic of CaSR, that leads to an increase cMGP production. This finding represents a basis for a new target for the prevention and therapy of patients with increased vascular calcification and shows an encouraging perspective for the future.
#1514 Elevated FGF23 increases systolic, and diastolic blood pressure, and pulse pressure in non-dialysis CKD patients
Authors: Rodelo-Haad Cristian , López Isabel López , Garcia-Saez Raquel , Jurado Daniel , Martin-Malo Alejandro , Rodriguez Mariano , de Mier M Victoria Pendon-Ruiz , Ojeda Raquel , Peregrín Cayetana Moyano , Soriano Sagrario , Santamaria Rafael , Muñoz-Castañeda Juan R
Published: May 2024

Background and Aims

Arterial stiffness is associated with high blood pressure. Elevated fibroblast growth factor 23 (FGF23) has been shown to produce changes in the phenotype of vascular smooth muscle cells that may cause an increase in arterial stiffness and an impairment of vascular function. Thus, we aimed to evaluate whether, in g5 non-dialysis CKD patients, higher concentration FGF23 is associated with elevated systolic (SBP), diastolic blood pressure (DBP), and pulse pressure (PP).

Method

We included 159 g5 non-dialysis CKD patients. Generalized additive models analyzed the association between intact FGF23, SBP, DBP, and PP. The body composition measurement was used to evaluate overhydration (OH). Given the potential non-linear relationship between iFGF23, with the other variables, iFGF23 was categorized into tertiles (T1 ≤ 389 pg/ml, T2 = 389—517 pg/ml, and T3 = >517 pg/ml).

Results

The mean age was 65.2 ± 14.7 years. 46% (n = 73) were female. The mean values of SBP and DBP were 158.8 ± 21.3 mmHg, and 87.2 ± 12.3 mmHg respectively, and the PP was 76.6 ± 20 mmHg. The median concentration of iFGF23 was 468.3 (268.8—904.9) pg/ml. It was observed a positive correlation between iFGF23 tertiles and SBP (p < 0.001), DBP (<0.01), PP (p = 0.02), and OH (p < 0.01) (Fig. 1). Multivariate generalized additive models showed an independent association of iFGF23 with SBP (Beta 5.16, CI 34-68), DBP (Beta 38.7, CI 24-53), and PP (Beta 36.3, CI 22.2-50.4). This association was not influenced by OH (%). Residual diuresis did not attenuate the association of iFGF23 with SBP, DBP, and PP.

Conclusion

Elevated FGF23 was associated with higher SBP, DBP, and PP in g5 non-dialysis CKD patients. This association was not modified by OH and residual diuresis.
#1725 Co-relation of bone mineral density (BMD) with static bone histomorphometric parameters in haemodialysis patients
Authors: Shukla Ravindra , Chaturvedy Manish , Das Tapabrata , Jhorawat Rajesh , Bajpai Nitin Kumar , Elhence Poonam , Mittal Madhukar , Banerjee Mithu , Goel Akhil Dhanesh
Published: May 2024

Background and Aims

A mineral bone disorder of CKD (CKD MBD) is a complication with abnormal bone turnover, mineralization, volume, vascular calcification, and a spectrum of biochemical abnormalities. This clinical study was designed to determine the correlation between BMD (DEXA parameter) and static bone histomorphometry in hemodialysis patients.

Method

This was a cross-sectional study in patients undergoing maintenance hemodialysis aged 18-60 years. Bone biopsy was done from the iliac crest, fixed in alcohol, processed, and stained by RGB trichrome stain. Histomorphometric analysis was done by using NIH software (image J) and Adobe Photoshop software for image masking into black and white for volume calculation. Determination of BMD was performed by DEXA SCAN (Model HORIZON A). The detection sections included the central skeleton's three areas- anteroposterior lumbar (L1-L4) spine, proximal femur (femoral neck), and distal radius.

