bluuebunny/crossref_metadata_2025 huggingface dataset:
#3595 DIALYSIS MODALITY AFFECTS SENESCENCE-RELATED PHENOTYPE OF T AND B LYMPHOCYTES
Authors: Lioulios Georgios , Fylaktou Asimina , Tourountzis Theodoros , Christodoulou Michalis , Moysidou Eleni , Giamalis Panagiotis , Tsouchnikas Ioannis , Papagianni Aikaterini , Stangou Maria
Published: June 2023

Background and Aims

Hemodiafiltration (HDF) is characterized by enhanced clearance of middle molecular weight toxins and therefore, it is considered superior to hemodialysis (HD), especially in higher hemofiltration volumes. Although proinflammatory cytokines are lower in HDF, its impact on immune phenotype has not been studied, so far. In this study we compared the lymphocytes’ senescent phenotype between HD and HDF patients.

Method

Senescent and exhausted related lymphocyte markers, including CD45RA, CCR7, CD28, CD57 and PD1 on T cells and CD27 and IgD on B cells, were assessed by flow cytometry in 35 ESRD patients on HD and 25 ESRD patients on HDF of similar age, sex, and ethnicity. Moreover, we evaluated the association of these markers with hemofiltration volume.

Results

Patients on HDF had significantly reduced CD4+CD28- T lymphocytes, 31(18-74) vs 50(36-131)cells/μL, respectively, p = 0.019, which was restricted only in the CD28-CD57- T cells compartment, [17(9-25) vs 31(19-50)cells/μL, p = 0,002], while terminally differentiated CD28-CD57+ did not differ between the two groups [14(4-49) vs 23(7-52)cells/μL, p = 0,22]. Expression of CD57 molecule on CD4+ T cells depended on dialysis vintage (r = 0.27, p = 0.03). Moreover, HDF patients had lower percentage of CD4+PD1+ exhausted T cells [8.5(6.8-11.7) vs 13.7(8.7-19.5) % for HDF and HD respectively, p = 0.006]. CD8+PD1+ T cells were also lower in HDF patients, without reaching statistical significance [17.4(8.5-41) vs 34(12,7-52.9) % for HDF and HD respectively, p = 0.06]. Hemofiltration volume was negatively correlated to effector memory CD8+ T cells re-expressing CD45RA count (CD8+ EMRA), (r = -0.46, p = 0.027) and positively correlated to total B cells count (r = 0.46, p = 0.025). However, not all B cell subsets were equally affected, with only naïve IgD+CD27- B cells and switched memory IgD-CD27+ B cells count showing positive correlation with hemofiltration volume (r = 0.53, p = 0.008 and r = 0.5, p = 0.015, respectively).

Conclusion

Hemodiafiltration and high filtration volumes may have beneficial effects on adaptive immunity, predisposing to less senescent and exhausted T and B cell phenotypes.
#3620 AGING-RELATED RENAL FIBROSIS WAS ALLEVIATED VIA CONSERVING MITOCHONDRIAL FUNCTION AND AUTOPHAGY IN NLRP3 KO MICE
Authors: Kim Yang-Gyun , Lee Sang-Ho , Moon Ju-Young , Jung Su Woong , Jeong Kyung Hwan , Hwang Hyeon Seok , Kim Jin Sug , Cho Minhae
Published: June 2023

Background and Aims

Nod-like receptor family, pyrin domain containing-3 (NLRP3) activation in kidney diseases contributes to aggravating disease progression and fibrosis. However, the role of NLRP3 in renal aging is not clear. This study was designed to identify whether the NLRP3 KO mice could be protected from renal aging.

Method

NLRP3 KO and counterpart wild-type (WT) mice were used at different ages (3 months, 12 months, and 24 months). Plasma, urine, and kidneys were collected.

Results

Plasma creatinine and blood urea nitrogen (BUN) increased with aging, while BUN was significantly decreased in NLRP3 KO old mice (24M) compared with WT old mice. NLRP3 ablation contributed to decreasing tubular vacuolization, tubulointerstitial fibrosis, and atypical autophagosomes with aging. In line with it, renal fibrosis markers, such as connective tissue growth factor, and fibronectin were alleviated in RT-PCR tests. Immunoblot results showed that autophagy with mitochondrial biogenesis increased in old NLRP3 KO mice. In addition, phosphorylated AMP-activated protein kinase and persoxisome proliferator-activated receptor gamma coactivator 1α were increased in old NLRP3 KO mice. Transcriptional expression data using kidney RNA bulk sequencing showed augmentation of autophagy and mitochondrial biogenesis in old NLRP3 KO mice.

Conclusion

NLRP3 absence prevented aging-related renal fibrosis via maintaining renal mitochondrial biogenesis and autophagy.
#3635 THERAPEUTIC STRATEGIES TARGETING RAGE IMPROVES RENAL OUTCOME IN LUPUS NEPHRITIS
Authors: Taguchi Kensei , Yokota Yunosuke , Kodama Gou , Itou Sakuya , Fukami Kei
Published: June 2023

Background and Aims

Lupus nephritis (LN) occurs in up to 60% of patients with systemic lupus erythematosus (SLE). Despite of current development of immunosuppressant agents, LN still impairs the survival and quality of life in SLE patients. Receptor for advanced glycation endproducts (RAGE) is a multi-ligand receptor that belongs to the immunoglobulin superfamily, which is strongly associated with innate immune system. In the present study, we examined whether RAGE is involved in the development of LN. Further, we explored the therapeutic impact of DNA-aptamer directed against RAGE on lupus-related kidney injury.

Method

[Protocol 1] RAGE expression in kidneys and urinary RAGE excretion (uRAGE) were determined at 8, 12, 16, 18, 20-week-old by real-time PCR and ELISA, respectively in MRL/lpr, SLE-prone mice. [Protocol 2] LN was induced by peritoneally injecting pristane in wild type and RAGE globally knockout mice. [Protocol 3] MRL/lpr mice were subcutaneously administrated with DNA-aptamer raised against RAGE (RAGE-apt) or Control-aptamer (Ctrl-apt) for 10weeks.

