bluuebunny/crossref_metadata_2025_split huggingface dataset:
#4810 DIAGNOSTIC AND THERAPEUTIC IMPACTS OF AIM ON END-STAGE KIDNEY DISEASE
Authors: Miyazaki Toru , Arai Satoko 
Published: June 2023

Abstract

Background and Aims
End-stage kidney disease (ESKD) is life-threating, and indispensably requires dialysis which however imposes huge burdens on patients’ QOL and medical expense. No therapies to prevent CKD progression to the end-stage have reached clinic to date. Patients undergoing dialysis exhibit a high mortality mainly due to cardiovascular diseases (CVDs), but no biomarkers are available to predict the patients’ death and the incidence of cardiovascular disease (CVD), the major cause of death, before initiation of dialysis. AIM is a macrophage-derived circulating protein present in blood at relatively high levels (∼5 μg/mL). We initially identified AIM as a supporter of macrophage survival, and it is now known as a facilitator of repair in many diseases. In healthy state, AIM associates with IgM pentamer through disulfide-bond formation and charge-based interaction with IgM-Fc, using the solitary cysteine residue and the positively charged-amino acid cluster present at the carboxyl-terminus. During various diseases including acute kidney injury, hepatocellular carcinoma and peritonitis, AIM dissociates from IgM and binds to the body-derived types of inflammatory elements using the identical sites necessary for binding to IgM, thereby promoting their phagocytic removal by phagocytes.

Method
In 561 CKD patients of all stages and 310 dialysis patients, we analyzed the serum AIM and the serum solute profiles, and thereby assessed their efficacy in predicting survival and CVD risk after dialysis induction. Additionally, a therapeutic efficacy of recombinant AIM (rAIM) in preventing CKD progression to end-stage was addressed in house cats, that are highly susceptible to CKD and show a similar disease course to humans.

Results
AIM dissociated from IgM pentamer along CKD progression. Dialytic patients showing low levels of AIM dissociation before initiation of dialysis harbored less serum detrimental solutes, exhibited lower risk of CVD and had better survival than those with high grades of AIM dissociation, suggesting that the IgM-free AIM represents the state of serum toxic solutes, and predicts patients’ prognosis before initiation of dialysis. In addition, treatment of pre-uremic (late IRIS stage 3) cats, 50% of which died of severe uremia within 196 days after diagnosis, with recombinant AIM prevented aggravation of renal function and inflammation, as well as serum toxic solute profile, thereby improving the cats’ survival dramatically. Importantly, the same serum toxin/inflammatory solutes regulatable by rAIM in cats influenced dialysis patients’ prognosis.

Conclusion
There results promise the effects of AIM treatment in humans, reducing the need for dialysis. Our findings could be a platform for new CKD therapies and predictive diagnoses to improve the prognosis of patients with ESKD.
#4845 EFFECT OF OMEGA-3 FATTY ACID ON MITOCHONDRIAL MEMBRANE FATTY ACID AND COMPARISON WITH ERYTHROCYTE MEMBRANE IN ADENINE INDUCED UREMIC RATS
Authors: Yang Dong Eun , Lee Su MI , Kim Jun Chul , An Won Suk 
Published: June 2023

Abstract

Background and Aims
The kidney has the second highest mitochondrial content in the human body. Fatty acids (FAs) are one of the important energy sources and main constituents of cell membranes. Higher erythrocyte membrane oleic acid contents are related to acute coronary syndrome and omega-3 FA can reduce oleic acid contents. We investigated whether omega-3 FA modifies not only erythrocyte membrane FA but also mitochondrial membrane FA of kidney in adenine-induced uremic rats.

Method
Male Sprague-Dawley rats were fed diets containing 0.75% adenine and 2.5% protein for three weeks. Next, rats were randomly divided into six groups that were fed diets containing 2.5% protein and saline with cholecalciferol (3000 IU/kg/week) or omega-3 FAs (300 mg/kg/day) with cholecalciferol were supplemented by gastric gavage for four weeks: normal control (n = 7), adenine control scarified at 3 weeks (n = 6), adenine control scarified at 5 weeks (n = 5), adenine control scarified at 7 weeks (n = 5), omega-3 FAs group scarified at 5 weeks (n = 5), and omega-3 FAs group scarified at 7 weeks (n = 5). The mitochondrial isolation kit was used for renal mitochondria extraction. The mitochondrial and erythrocyte membrane FA contents were measured using gas chromatography.