Results

A total of 46 patients on maintenance hemodialysis were included. Thirty-one (67.39%) were male, and the mean age was 34.43 ± 12.5 years. Amongst the study population, 60.87% (28) patients had osteopenia, 19.57%(9) patients had osteoporosis, and 19.57%(9) patients had normal BMD. Out of 46, four biopsies were inconclusive, 50% (21) had adynamic bone disease, 19.05%(8) had high turnover bone disease, 19.05%(8) had high mixed uremic osteodystrophy and 11.9%(5) patients had normal parameters. Among biochemical parameters, serum iPTH, ALP, and calcium had a significant association with bone turnover. BMD was significantly associated with age. However, it had no significant association with dialysis vintage, sex, or the type of renal osteodystrophy. Static bone histomorphometric parameters were not significantly associated with the T score.

Conclusion

PTH, ALP, and serum calcium were significantly associated with bone turnover. Adynamic bone disease was the most common renal osteodystrophy. BMD was not significantly associated with static bone histomorphometric parameters in our study.
#2332 Systemic immune-inflammation index is associated with chronic kidney disease: evidence from NHANES 2009-2018
Authors: Li Jinxi , Chen Xinyun , Shi Fangyu , Gou Shenju , Fu Ping
Published: May 2024

Background and Aims

The systemic immune-inflammation index (SII), a novel inflammation index, reflects systemic inflammatory and immunologic conditions throughout the human body. However, the relationship between SII and chronic kidney disease (CKD) remains unknown. The purpose of this study was to investigate the possible relationship between SII and CKD.

Method

The cross-sectional study included participants with complete information on SII (platelet × neutrophil/lymphocyte count), serum creatinine (Scr), or urinary albumin-to-creatinine ratio (UACR) from the 2009-2018 National Health and Nutrition Examination Survey (NHANES). CKD was defined as the presence of either low estimated glomerular filtration rate (eGFR) or albuminuria. Univariate and multivariate logistic regression and restricted cubic spline regression were used to assess the linear and nonlinear association between SII and renal function. Subgroup and interactive analyses were performed to explore potential interactive effects of covariates. Missing values were imputed using random forest.

Results

A total of 23 236 participants were enrolled in the study, of whom 4518 (17.9%) were diagnosed with CKD. After adjustment for covariates, the odds ratios (ORs) for prevalent CKD were 1.01 (95% CI = 0.91-1.11, p >0.05) for the Q2 group, 1.18 (95% CI = 1.08-1.30, p < 0. 001) for the Q3 group, and 1.64 (95% CI = 1.50-1.80, p < 0.001) for the Q4 group. In the association between SII and CKD, there was a significant interaction in age (p for interaction < 0.05). And non-linear association between SII levels and CKD in the whole population (p for non-linear = 0.001). All sensitivity analyses supported the positive association between SII and CKD.

Conclusion

SII was positively correlated with increased risk of CKD. The SII may serve as a practical and cost-effective tool for identifying and intervening the individuals at risk for CKD.
#1003 Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of AZD2373, an antisense oligonucleotide targeting APOL1
Authors: Greasley Peter J , Agrawal Nikhil , Althage Magnus , Sanchez Jose , Kirk Sarah , Egeland Erlend Johannessen , Åstrand Magnus , Westergren Helena , Sherwood James , Mccarthy Michael , Patel Uptal , Macphee Iain
Published: May 2024

Background and Aims

APOL1 mediated kidney disease (AMKD) is associated with toxic gain of function variants in people of African ancestry carrying the high-risk APOL1 genotypes (G1 and G2). APOL1 protein is part of the innate immune system but not considered essential. AZD2373, an antisense oligonucleotide that targets APOL1 mRNA to reduce its protein synthesis, is in development for AMKD. In genomic APOL1-transgenic mice, AZD2373 reduced APOL1 expression in kidney and liver, reduced plasma APOL1 protein concentration, and prevented development of IFN-γ induced proteinuria in high-risk genotype mice. In a single ascending dose study (NCT04269031), AZD2373 was well tolerated. We assessed the safety and tolerability of AZD2373 in a multiple ascending dose study including pharmacokinetics, and pharmacodynamic effect on APOL1 plasma protein levels.