Results

[Protocol 1] uRAGE, but not urinary protein excretion, was increased in 8-week-old MRL/lpr mice when compared to that of the control of MRL/MPJ mice. uRAGE is positively correlated with urinary NAG, a tubular injury marker, suggesting that uRAGE can predict the onset and the progression of LN. Immunofluorescence staining demonstrated that RAGE was upregulated in distal tubules but not in glomerulus in early stage, meanwhile RAGE started to be extensively expressed in nephron at late stage of LN. Not only tubules, but RAGE was also found in infiltrated macrophages in glomerulus. In proximal tubules (PTC), RAGE was co-localized with cathepsine D, a lysosomal aspartyl protease, and Rab7, a marker of late endocytosis, suggesting that PTC RAGE is involved in endosome-related protein degradation. [Protocol 2] Pristane-induced the increase in systolic blood pressure was reduced with improvement of renal dysfunction in RAGE knockouts. RAGE knockouts also showed less fibrosis with the decrease in macrophage infiltration when compared to wild type mice in pristane-induced lupus nephritis. [Protocol 3] Similar to RAGE knockouts, administration of RAGE-apt reduced systolic blood pressure and attenuated the renal dysfunction. RAGE-apt also ameliorated mesangial expansion, crescent formation, and macrophage infiltration into glomerulus in MRL/lpr mice. The level of pro-inflammatory cytokines gene expression including IL-6, TNF-a, and MCP-1 was reduced by RAGE-apt, but not Ctrl-apt, in MRL/lpr mice.

Conclusion

RAGE could be involved in the pathogenesis of LN, and RAGE-DNA aptamer might be one of the promising therapeutic strategies for preventing the development of LN.
#3650 LINACLOTIDE IS PROTECTIVE AGAINST RENAL ISCHEMIA-REPERFUSION INJURY
Authors: Hitaka Yukihiro , Nakamura Kimihiko , Isoyama Naohito , Shiraishi Koji
Published: June 2023

Background and Aims

Renal ischemia-reperfusion injury is associated with delayed graft function and poor long-term graft survival following transplantation. Linaclotide is a guanylate cyclase C (GC-C) receptor agonist that increases intracellular cGMP concentrations and promotes intestinal transport capacity by activating the GC-C receptor. Since CKD is a deficiency of cGMP in the kidney, increasing cGMP in the kidney by linaclotide would suppress fibrosis, protecting the kidney.

Method

An AKI rat model of unilateral nephrectomy plus contralateral ischaemia (30 min) and impaired reperfusion (up to 14 days) was used. Linaclotide was administered before and after surgery for 2 weeks, and blood and renal tissue samples were collected to determine its effect on renal function and whether it was protective against the progression of CKD.

Results

In the I/R injury+ group, creatinine levels were lower in the linaclotide-treated group than in the non-treated group. Sirius red staining showed significant improvement in fibrosis. The hydroxyproline content of kidneys was determined by the basic hydroxyproline method. RNA seq showed that genes down-regulated in I/R injury+ were the oxidative stress markers SOD3 and Gpx1. The expression of genes down-regulated in I/R injury+ was up-regulated to a degree similar to that in I/R injury- by treatment with linaclotide. These data suggest that linaclotide may ameliorate renal fibrosis by suppressing renal dysfunction through its antioxidant effects.

Conclusion

The antioxidant effect of linaclotide was found to suppress the decrease in renal function caused by I/R. We would like to apply this finding to human renal transplantation in the future to prevent renal function deterioration due to I/R.
#3654 ABO-INCOMPATIBLE KIDNEY TRANSPLANTATION LOWERS INCIDENCES OF DE NOVO DONOR-SPECIFIC ANTIBODIES AND CHRONIC ANTIBODY-MEDIATED REJECTION
Authors: Weidmann Lukas , Lopez Kai Castrezana , Schmid Nicolas , Mueller Thomas , Schachtner Thomas
Published: June 2023

Background and Aims

ABO-incompatible kidney transplantation has been associated with an increased risk for antibody-mediated rejection (ABMR) and early graft loss attributable to isoagglutinins. Its impact on the development of de novo donor-specific HLA antibodies (DSA) and DSA-induced chronic ABMR, however, remains less well studied.

Method

We analyzed 297 kidney transplant recipients (KTRs) who underwent living donor transplantation at the University Hospital Zurich from 2009 to 2021. 58 ABO-incompatible (iABO) KTRs were compared to 239 ABO-compatible (cABO) KTRs concerning the development of de novo donor-specific antibodies (DSA) and antibody-mediated rejection (ABMR). ABO desensitization was performed using rituximab and antigen-specific immunoadsorption. The HLA-derived epitope-mismatches were calculated per HLA-locus and in total using the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm. High-resolution re-typing was performed from protocol kidney allograft biopsies if necessary.

Results

The incidence of TCMR/ABMR in the first post-transplant year was comparable between iABO KTRs (19%) and cABO KTRs (13%; p = 0.207). De novo DSA were detected in only 1 of 58 iABO KTRs but 12 of 239 cABO KTRs in the first post-transplant year and 2 of 58 iABO KTRs but 50 of 239 cABO KTRs in the long-term follow-up (p = 0.001). ABMR was diagnosed in only 1 of 58 iABO KTRs but 28 of 239 cABO KTRs after the first post-transplant year (p = 0.021). iABO kidney transplantation decreased the risk of de novo DSA development (HR 7.222, CI 1.755-29.722, p = 0.006) and ABMR (HR 7.362, CI 1.000-54.239; p = 0.050) after the first-post-transplant year independent from the presence of preformed DSA. Total PIRCHE-II scores and PIRCHE-II scores per locus were not associated with the development of de novo DSA in all 297 living-donor KTRs (p>0.05).

