bluuebunny/crossref_metadata_2025 huggingface dataset:
#5517 IN CHRONIC KIDNEY DISEASE, IRON DEFICIENCY-INDUCED ANEMIA IS ASSOCIATED WITH HIGHER LEVELS OF FGF23 THAT ARE NOT REDUCED BY IRON ADMINISTRATION
Authors: Valdés-Díaz Karen , Lopez-Baltanas Rodrigo , Romero Ana Torralbo , Membrives Cristina , Moreno Julio Manuel Martínez , Dominguez Casimiro Valle , Rodriguez Mariano , Cabrera Maria Sagrario Soriano , Muñoz-Castañeda Juan R , Ortiz Maria Encarnacion Rodriguez , Martin-Malo Alejandro
Published: June 2023

Background and Aims

Iron (Fe) deficiency significantly contributes to anemia in chronic kidney disease (CKD). High FGF23 levels, commonly found in CKD, are related to adverse outcomes in patients. In the normal setting, an association between Fe deficiency and FGF23 has been observed. However, it is unknown whether Fe deficiency-induced anemia might contribute to the excessive FGF23 levels in CKD. Thus, this study was intended to evaluate the interplay between Fe deficiency, CKD, and FGF23.

Method

Male Wistar rats with normal renal function received either standard (40 ppm Fe) or Fe-deficient (4 ppm Fe) diets for 6 weeks to induce anemia. Then, several normal and all the anemic rats were switched to an adenine-enriched (0.6%) diet to induce renal damage. Groups of anemic-uremic animals were treated with oral (ferric citrate, FC and ferrous sulfate, FS) or intravenous (ferric carboxymaltose, FCx) Fe at a dose of 9 mg/kg for 5 weeks. Hematological and mineral metabolism parameters were determined at sacrifice. All experimental protocols were approved by the Ethics Committee for Animal Research of the University of Córdoba.

Results

Plasma and serum biochemistries are shown in Table 1. CKD per se was associated with derangements in hematological parameters. The presence of Fe deficiency-induced anemia further decreased these parameters, being statistically significant in the case of serum Fe (P = 0.003). Iron therapy improved hematocrit, hemoglobin, and Fe levels, although statistical significance for all of them was only reached when FC was administered (P = 0.012, P = 0.038, and P = 0.002, respectively). As expected, CKD rats exhibited disturbances in mineral metabolism. Interestingly, uremic and anemic rats showed higher intact (P = 0.039) and c-terminal (P = 0.048) FGF23 levels when compared with CKD group. Despite normalization of serum Fe, intact FGF23 further increased following administration of FS (P = 0.022), and same trend was observed with all the compounds. However, cFGF23 levels remained unchanged in all the Fe-treated groups.

Conclusion

The presence of Fe-induced anemia in an experimental model of CKD is associated with further increases in the levels of both intact and c-terminal FGF23. Thus, other factors distinct than serum Fe might influence FGF23 levels. Our results support the need for investigating the precise mechanisms underlying the relationship between Fe and FGF23 to optimize the clinical management of anemia, particularly in the context of renal dysfunction.
#5522 USING THE KIDNEY FAILURE RISK EQUATION TO PREDICT END-STAGE KIDNEY DISEASE IN CKD PATIENTS OF SOUTH ASIAN ETHNICITY: AN EXTERNAL VALIDATION STUDY
Authors: Maher Francesca , Teece Lucy , Major Rupert , Brunskill Nigel , Booth Sarah , Gray Laura
Published: June 2023

Background and Aims

The Kidney Failure Risk Equation (KFRE) predicts the 2- and 5-year risk of needing kidney replacement therapy (KRT) using four risk factors – age, sex, urine albumin-to-creatinine ratio (ACR), and creatinine-based estimated glomerular filtration rate (eGFR). Although the KFRE has been recalibrated in a UK cohort, this did not consider minority ethnic groups. Further validation of the KFRE in different ethnicities is a research priority. The KFRE also does not consider the competing risk of death, which may lead to overestimation of KRT risk. This study externally validates the KFRE for patients of South Asian ethnicity and compares methods for accounting for ethnicity and the competing event of death.

Method

Data were gathered from an established UK cohort containing 35,539 individuals diagnosed with chronic kidney disease. The KFRE was externally validated and updated in several ways taking into account ethnicity, using recognised methods for time-to-event data, including the competing risk of death. A clinical impact assessment compared the updated models through consideration of referrals made to secondary care.

Results

The external validation showed risk of KRT differed by ethnicity. Model validation performance improved when incorporating ethnicity and its interactions with ACR and eGFR as additional risk factors. Further, accounting for the competing risk of death improved prediction. Using a criteria of 5 year ≥5% predicted KRT risk, the competing risks model resulted in an extra 3 unnecessary referrals (0.59% increase) but identified an extra 1 KRT case (1.92% decrease) compared to the previous best model. A hybrid criteria of predicted risk using the competing risks model and the previous guidelines should be used in referrals to secondary care.

Conclusion

The accuracy of KFRE prediction improves when updated to consider South Asian ethnicity and to account for the competing risk of death. This may reduce referrals whilst identifying risks of KRT and could further individualise the KFRE and improve its clinical utility. Further research should consider other ethnicities.
#5531 MOLECULAR IMAGING OF PDGFR-β IN KIDNEY FIBROSIS
Authors: Klinkhammer Barbara Mara , Moeckel Diana , Wagner Maike , Kiessling Fabian , Lammers Twan , Boor Peter
Published: June 2023

Background and Aims

Chronic kidney disease affects >10% of the world's population and is associated with high mortality and morbidity. The best predictor of CKD progression is the extent of fibrosis, i.e., pathological deposition of extracellular matrix (ECM) and loss of functional kidney parenchyme. Currently, there are no specific treatment options and invasive biopsies remain the gold standard for diagnosis. Multiple signaling pathways are involved in fibrosis, including platelet-derived growth factor (PDGF) signaling. Mesenchymal stromal cells express both PDGF receptors PDGFR-α and PDGFR-β, whose activation drives proliferation, migration and production of extracellular matrix, i.e., key processes involved in fibrosis initiation and progression. Based on these notions, we set out to study the bicyclic PDGFR-β-binding peptide (BiPPB) for diagnosis, quantitative imaging and treatment monitoring of kidney fibrosis.