Results
Compared to the normal control group, serum creatinine levels in adenine control group was significantly increased and improved in omega-3 FA group. Compared with adenine control, erythrocyte and mitochondrial membrane monounsaturated FA contents including oleic acid and arachidonic acid (AA) levels were significantly decreased in omega-3 FA group. FA compositions were similar between erythrocytes and mitochondrial membranes in each group. Monounsaturated FA contents including oleic acid, and eicosapentaenoic acid were higher and saturated FA was lower in the mitochondrial membrane than erythrocyte membrane in adenine control group.

Conclusion
Omega-3 FA affects not only erythrocyte membrane FA but also mitochondrial membrane FA in uremic rats. Erythrocyte membrane FA contents can reflect mitochondrial membrane FA contents of the kidney.
#4870 MORTALITY OF ELDERLY PATIENTS WITH ACUTE KIDNEY INJURY UNDERGOING CONTINUOUS RENAL REPLACEMENT THERAPY: IS AGE A RISK FACTOR?
Authors: Kim Ji Hye , Pyo MI Ryoung , Park Jin Ah , Eum Sang Hun , Min Ji Won , Koh Eun Sil , Ko Eun Jeong , Kim Hyung Duk , Chung Byung Ha , Shin Seok Joon , Yang Chul-Woo , Yoon Hye Eun 
Published: June 2023

Abstract

Background and Aims
The incidence of elderly patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is increasing. However, there is little evidence on the difference of mortality rates according to age in elderly patients. This study aimed to evaluate the age effect and predictors for mortality in elderly patients with AKI requiring CRRT.

Method
A retrospective analysis was performed in elderly patients with AKI who underwent CRRT. A total of 480 patients aged ≥ 65 years were stratified into three groups according to age: youngest-old (age 65 - 74 years, n = 205), middle-old (age 75 - 84 years, n = 217), and oldest-old (age ≥ 85 years, n = 58). The 28-day and 90-day survival rates were compared between three groups and predictors for mortality were analysed.

Results
The 28-day and 90-day survival rates were not different between three age groups (P = 0.156 and P = 0.189, respectively). The oldest-old group did not show an inferior survival rate to other two groups. For 28-day mortality, prothrombin time [hazard ratio (HR) = 1.37, 95% confidence interval (CI) = 1.01 – 1.88, P = 0.046] and urine output at the start of CRRT (HR = 0.999, 95% CI = 0.998 – 1.000, P = 0.012) and CRRT duration (HR = 0.89, 95% CI = 0.83 – 0.95, P = 0.001) were predictors. For 90-day mortality, mean arterial pressure (HR = 1.02, 95% CI = 1.00 – 1.05, P = 0.019), admission duration (HR = 0.97, 95% CI = 0.95 – 0.99, P &lt; 0.001) and CRRT duration (HR = 0.96, 95% CI = 0.91 – 0.99, P = 0.036) were predictors. The middle-old group or the oldest-old group did not exhibit higher risk compared to the youngest-old group for 28-day and 90-day mortality.

Conclusion
An older age was not a risk factor for mortality in elderly patients with AKI undergoing CRRT. This implicates the importance of active management and application of CRRT in critically ill elderly patients with AKI.
#4875 MANAGEMENT OF TUBULOINTERSTITIAL DISEASE IN PREGNANCY: TEN-YEARS EXPERIENCE OF A NEPHRO-OBSTETRIC CLINIC
Authors: Nogueira Estela , Peres Nadiesda , Godinho Iolanda , Jorge Sofia , Centeno Mónica , Pinto Luísa , Lopes José António 
Published: June 2023

Abstract

Background and Aims
Tubular renal acidosis and salt losing nephropathies are rare conditions but their management during pregnancy that can be challenging due to the physiological adaptation of kidney function. Herein, the authors report the management and outcomes of 7 gestations in patients with Gitelman disease (GS) and renal tubular acidosis (RTA).

