bluuebunny/crossref_metadata_2025 huggingface dataset:
#3096 Exploratory population-based screening of kidney function and heavy metal water source levels in a highly incident CKDu area in Guatemala
Authors: Lou-Meda Randall , Mcsc Annie , González Aguilar , Catalina Álvarez Ana
Published: May 2024

Background and Aims

Chronic kidney disease of unknown etiology (CKDu) has exponentially increased in the rural areas of the Pacific Coast in Central America. A multifactorial etiology has been postulated including exposure to environmental nephrotoxins such as heavy metals. The Pacific Coast of Guatemala has a volcanic topography with a high content of heavy metals, and the rural communities use ground water as their regular drinking consumption. Since the highest age group affected by CKDu are young adults, we postulated an exposure during childhood impacting later in life. We aim to identify changes in kidney function in children and adolescent healthy population from a highly incident CKDu area, and the heavy metal levels from water sources as a hypothesis generation exploratory study.

Method

We performed a population-based cross-sectional study of children and adolescents (below 17 y/o) from La Democracia municipality that were randomly chosen using Epidat software 3.1 from 10 different local schools from March 2019 to March 2020. The study was approved by external ethics board committee external-independent research ethics board committee. Subjects were excluded if they had known diagnosis of CKD, kidney replacement therapy or hypertension. The screening was performed in three different steps including a background assessment questionnaire, clinical assessment, and biochemical testing including creatinine from blood drop using StatSensor XpressTM to calculate estimated glomerular filtration rate (eGFR), urine dipstick, urinary creatinine, and protein. We measured arsenic (33As), cadmium (48Cd), mercury (80Hg), and lead (82Pb) in 21 water wells around the 10 screened schools, while only arsenic (33As), cadmium (48Cd) and mercury (80Hg) were measured in the urine of a small subset of the samples (data not shown in the results).

Results

A total of 508 randomly selected subjects’ and parents’ consent for screening but only 506 completed assessment. The median age was 14 y/o (IQR 11-17) 50% being female, with a close to 30% of the sample having obesity. The blood pressure was abnormal in 28% of the sample and at least 30% of them had an abnormal urine dipstick. The overall eGFR was 98, being the 25th%tile close to 83 ml/min/1.73 m2 BSA (Tables 1 and 2). Water sources showed higher than recommended levels of all heavy metals tested. Interestingly, the schools “Campiña” showed high levels of Arsenic and Cadmium in water sources, being the subjects tested coincidentally among the lowest eGFR of sample.

Conclusion

CKDu is an entity devastating low-resourced communities with young adults being the most affected. A likelihood for a link of early exposure needs to be further explored. Addressing the postulated hypothesis are key to implement preventive strategies, including screening earlier in life such as pediatric population.
#255 PaCE CKD: the impact of caregiving on health states and work productivity in chronic kidney disease: results from an international survey
Authors: Sanchez Juan Jose Garcia , Wu Mai-Szu , Chadban Steven , Correa-Rotter Ricardo , Reichel Helmut , Elsayed Hesham , Rangaswami Janani , Esposito Ciro , Hull Richard , Pentakota Surendra , West Bronwyn , Kularatne Thames , Fifer Simon
Published: May 2024

Background and Aims

Patients with chronic kidney disease (CKD) often rely on informal caregivers for support with their condition, but the effect of these responsibilities on caregivers’ lives is poorly understood. The aim of this study was to quantify the effect of CKD on caregivers’ health states and work productivity across five countries compared with the general population.

Method

Unpaid informal caregivers of patients with CKD, hereafter referred to as caregivers, in Germany, Mexico, Taiwan, the US, and the UK were enrolled to a non-interventional survey. Caregivers of patients with early (stages 1-3) to advanced (stages 4-5) CKD, including those receiving dialysis were enrolled in the study. A general population cohort was included, matched in sample size and demographic characteristics. The surveys assessed health states and work productivity with the following instruments:

Results

Across five countries, an average of 112 (range: 94–138) caregivers were enrolled to the study. Most respondents cared for a patient receiving dialysis—in Germany (65%), Mexico (65%), UK (67%), US (81%), though less than half (48%) of respondents in Taiwan cared for a dialysis dependent patient. Frequently reported caregiving duties were help with household duties and driving to medical appointments.

Caregivers in Germany, Mexico, the US, and UK experienced significantly impaired health states compared with the general population, as demonstrated by lower EQ-5D-5L utility scores. The greatest difference was observed from respondents in Mexico, with 16% lower mean [SD] index scores compared with the general population (0.79 [0.18] versus 0.94 [0.07]). Caregivers of dialysis dependent patients had similar CarerQol utility scores as those caregiving for non-dialysis dependent patients. Caregivers for dialysis dependent patients reported more problems across all CarerQol domains than caregivers for non-dialysis dependent patients. Caregivers in the UK reported significantly more financial problems (33%) as a result of caregiving; caregivers in the US reported significantly more problems (30%) in combining daily activities with care tasks. Caregiving also had a negative effect on work productivity. Rates of absenteeism, presenteeism, work impairment and non-work activity impairment were worse in caregivers compared with the general population. The largest effects were observed in Mexico where a 40% increase in non-work activity impairment was reported.