Method

The biodistribution and kidney accumulation of Cy7-labeled BiPPB and a scrambled peptide control were visualized and quantified using in vivo computed tomography - fluorescence molecular tomography (CT-FMT), ex vivo fluorescence reflectance imaging (FRI) and microscopy. This was done in three different mouse models of kidney fibrosis: the unilateral ischemia-reperfusion injury (I/R), the adenine-induced nephropathy (Adenine) and a transgenic model with constitutive PDGFR-β activation specifically in renal mesenchymal cells leading to increased PDGFR-β expression and expansion of PDGFR-β+ cells (Mutant). In the latter model, we also monitored pharmacological PDGFR-β inhibition with imatinib. Kidney fibrosis and therapeutic efficacy findings were verified by immunohistochemistry (IHC).

Results

In vivo 3D CT-FMT imaging and ex vivo 2D FRI showed strong accumulation in fibrotic kidneys for Cy7-labeled BiPPB, whereas only moderate amounts accumulated in the contralateral (I/R) and healthy (Adenine) kidney over 48 hours after i.v. injection. The accumulation of the scrambled BiPPB was also significantly lower compared to the specific BiPPB. In transgenic Mutant mice with specific activation of mesenchymal cells and primary renal scaring significantly more Cy7-BiPPB accumulated in the kidneys in comparison to healthy wildtype littermates. In combination with imatinib treatment for three weeks (Mutant imatinib) the accumulation of Cy7-BiPPB was decreased (Fig. 1a-c). This was confirmed ex vivo by significantly increased probe accumulation (2D FRI; Fig. 1d) and PDGFR-β expression (immunohistochemistry (IHC) Fig. 1e) in fibrotic kidneys, which was diminished by imatinib treatment.

Conclusion

Our findings demonstrate the potential of PDGFR-β-based imaging agents for non-invasive and quantitative monitoring of renal fibrosis progression and therapy response.
#5532 COVID-19 INFECTION MODIFIES GLOMERULAR DISEASE EVOLUTION
Authors: Ojeda Felipe Ignacio , Rivera Miguel Giovanni Uriol , Rodenas Estela de Los Angeles Mas , Arias-Camisón Paloma Livianos , Mulet Aina Obrador , Arrufat Gemma , Zamora Maria Gomez , Mendoza Sonia Cleofe Jimenez
Published: June 2023

Background and Aims

A fibrotic effect of the SARS-Cov2 virus (Covid-19) has been described and the risk for acute renal failure in glomerular disease (GD) patients; however, the long-term renal effect in these patients is unknown. We evaluate the impact of the Covid-19 infection on eGFR, the influence of proteinuria, the effect of the drugs used to control glomerulonephritis and the use of Paxlovid (nirmatrelvir/ritonavir) for covid infection control.

Method

We retrospectively evaluate the eGFR (mL/min/1.73m2) at month 12 and 6 before infection (pre-infection period), during infection, 6 months after infection and at the last visit post-infection in renal biopsy-proven glomerulonephritis patients. Patients were included from January/2020 to July/2022. All patients were followed up for six months or more from infection.

Results

Forty-seven patients were included. The mean follow-up was 13 months (min: 6-max = 33). Sex Female 24 (52%), Age (mean[SD]) = 47 (14) years. 39(85%) were vaccinated before infection. At infection time, 31(66%) of the patients presented proteinuria (protein/creatinine ratio > 0,2 mg/mg). 27(54%) received oral steroids, 27(54%) mycophenolate, 24(51%) prednisone, and 27(54%) renin-angiotensin system inhibitors (RASi). Four (8%) started chronic renal replacement therapy during the follow-up, and 12(25%) required hospital admission. During the pre-infection period, eGFR remained stable (mean change (95%CI): -2.2 (-8.2 to 3.7) mL/min/1.73m2, P = 1. Compared with month six before infection, eGFR decreased at the end of the follow-up by 9.1 (95% CI: 0.96 to 17.2) mL/min/1.73m2, P = 0.019. After stratifying by the presence of proteinuria, eGFR decreased only in those with proteinuria 14.5 (95%CI: 3.7 to 25.4) mL/min/1,73m2, while no changes were observed in those without proteinuria. No changes in proteinuria level after infection were observed. No interaction between drugs used, hospitalisation requirements and eGFR evolution was observed. In the sub-group of patients treated with Paxlovid (all previously vaccinated) after six months of follow-up, no patients required hospitalisation; however, eGFR evolution was similar to the whole group, which decreased only in those with proteinuria at baseline.

Conclusion

The Covid-19 infection in proteinuric GD patients changed the renal function evolution dramatically. The medication used (mycophenolate, steroid and RASi), including Paxlovid, did not influence this evolution. At the end of the follow-up, the accelerated renal function deterioration continues. Urgent therapeutic measures for controlling eGFR decline in these patients are needed.
#5535 CALCIUM EXCRETION FRACTION AS AN EMERGING PARAMETER FOR AN ACCURATE DIFFERENTIAL DIAGNOSIS OF ACUTE KIDNEY INJURY
Authors: Aranzábal María Alejandra Cortiñas , Sánchez Loreto Mariscal de Gante , Villanueva Laura Salanova , Ruano Pablo , Quiroga Borja
Published: June 2023

Background and Aims

Urinary parameter determination is an essential tool for differentiating acute kidney injury (AKI) etiology. The most used ion in clinical practice is sodium (and its excretion fraction, NaEF), followed by urea (UreaEF) (that is useful in certain circumstances such as diuretic treatment). However, tubular transport includes other anions and cations that have not been widely studied. In the present study, we aim to evaluate the relation between AKI etiology (i.e. functional vs acute tubular necrosis) and calcium excretion fraction (CaEF).