Conclusion

Our findings suggest that iABO kidney transplantation is associated with a lower incidence of de novo DSA and ABMR in the long term, independent from the HLA-derived epitope mismatch load. Whether this protective effect offers new therapeutic options against kidney allograft injury needs to be investigated in future studies.
#3706 EFFECT OF CHOLECALCIFEROL INTAKE ON NOVEL INFLAMMATORY INDICATORS IN HEMODIALYSIS PATIENTS
Authors: Ghazy Mona Alshahawey , Elwakeel Lamia , Sabri Nagwa , Said Tamer El , Maher Radwa
Published: June 2023

Background and Aims

Hemodialysis patients (HD) are in a chronic state of systemic inflammation, with vast majority of these patients are vitamin D deficient. Vitamin D appears to be a strong controller of inflammation. It's well known that C-reactive protein (CRP) is considered the gold of inflammatory markers. Recently, neutrophil- to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been shown to be inexpensive, readily available indicators of systemic inflammation. This study is to demonstrate the pleotropic effects, the efficacy and the safety of two dosing regimens of cholecalciferol; (weekly regimen vs monthly regimen) on novel inflammatory indicators in HD population.

Method

A prospective, randomized trial was carried out to evaluate the effect of weekly versus, monthly oral cholecalciferol, on vitamin D (25(OH)D) levels, on inflammatory markers and secondary hyperparathyroidism in HD patients. Fifty eligible HD patients were randomly assigned to either Group A (Once weekly oral 50.000IU Cholecalciferol) or Group B (One monthly, oral 200.000IU Cholecalciferol), for 3 months’ period. Serum levels of high sensitive CRP (hsCRP), NLR, PLR, were all assessed at baseline and at the end of the study.

Results

Cholecalciferol significantly increased serum levels of 25(OH)D in both groups. A significant decrease in serum hsCRP levels (p <0.001) and NLR was noted only in Group A. No significant difference in calcium or phosphorus levels was noticed. No side effects or adverse events were reported.

Conclusion

Weekly (50.000 IU) oral cholecalciferol appears to have a beneficial action on replenishing 25(OH)D levels in HD patients, with an ameliorative action on inflammatory status as well. NLR seems to be an effective, non-expensive inflammatory indicator in HD.
#3746 RISK OF PROGRESSIVE CHRONIC KIDNEY DISEASE WITH NEPHROSCLEROSIS ON KIDNEY BIOPSY DEFINED USING AGE-BASED VERSUS YOUNG ADULT-BASED THRESHOLDS
Authors: Asghar Muhammad , Denic Aleksandar , Mullan Aidan , Alexander Mariam , Rule Andrew
Published: June 2023

Background and Aims

The tissue pathology of both aging and chronic kidney disease (CKD) is nephrosclerosis defined by globally sclerotic glomeruli (GSG) and interstitial fibrosis and tubular atrophy (IFTA). We sought to determine if risk of CKD outcomes is better predicted by age-based or young adult-based thresholds for nephrosclerosis.

Method

Using the Aging Kidney Anatomy study, living kidney donors, kidney tumor patients, and native kidney disease patients had kidney biopsy images analyzed morphometric to quantify %GSG, %IFTA, and IFTA foci density (Figure 1). Using normotensive donors, young (18-29 y) thresholds and age-based (18-29 y, 30-39 y, 40-49 y, 50-59 y, 60-69 y, 70+y) 95th percentile thresholds were defined. Progressive CKD was defined as a 40% decline in serum creatinine based estimated GFR or kidney failure (dialysis or transplantation) from a 4-month post-biopsy baseline (due to the nephrectomy event in tumor patients and due to the common occurrence of acute kidney injury in the native kidney disease patients at the time of biopsy). The age-adjusted risk of progressive CKD in tumor patients and native kidney disease patients was compared between those with nephrosclerosis that was “normal compared to young”, “normal for age but abnormal compared to young”, and “abnormal for age” (Figure 2).

Results

There were 2583 normotensive living kidney donors, 1363 tumor patients, and 314 native kidney disease patients studied. The 95th percentiles for 18-29y to 70+y age groups among normotensive donors were 1.7% to 16% for %GSG, 0.18% to 6.5% for %IFTA, and 8.2 to 59.3 per cm2 for IFTA foci density. The risk of CKD outcomes did not differ between tumor patients and native kidney disease patients with nephrosclerosis “normal compared to young” versus “abnormal compared to young but normal for age” in both cohorts. Thus, these two categories were combined into “normal for age”. The risk of progressive CKD over a median 5.5 years follow-up for tumor patients was higher with %GSG, %IFTA, and IFTA foci density that was abnormal for age vs normal for age (HRs 2.28, 2.41, and 3.11, respectively, p<.0001 for all). The risk of progressive CKD over a median 7.2 years follow-up for native kidney disease patients was higher with %GSG, %IFTA, and IFTA density that was abnormal for age vs normal for age (HRs 1.87, 2.65, and 3.11, respectively, p<.0001 for all).

Conclusion

There is a substantial increase in nephrosclerosis from aging alone in healthy adults that is not prognostic for CKD outcomes. Age-based thresholds better identify clinically relevant CKD.
#3759 URINARY DCR2/CR LEVEL PREDICTS RENAL OUTCOME IN PATIENTS WITH ACUTE KIDNEY INJURY
Authors: Yi Xiangling , Chen Kehong , Luo Jia , Chen Jia , He Yani
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is a well-recognized complication of critical illness which increases the risk of morbidity and mortality. It has been reported that about 30% of AKI patients developed to chronic kidney disease (CKD), and even to end-stage renal disease (ESRD). It is urgent to explore novel biomarkers to evaluation the renal outcome of AKI. Decoy receptor 2 (DcR2), a senescent marker, is expressed specifically in senescent tubular epithelia. And urinary DcR2 (uDcR2) is associated with renal fibrosis in chronic kidney disease. The aim of study is to investigate the association of urine DcR2 with renal outcome of AKI.