Conclusion

This study highlights the global burden for caregivers of patients with CKD. The broader impact of disease on caregivers should be accounted for when considering interventions relating to CKD.
#1321 Long term outcomes in people with fluctuating criteria for the diagnosis of chronic kidney disease
Authors: Taal Maarten W , Lucas Bethany , Mcintyre Natasha , Mcintyre Christopher , Fluck Richard
Published: May 2024

Background and Aims

The diagnostic criteria for chronic kidney disease (CKD) recognise that measures of kidney function may fluctuate in the short term by requiring that abnormalities must persist for at least 90 days to support the diagnosis. Nevertheless, studies have reported that even people who meet the diagnostic criteria may have transient or prolonged improvement in kidney function in the absence of specific treatment. In this study we used the opportunity afforded by long term follow-up of a cohort recruited from primary care to assess the impact on outcomes of fluctuations in CKD diagnostic criteria.

Method

Participants with confirmed CKD stage 3 were recruited from primary care practices in 2008-2010. Clinical assessment and protocol laboratory tests were performed at baseline, 1 and 5 year study visits. In 2019-20, information on deaths and latest available outpatient estimated GFR (eGFR) and urine albumin to creatinine ratio (UACR) values was obtained from electronic records. Participants with eGFR ≥60 ml/min/1.73 m2 and UACR <3 mg/mmol were regarded as being in “remission” at each time point. CKD progression was defined as a decline in eGFR of ≥25% and progression to a more advanced stage (KDIGO definition).

Results

The cohort included 1741 participants with median (IQR) age 74 (67-79) years, eGFR 53.8 (45.3-61.7) ml/min/1.73 m2 and UACR 0.3 (0.001-1.5) mg/mmol at baseline. During a median observation period of 9.8 (9.2-10.0) years, 680 participants (39.1%) died and CKD progression was observed in 430 of 1402 (30.6%) but only 24 (1.4%) progressed to CKD stage 5. The prevalence of remission was 495/1737 (28.5%) at baseline, 424/1618 (26.2%) at year 1, 335/1236 (27.1%) at year 5 and 176/1190 (14.8%) at year 10. Remission was present at all three visits in 15.4%, two visits in 13.0% and one visit in 15.8%. Participants with diabetes and those treated with a renin-angiotensin system inhibitor evidenced a lower prevalence of remission at all time points. Blood pressure control to <130/80 mmHg was not associated with remission. Evidence of remission at 1, 2 or 3 study visits was associated with progressively lower incidence of persistent CKD, CKD progression and death at 10 years (Table, p < 0.001 for all trends). No participants with an episode of remission had progressed to CKD stage 5 at 10 years.

Conclusion

A substantial minority of people diagnosed with CKD in primary care exhibit fluctuating diagnostic criteria. People with one or more episodes of remission appear to have a better prognosis than those with persistent CKD but remain at risk of CKD progression. They can therefore be reassured that an episode of remission is associated with an improved prognosis but long-term monitoring of kidney function is still warranted.
#2223 Glycosylated hemoglobin levels and bone phenotype in patients with end-stage kidney disease
Authors: Hauge Sabina Chaudhary , Jørgensen Hanne Skou , Claes Kathleen , D'haese Patrick , Verhulst Anja , Cavalier Etienne , Hansen Ditte , Evenepoel Pieter
Published: May 2024

Background and Aims

Diabetes mellitus is common as both cause and comorbidity of patients with chronic kidney disease (CKD). Both diabetes and CKD are states of increased fracture risk compared to healthy controls, with multiple potential contributing mechanisms. In type 2 diabetes, hyperglycemia contributes to the accumulation of advanced glycation end-products and osteocyte dysfunction, and it may play a pathogenic role in bone fragility. In this study, we wanted to examine the association between glycemic status and bone phenotype in patients with end-stage kidney disease (ESKD).

Method

This is a cross-sectional cohort study of 626 patients with CKD G5-5D referred for kidney transplantation between April 2006 and December 2013. Patients with type 1 diabetes were excluded. Patients were divided into quartiles based on HbA1c. Laboratory parameters of bone mineral metabolism (including biointact parathyroid hormone (PTH), fibroblast growth factor-23 (FGF23), and sclerostin), and bone turnover markers (bone alkaline phosphatase (BALP), trimeric pro-collagen type 1 N-terminal pro-peptide (intact P1NP), and tartrate-resistant acid phosphatase 5b (TRAP5b)) were measured. Bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DEXA) (n = 537), bone histomorphometry (n = 180), and bone trabecular score (TBS) (n = 192) were available for subsets of patients.

Results

The median HbA1c were 4.8% in Q1, 5.1% in Q2, 5.4% in Q3, and 5.9% in Q4. Age and BMI differed across quartiles, with the highest age and BMI in Q4. Differences in bone turnover markers were found, with decreasing bone formation (BALP and intact P1NP) and decreasing bone resorption (TRAP5b) with ascending quartiles (Fig. 1). No differences across quartiles were found for FGF23, or circulating levels of sclerostin; however a weak, positive correlation between HbA1c and sclerostin was noted (rho = 0.08, p = 0.047). Overall, BMD at lumbar spine, femoral neck, and total hip increased across quartiles, the highest values in Q4 (Table 1). There were no differen in bone histomorphometry or TBS based on glycemic status.

Conclusion

Chronic hyperglycemia associates with suppressed bone turnover and higher BMD in patients with ESKD, even in non-diabetics. Potential mechanisms linking glucose metabolism to bone quantity and quality requires further investigation.
#1564 Clinical implication of hyperfiltration and metabolic syndrome on the cardiovascular events, kidney failure, and all-cause mortality
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

Renal hyperfiltration (RHF) and metabolic syndrome (MetS) increase the risk of cardiovascular disease, end stage kidney disease (ESKD), and all-cause mortality. While RHF is strongly related to the metabolic risk, it is little known how the combined association of these two factors affects the risk of MetS-related complication, cardiovascular disease, and all-cause mortality.