Method

In this phase 1, randomized, single-blind, placebo-controlled study (NCT05351047) in healthy male volunteers of West African ancestry, participants were enrolled after a pre-screening study where they were genotyped for APOL1 prospectively; 18 participants had either 1 copy or 2 copies of the G1/G2 APOL1 high-risk allele. Low, medium and high dose cohorts each with 8 participants each receiving six weekly subcutaneous injections of either AZD2373 (n = 6) or placebo (n = 2) and were subsequently followed up for 9-weeks post-last dose. The primary objective was safety and tolerability; secondary objectives included assessment of pharmacokinetics and pharmacodynamics of AZD2373.

Results

In total, 24 participants were randomized and completed the study. No major safety and tolerability concerns were reported up to the highest dose of AZD2373 administered. The most common adverse event was injection site reactions which were dose-dependent, mild to moderate in severity and did not lead to treatment discontinuation. After dosing, AZD2373 had a rapid distribution phase (hours) and prolonged elimination phase (days to weeks). Clearance was similar across dose levels after single and repeated dosing, and the renal contribution to overall clearance was minimal. Exposure generally increased in a dose proportional manner. Plasma APOL1 was knocked down in a dose dependent manner (Figure).

Conclusion

Repeated doses of AZD2373 were safe and well tolerated, reducing plasma APOL1 concentrations in a dose- and time-dependent manner in healthy males of West African ancestry.
#150 Effect of dapagliflozin in patients with CKD depending on primary kidney disease
Authors: Abdullaev Sherzod , Daminov Botir , Sharapov Olimkhon
Published: May 2024

Background and Aims

Multiple trials have reported that SGLT2 inhibitors reduce the risk of its primary composite outcome of kidney disease progression or cardiovascular death in a wide range of patients with CKD. Our aim was to compare effects on kidney outcomes among the different types of kidney diseases.

Method

Eligible patients with eGFRs ≥30-45, or ≥45-90 ml/min/1.73 m2 with a urinary albumin-to-creatinine ratio of ≥300 mg/g, and receiving renin angiotensin system inhibitor, where indicated and tolerated were randomized to dapagliflozin 10 mg once daily vs placebo. Kidney disease progression was defined as a sustained ≥30% eGFR decline from randomization or to <10 mL/min/1.73 m2, start of maintenance dialysis or receipt of a kidney transplant, or renal death, and the effects of dapagliflozin were analyzed using a pre-specified Cox model. Testing for heterogeneity of effect between pre-specified kidney disease subgroups was performed, including exploratory analyses by specific glomerular disease etiologies.

Results

362 participants were followed for a median of 2.0 years. 90 (24.8%) had diabetic kidney disease, 126 (34.8%) had glomerular disease, 94 (26%) had hypertensive or renovascular disease, and 52 (14.4%) had other or unknown causes. Overall, dapagliflozin reduced the risk of kidney disease progression by 34% (dapagliflozin 29/178 vs placebo 48/184; hazard ratio 0.62, 95% CI 0.51-0.78). This relative risk reduction appeared broadly similar in subgroup analyses by primary cause of kidney disease and by different types of glomerular disease.

Conclusion

Our study with a few numbers of patients with diabetic and non-diabetic causes of CKD showed that dapagliflozin reduced risk of kidney disease progression with relative risk reductions that were broadly similar across the different CKD etiologies.
#1277 Comparing advanced glycation end products removal in super high-flux hemodialysis versus high-volume hemodiafiltration: a randomized, crossover study
Authors: Thanaprirax Ployrawee , Nongnuch Arkom , Boongird Sarinya , Assanatham Montira
Published: May 2024

Background and Aims

Expanded hemodialysis using super high-flux membrane, is a promising therapy for effectively clearing middle molecule uremic toxins. However, its impact on advanced glycation end products (AGEs), which is related to an increase in cardiovascular mortality [1], remains inconclusive. Previous studies demonstrated that AGEs increased over time in patients treated with high-flux hemodialysis (HD) [2, 3] while remaining stabilized in online hemodiafiltration (ol-HDF) [3]. This study aims to compare the longitudinal tissue AGEs measured by skin autofluorescence (SAF) between super high-flux hemodialysis (SHF-HD) and high-volume post-dilution ol-HDF.