Method
Retrospective analysis of maternal, obstetric and perinatal outcomes of pregnant women with tubulointerstitial diseases surveilled at our Nephro-Obstetric clinic from 2011 to 2021.

Results
We evaluated 7 pregnancies in 5 women. Mean age was 29 years [21-36]. They were all caucasian. Genetic diagnosis was performed during pregnancy in only one patient. Tubular disorder was caused by Gitelman disease in 3 patients and by renal tubular acidosis in 2 patients (ATP6VA4 and REN genes mutations). There were 4/1 patients in CKD G1/G3a, respectively, and none developed renal function deterioration. Only one patient developed transient proteinuria during both gestations and all patients had a low blood pressure profile. Management during the first trimester was especially challenging in GS patients, due to nausea, vomiting and hyperemesis gravidarum, which required hospital admission for intravenous potassium chloride therapy in all GS patients during the first trimester. Potassium levels in GS patients were generally below normal levels throughout pregnancy (mean 3 meq/L; 2,2-3,4 meq/L), even with progressive increase in therapy. Pre-pregnancy potassium chloride replacement increased from 4–10 tablets of 600 mg/day to a maximum of 9–21 tablets/day. One patient was also treated with spironolactone. The need for oral magnesium slightly increased from 2–3 ampoules of 1500mg/day to 2–4 ampoules/day. GS patients frequently complained of astenia and cramps. Regarding RTA patients, there was also a need to increase sodium bicarbonate dosage from 3–4.5g/day to a maximum of 2–8g /day. Regarding obstetric and perinatal outcomes, none of the patients developed preclampsia, mean gestational age at delivery was 40 weeks (38-41), mean birth weight was 3233g (2775-3825) and mean Apgar score was 10/10/10 at 1st, 5th and 10th minutes respectively.

Conclusion
In GS patients, management in the first trimester of pregnancy can be challenging due to nausea and vomiting, generally requiring admission for therapy with iv potassium. In spite of increasing doses in oral supplementation, ionic and acid base homeostasis during pregnancy is difficult to achieve. In our small series, maternal, obstetric and perinatal outcomes do not seem to be affected by this unbalance.
#4884 DISRUPTION OF THE INTESTINAL MUCOSAL BARRIER IN CHRONIC KIDNEY DISEASE IS RELATED TO REDUCED EXPRESSION OF THE TIGHT JUNCTIONS' COMPONENTS
Authors: Georgopoulou Georgia Andriana , Papasotiriou Marios , Bosgana Pinelopi , Delastic Anne-Lise , Papachristou Evangelos , Goumenos Dimitrios , Zolota Vasiliki , Thomopoulos Konstantinos , Assimakopoulos Stelios 
Published: June 2023

Abstract

Background and Aims
Patients with chronic kidney disease (CKD) present evidence of systemic inflammation without clinical infection. This is partly attributed to intestinal barrier dysfunction resulting in increased gut permeability with microbial and endotoxin translocation. However, the potential mechanism(s) implicated in increased gut permeability remain unclear. In this study, we investigated several parameters of the intestinal barrier in patients with CKD of various stages.

Methods
Thirty-three patients with CKD were prospectively enrolled. Patients were divided in stage I-IV CKD (group A, n = 17, 9 of them with IgA nephropathy) or end-stage kidney disease (ESKD) (group B, n = 16) and were compared with 11 healthy controls (group C). Duodenal biopsies from all subjects, obtained by endoscopy, were examined histologically for evaluation of the villous length and apoptotic bodies in cryptal epithelium. Intraepithelial CD3+ T-lymphocytes, expression of occludin and claudin-1 in the intestinal epithelium were evaluated by immunohistochemistry. Circulating endotoxin concentration was measured by enzyme-linked immunosorbent assay and cytokine levels [interleukin (IL)-1β, IL-6, IL-8, IL-10, TNF-a] by flow cytometry.