Method

We reviewed the National Health Insurance Service database of Korea for people who received national health screenings between 2009 and 2011. RHF was defined as estimated glomerular filtration rate (eGFR) > 95th percentile after stratification for age, sex, height and weight, and normal renal filtration defined as eGFR 25-75th percentile. MetS was considered as the presence of three or more of the metabolic risks. Individuals were compared based on the presence of RHF and MetS. Age, sex, and Charlson comorbidity index matching were performed to reduce the selection bias in the study population. Finally, a total of 276,952 patients were matched, with 69,238 patients in each group, in a 1:1:1:1 ratio based on both their metabolic status and the presence of RHF.

Results

In multivariate Cox analysis, in comparison to normal renal filtration without MetS, RHF without MetS does not increase the risk of progression to ESKD. RHF patients increased the risk of progression to ESKD (aHR 2.75, 95% CI 1.38-5.50) only when combined with MetS. Moreover, irrespective of metabolic status, the risk of cardiovascular events (without MetS: aHR 1.08, 95% CI 1.00-1.17), (with MetS: aHR, 1.49; 95% CI, 1.38-1.60) and all-cause mortality (without MetS: aHR 1.29, 95% CI 1.20-1.40), (with MetS: aHR, 1.49; 95% CI, 1.37-1.62) increases significant in RHF patients. Notably, RHF synergistically increases the risk of cardiovascular events when accompanied with MetS (p for interaction = 0.041). However, RHF increases the risk of all-cause mortality more significantly without MetS than with MetS (p for interaction = 0.005).

Conclusion

The clinical implication of RHF is dependent on MetS status, and a significant interaction between the two factors is observed. To establish a treatment strategy for patients with RHF, MetS status must be considered.
#1910 Echocardiographic findings in patients with advanced diabetic kidney disease and obstructive sleep apnea
Authors: Nielsen Sebastian , Nyvad Jakob Tobias , Grove Erik Lerkevang , Poulsen Per Løgstrup , Laugesen Esben , Christensen Kent Lodberg , Buus Niels Henrik
Published: May 2024

Background and Aims

Obstructive sleep apnea (OSA) is associated with accelerated development of cardiovascular disease. The prevalence of OSA is increased in both type 2 diabetes (DM2) and in chronic kidney disease, and is very high in patients with diabetic kidney disease. However, the contribution of OSA to alterations in cardiac structure and function in diabetic kidney disease remains unknown. We therefore compared cardiac structure and function in diabetic kidney disease patients with or without OSA.

Method

In a cross-sectional study, 120 patients with DM2, a urine albumin-creatinine ratio (UACR) > 30 mg/g and an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 were tested for OSA. OSA severity was quantified by the apnea-hypopnea-index (AHI). Patients without OSA (AHI < 5 events/hour) were compared to patients with moderate (AHI 15-29 events/hour) or severe OSA (AHI ≥30 events/hour). Transthoracic echocardiography was conducted in all patients to evaluate cardiac structure and function. Linear regression analyses were used to assess the associations between OSA and echocardiographic parameters.

Results

AHI-data were available for 114 patients; 43 had no OSA, 33 had mild OSA and 38 had moderate-severe OSA. A total of 74 patients (73% men), 39 with no OSA and 35 with moderate-severe OSA, had complete data for both echocardiography and OSA. Their mean age was 71.5 ± 9.4 years, mean eGFR was 32.2 ± 12.3 mL/min/1.73 m2 and the median UACR of 533 (192–1707) mg/g. Age, smoking status, diabetes duration, eGFR, blood pressure, antihypertensive medicine, chronic obstructive pulmonary disease and atrial fibrillation were not significantly different between patients with and without OSA. Patients with moderate-severe OSA had significantly larger left atrial volume index (LAVI) (39.0 ± 19.6 vs. 28.1 ± 10.5 mL/m2, P = 0.0035), left ventricular mass index (LVMI) (49.2 ± 12.0 vs. 41.8 ± 9.7, g/m2, P = 0.0043), and right ventricular diameter (34.3 ± 5.8 vs. 28.4 ± 4.4 mm, P < 0.0001) compared to those without OSA (Fig. 1). Global longitudinal strain (GLS) was significantly reduced in OSA patients (−14.9 ± 3.1 vs. −16.6 ± 2.8, P = 0.0196), while no difference was observed in LV ejection fraction (54.4 ± 8.1 vs. 56.5 ± 6.2, p = 0.21). The association between OSA and LAVI, LVMI, right ventricular diameter and GLS remained significant after adjustment for age, sex, eGFR and mean arterial pressure.

Conclusion

Moderate-severe OSA is independently associated with alterations in cardiac structure and function in patients with diabetic kidney disease and reduced renal function. OSA could be an independent contributor to the development of heart failure in patients with diabetic kidney disease.
#1311 Cardiac damage in a multifactorial DKD/CKD mouse model resembles HFpEF and can be reduced by standard-of-care treatment
Authors: van Koppen Arianne , Pieterman Elsbet , Hinke Simon , Nguyen Tri , Dendooven Amélie , Bajema Ingeborg , van Goor Harry , Smits Anke , Stoop Reinout
Published: May 2024

Background and Aims

We developed a diet-induced hypertension-accelerated mouse model of diabetic kidney disease characterized by progressive loss of GFR resulting in chronic kidney disease. Since cardiovascular disease is the major cause of death in CKD, we characterized the functional and structural cardiac damage in this model. Additionally, we studied the efficacy of combination therapy with an ACE-inhibitor (Lisinopril) and SGLT2-inhibitor (Dapagliflozin) on cardiac histopathology.