Method

This is a transversal study including consecutive patients with diagnosis of AKI. Patients with suspicion of non-functional or ATN etiology (such as those with proteinuria, hematuria) were excluded. At admission, we collected epidemiological data, comorbidities and active treatments. AKI etiology was determined based on urinary parameters (sodium, urea) and recovery pattern of kidney function after treatment instauration. We compared CaEF in patients with ATN and functional AKI in the whole sample and among patients with and without previous CKD and diuretic prescription.

Results

We included 94 AKI episodes (55% female, 76±15 years). Forty-five (48%) patients had chronic kidney disease (CKD) at baseline and 56 (60%) were receiving treatment with diuretics. Of the 94 AKI, 78 (83%) presented a functional etiology and 16 (17%) were catalogued as ATN. Median CaEF was 1.09 (0.63-2.58) %. CaEF was associated to the etiology of AKI. In patients with functional AKI, median of CaEF was 0.95 (0.60-1.84) % in contrast to ATN (2.33 [1.22-7.27] %)(p<0.001). CaEF presented a positive and significant correlation to NaEF (ρ 0.574, p<0.001) and UreaEF (ρ 0.409, p<0.001). An adjusted regression model including the presence of CKD at baseline and diuretic treatment showed that CaEF independently predicted ATN (OR per 1% increase 1.42, 95%CI [1.16-1.75), p<0.001]. In patients without CKD, CaEF predicted ATN (OR 1.61, 95%CI [1.13-2.28], p = 0.008), in contrast to the cohort with CKD where only a trend was demonstrated (OR 1.29, 95%CI [0.99-1.69], p = 0.057) (Figure 1). CaEF also predicted ATN irrespective of the diuretic prescription at baseline (OR 1.35, 95%CI [1.05-1.74], p = 0.018 for diuretic users and OR 1.57, 95%CI [1.06-2.32], p = 0.025 for non-diuretic users) (Figure 1). Receiving operator curves (ROC) demonstrated a 0,712 area under the curve (AUC) of CaEF >1.6% for ATN, that was the best value for diagnosis in terms of sensitivity and specificity. CaEF>1,6% predicted ATN (OR 8.09, 95%CI [2.32-28.2], p = 0.001) after adjusting for the presence of CKD at baseline and diuretic treatment.

Conclusion

CaEF could help in the identification of the AKI etiology as higher values (i.e. >1.6%) are independently associated with ATN.
#5556 QUALITY OF LIFE IN FAMILY CAREGIVERS OF END STAGE KIDNEY DISEASE PATIENTS: A PROSPECTIVE STUDY
Authors: Vovlianou Stavroula , Koutlas Vasileios , Papoulidou Fani , Tsigaras George , Milionis Haralampos , Skapinakis Petros , Ntounousi Evangelia
Published: June 2023

Background and Aims

Family caregivers of patients with end stage kidney disease (ESKD) face the challenge of demanding patients’ care, in addition to their own daily tasks, which affect their well-being and quality of life (QoL). The aim of this prospective study was to assess and describe the QoL of family caregivers of ESKD patients at the beginning of kidney replacement therapy (KRT) and one year later.

Method

Sixty - two ESKD patients and their caregivers were recruited. Caregivers’ QoL was assessed with the Short Form-36 questionnaire and EuroQol-5Dimension-3Level. QoL of caregivers and patients was measured twice, three months after initiation of KTR (T0) (53 patients started hemodialysis and 9 peritoneal dialysis) and after the first 12 months of KTR(T1), in order to investigate the possible changes of QoL during this crucial period.

Results

The mean value (Table 1) of caregivers’ physical component summary (PCS) subscale was found to change significantly during study period (T0: M = 54.21, SD = 8.06 vs T1: M = 51.58, SD = 10.46, (t(61) = 2.02, p = .048). Caregivers presented a statistically significant decrease (p <.05) in physical health after one year of KRT. Likewise, the EQ-5D Index and the EQ-5D visual analogue scale (VAS) showed a statistically significant decline (p = .046 and p<.001 respectively). Finally, correlation of means of QoL dimensions between ESKD patients and their caregivers did not yield statistical significance in the particular longitudinal study.

Conclusion

The results provide evidence that the overall caregivers’ QoL scores deteriorated over the one-year period of KTR. Further studies of larger sizes and with a longer duration will probably better define the QoL variations of ESKD patients’ caregivers. Both groups may be benefit from an educational program before patients initiate KTR.
#5577 PERITONEAL DIALYSIS COMPLICATIONS IN PEDIATRICS: A TUNISION EXPERIENCE
Authors: Abdellatif Abir , Jellouli Manel , Bousetta Abir , Sayari Taha , Gargah Tahar
Published: June 2023

Background and Aims

Peritoneal dialysis (PD) is the preferred chronic dialysis modality for children suffring from chronic end-stage renal failure (CKD). But, it presents different infectious and non-infectious complications, causes of important morbidity and mortality. In this study, we aimed to describe the deferent infectious and mecanical complications observed in children on PD and to investigate the risk factors for the occurrence of different infectious and mechanical complications.

Method

In this study, we retrospectively collected the records of 99 patients who were treated with PD within the last eleven years (2010-2020) in the department of pediatrics of the University Hospital Charles Nicolle of Tunis. Analysis examining possible risque factors were performed using parametric and non-parametric tests and multivariate logistic regression in multivariate analysis.