Method

153 biopsy-proven AKI patients were included from Daping Hospital, Army Medical University from January 2018 to October 2022. A composite renal endpoint included creatinine more than 50% higher than the baseline or ESRD after 90 days. All patients were divided into positive endpoints (n = 75) and negative endpoints (n = 78). The clinical characteristics were collected, and the pathological injury was scored. uDcR2 levels were measured using enzyme-linked immunosorbent assay and normalized to urinary cre (uDcR2/Cr). The correlation of uDcR2/Cr levels with renal function and renal pathological scores were analyzed. The logistic regression analysis was used to investigate the association of uDcR2/Cr with endpoint positive, after adjustment for probable causes of both exposure and outcome. The association of uDcR2/Cr with the composite renal endpoint using Kaplan-Meier curves were calculated.

Results

The level of uDcR2/Cr was positively correlated with cystatin C, and negatively correlated with estimated glomerular filtration rate (eGFR). And uDcR2/Cr was positively associated with renal pathological acute scores. Univariate logistic regression results increase the risk factors for poor kidney prognosis are age, female, with hypertension or (and) CKD, eGFR, Cystine C and uDcR2/Cr. Multivariate logistic regression analysis showed that the effect of uDcR2/Cr on renal outcome was statistically significant. After a median follow-up of 16 months, 75 participants achieve endpoint and there were 16 patients with end-stage renal disease. The ROC curve was used to analyze the value of uDcR2/Cr for predicting kidney prognosis in AKI with an area under the curve of 0.72 and the cut-off value of 365ng/g Cr. The median time from at the time of AKI to endpoint in the uDcR2/Cr≥365ng/g Cr group (7.6 months) was significantly shorter compared to the uDcR2/Cr<365ng/g Cr group (36.6 months).

Conclusion

Urinary DcR2/Cr is closely associated to kidney injury and renal prognosis of AKI, suggesting that uDcR2/Cr could sever as a novel biomarker for predicting adverse outcomes in patients with AKI.
#3768 CDYL IS A THERAPEUTIC TARGET FOR ACUTE KIDNEY INJURY BY REGULATION PYROPTOSIS
Authors: Xiang Ting , LI Lingzhi , Yiting Wu , Fu Ping , MA Liang
Published: June 2023

Background and Aims

Pyroptosis as a necrosis type related to inflammation, is involved in various diseases, including acute kidney injury (AKI). Here, we report that Chromodomain Y-like (CDYL) is critical for pyroptosis regulation in AKI.

Method

Cisplatin-induced mouse model and cisplatin-induced TCMK-1 cell model of AKI were established, serum creatinine (Cr) and blood urea nitrogen (BUN) were measured to evaluate kidney function, and renal tissue lesions were observed by HE staining. The expression of gene/protein in relation to inflammation and pyroptosis were measured by qPCR and western blot. The CDYL was overexpression in mice by rapid injection of a volume of naked plasmid DNA solution (30 ug) through the tail vein 2 hours before intraperitoneal injection of cisplatin.

Results

The results indicate that CDYL was increased in cisplatin-induced and sepsis-induced AKI, and overexpression of CDYL in mice would significantly increase the expressions of NGAL, NLRP3, Caspase-1, GSDMD, IL-1β, MCP-1, TNFα and IL-6 (Fig. 1). RNA-seq shown that the genes were mainly enriched in fatty acid metabolic process when CDYL overexpression, and FABP4 was finally identified as the key downstream factor (Fig. 2). Overexpression of CDYL in cisplatin-induced AKI further aggravated renal injury compared with the model mice, as indicated by the increased inflammation and pyroptosis protein expression, and worse tissue architecture, while the knockout of FABP4 will attenuate the injury (Fig. 3). In addition, treatment with CDYL inhibitors could attenuate inflammation and pyroptosis in cisplatin-induced renal injury (Fig. 4) and cisplatin-stimulated TCMK-1 cells (Fig. 5).

Conclusion

CDYL played a role in inflammation and pyroptosis regulation in AKI. Inhibition of CDYL could suppress renal inflammatory response and pyroptosis, and improve kidney function via modulation of FABP4 expression. The results highlighted that CDYL might represent a potential therapeutic target against AKI.
#3829 ARTERIAL STIFFNESS AND METABOLIC SYNDROME INDICES IN RENAL TRANSPLANTATION PATIENTS
Authors: Guliyev Orkhan , Mamedzade Ayten , Ismayilova Shalala , Jabrayilov Jabrayil
Published: June 2023

Background and Aims

Although renal transplantation improves survival, cardiovascular morbidity and mortality still remain as a significant problem compared with nonrenal populations. In end stage renal disease metabolic cardiovascular risk factors such as hypertension, hyperuricemia, obesity and diabetes mellitus have been confirmed to be positively correlated with arterial stiffness. Arterial stiffness is an important characteristic of the arterial wall and can be assessed noninvasively by the measurement of carotid-femoral pulse wave velocity (PWv). The aim of this study is to evaluate the risk factors for arterial stiffness in kidney transplant recipients.

Method

One hundred and forty nine kidney transplant recipients from our renal transplant outpatient clinic were enrolled into the study. All patients were evaluated for their standard clinical (age, gender, duration of hemodialysis, post-transplant time), biochemical parameters. Anthropometric and body composition analyses were performed for all patients. Body compositions were analyzed by using the Body Composition Analyzer (Tanita BC- 420MA). PWv was determined from pressure tracing over carotid and femoral arteries using the SphygmoCor system.