Method

Male KKAy mice underwent uninephrectomy. After recovery mice received high fat diet (45% LARD) and drinking water with or without 50 mg/L LNNA (wk0). At 12 weeks, imaging was performed to study cardiac function and mice were terminated at week 13. In the intervention study, at week 4, lisinopril (2.5 mg/kg/day; drinking water) and at week 8 dapagliflozin (5 and 20 mg/kg/day; foodadmix) treatment were started. At week 16 mice were terminated and lung and heart weight and cardiac histology were determined.

Results

Upon termination, macroscopic evaluation of the hearts showed extensive scar tissue formation on the outside of the left ventricle. Histological evaluation showed the presence left ventricular hypertrophy, coronary calcification and myocardial fibrosis in male KKAy mice with UNX, HFD and LNNA. KKAy mice with UNX and HFD but without LNNA also showed myocardial fibrosis, monocyte infiltration and focal mineralization. Imaging showed preserved ejection fraction, a significant reduction, increased left ventricle posterior wall thickness and decrease left ventricle inner diameter. Treatment with combination therapy reduced lung wet weight, significantly reduced heart weight and significantly decreased cardiac fibrosis. Macroscopically, less scar tissue was observed after treatment.

Conclusion

This multifactorial mouse model shows cardiac damage on a background of hypertension, diabetes, renal dysfunction and obesity. Functional measurement including preserved ejection fraction, left ventricle hypertrophy, diastolic dysfunction and increased fibrosis resembling the clinical HFpEF phenotype.

Combination therapy with Lisinopril and Dapagliflozin reduced cardiac weight and cardiac fibrosis. This indicates cardiac involvement in the DKD mouse model which confirms that this multifactorial model is clinically relevant.
#1088 Interaction of general obesity and abdominal obesity with frailty in patients with chronic kidney disease: a nationally representative analysis
Authors: Yang Changyuan , Qin Xindong , Duan Ruolan , Avesani Carla Maria , Cai Qingqing , Xia Ai , Shen Lingshan , Zhong Jingyi , Liu Xusheng , Lindholm Bengt , Lu Fuhua , Su Guobin
Published: May 2024

Background and Aims

General and abdominal obesity are prevalent, with established associations to frailty in the elderly. However, few studies investigated these associations in patients with chronic kidney disease (CKD), yielding inconsistent results. We explored the relationship between general and abdominal obesity and frailty in CKD patients.

Method

This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES 2003-2018). Frailty was evaluated by the 36-item frailty index. General obesity was defined as body mass index (BMI) above 30 kg/m2, and abdominal obesity was identified if waist circumference (WC) reached 102 cm in men and 88 cm in women. The association of general and abdominal obesity with frailty were analyzed using weighted multivariate logistic regression and restricted cubic splines. The interaction of general and abdominal obesity with frailty was examined.

Results

5604 adult patients (median age 71 years, 42% men) with CKD were included in this analysis, with a median estimated glomerular filtration rate of 57.3 mL/min/1.73 m2. The prevalence of frailty was 40.7%. The prevalence of general obesity and abdominal obesity was 43.3% and 71.5%, respectively. Neither general nor abdominal obesity alone was associated with frailty. There was interaction between general and abdominal obesity with frailty (Table 1). Compared to individuals with normal BMI and WC, those with both general and abdominal obesity, rather than either alone, exhibited significantly increased odds of frailty [odds ratio (OR): 1.53, 95% confidence interval (CI): 1.20-1.95]. General obesity was associated with being frail when CKD patients had abdominal obesity (OR: 1.59, 95% CI: 1.08-2.36) (Fig. 1).

Conclusion

There may be an interaction between general and abdominal obesity with frailty in patients with CKD. Interventions aimed at preventing frailty should consider both aspects.
#1981 Experience with the use of semaglutide in cardiorenal syndrome patients followed in a cardiorenal unit (CRU)
Authors: Vidas Maria De San Miguel Marques , Crespo Silvia , Cobo Marta , Montero Esther , Lopez-Azor Juan Carlos , González Julia , Portolés Jose Maria
Published: May 2024

Background and Aims

GLP-1 receptor agonists are antihyperglycemic drugs that have shown an interesting cardio and nephroprotective effect beyond glycemic control and also induce weight loss, which is likely a facilitating element in the renal and cardioprotection of patients with elevated BMI. Patients with cardiorenal syndrome are often approached as particularly complex cases, which can lead to the underutilization of certain therapeutic groups. We have analyzed the use of semaglutide in patients followed in the CRU of Puerta de Hierro University Hospital to evaluate the drug's efficacy in glycemic and weight control and its safety profile.

Method

Retrospective real-life analysis performed in patients who received semaglutide while being under follow-up in the CRU, from January 21-December 22. Follow-up time was 6 months. Patients who had previously been on GLP1-AR treatment, on renal replacement therapy, or while waiting for any percutaneous or surgical cardiovascular procedure were excluded from the study.