Results

Ninety-nine children were on PD. All our patients were on automated PD. The sex ratio was 1.02. The overall duration of the PD was 290 years with an average of 2.93 years± 1.92 years. The average age at the beginning of PD was 9.75± 4.67 years. Sixty-nine patients had infectious complications, of which 65 patients had 120 episodes of peritonitis (IP) with a rate of 0.41 episodes per patient-year, 10 patients had exit-site infection and 3 patients had a tunnel infection. Mechanical complications were noted in 63 patients with a catheter revision rate of 1 per 38 patient-months. We noted an hernia in six patients, hemoperitoneum in seven patients, pancreatitis in three patients and no cases of hydrothorax. Analysis of PD complications risk revealed the following factors : poor adherence to treatment (p = 0.018 and p = 0.011) and weight less than 15 Kg (p = 0.041, p = 0.02) for infectious complications and IP respectively, comorbidity (p = 0.005) for mechanical complications, comorbidity (p = 0.008) and history of PI (p = 0.46) for catheter revision.

Conclusion

Ongoing educational programs for doctors, nurses and caregivers are needed to limit infectious complications. A collaboration between the pediatric nephrologist and the pediatric surgeon is recommended to improve catheter insertion techniques and prevent mechanical complications.
#5590 PRE-DIALYSIS TRAJECTORIES OF ESTIMATED GFR AND CONCURRENT TRENDS OF CKD-RELEVANT BIOMARKERS
Authors: Tsao Hsiao-Mei , Lai Tai-Shuan , Lin Shuei-Liong , Chou Yu-Hsiang , Chen Yung-Ming
Published: June 2023

Background and Aims

The glomerular filtration rate (GFR) decline varies in patients with advanced chronic kidney disease (CKD), and the concurrent changes in CKD-related biomarkers are unclear.

Method

We adopted a group-based trajectory model to categorize CKD patients by their pre-dialysis eGFR trajectory and then analyzed the concurrent changing trends of CKD-relevant biomarkers, including urine protein-creatinine ratio (UPCR), albumin, and uric acid.

Results

Using longitudinal data from two years before dialysis initiation, 1,758 CKD patients were included. We identified three distinct eGFR trajectories: persistently low eGFR levels, progressive loss of eGFR, and accelerated loss of eGFR. Eight of the 15 biomarkers showed distinct patterns among the trajectory groups. Compared to the group with persistently low eGFR values, the other two groups were associated with a more rapid increase in the serum urea level and UPCR, especially in the year before dialysis initiation, and a more rapid decline in hemoglobin and platelet counts. Rapid eGFR decline was associated with lower levels of albumin and potassium, and higher levels of MCHC and WBC. The albumin level in the group with an accelerated loss of eGFR was below the normal range. Overall, there was a total of 691 (39.3%) deaths observed during the follow-up period. In the 2-year and 5-year follow-up, 302 (17.2%) and 549 (31.2%) deaths were observed, respectively. The corresponding median follow-up times were 2 years (IQR:1.6 – 2.0) and 3.3 years (IQR:1.6 –5.0). Kaplan–Meier survival plots showed that the eGFR trajectory was significantly associated with the risk of mortality two years and five years after dialysis, with the log-rank test P = .0057 and P = .0001, respectively

Conclusion

The changes in CKD biomarkers were delineated with disease progression. The results provide information to clinicians and clues to elucidate the mechanism of CKD progression.
#5591 CIRCULATING ACTIVIN A REFLECTS THE SEVERITY OF RENAL FIBROSIS IN BIOPSY-PROVEN KIDNEY DISEASES—THE TAIPEI RENAL BIOPSY COHORT STUDY
Authors: Tsai Ming-Tsun , Ou Shuo-Ming , LI Szu-Yuan
Published: June 2023

Background and Aims

Despite considerable evidence indicating circulating activin A as a novel renal biomarker, its performance for predicting the severity of renal fibrosis and major adverse renal events (MARE) has not yet been extensively studied.

Method

We sought to assess the relationship between plasma activin A, renal fibrosis severity, and incidence of MARE in 339 patients undergoing clinically indicated native renal biopsies. To determine the primary source of circulating activin A, RNA-sequencing and histological analyses were performed on kidney biopsy specimens from patients with chronic kidney disease (CKD). We also conducted in vitro experiments to investigate whether inhibiting endogenous activin A could attenuate TGF-β-mediated activation of cultured fibroblasts.

Results

The median baseline eGFR and proteinuria were 36 mL/min/1.73 m2 and 2.9 mg/mg creatinine, respectively. After multivariable adjustment, elevated plasma activin A was associated with the extent of renal fibrosis. Histological analysis showed increased activin A expression in kidney tissues from patients with CKD, mainly in interstitial myofibroblasts. RNA-sequencing of tubulointerstitial tissue from human biopsy samples also revealed a direct correlation between tissue activin A mRNA expression and plasma activin A levels. During a median follow-up of 22 months, 113 participants suffered MARE. Cox proportional hazards analysis revealed that plasma activin A was associated with higher risk of renal events; however, the association became insignificant after correcting for confounders. Results from in vitro studies demonstrated that knocking down activin A expression could prevent TGF-β-induced activation of NRK49F fibroblasts.

Conclusion

The findings of this study support activin A as a potential diagnostic and therapeutic target in fibrotic kidney disease.
#5608 THE INFLUENCE OF AMBULATORY BP ON THE ASSOCIATIONS OF SEX WITH CARDIOVASCULAR EVENTS AND MORTALITY IN DIALYSIS PATIENTS: A PROSPECTIVE COHORT STUDY
Authors: Sarafidis Pantelis , Theodorakopoulou Marieta , Iatridi Foteini , Georgiou Areti , Karagiannidis Artemios , Karkamani Eleni , Tsitouridis Alexandros , Faitatzidou Danai , Papagianni Aikaterini
Published: June 2023

Background and Aims

Male patients with pre-dialysis CKD have worse ambulatory BP control than females and this is associated with higher mortality risk. Male hemodialysis patients have higher ambulatory BP levels compared to females. The aim of this study was to investigate the influence of ambulatory BP on the associations of sex with cardiovascular events and mortality in hemodialysis individuals.