Results

Patients were divided into two groups according to PWv levels. The frequency of patients with PWv ≥ 7 m/s was higher in patients with new onset diabetes (55.9%), hyperuricemia (uric acid level type="Periodical" type="Periodical" type="Periodical" type="Periodical" type="Periodical" type="Periodical" type="Periodical" type="Periodical"> 7 mg/dl) (p:0.029, 0.05). Higher carotid-femoral PWv was significantly related with systolic (p:0.003) and diastolic blood pressure (p:0.002), uric acid (p:0.0001) and fasting glucose (p: 0.02) levels. According to body composition analyses, muscle mass, visceral fat ratio and body weight were significantly higher in patients with PWv ≥ 7 m/s (p < 0.005). In patients with high PWv, sagittal abdominal diameters and waist circumferences were significantly higher than patients with PWv < 7 m/s. When criteria for metabolic syndrome were assessed there were a significant increase in pulse wave velocity in patients with 0-1; 2-3; and 4-5criteria (p < 0.01).

Conclusion

In post transplantation period, metabolic syndrome indices as high blood pressure, hyperuricemia, hyperglycemia and increased waist and hip circumferences are closely related with arterial stiffness. For cardiovascular risk reduction after renal transplantation; blood pressure, serum glucose and uric acid levels should be under strict control.
#3831 TRIMER FORMATION ASSAY SUCCESSFULLY EVALUATES THE EFFECTS OF COL4A VARIANTS IN FSGS PATIENTS
Authors: Isaranuwatchai Suramath , Sratongjoung Wannika , Ingrungruanglert Praewphan , Chanakul Ankanee , Suphapeetiporn Kanya , Praditpornsilpa Kearkiat , Israsena Nipan
Published: June 2023

Background and Aims

Variants in COL4A3, COL4A4 and COL4A5 genes were the most common variants associated with focal segmental glomerulosclerosis (FSGS). Split-luciferase-based trimer formation assay of α345 collagen is a technique that test collagen structure formation by transfect COL4A3/4/5 plasmids into cells. This method was recently used to successfully determine the pathogenicity of variants in COL4A5 gene in Alport syndrome patients. We used the trimer formation assay to evaluate the variants found in our FSGS patients and correlate with genomic variants of COL4A gene.

Method

We transfected wild-type COL4A3-SmBiT, COL4A4-LgBiT and COL4A5 plasmids into human embryonic kidney cells. In wild-type plasmids, α345 collagen will be formed, then SmBiT and LgBiT will properly fuse, and luminescence will be measured (Figure 1A). We selected the pathogenic and likely pathogenic variants in three FSGS patients from our FSGS cohort, which are two missense variants in COL4A4 (c.1805G>A, p.Gly602Glu and c.2752G>A, p.Gly918Arg), and a deletion in COL4A4, leading to frameshift and premature stop codon (c.905delG, p.Gly302ValfsTer32). We also used COL4A4, c.2906C>G, p.Ser969Ter and COL4A4, c.1396G>A, p.Gly466Arg as nonsense and missense mutation negative controls, respectively. We did the mutagenesis in COL4A4-LgBiT plasmid and repeat the steps as in wild-type plasmids. If the variants caused abnormal protein structure, SmBiT and LgBiT will not properly fuse, and luminescence will be measured less than wild-type (Figure 1B).

Results

The luminescence of nonsense control and missense control were at 22.50% and 23.58% of relative light unit (RLU) from cells expressing wild-type, respectively. The luminescences of cells expressing mutated plasmid were at 33.68%, 30.94% and 19.74% of RLU from cells expressing wide type for c.905delG, c.1805G>A and c.2752G>A, respectively. (Figure 1C) The lower luminescence means cells with mutated plasmids produced less normal α345 collagen than cells with wild-type plasmids. The results confirmed that these three variants could really cause abnormal α345 collagen in cell model.

Conclusion

This is the first study to demonstrate that split-luciferase-based trimer formation assay of α345 collagen can be used as a functional study to evaluate the effect of COL4A3/4/5 variants in FSGS.
#3862 TGF-β1/ SMAD SIGNALLING IN ANCA ASSOCIATED GLOMERULONEPHRITIS
Authors: Chalkia Aglaia , Gakiopoulou Harikleia , Bora Margarita , Aggelis George , Vasilopoulos Dimitrios , Petras Dimitrios
Published: June 2023

Background and Aims

The transforming growth factor-β1 (TGF-β1) is a pleiotropic cytokine, with distinct roles both in fibrosis and inflammation and acts through the Smad signalling in renal injury. We sought the expression of TGF-β1/Smad signalling in ANCA associated glomerulonephritis (AAGN) and we assessed this expression in correlation with the renal injury at diagnosis as well as the renal progression.

Method

We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3) and Smad7 semi-quantitatively and quantitatively using computerized image analysis program in different compartments of 11 renal biopsies with AAGN and the results were statistically analysed with clinicopathological parameters. We also used healthy controls and disease controls with other types of Glomerulonephritis (GN).

Results

The expression of TGF-β1, pSmad3 and Smad7 were higher in AAGN, compared to healthy controls and other types of GN. The glomerular pSmad3 presented preferable expression at mesangial and endothelial cells and its intensity was correlated with higher chronicity index [global glomerulosclerosis (p<0.001) and interstitial fibrosis (p = 0.03)] (Figure 1). We also reported that the intensity of Smad7 was correlated with higher activity index [cellular crescents (p = 0.03), and fibroid necrosis (p<0.001)] (Figure 2). TGF-β1 expressed at peritubular capillaries around the areas of tubulitis and its expression was correlated with more severe renal injury at diagnosis [higher creatinine (p = 0.019) and proteinuria (p = 0.008)]. At last follow-up (median time 5 years) we reported a significant worst renal function with higher intensity pSmad3 (p = 0.05) and TGF-β1 (p = 0.005), while the expression of Smad7 tended to be beneficial in the maintenance of eGFR (p = 0.055).