Results

41 patients, 14 on oral semaglutide and 24 on subcutaneous semaglutide were analyzed. Demographic data and main comorbidities are shown in the table and were similar in both formulations. 53% of the patients were on maximum semaglutide dose at the end of follow-up (59.3% sbc and 42.9% oral, p 0.3). Weight loss and decrease in HbA1C% were significant without differences between formulations. We observed a significant decrease in systolic blood pressure of 11.1 (18) p 0.007 also similar in both drug formulations. No significant modifications in renal parameters were observed during follow-up. Adverse events were observed in 9 patients (22%), mainly gastrointestinal intolerance, and were more frequent with oral formulation (50% vs. 7.4%, p 0.004). 6 patients (14%) stopped semaglutide treatment without differences between formulation groups. 3 patients experienced at least one episode of HF decompensation, but no other events, hospitalizations, or deaths were observed. 3 (7.9%) patients experienced an eGFR decrease of> 30% without differences among the formulation groups.

Conclusion

We conclude that semaglutide in both formulations is an excellent option for glycemic and weight control in CRS patients’ blood pressure, with an additional significant improvement in blood pressure control and a good safety profile in this special population.
#1763 Risk factors and clinical prediction models for osteoporosis in predialysis chronic kidney disease patients
Authors: Chen Liangmei , Liu Fanna , Kuang Chaoying
Published: May 2024

Background and Aims

The research concerning osteoporosis among individuals with predialysis chronic kidney disease (CKD) has been relatively neglected in existing literature. Furthermore, the risk factors for osteoporosis in this demographic have not been adequately investigated. The objective of this study was to explore the risk factors associated with osteoporosis in predialysis CKD patients and to construct a predictive model capable of estimating the likelihood of osteoporosis in these individuals.

Method

A retrospective study was conducted on 326 predialysis CKD patients. Relevant clinical examination results and measurements of bone mineral density (BMD) using dual-energy X-ray absorptiometry were collected. Binary logistic regression was utilized to explore the risk factors associated with osteoporosis and to develop predictive models.

Results

In male predialysis CKD patients, age represents a risk factor, while 25-(OH)-Vitamin D acts as a protective factor against osteoporosis. Among female patients, age, underweight status, NBAP, and advanced CKD (G5) are significant risk factors for osteoporosis, whereas PTH serves as a protective factor. In pre-dialysis CKD patients in stages CKD1-4, age, underweight status, and NBAP are identified as risk factors for osteoporosis. For G5 predialysis patients, advanced age and NBAP pose a high risk of osteoporosis, while 25-(OH)-Vitamin D and PTH exhibit protective effects. Additionally, nomogram models illustrating the risk of osteoporosis in pre-dialysis patients of different genders and renal function stages were created.

Conclusion

Age, underweight, severity of renal dysfunction, NBAP, PTH, and 25-(OH)-vitamin D are strongly associated with osteoporosis in predialysis CKD patients.
#2505 PTEN ablation in osteocytes exacerbates anemia in mice with subtotal nephrectomy
Authors: Tocados Juan Miguel Díaz , Pérez-Gómez Aurora , Coral Juan Diego Domínguez , García-Carrasco Alicia , Bardaji Ana Martinez , Caus Maite , Sanjuan Auria Eritja , Bozic Milica , Valdivielso José Manuel
Published: May 2024

Background and Aims

The identification of novel roles for bone as a principal endocrine organ has grown in recent decades, being now recognized for its contribution to the regulation of numerous systemic functions. In previous studies, we observed that 5/6Nx mice with osteocytic deletion of phosphatase and tensin homolog (PTEN), exhibited higher bone volume in 5/6Nx mice, consistent with studies under normal renal conditions. However, we also noted a decrease in blood hemoglobin levels, prompting further exploration.

This study aims to elucidate the causative actions by which specific PTEN deletion in osteocytes influences red blood cell (RBC) homeostasis and to identify its possible involvement in anemia development.

Method

To achieve this goal, we used mice with targeted PTEN deletion in osteocytes (PTEN Ocy-cKO) by crossing DMP1-Cre ± and PTENflox/flox mice, subjected to subtotal nephrectomy (5/6Nx) at 2 months of age. Two weeks post-surgery, bone and blood samples were collected for plasma biochemistry, blood count, RBC membrane integrity, and preliminary bone+bone marrow proteomic analysis. Cre-negative mice and animals with normal renal function were included as controls.

Results

Our findings revealed that PTEN Ocy-cKO mice, under both normal and reduced renal function conditions, showed higher bone volume than corresponding controls. In terms of blood homeostasis, PTEN Ocy-cKO mice with normal renal function showed splenomegaly and a lower number of circulating RBCs. Notably, PTEN Ocy-cKO mice undergoing 5/6Nx experienced a profound decrease in RBC number in only two weeks, independent of renal erythropoietin expression. Further exploration ruled out bone marrow failure as a cause, as the erythroid progenitor (CD45-CD71+Ter119+) population remained similar in both groups. Extramedullary hematopoiesis was observed in the spleen, in addition to increased circulating reticulocyte number in the PTEN Ocy-cKO mice. Finally, altered RBC membrane protein patterns in PTEN Ocy-cKO mice suggested reduced mechanical/osmotic resistance. Preliminary proteomic analysis identified downregulation of Slc4a1 (Band3) and Phosphofructokinase (Pfkm), whose deficiencies have been previously linked to anemia.