Method

129 male and 91 female hemodialysis patients with valid 48-hour ABPM were followed prospectively for 53.4±31.1 months. The primary endpoint was cardiovascular mortality; the secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, resuscitation after cardiac arrest, hospitalization for heart failure, coronary or peripheral revascularization procedure.

Results

Cumulative-freedom from the primary endpoint was significantly lower for women (logrank-p = 0.032), while cumulative-freedom from the secondary endpoint did not differ significantly between the two groups (logrank-p = 0.644). The crude risk for cardiovascular mortality was significantly higher for women (HR = 1.613, 95% CI [1.037, 2.509]). The crude risk for the combined cardiovascular endpoint was not different between the two genders (HR = 0.918, 95% CI [0.638, 1.320]). After adjusting for other risk factors (age, diabetes, dialysis vintage, coronary disease) no significant differences in the risk for both the primary and the secondary endpoint were observed between women and men (primary: HR = 1.464 (95% CI [0.929, 2.307]), secondary: 0.866 (95% CI [0.596, 1.260])). After additional adjustment for 44-hour ambulatory BP the above relationships did not alter (primary: HR = 1.498, 95% CI [0.947, 2.368]), secondary: (HR = 0.911, 95%CI [0.625, 1.327])).

Conclusion

In contrast to patients with pre-dialysis CKD, ambulatory BP does not appear to significantly influence the relationship between gender and adverse cardiovascular outcomes in hemodialysis patients.
#5619 THE ASSOCIATION BETWEEN THE LEVELS OF URIC ACID AND RENAL OUTCOMES IN EARLY CKD PATIENTS: A MULTI-CENTER REAL-WORLD DATA ANALYSIS
Authors: Luo Yuxin , Song Qirong , Fu Sha , Liu Qin , Chen Xiaohong , Nie Sheng , Chen Junzhe , Tang Ying
Published: June 2023

Background and Aims

It is well known that serum uric acid (SUA) plays an important role both in patients with and without chronic kidney disease (CKD). However, the effect of SUA on renal outcomes of CKD patients, especially with asymptomatic hyperuricemia, remains controversial. Therefore, our study explores the relationship between SUA and adverse events in early CKD (stage 1-3) patients in a real-world setting.

Method

This multi-center real-world study analyzed the data from Chinese Renal Data System (CRDS). Eligible CKD patients (eGFR) (estimated glomerular filtration rate≥30 mL/min/1.73 m2) were enrolled. The primary endpoint is the decline of renal function defined as at least 40% decrease in eGFR. The secondary endpoints include onset of composite cardiovascular events and all-cause mortality. A multivariable cox regression model were used and the associations between levels of mean SUA and all endpoints were evaluated on a continuous scale with restricted cubic spline (RCS) curves based on Cox proportional hazards models. Kaplan-Meier survival curves were used to illustrate the ability of SUA to predict the end points.

Results

25,202 adults (mean [SD] age, 52.59 [17.90] years, 8,212 male [46.1%], 9,604 female [53.9%]) were included in this study. During a median follow-up period of 2.61 years, 3,451 (15.9%) at least 40% decreased in eGFR. After adjustment for confounders, higher uric acid concentrations were independently associated with the higher risk for the decline of renal function [Per SD increment adjusted hazard ratio [aHR]: 1.41, 95%CI 1.36-1.47]; composite cardiovascular events [Per SD increment [aHR]: 1.04, 95%CI 1.01-1.07], all-cause mortality [Per SD increment [aHR]:1.32, 95%CI 1.14-1.54]. RCS curves showed that HRs for renal function progression, all-cause mortality and composite cardiovascular events increased significantly with the increase of SUA concentration in CKD patients. Results were consistent in stratified analyses. The KM curves suggested that patients with asymptomatic hyperuricemia had a substantially worse survival rate for renal function.

Conclusion

SUA is an independent risk factor for the decline of renal function, cardiovascular events and all-cause mortality in early CKD patients (stage 1-3). Treatment of asymptomatic hyperuricemia may be a potential avenue to improve outcomes in CKD patients.
#5624 REMDESIVIR IN COVID-19 PATIENTS WITH KIDNEY DISEASE: A STUDY ON THE RENAL FUNCTION AND OUTCOMES
Authors: Lagura Crystal Faye
Published: June 2023

Background and Aims

The COVID-19 pandemic has created a global catastrophe with mortality rates higher in older adults and people with chronic comorbid conditions In which patients with chronic kidney disease were the most vulnerable population. Remdisivir, an antiviral nucleotide, showed promising results in individuals with COVID-19 infection. However, despite its shortened time to recovery in adults hospitalized with COVID 19, individuals with ESRD and high stage AKI were not included in clinical trials, thus when granted an emergency use authorization it was recommended to avoid use in patients with eGFR <30mL/min “unless benefit outweighs the risk”. In this study, in the absence of Molnupiravir, the current drug of choice, we wished to study its safety by determining its effects on renal status of individuals with known kidney dysfunction. The study aims to determine the effect of Remdesivir on renal function and outcomes among COVID19 patients with kidney disease.

Method

The study utilized a retrospective research design. The study included patients who were 19 years old and above, with RT-PCR confirmed COVID19 infection treated with Remdesivir and who were confirmed to have kidney disease.

Results

106 patients were included; the mean age was 62.25±13.96 years old, more than half of the population were males. The majority of the population had AKI while the rest had CKD and 25% underwent renal replacement therapy. Most of them were classified with severe and critical COVID infection (Table 1). To determine effects on renal function laboratory parameters were determined at baseline and after completion of treatment. There was an overall significant improvement in egfr (<0.01), albuminuria (0.013) and in acid-base balance (0.003) and odds ratio showed that none of the demographic, clinical and laboratory profile significantly in-creased the chance of death in terms of overall clinical outcome (Table 2). To determine risk factors of patients that may contribute to patients outcome, odds ratio showed that none of the demographic, clinical and laboratory profile significantly increased the chance of death among patients who took Remdesivir. (Table 3). In terms of overall clinical outcome, this study had a mortality rate of 4.9% (Table 4).