Conclusion

The TGF-β1/Smad signalling is activated in AAGN and its expression is correlated with renal injury both at diagnosis and renal progression.
#3932 INSULIN RESISTANCE IN PEDIATRIC CKD PATIENTS
Authors: Sallam Dina E
Published: June 2023

Background and Aims

Pediatric chronic kidney disease (CKD) is associated with disturbance of glucose metabolism & insulin receptor sensitivity leading to impaired glucose tolerance & insulin resistance (IR), which are potential risk factors for cardiovascular disease (CVD). Hyperinsulinemia and IR are not extensively investigated in children with CKD, especially in different stages of CKD. The aim of our study was to detect hyperinsulinemia & IR in pediatric CKD patients.

Method

A total of 87 children and adolescents; 58 with chronic kidney disease (CKD); (29 CKD stage 2-4, pre-dialysis group & 29 CKD stage 5 on regular hemodialysis, CKD5d group) & 29 age & gender matched controls were enrolled in the current cross-sectional study. Homeostasis model assessment of insulin resistance (HOMA-IR) using fasting insulin & glucose, where IR was considered if HOMA-IR was 4.39.

Results

Fasting insulin & glucose hadn't significantly changed between CKD patients & controls (p = 0.7, 0.3 respectively), while IR represented by HOMA-IR was found in a total of 11 (12.6%) CKD patients (6, 6.89% CKD5d & 5, 5.74% CKD 2-4) with no significant difference between pre-dialysis & dialysis groups (p>0.05), while it was significant with controls (p = 0.039), meanwhile, the total means of HOMA-IR between were no statistically significant between all CKD patients & (p = 0.64). HOMA-IR correlated positively to dialysis durations (p = <0.001, <0.001 respectively), but hadn't changed with BMI.

Conclusion

Pre-dialysis & dialysis CKD pediatric patients are at a high risk of IR & hence CVD. CKD & dialysis durations are independent risk factors for IR.
#3935 AUDIOLOGICAL ASSESSMENT IN PEDIATRIC CKD PATIENTS
Authors: Sallam Dina E
Published: June 2023

Background and Aims

Many similarities exist between the nephron & ear infrastructures, making them vulnerable to same risk factors. Idiopathic sensory neural hearing loss is frequent in pediatric patients with chronic kidney disease (CKD). Our aims were to determine the prevalence, type, & degree of hearing impairment in pediatric CKD patients.

Method

This cross-sectional study was carried out at pediatric dialysis & nephrology unit at Children's hospital & Audiology unit, Faculty of Medicine Ain Shams University, included 45 CKD patients’ stage 2-4, 45 CKD patients’ stage 5 on hemodialysis, & 90 children as controls. Detailed history, physical, otological examinations & audiological assessment by standard pure tone audiometry, speech audiometry & tympanometry, IQ test, in addition to some laboratory investigations were done for all our studied patients.

Results

The mean IQ was significantly lower in CKD patients than the controls, however, it was significantly higher in dialysis than non-dialysis groups (p = 0.05). Pure tone audiometry showed 16.6% of out CKD patients had hearing loss, which was mainly sensory neural (SNHL); (53.3%), that was significantly higher compared to the control group (p < 0.001). A mild degree of high-frequency hearing loss was frequently reported. These findings weren't significantly different between dialysis & non-dialysis patients, but were significant compared to control group (P<0.001). Regarding speech discrimination scores, controls had a higher significant change compared to CKD patients. Regarding Tympanometry test results, most of CKD patients & the controls had normal middle ear pressure. The most determining factor affecting the hearing loss in our patients was the IQ.

Conclusion

High-frequency SNHL is not uncommon in CKD pediatric patients, in addition to low IQ. It's recommended to do a routine audiological evaluation & follow up for early diagnosis & intervention.
#3999 PROTEINURIA AND PROGRESSION OF IGA NEPHROPATHY. HAVE WE REACHED THE POINT OF NO RETURN?
Authors: Echeverri Carolina Isabel Movilla , Gómez Cristina Andrades , Arellano Macarena Naranjo , Garcelán Carmen Alarcón , Cárdenas Fátima Cazalla , Chaves Virginia Cabello , Mendoza Manuel López , Couñago Inmaculada Gómez , Batalha Paula , Valdivia Miguel Ángel Pérez
Published: June 2023

Background and Aims

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, associated with an incidence of 2.5/100.000 cases per year and progression to end-stage kidney disease (ESKD) in 20% patients within 10 years. Proteinuria has been identified as the greatest risk factor for ESKD in IgAN. The aim was to evaluate the correlation between proteinuria and major adverse renal events (MARE). We define MARE as 40% decline in glomerular filtration rate (eGFR), initiation of kidney replacement therapy (either dialysis or kidney transplantation) or death whether from renal cause or cardiovascular-related.

Method

In this retrospective observational single-center study, we included all biopsy-proven IgAN patients older than 18 years with proteinuria >500 mg/24h, diagnosed between 2006-2017 and followed up to January 2022. Clinical, analytical, and histological findings were collected at time of diagnosis and during follow-up. Uni and multivariable Cox regression were performed to establish correlation between our data and the main event. A linear mixed-effects model was used to estimate eGFR slope.

Results

A total of 124 patients were included. Mean age and eGFR were 40 ±15 years and 59 ml/min (IQR: 33-94 ml/min) respectively, with a median proteinuria of 1.44 g/24h (IQR 0.7-2.3). 64% of patients were treated with corticosteroids. In the multivariate analysis, we found that IFTA >25% had a statistically significant risk of MARE (IFTA T1 HR 3.1; 95% CI 1.52-6.6; p = 0.002; IFTA T2 HR 6.6; 95% CI 1.46-16.12; p<0.001), history of cardiovascular disease presented 3.7 times higher risk of MARE (HR 3.7; 95% CI 1.46-9.6 p = 0.015). Patients with proteinuria >3 g/24h showed significantly higher hazard ratio (HR 2.36 95%CI 1.16-4.8 p = 0.01) for MARE. In the 3-year linear mixed-effects model, patients with proteinuria above 3 g/24h had an annual eGFR slope of -6.3 ml/min (-9.6 to -3.1 95%CI). Nevertheless, proteinuria between 1.5 to 3 g/24h had an annual eGFR slope of -2.1 ml/min (-4.9 to 0.62 95% CI), finding no statistical difference in comparison to patients with proteinuria <1.5 g/24h.