Conclusion

In conclusion, our results propose that osteocytes contribute to RBC homeostasis through a pathway downstream of PTEN, and open a new avenue for understanding anemia in chronic kidney disease and a potential target for future treatments.
#2987 Describing inflammatory markers in end-stage renal disease and hemodialysis
Authors: Martínez Jordi Calabia , Saltos Jehimy Jean Alvarez , Carcasi Mara Lisbet Cabana , Ribas Ana Merino , Alemany Nadia Martín , Suárez Gabriel Manuel González , Cantalejo Leyre Garcia , Devia Claudia Marcela Castillo , Paez Cristina Noboa , Soler Laura Boix , Baptista Yanel Adriana Acosta , Escuder Pere Torguet
Published: May 2024

Background and Aims

There is an increased inflammatory state in patients with End-Stage Renal Disease (ESRD). It is crucial to investigate if the decline in renal function influences on the levels of infectious and inflammatory parameters, particularly procalcitonin (PCT) which exhibits the highest specificity for bacterial infections. Additionally, it would be useful establish a PCT cut-off-value for patients on renal replacement therapy and ESRD in the absence of infection, facilitating the differentiation between those with and without bacterial infection.

The aim of this study is to analyze infectious and inflammatory parameters, including PCT, in ESRD and HD patients. A secondary objective is to explore the link among inflammatory markers between themselves and with some specific clinical conditions.

Method

A cross-sectional observational comparative study was conducted involving HD patients (Group 1) and ESRD (Group 2). We assessed PCT, C-Reactive Protein (CRP), Sedimentation Velocity (SV), and Ferritin, among others. Patients with active infection were excluded. For HD patients, analytical extraction was conducted before the midweek session.

Results are presented as mean ± standard deviation for variables exhibiting a normal distribution, and as the median for variables displaying a non-normal distribution. Normality was assessed using the Shapiro-Wilk test. Group comparisons were conducted using Mann Whitney test for variables with a non-normal distribution. Relationships between parameters were examined using the Spearman correlation test and linear regression analysis. Significance was established at p < 0.05. The statistical software utilized was Jamovi (Version 2.3).

Results

We found in HD patients (Group 1) when compared to ESRD patients (Group 2) higher PCT levels, higher ferritin levels, and lower albumin levels, with statistical significance (Table 1).

Conclusion

There is a decrease in albumin levels and an increase in PCT, and ferritin levels in HD patients compared to ESRD patients. We observed that RCP, and ferritin were independent predictive factors of PCT levels, but, unexpected, diabetes was not. Given the fact that ESRD, and HD patients are in a chronic inflammatory status, it is difficult to assess the acute infectious severity in these patients. For that reason, the cut-off-values of inflammatory parameters in these patients in a non-infectious time-point needs to be clarified.
#1848 Body composition and multimorbidity in patients with chronic kidney disease
Authors: Randhay Ashveer , Kokab Khushbakht , Khan Farrah , Selby Nicholas , Taal Maarten W , Eldehni Tarek
Published: May 2024

Background and Aims

Frailty and multimorbidity are increasingly prevalent, particularly in the chronic kidney disease (CKD) population, and they seem to be more pronounced and accelerated in people receiving haemodialysis. We aimed to study the relationship between body composition, frailty and multimorbidity in people with CKD and end stage renal disease (ESRD) on haemodialysis (HD).

Method

This was a single centre study, involving 42 patients with CKD stage 3 to 5 (pre-dialysis) and 29 patients receiving in-centre haemodialysis. InBody 770 was used to measure body composition using bioelectrical impedance analysis. Multimorbidity of participants were assessed using the simplified Cambridge multimorbidity score. Frailty assessment was performed using the Clinical Frailty Scale.

Results

Phase angle was lower in later stages of CKD—mean phase angle in CKD stage 3 was 5.28°, stage 4 was 4.44 and stage 5 was 4.13 (p = 0.008). Visceral adiposity correlated with multimorbidity scores but in a multivariate regression analysis (including albumin and visceral fat area) only whole body phase angle independently predicted multimorbidity in CKD stage 4-5 (adjusted R2 for the whole model = 0.47, p = 0.007). In haemodialysis patients, there was no correlation between multimorbidity and phase angle (r = −0.149, p = 0.441). However, there was a significant correlation between frailty score and whole body phase angle in this group (r = −0.559, p = 0.002). In a univariate analysis, age (R2 = 0.2, Beta = 0.045, p = 0.015), albumin (R2 = 0.217, Beta = −0.214, p = 0.009) and skeletal muscle mass (R2 = 0.282, Beta = −0.101, p = 0.003) predicted frailty score in haemodialysis patients. In multivariate regression analysis age, albumin level and skeletal muscle mass continued to independently predict frailty scores in HD patients (adjusted R2 for the whole model = 0.503).

Conclusion

Phase angle measurement refers to cell membrane integrity and fat-free mass, with higher values suggesting improved cell health. Using body composition measures, in particular phase angle, is a useful measure to predict multimorbidity and frailty in CKD patients. They are quick, accessible and easy to use tools that can be incorporated in clinical practice routinely. The relationship between visceral adiposity and multimorbidity merits further investigation. Preservation of skeletal muscle mass through nutritional and exercise interventions could be a clinical target to reduce frailty in this population.
#206 The effect of dapagliflozin on anemia in patients with CKD
Authors: Abdullaev Sherzod , Igamberdieva Ranokhon
Published: May 2024

Background and Aims

SGLT2 inhibitors confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). Some studies have analyzed the effects of SGLT2is on hemoglobin levels. Potential mechanisms for rising hemoglobin include hypoxia-induced activation of HIF2α, hepcidin inhibition resulting in iron metabolism modulation, and hemoconcentration. We aimed to evaluate the effect of dapagliflozin on anemia in CKD patients.