Conclusion

Use of Remdesivir in patients with AKI, CKD and ESRD on dialysis was not associated with further renal function deterioration. Contrary to concerns there was rather an overall significant improvement in EGFR, degree of albuminuria and acid-base balance after treatment regardless of their disease severity and its use in patients on hemodialysis have not shown any detrimental impact on mortality.
#5642 ASSOCIATION BETWEEN FIBROBLAST GROWTH FACTOR 23 AND TRABECULAR BONE SCORE IN EARLY STAGES OF CKD
Authors: Kužmová Zuzana , Kužma Martin , Gazova Andrea , Killinger Zdenko , Jackuliak Peter , Kyselovič Ján , Payer Juraj
Published: June 2023

Background and Aims

Newer markers of kidney damage and mineral and bone changes in chronic kidney disease (CKD) are needed. The fracture risk increases with worsening of CKD with highest incidence in later stages. Thus methods for early bone status assessment and laboratory marker of kidney function is needed. Aim of the study was to evaluate bone mineral density (BMD) and trabecular bone score (TBS) – a novel surrogate of trabecular bone microstructure, in relationship with newer laboratory markers of CKD, such as fibroblast growth factor 23 (FGF23) and klotho.

Method

A cross-sectional study during July 2018-July2019 was conducted. Plasma levels of soluble klotho and FGF23 were determined by ELISA (enzyme-linked immuno -assay). All patients undergone bone mineral density (BMD) and trabecular bone scores (TBS) measurement. Patients were divided into 2 groups as follows: A - patients in stages G1 - G3; B - patients in stages G4 – 5 accoridng to KDIGO.

Results

A total of 74 CKD patients (42 males and 32 females; mean age 68.8 years) were included in the study. Greater FGF23 levels in group B(N = 15) in comparison to group A (N = 59)(p = .001) were observed. FGF23 was associated with glomerular filtration (GF)(R = -0.43; p = 0.003), with greater levels of FGF23 at GF less than 0.8 ml/s. Significant difference in TBS within first 3 CKD stages (mean TBS in G1 = 1.374 vs. G2 = 1.304 vs. G3a = 1.24; p = 0.03) and negative correlation of FGF23 and TBS (R = -0.33; p = 0.05) and a positive correlation between klotho and TBS (R = 0.419; p = 0.04) was observed.

Conclusion

This study confirmed that FGF23 is associated with TBS. However, TBS reflects kidney function decline only in first 3 stages of CKD. Thus, FGF23 together with TBS are promising markers of early trabecular bone impairment in CKD.
#5655 NEUTROPHIL TO LYMPHOCYTE RATIO, TOTAL IRON BINDING CAPACITY, SERUM ALBUMIN AND SYSTEMIC INFLAMMATION IN CHILDREN WITH CHRONIC KIDNEY DISEASE
Authors: Karava Vasiliki , Kondou Antonia , Dotis John , Taparkou Anna , Farmaki Evangelia , Kollios Konstantinos , Printza Nikoleta
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is widely linked to chronic inflammation, with a higher incidence in the advanced stages of the disease. Recognition of systemic inflammation may be useful for prompt diagnosis and management of various CKD related disorders and may open the door towards the development and application of anti-inflammatory strategy treatments. This case-control and cross-sectional study investigates the association of neutrophil to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), total iron binding capacity (TIBC) and serum albumin with high serum interleukin-6 (IL-6) in children with chronic kidney disease (CKD).

Method

NLR and PLR were measured in 53 patients (median age: 12.9 years) and 25 healthy controls, stratified by age and sex. Lipid and iron profile, glucose tolerance parameters, serum albumin, uric acid and IL-6 were measured in the patient group.

Results

Compared to controls, NLR and PLR were higher in patients (p = 0.004 and p = 0.032 respectively), and particularly in those with CKD on dialysis (CKD 5D) (17 patients) (p<0.001 and p = 0.001). LnIL-6 was correlated to NLR (rs = 0.344, p = 0.014), albumin (rs = -0.350, p = 0.011) and TIBC (rs = -0.345, p = 0.012) after adjustment for CKD stage, while the correlation between lnIL-6 and PLR was not significant (rs = 0.206, p = 0.151). Patients with NLR ≥1.7, TIBC ≤300 μg/dl and albumin ≤3.8 g/dl presented a higher risk for increased IL-6 (15 patients) regardless CKD stage (OR 5.499, 95% CI 1.272-22.017, p = 0.016, OR 9.818, 95% CI 2.311-41.706, p = 0.002 and OR 7.543, 95% CI 1.891-30.083, p = 0.004). NLR ≥1.7 and TIBC≤ 300 μg/dl predicted high IL-6 with the highest sensitivity (73.3%), while NLR ≥1.7, TIBC≤ 300 μg/dl and serum albumin ≤ 3.8 g/dl with the highest specificity (97.4%).

Conclusion

Both NLR and PLR increase in pediatric CKD, especially in CKD 5D. NLR rather than PLR may serve as diagnostic marker of systemic inflammation in pediatric CKD, along with TIBC and serum albumin.
#5673 ESTIMATING AND VALIDATING MEASURES OF CKD PREVALENCE AND INCIDENCE USING OBSERVATIONAL AND CLAIMS DATA IN PERSONS AGED 70+
Authors: Bothe Tim , Fietz Anne-Katrin , Pöhlmann Anna , Schaeffner Elke , Mielke Nina , Ebert Natalie
Published: June 2023

Background and Aims

Estimating prevalence and incidence of chronic kidney disease (CKD) based on claims data often underlies bias and limitations due to uncertainty of diagnostic validity. We investigated CKD prevalence and incidence over time using data from a community-dwelling cohort of individuals aged 70+ linked to individual claims data. We assessed the diagnostic validity of the claims-based compared with the eGFR-based CKD definition.