Results
Patients in groups A and B presented significantly higher serum endotoxin, IL-8 and IL-10 levels compared to controls (p&lt;0.01, both groups). Patients in group B presented additionally significantly higher IL-6 levels compared to controls (p&lt;0.01). Occludin expression was significantly decreased in groups A and B compared to group C (p&lt;0.0001 and p&lt;0.001, respectively). Interestingly, in CKD patients (groups A and B) a gradient of occludin expression along the length of the villi, from crypt to tip was recorded with greater loss of its expression at villous tip. Claudin-1 expression was significantly decreased in crypts in groups A and B compared to group C (p&lt;0.0001 and p&lt;0.01 respectively). Endotoxin concentrations were inversely correlated with intestinal occludin (p&lt;0.0001) and claudin-1 (p&lt;0.01) expression and positively correlated with serum IL-6 (p&lt;0.05) and IL-8 (p&lt;0.001) levels. Subgroup analysis for patients with IgA nephropathy showed similar histological findings for occludin and claudin-1 expression as well as for serum endotoxin levels.

Conclusion
Decreased enterocytes’ occludin and claudin-1 expression, might represent an important mechanism of intestinal barrier disruption and increased gut permeability in patients with CKD.
#4901 THE EFFECT OF CHRONIC KIDNEY DISEASE IN CONTRAST-ENHANCED ULTRASONOGRAPHY WITH ARRIVAL TIME PARAMETRIC IMAGING
Authors: Marc Luciana , Lupusoru Raluca , Mihaescu Adelina , Schiller Oana-Marina , Chisavu Lazar , Pascota Razvan Dragota , Olariu Nicu , Schiller Adalbert 
Published: June 2023

Abstract

Background and Aims
CEUS is a reliable method to diagnose ischemic renal pathologies such as infarction, identify renal abscesses, discriminate between renal tumors and anatomical variants, describe complex cyst lesions, and monitor non-surgical renal lesions. Few studies explore the relationship between CEUS and the diagnosis or progression of CKD. The aim of this study was to evaluate the relationship between contrast-enhanced ultrasonography with arrival time parametric imaging (CEUS-PAT) and CKD.

Method
We prospectively evaluated 64 subjects (37 liver cirrhosis patients and 27 healthy volunteers) using CEUS-PAT to detect if the presence of CKD influences the arrival time of the contrast in the kidney. CKD was defined according to KDIGO 2021 guidelines. Ultrasonography was performed using the LOGIQ E9 (GE Healthcare, Chalfont St.Giles-UK) system, probe C1-6. CEUS was performed on each subject using SonoVue (Bracco SpA, Milan, Italy) as a contrast agent (1/2 of a vial). A 2.5 mL contrast substance followed by a 5 mL normal saline solution was infused in the cubital vein. A ratio between the arrival time of the substance in the kidney and liver was calculated. Subjects were in fasting conditions for at least 12 h. Laboratory data were extracted from the patient's GP file. The study was conducted between January -December 2018. All patients provided their informed consent for the procedures.

Results
The study included 64 subjects, mean age of 58.98 ± 8.90 years, predominantly male gender (56.3%). Of the 64 patients, 13 (20.3%) had chronic kidney disease. All patients with chronic kidney disease had liver cirrhosis. When comparing the two groups, with and without CKD, there was a significant difference between the ratio of the arrival time of the contrast agent into the kidney and liver, 0.85 ± 0.09 vs 0.65 ± 0.19, p = 0.0005. The factors associated with kidney disease were liver steatosis (p&lt;0.0001), age over 60 years (p = 0.01) and low albumin (p&lt;0.0001).

Conclusion
Our study indicated that the presence of CKD influences the contrast agent arrival time in the kidney. Further studies are needed to establish the predictive significance of CEUS-PAT data in CKD patients.
#4913 ANALYSIS OF THE LIPID PROFILE IN THE RENAL PATIENT AND SUB-ANALYSIS OF THE POPULATION WITH POLYCYSTIC KIDNEY DISEASE
Authors: Ruiz Alfonso Lara , Heres Salia Pol , Cintra Melissa , Velilla Teresa Arrobas , Flores Rocío Molas , Lazo Mercedes Salgueira 
Published: June 2023

Abstract

Background and Aims
Dyslipidemia is frequent in patients with chronic kidney disease (CKD), it constitutes a factor of progression of both cardiovascular risk (CVR) and CKD itself. It has its own characteristics, which are modified with the ERC stadium. The subgroup of patients with Polycystic Kidney Disease (PKD) presents its own characteristics. The aim of the study was to analyze the lipid profile in the renal population and the differences in the PKD group.