Conclusion

Typically, the threshold of proteinuria >1 g/24h has been marked as the start of immunosuppression in this nephropathy. Several studies published in recent years (as example STOP IgAN) question this paradigm. According to our data, there is a strong association between proteinuria >3 g/24h and major adverse renal events. Patients with proteinuria between 1.5 to 3 g/24h had a similar behaviour as our reference group (proteinuria <1.5 g/24h). These results might provide new evidence supporting a more conservative approach and start receiving glucocorticoids if proteinuria is > 3 g/24h.
#4074 FRACTIONATED PLASMA SEPARATION AND ADSORPTION INTEGRATED WITH CONTINUOUS VENO-VENOUS HEMOFILTRATION IN PATIENTS WITH ACUTE LIVER FAILURE
Authors: Dong Jianhua , Huang LI , LI Chuan , Wu Bian , Yang XI , Ge Yongchun
Published: June 2023

Background and Aims

To observe the clinical efficacy and safety of fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute liver failure (ALF).

Method

In this retrospective study, we enrolled patients with ALF (serum total bilirubin>10mg/dl or Model for End-Stage Liver Disease (MELD) Score>18) hospitalized from 2017 to 2022.All patients received the treatment of FPSA-CVVH.The primary measure of treatment efficacy was the reduction ratios (RRs) of bilirubin after each session of FPSA-CVVH.

Results

8 patients (68 males and 10 females) with ALF were enrolled. 66 patients (84.6%) exhibited acute kidney injury and required renal replacement therapy (RRT). The score of MELD at baseline was 22.9±7.5. The concentration of serum total bilirubin was 22.05±5.94mg/dL, direct bilirubin was 16.33±4.60mg/dL and indirect bilirubin was 3.43±1.60mg/dL.187 sessions of FPSA-CVVH treatment with 8 hours each were performed. After a single session, serum total bilirubin, direct bilirubin and indirect bilirubin were significantly decreased. RRs was 52.0±7.6% for total bilirubin, 59.4±13.0% for direct bilirubin and 36.9±15.4% for indirect bilirubin. 2 patients changed the filters due to blood coagulation. And other 2 patients exhibited bleeding, including gastrointestinal bleeding and Oozing bleeding. 29 patients (37.2%) survived in discharging from hospital, 12 patients recovered with their liver function, and the remaining 17 patients still needed intermittent artificial liver support therapy.

Conclusion

FPSA-CVVH therapy was a novol and effective artificial liver support therapy in patients with ALF. It may be considered as a “bridge technique” to the recovery of liver function in critical ill patients with ALF.
#4089 SARCOPENIA AS A PREDICTOR OF MORTALITY IN KIDNEY TRANSPLANT RECIPIENTS
Authors: Kosoku Akihiro , Iwai Tamoaki , Kabei Kazuya , Nishide Shunji , Machida Yuichi , Uchida Junji
Published: June 2023

Background and Aims

Sarcopenia is a risk factor for adverse outcomes in older adults and dialysis patients, but this has yet to be confirmed in kidney transplant recipients. This study aimed to investigate the association of sarcopenia with all-cause mortality in kidney transplant recipients.

Method

In this single-center prospective cohort study, kidney transplant recipients were evaluated at baseline muscle mass, muscle strength, and physical performance using a hand dynamometer, 10-m walk test, and bioelectrical impedance analysis, respectively. Sarcopenia was defined according to the Asia Working Group for Sarcopenia 2019 criteria. Propensity score matching was used to reduce bias between the sarcopenia and non-sarcopenia groups, adjusted for three potential confounding variables including age, sex, and body mass index. After a 5-year follow-up, patient survival was assessed by the Kaplan-Meier method and Cox proportional hazards model in the matched cohort.

Results

Out of 212 patients (median age, 54 years; median transplant vintage, 79 months) enrolled in this study, patients who had sarcopenia at baseline was 33 (16%). After 1:1 propensity score matching, a matched cohort with 62 patients was generated. In the matched cohort, the overall incidence density rates of mortality were 48.8 and 6.75 per 1000 person-years in the sarcopenia and non-sarcopenia groups, respectively. The survival curves estimated using the Kaplan-Meier method indicated that the sarcopenia group was significantly lower cumulative survival than the non-sarcopenia group (log-rank test, p = 0.025). Moreover, the sarcopenia group had a significantly higher mortality risk than the non-sarcopenia group (hazard ratio = 7.59, 95% confidence interval = 1.93–61.7).

Conclusion

Sarcopenia was a significant predictor of mortality in kidney transplant recipients.
#4093 OSTEOSARCOPENIA AMONG PATIENTS UNDERGOING HEMODIALYSIS IS RELATED WITH MORTALITY
Authors: Xiang Ting , Zhou Li , Fu Ping
Published: June 2023

Background and Aims

Sarcopenia and osteoporosis are closely interconnected and associated with adverse health outcomes. Osteosarcopenia means the concurrent presence of the two conditions and has rarely been reported in hemodialysis patients. Whether hemodialysis patients with osteosarcopenia are at greater risk of mortality than those with either condition alone remains unknown. The aim of this study was to explore the prevalence of sarcopenia and its association with osteoporosis and to determine its impact on survival risk in hemodialysis patients.