Method

In this open-label prospective cross-over 24-week trial, twenty-two prevalent HD patients were randomly assigned to undergone two sequences of 24-week treatment periods: SHF-HD followed by high-volume postdilution ol-HDF or vice versa, with a 4-week wash-out period with high-flux HD between. SAF was measured at baseline and 24 weeks. Midweek pre-HD measurements of beta-2 microglobulin (B2M), serum albumin, normalized protein catabolic rate (NPCR) and Kt/V were obtained every 8 weeks. The amount of dialysate albumin was collected by continuous sampling of spent dialysate method and determined by immunoturbidimetric assay

Results

Seventeen out of twenty-two patients completed the study. At baseline, SAF levels (3.88 ± 0.14 vs 3.99 ± 0.14 AU, p = 0.463) and pre-HD B2M (22.66 ± 1.41 vs 21.09 ± 1.41 mg/L, p = 0.228) were similar between the SHF-HD and ol-HDF groups. After 24 weeks, SAF levels showed no significant change in SHF-HD (from 3.88 ± 0.14 to 3.91 ± 0.14 AU, p = 0.846) and ol-HDF (from 3.99 ± 0.14 to 3.95 ± 0.14 AU, p = 0.796), with a mean difference of change 0.06 (95% CI −0.34, 0.47, p = 0.75). Similarly, mid-week pre-HD serum B2M at 24 weeks exhibited no significant change in the SHF-HD group (22.66 ± 1.41 to 22.18 ± 1.47 mg/L, p = 0.722) and the ol-HDF group (21.09 ± 1.41 to 21.83 ± 1.45 mg/L, p = 0.577), with a mean difference of change −1.22 (95% CI −4.94, 2.49, p = 0.519). The spKt/V urea did not exhibit any notable differences. Furthermore, pre-HD levels of all small uremic toxins after the 24-week periods did not differ between both groups. Nutritional status measured by serum albumin and NPCR were comparable despite higher dialysate albumin loss in postdilution ol-HDF group (0.82 ± 0.04 vs 1.92 ± 0.12 g, p < 0.001 in SHF-HD and ol-HDF, respectively)

Conclusion

After 24 weeks of treatment, SHF-HD demonstrated levels of AGEs, pre-HD serum B2M, and serum albumin comparable to high-volume ol-HDF. If high-volume postdilution ol-HDF is not feasible, SHF-HD may serve as a valuable alternative treatment for stabilizing AGEs in chronic hemodialysis patients.
#1813 Safety and efficacy of reducing hemodialysis fluid flow rate—contribution to planetary health
Authors: Woitas Rainer , Haarhaus Mathias , Pfab Thiemo , Nedess Martin , Krupsack Helma , Macário Fernando
Published: May 2024

Background and Aims

Historically, increasing dialysate flow rates (Qd) have been recommended to improve hemodialysis (HD) efficiency. For decades, Qd has routinely been set to a fixed rate of 500 ml/min. A standard HD treatment uses on average around 500 L of water [1], resulting in a consumption of 78 000 L per patient and year with an additional estimated 10 000 L for post-dilution hemodiafiltration. This corresponds to the annual water consumption of 1.5 persons in developed countries and considerably more in developing countries. We investigated the effect of reducing dialysate flow rates on HD safety and efficacy.

Method

This is a prospective single-center non-blinded observational study. We investigated the effect of a 1:1 adjustment of online Qd to blood flow rate by adjusting autoflow (AF) settings of the dialysis monitor to a calculation factor of 1.0 with a lower Qd limit of 350 ml/min (AF 1.0 mode). We examined the effect on dialysis efficacy, metabolic markers, and anemia in routine biochemical analyses, and calculated energy, water, and waste savings in 116 stable chronic HD patients. Data were compared with previous turnover in energy, waste, and water, as well as with clinical results prior to the mentioned modifications.

Results

After 12 months of HD treatment with AF 1.0 mode we observed reductions of 10% in electricity consumption, 19% in raw water consumption, and 24% in dialysate concentrate consumption. Conversely, we did not observe deteriorations in treatment quality or dialysis dose (Table 1), nor phosphate or hemoglobin.

Conclusion

Long-term HD treatment with reduced dialysate fluid flow rates led to substantially improved water and carbon footprints with potential effects on planetary health and economic savings, while dialysis quality remained unchanged.