Method

We conducted a prospective study in patients in a single center with eGFR 35-90 ml/min/1.73 m2 who received dapagliflozin 10 mg daily between 6/2022 and 10/2023. The primary outcome was the mean difference in hemoglobin levels 5 months prior and 8 months after initiation of SGLT2i therapy.

Results

Among 132 patients screened from 6/2022 to 10/2023, 53 were prescribed dapagliflozin 10 mg daily, with a mean eGFR of 53.2 ml/min/1.73 m2. Of those 53 patients, 28 (52.8%) were males and 25 (47.2%) females. No one received any iron supplements or erythropoietin therapy. The mean hemoglobin level 5 months before initiating SGLT2i therapy was 10.5 g/dL, with a mean drop of 0.10 g/dL (95% CI, –0.22 to + 0.06) in 5 months. Eight months following the addition of SGLT2is, patients experienced an increase in hemoglobin levels of 1.03 g/dL (95% CI, 0.84 to 1.14). Overall, we observed a mean hemoglobin difference of 1.13 g/dL (95% CI, 0.84 to 1.41, p < 0.01) before and after initiating SGLT2i therapy.

Conclusion

The use of dapagliflozin for eight months resulted in a significant elevation in hemoglobin levels in patients with CKD. Further studies can explore of better understanding of the effect and confirm the mechanisms that explain this finding. Elevation of hemoglobin with SGLT2is may be closely linked to the reduction of cardiovascular mortality and heart failure.
#749 Components in blood collection tubes interfere with the spectral signatures of patients with kidney disease: analysis by infrared microspectroscopy
Authors: Da Silva Jéssica Verônica , Nepomuceno Gabrielle Teodoro , Batista Andre Mourão , Veiga Glaucia , Fonseca Fernando , Martinho Herculano Da Silva , Carneiro-Ramos Marcela
Published: May 2024

Background and Aims

Kidney disease is a worldwide public health problem, affecting between 8%-16% of the global population. Chronic Kidney Disease (CKD) is a silent disease and its detection is often late, making the treatment difficult. Considering the emerging Fourier-Transform Infrared spectroscopy (FTIR) as a biophotonic resource for the biomedical sciences, we aimed to identify spectral signatures related to biomarkers of CKD in human blood serum using the microscopy FTIR option.

Method

Blood serum samples from 17 healthy in comparison to 33 CKD patients were analyzed by micro-reflectance FTIR spectroscopy. The first aspect to be addressed refers to the possible influence of components present in the container tube. Here we showed that separator gel in VACUETTE® tubes is a relevant source of spectral interference which could decrease the accuracy of discrimination from 85% to 65%. Acquiring a diluted gel signal as a background would improve the discrimination performance in spite of some gel bands still present in sample data.

Results

In this case, our results indicated that vibrations associated with galactose-4-sulfate, CH2 bending of the methylene chains, C=C in lipids and fatty acids, C=N stretching, CH bending vibration from the phenyl rings, N-H bending vibration coupled to C-N stretching and β-sheet of Amide II and ring base are modulated in blood serum samples of chronic kidney disease patients compared to healthy patients. Urinary trypsin inhibitors, fatty acids, phenolic derivatives, tryptophan, and plasminogen were the biomolecules related to these assignments were the biomolecules related to these assignments.

Conclusion

In conclusion, FTIR is a viable option for fast diagnosis of chronic kidney disease being also a powerful tool for monitoring the disease. Due to its capability of large batch analysis, the micro-FTIR would be an eligible technology for clinical laboratories in healthcare facilities. However, for direct clinical applications, ATR-FTIR would be the option of choice.
#2347 Multi-omics analysis identifies traditional Chinese medicine targets for chronic kidney disease
Authors: Tang Lei , Zeng Xiaoxi
Published: May 2024

Background and Aims

As a major public health problem, chronic kidney disease (CKD) has substantial comorbidities and disease burden. It is necessary to discover new therapeutic targets considering its irreversibly. Traditional Chinese medicine (TCM) has become indispensable for the integrated treatment of CKD. The current study aims to explore potential new TCM targets in high-throughput experiment- and reference-guided database (HERB) that are related to renal phenotypes utilizing multi-omics.

Method

We conducted comprehensive Mendelian Randomization and Bayesian colocalization on more than 2,000 HERB target integrating genomes and transcriptomes, using summary statistics of genome-wide association study and cis gene expression quantitative trait loci. The results were validated through differential gene expression in public database, previous literature reports and clinical kidney biopsy specimens.

Results

In all, we discovered 34 targets associated with renal phenotypes among the 2,421 HERB TCM targets in the data mining part. Among them, most of the targets can be validated by differential gene expression analysis in GEO and Nephroseq, and have been reported by basic research, thus confirming the reliability of this method. In addition, PRKCI, KNG1, PKN3, GGT7, GBA, APEH and GSTA2 are expected to be potential new therapeutic targets for CKD. Immunohistochemical staining using clinical kidney biopsy specimens of PKN3 and KNG1, two targets with the highest evidence level, further confirm the results.