Method

A total of 209 adults undergoing hemodialysis were enrolled from the dialysis center in the West China Hospital of Sichuan University. Muscle mass, handgrip strength, bone mineral density (BMD), and biochemical parameters were assessed. All deaths were recorded during a follow-up of 34.8 ± 13.8 months.

Results

Seventy-eight patients were diagnosed with sarcopenia with a prevalence of 37.3%. After adjustment for potential confounders, age (OR = 1.094, P <0.001), female (OR = 3.44, P = 0.005), diabetes (OR = 3.756, P = 0.008), CRP (OR = 1.09, P = 0.015), serum magnesium (OR = 0.06, p = 0.042) and BMI (OR = 0.701, P <0.001) were independently associated with sarcopenia (Table 1). Among the 209 patients, 103 patients completed the BMD assessment. The prevalence of osteosarcopenia was 22.3%, while 20.4% of participants had sarcopenia alone and 12.6% had osteoporosis alone. The respective proportions of patients who died were 10.9% for nonsarcopenia/nonosteoporosis, 15.4% for osteoporosis alone, 47.6% for sarcopenia alone, and 47.8% for osteosarcopenia. Cox regression analysis showed that osteosarcopenia was independently associated with all-cause mortality (HR = 3.541, 95% CI: 1.035-12.117), while osteoporosis alone and sarcopenia alone were not (Table 2).

Conclusion

Patients undergoing hemodialysis had a high incidence of sarcopenia and osteosarcopenia, muscle mass and strength showed a significant association with BMD, and osteosarcopenia might have a powerful impact on mortality in those patients.
#4109 THE IMPACT OF IMPLEMENTING AN INNOVATIVE OBSTETRIC NEPHROLOGY SERVICE ON MATERNAL AND FETAL OUTCOMES IN WOMEN AT RISK OF PR-AKI
Authors: Shemies Rasha Samir , Nagaty Kareem , Younis Dalia , Elnaggar Sherouk , Khreba Nora , Mosbah Alaa , Taman Mohamed , El-Kannishy Ghada , Sayed-Ahmed Nagy , Sobh Mohamed
Published: June 2023

Background and Aims

Pregnancy Related Acute kidney injury (PR-AKI) is a global health problem with substantial maternal and fetal morbidity and mortality. Late referral, and late diagnosis of women with risks of PR-AKI represent the major barriers for curtailment of this ugly trend, particularly in the developing world. Our past experience per se revealed striking maternal and fetal mortality of women with PR-AKI. Great strides are strongly needed to save maternal and fetal lives. This study assessed the impact of implementing an innovative obstetric nephrology service (ONS) and healthcare program on maternal and fetal outcomes in women at risk of PR-AKI.

Method

An innovative interdisciplinary obstetric nephrology clinic was established in 2020 to improve the quality of care for pregnant women at risk of PR-AKI. The service was staffed by both nephrologists and obstetricians. Women who presented to the clinic were stratified into low, moderate, and high-risk groups. A risk stratification-based care program was adopted. Very high-risk women were admitted to the maternal care unit. The study compared the outcomes of ONS-treated women who completed their follow up (n = 43) versus two groups of conventionally treated women (n = 40) and women presented before service (n = 40).

Results

Although they had greater pre-existing risks, ONS-treated women had no reported maternal or fetal mortality compared to women in the conventionally treated group (11.8% and 51.5% respectively), and to women presented before service (22.5% and 45% respectively). Progression to end-stage renal disease was significantly less in ONS-treated women compared to both conventionally treated and those treated before service (3% versus 13.2% and 37.5% respectively).

Conclusion

Easily feasible Obstetric nephrology service implementation and adoption of early referral program and diagnosis policies were associated with better maternal and fetal survival as well as better renal outcomes. Provision of parallel services is strongly recommended to decrease the magnitude of PR-AKI.
#4125 CHANGES OF MEDICAL COSTS AND NUMBER OF USES OF CONTINUOUS RENAL REPLACEMENT THERAPY UNTIL RECENT SIX YEARS IN SOUTH KOREA
Authors: Kim Hyung-Jong , Chang Jae Hyun , Jung Sang Hyun , Park Keun Hyung
Published: June 2023

Background and Aims

Continuous renal replacement therapy (CRRT) is a necessary dialysis treatment method applied to patients with acute renal injury at intensive care unit. In South Korea, the use of such CRRT is increasing, and the cost of health insurance used for CRRT is also increasing. In this study, the pattern and medical costs increase of CRRT usage until recent 6 years were investigated.

Method

From 2016 to 2021, the number of CRRT claims was investigated using data from the National Health Insurance Review and Assessment Service. CRRT costs is applied by a resource-based relative value score in Korea. CRRT can be charged as continuous venovenous hemodialysis, continous venovenous hemofiltration, and continuous venovenous hemodiafiltration depending on the treatment mode. The CRRT cost differs from the very day and the next day's cost, and the cost of the very day includes the femoral hemodialysis catheter insertion cost, which is higher than the next day's cost.

Results

CRRT medical practice is gradually increasing. The number of CRRT the very day increased from 15,640 cases in 2016 to 20,883 cases in 2021, and it continues to increase from 81,649 cases CRRT the next day in 2016 to 121,376 cases CRRT the next day in 2021. The CRRT relative value score is higher than the conventional hemodialysis(HD) and the CRRT relative value score is 9715 points higher than the conventional HD 1065 points. The total cost of CRRT increased by about KRW 52.5 billion (approximately 38,363,171 dollars) in 2021 from about KRW 17.3 billion (approximately 12,641,578 dollars) in 2016. In addition to CRRT medical practice costs, dialysis fluid, anticoagulant costs, and material costs are added, and so actual CRRT-related costs are more expensive.

Conclusion

CRRT is essential and it seems necessary to consider medical practices or medical costs that are important for essential medical care. CRRT is a high-cost treatment method that requires definitive guidelines or consensus on the initiation and discontinuation of CRRT.