Method

We assessed CKD prevalence and incidence in two data sources: 1) eGFR values of participants aged 70+ (n = 2,069) of the Berlin Initiative Study (BIS), including five biennial study visits from 2009-2019, and 2) claims data of BIS participants matched on person-level. Using eGFR, we defined CKD prevalence as eGFR <60 ml/min/1.73m² calculated with the creatinine-based CKD-EPI (2009) equation. For each study visit, prevalent CKD cases were considered as incident if eGFR was ≥60 ml/min/1.73m² in the respective previous study visit. In claims data, in- and outpatient ICD-10 diagnoses (N18.3, N18.4, N18.5, N18.8, N18.9, N19) in the year preceding and/or following the study visit date were used to determine CKD prevalence. Incidence was defined as prevalent cases without a diagnosis in the year preceding the first CKD diagnosis. The denominator for incidence was defined as all persons at risk, i.e., who were not prevalent in a respective previous study visit and still under observation. We assessed the diagnostic validity of claims-based CKD prevalence and incidence using eGFR data as a reference. Analyses were stratified by sex.

Results

Between 2009 and 2019, CKD prevalence increased from 0.42 to 0.51 based on eGFR and from 0.30 to 0.43 based on claims data. Incidence varied between 0.16–0.22 using eGFR and 0.07–0.13 using BIS claims data. There was no clear time trend for incidence in any data source. Diagnostic validity of claims-based CKD prevalence and incidence detection is displayed in Table 1. Sensitivity for prevalence increased while other indicators remained stable over time. Detection of incident cases showed lower sensitivity (0.18–0.30 vs. 0.58–0.70) and PPVs (0.40–0.60 vs. 0.79–0.83) compared to prevalence, respectively. Prevalence and incidence based on claims data were slightly higher in males compared to females (Figure 1).

Conclusion

Using the eGFR-based or claims-based definition of CKD we found an increase in prevalence between 2009 and 2019. This might be due to the introduction of the KDIGO guidelines in 2012. During the same time, CKD incidence rates were stable. Comparing the claims-based with eGFR-based CKD definition, we found a sensitivity of 0.58-0.70 for prevalence and 0.18-0.30 for incidence, indicating that there is a risk of underdetection of CKD when using solely claims data, in particular for incident cases.
#5674 HYPERURICEMIA AND HIGH URINARY URIC ACID LEVELS ARE THE NEW EARLY PREDICTORS OF CONTRAST-ASSOCIATED ACUTE KIDNEY INJURY
Authors: Cadri Vilma , Toska Loriana , Strakosha Ariana , Rista Elvana , Pasko Nevi , Imeraj Matilda , Barbullushi Myftar , Dibra Alban
Published: June 2023

Background and Aims

Contrast associated acute kidney injury (CA-AKI) is recently evidenced with lower frequency although yet worldwide its incidence ranges from 0-24%. Recent studies and meta-analysis have reported that hyperuricemia seem to be a useful biomarker in the early prediction of CIN incidence. The role of urine PH and spot uric acid to creatinine ratio (UACR) provide controversial evidence on the occurrence of CA-AKI. This research aims to gather evidence on the effect of uricemia, urine PH and UACR on the development of CA-AKI in acute conditions like primary percutaneous coronary interventions (PCI).

Method

A sample of 100 patients who underwent emergency coronary angiography in Cardiology Intensive Care Unit/UHCN-Tirana/Albania from October 2021- March 2022 were enrolled. Among these patients CA-AKI incidence was monitored, while CA-AKI was defined as an increased creatinine levels of more 25% of the baseline in a time window of 48-72h after the contrast. The analyses of the results were performed using ANOVA test for differences in parameters among CA-AKI/Non – CA-AKI patients. In order to understand the effect of each factor on the probability of experiencing CA-AKI a binary logistic regression model was constructed. Statistical analyses were performed using R-software.

Results

The general incidence of CA-AKI is 40%, while being different for men and women, with men incidence being 60%. The mean age for the patients observed was age 64.7 years old. The ANOVA analyses showed that incidence of patients experiencing CA-AKI is significantly different for chronic kidney disease patients (p (0.001, OR = 32.67 (95%CL 9.65-110.55), patients with diabetes (P 0.0033, OR = 4.64 (95%Cl 1.69-12.68) and hypertension (p 0.055, OR = 7.80 (95%Cl 0.96-63.56). The binary logistic regression showed that probability to experience CIN is significantly impacted by UACR post contrast model 1 :3.123 (2,385) with marginal effect 22.72, BMI index model 1: (−0.850) 0.25 with marginal effect 1.28, Uricemia model 1: (1,128) 0.52 with marginal effect 1.68 and Natremia level before contrast model 1: (−1,831) 0.0011 with marginal effect 7.81. Statistical significance for these results is 99% (as manifested by p-value).

Conclusion

CA-AKI post PCI is still the Achilles Heel of interventional cardiology. The results confirm that the increase of uricemia and BMI doubles the risk for CA-AKI. Uricemia is confirmed as an important prognostic factor for development of CA-AKI. High urinary uric acid levels post contrast define UACR independent early risk factor for CA-AKI.
#5689 ASSOCIATION BETWEEN INTERLEUKIN-37 RS3811047 POLYMORPHISM AND LUPUS NEPHRITIS IN AN EGYPTIAN POPULATION
Authors: Ismaeel Samah , Omar Hamdy , Ellawindy Alia , Omar Hanan , Hashem Asma , Tawfeek Marwa
Published: June 2023

Background and Aims

Systemic lupus erythematosus (SLE) is a chronic, clinically heterogenous, autoimmune disorder with unpredictable course and features ranging from mild skin affection to life-threatening involvement of major organs. Interleukin 37 (IL-37) is a cytokine with anti-inflammatory and immune-suppressive effects; it suppresses both innate and adaptive immune responses, thus protecting against excessive inflammation-induced tissue damage.

Aim

investigate the association of IL-37 (rs3811047) polymorphism with lupus nephritis in Egyptian population.