Conclusion

Integration of multi-omics can extensively and efficiently screen potential drug targets related to CKD. The new targets discovered in the current study, especially PKN3 and KNG1, need to be further validated in basic research.
#1927 Efficacy and safety of ripertamab in paediatic glomerular disease
Authors: Yue Yuqi , Chen Qiuxia , Li Sijia , Zhu Chunhua , Feng Quancheng , Zhao Sanlong , Ding Guixia , Han Yuan , Cheng Xueqin , Zhao Fei
Published: May 2024

Background and Aims

Anti-B-cell treatment has been shown to be an efficient tactic for glomerular disease. Ripertamab as a novel anti-CD20 monoclonal antibody developed by China, has been structurally optimized to specifically bind to the transmembrane antigen CD20, with an amino acid difference in the constant region sequence compared to rituximab. This study reports the efficacy and safety of ripertamab in children with different glomerular diseases.

Method

We retrospectively report the data of 140 children with a diagnosis of glomerular disease and a treatment with ripertamab in a single center

Results

A total of 140 children (age, 11.2 ± 3.7 years; 58.6% boys) were included, 69/140 (49.3%) steroid-dependent nephrotic syndrome (SDNS), 38/140 (27.1%) steroid-resistant but CNIs-dependent nephrotic syndrome, 18/140 (12.9%) Lupus nephritis, 5/140 (3.6%) atypical hemolytic uremic syndrome, 4/140 (2.9%) ANCA associated vasculitis, 3/140 (2.1%) membranous nephropathy and 3/140 (2.1%) IgA vasculitis nephritis. The Median (IQR) duration of disease before the application of ripertamab was 4.4 (2.3, 7.4) years. They totally received 200 courses of ripertamab. A total of 83, 55, 1, and 1 patient received one, two, three, and four courses, respectively. Ripertamab 375 mg/m2 (maximum 500 mg) were injected per course. B cell depletion could be observed in 129/140 (92.1%) children one month after ripertamab. An additional course was administered due to recovery of B-cells or relapse. Median (IQR) follow-up was 0.8 (0.5, 1.1) years. The median relapse-free period after the first course was 4.7 months (IQR, 3.8, 5.6 months). Most of the relapses developed simultaneously with recovery of B-cells. About 36.7% of these children stopped steroid during the follow-up. One or more immunosuppressant (IS) drugs needed before ripertamab infusion could be withdrawn or reduced in 109/140 patients (77.9%). None of the patients developed life-threatening adverse events.

Conclusion

This study suggests that ripertamab could be an effective and safe treatment for various pediatric glomerular diseases.
#2925 PI3K/AKT/mTOR pathway regulates renal expression of Klotho
Authors: Pérez-Gómez Aurora , Tocados Juan Miguel Díaz , Coral Juan Diego Domínguez , García-Carrasco Alicia , Caus Maite , Schanstra Joost , Del Bello Arnaud , Klein Julie , Valdivielso José Manuel
Published: May 2024

Background and Aims

Renal Klotho expression decreases early in chronic kidney disease (CKD), increasing circulating FGF23 and phosphate levels. This negatively affects renal disease progression and cardiovascular complications. Preserving renal Klotho expression is of interest, but the underlying mechanisms are unclear. During early stages of CKD, kidneys activate mechanisms of hypertrophy, in which the PI3K/Akt/mTOR pathway plays a role. The main negative regulator of this pathway is PTEN, which reduces the activation of canonical insulin signaling. Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. However, complications may appear after transplantation, such as allograft reaction, compromising the function and the integrity of the transplanted kidney. Different immunosuppressants are currently administered to prevent this response, such as mTOR inhibitors or calcineurin antagonists. We aimed to investigate the role of PTEN and the PI3K/AKT/mTOR pathway in kidney Klotho levels and their possible implication in CKD.

Method

We measured renal Klotho levels, circulating FGF23, and phosphate in mice lacking PTEN in renal proximal tubular cells (PTEC) and in HK2 cells in vitro. We also examined normal mice with models of decreased renal mass caused by uninephrectomy (UNX) and 5/6 nephrectomy (SNX). Additionally, we tested the effect of mTOR inhibition. We analyzed PTEN and Klotho expression in kidney samples from CKD patients. Furthermore, we stablished whether there are improvements in Klotho expression in patients treated with an mTOR inhibitor versus other treatments.

Results

We found that PTEC with downregulated PTEN exhibited decreased Klotho expression both in vitro and in vivo, accompanied by increased mTOR activity. Animals with PTEN elimination in PTEC also showed increased circulating phosphate and FGF23 levels, as well as a decrease in the fractional excretion of phosphate. These alterations were normalized by treatment with rapamycin. Normal mice with UNX or SNX exhibited increased renal IGF-1 expression and activation of the PI3K/AKT/mTOR pathway. Furthermore, these mice showed a reduction in renal Klotho expression and an increase in circulating FGF23 and phosphate. Both of these alterations were restored with rapamycin administration.

In renal samples from CKD patients, we observed a positive correlation between the expression of PTEN and KLOTHO. Finally, kidney transplanted patients treated during 9 months with mTOR have an increase of 22.8% Klotho levels and patients with other treatments a 14%.

Conclusion

The overactivation of the PI3K/AKT/mTOR pathway in PTEC modulates Klotho levels in the kidney. Our findings represent a significant advancement in the search for new therapeutic targets to maintain and prevent reductions in renal Klotho levels, potentially benefiting kidney disease patients.