Method

This case-control study comprised 3 groups: 109 SLE patients without nephritis, 97 SLE patients with LN, and 240 healthy controls. History taking, clinical examination, disease activity in SLE patients was assessed and routine laboratory tests were done. Genotyping of the IL-37 rs3811047 polymorphism was done using real time polymerase chain reaction (PCR).

Results

The AA genotype was more frequently represented in LN patients (21.6%) compared to SLE patients without LN (7.3%) (p = 0.007), and carriers of the AA genotype had four times increased susceptibility to acquire LN compared to GG and GA genotype carriers (OR: 4.1). Likewise, the A allele was more represented in LN patients (43%) than in SLE patients without LN (30%) (p = 0.004), and the carriers of the A allele had nearly two times more risk of developing LN compared to carriers of the G allele (OR: 1.79). Moreover, the AA genotype was associated with LN susceptibility under the recessive genetic model (OR = 3.49, CI: 1.47-8.30) (p = 0.002), but not under other genetic models.

Conclusion

The AA genotype of the IL-37 rs3811047 polymorphism contributes to the development of SLE in Egyptian patients with doubled risk of acquiring LN in carriers of the allele A.
#5705 EFFICACY AND SAFETY OF SACUBITRIL/VALSARTAN IN PATIENTS WITH STAGE 3B-5 CKD AND HYPERTENSION
Authors: Zhou Qin , Yu Wenjuan , Shao Xiaofei , Liu Qin , Wang Honglei , Chen Junzhe , Tang Ying
Published: June 2023

Background and Aims

Sacubitril/valsartan (SV) plays a key role in improving left ventricular remodeling and prognosis in patients with heart failure. However its effects on kidney function in people with moderate to severe chronic kidney disease (CKD3b-5) are unknown. The present study was designed to assess the efficacy and safety of sacubitril-valsartan in patients with stage 3b-5 CKD and hypertension.

Method

In this randomized, double-blind, 3-month trial, patients with stage 3b-5 CKD and hypertension were randomly assigned to sacubitril/valsartan treatment group (n = 44, the doses of SV were up-titrated to sacubitril/valsartan 400 mg), and conventional antihyperensive treatment group (n = 40). The primary outcome was reduction in GFR from baseline at week 12.

Results

In total, 44 participants were assigned to sacubitril/valsartan group and 40 to crontol group (conventional antihyperensive group). Baseline measured GFR was 29.94±11.83, 27.86±10.14 mL/min/1.73 m2, respectively. There was no difference in measured GFR (P = 0.064). At week 12, there was a reduction in measured GFR in control group: 27.86±9.15 versus 22.03±11.41, but there was no significant difference (P = 0.155). Sacubitril/ valsartan could improve eGFR: 29.94±11.83 versus 32.05±14.57 (P = 0.018). We also observed that, compared with control group, sacubitril/valsartan decreased albuminuria: reductions in urinary albumin:creatinine ratio (ACR) in sacubitril/valsartan group was 89.5mg/g and reductions in urinary ACR in control group was -44.55mg/g. At week 12, Sacubitril/valsartan provided a significantly greater reduction in office mean sitting (ms) systolic BP (msSBP) than control group (20.75mmHg vs 12.88mmHg, P = 0.046). There was no serious adverse events in both groups. The incidence of hyperkalemia (potassium≥5.5 mmol/L) was 4.5% in SV group and 7.5% in control group.

Conclusion

The present data suggested that, in patients with stage 3b-5 CKD and hypertension, Sacubitril-valsartan could improve kidney function and decrease albuminuria, and was generally safe and well tolerated.
#5772 ESTIMATING CKD PREVALENCE AND INCIDENCE USING CROSS-SECTIONAL GERMAN CLAIMS DATA IN PERSONS AGED 70+
Authors: Bothe Tim , Fietz Anne-Katrin , Pöhlmann Anna , Schaeffner Elke , Mielke Nina , Freitag Julia , Krage Birgit , Ebert Natalie
Published: June 2023

Background and Aims

Little is known about trends over time and anticipated improvements in CKD diagnosis after the implementation of the Kidney Disease – Improving Global Outcomes (KDIGO) guidelines in 2012. We investigated CKD prevalence and incidence over time using claims data in persons aged 70+.

Method

We assessed CKD prevalence and incidence biennially in cross-sectional claims data of the German health insurance fund “AOK Nordost” for persons aged 70+ between 2012 and 2018. Data are available for n = 62,200 persons per year and were sampled equally distributed for five age strata (70-74, 75–79, 80–84, 85–89, ≥90) and for sex. CKD prevalence and incidence were estimated in 2012, 2014, 2016, and 2018 using in- and outpatient ICD-10 diagnoses (N18.3, N18.4, N18.5, N18.8, N18.9, N19). Incidence was defined as prevalent cases without a diagnosis in the four quarters preceding their first CKD diagnosis over all persons at risk (i.e., who were not prevalent in the respective previous year). Results are shown in total (standardized by age and sex using nationwide demographic distributions for a respective year) as well as stratified by age and sex. Cochran-Armitage test was applied to test time trends for incidence and prevalence from 2012–2018.

Results

Claims data-based CKD prevalence showed a significant constant increase from 0.18 in 2012 to 0.26 in 2018 (p <0.001). This time trend in CKD prevalence was consistent among all age and sex strata (Figure 1). Over the same time period, CKD incidence increased from 0.06 to 0.08 (p <0.001), while the percentage of persons at risk decreased from 0.81 to 0.72 between 2012 and 2018 due to increasing prevalence (Table 1). Both prevalence and incidence estimates were higher in males compared to females in all age strata (Figure 1).

Conclusion

The present cross-sectional analysis in claims data allows novel insights of CKD prevalence and incidence among older adults in Germany. CKD prevalence increased constantly over time after the introduction of the KDIGO guidelines in 2012. For CKD incidence, we detected only a small increase over the observation period. The extent of time trends for CKD incidence might be underestimated due to increasing prevalence.