Method
Retrospective observational study, includes population under follow-up in nephrology consultations in a health area, during 2018–2021. We analyzed lipid profile, renal function and whether they received statins. IBM SPSS Statistics V24 was used.

Results
3301 prevalent patients with kidney disease were collected, excluding those on renal replacement therapy (RRT), with glomerular filtration rate (GFR), glomerular filtration rate (GFR) &lt;10ml/min/1.73m² and proteinuria greater than 1.5g. Of these, 112 (3.4%) patients had PKD. 51% of the total CKD patients were under treatment with statins. The average number of Total Cholesterol (TC) was 170.4+/-43mg/dl, LDL 92.3+/-37mg/dl, HDL 50.3+/-15mg/dl and triglycerides (TG) 147.3+/-92mg/dl. In 37% of CKD patients, LDL was &gt;100mg/dl and only 35% had LDL&lt;75mg/dl. In the CKD group with a GFR &lt;60ml/min/1.73m² (N = 2337; 71%), there was a high prevalence of patients with LDL values &gt;100mg/dl (N = 784; 33.5%). In the case of GFR &lt;30ml/min/1.73m² (N = 981; 29.7%), the presence of LDL&gt;100mg/dl 30% (N = 297) was also frequent. In the subanalysis of patients with PKD, the mean TC was 182+/-40mg/dl, LDL 101.2+/-33mg/dl, HDL 56.4+/-17mg/dl, and TG 123.7+/-59mg/dl. 76% of the PKD had GFR &lt;60ml/min/1.73m² (N = 73), of which 43% presented LDL&gt;100mg/dl (N = 32). In PKD patients with GFR &gt; 60ml/min/1.73m² (N = 39), half (N = 22; 56.4%) also had LDL &gt;100mg/dl. In addition, 51% were taking a statin, despite this they had a mean TC 183mg/dl+/-46, LDL 102.7+/-39, HDL 53+/-15, and TG 142+/-69mg/dl.

Conclusion
The presence of elevated LDL was frequent in CKD, especially in the group with GFR &lt; 60ml/min/1.73m² without statin and in a quarter of patients with the same GFR with statin. It is notable in the PKD group, probably due to less awareness of strict CVR control.
#4996 TPPP3 REGULATES THE MICROTUBULE ACETYLATION AND PROMOTING YAP NUCLEAR RECRUITMENT IN HUMAN PODOCYTES
Authors: Chen Qilin , Jiang Yaru , Peng Liping , Jiang Huimin , Wan Junli , Feng Xiaoqian , LI Qiu 
Published: June 2023

Abstract

Background and Aims
Minimal change disease (MCD) is a podocytopathy more commonly seen in children, but it also accounts for 10%–25% of adult NS. Patients with MCD manifest with abundant albuminuria, which is related to the damage of the glomerular filtration barrier. Podocytes are major components of the glomerular filtration barrier and play a crucial role in maintaining the integrity of the glomerular filtration barrier. Alterations in podocyte actin critically affect podocyte function. Tubulin polymerization-promoting protein family member 3 (TPPP3) is regulator of microtubule dynamic that has microtubule bundling activity. However, the mechanism of TPPP3 involved in podocyte apoptosis is remains unknown.

Method
Single-cell RNA sequencing comprehensively characterized the expression of TPPP3 in human glomeruli. We cultured human immortalized podocyte cells (HPC) in vitro, and constructed the HPC injury model. Immunofluorescence, western blot were used to determine the expression of TPPP3, α-tubulin, acetylated tubulin, phosopho-YAP1, Podocyte apoptosis was determined by Annexin V APC Apoptosis Detection Kit.

Results
TPPP3 was specifically expressed in human glomerular podocytes, and its expression level was significantly decreased in the cases of MCD and ADR induced podocyte injury(P&lt;0.05). Knockdown of TPPP3 leaded to decreasing expression of acetylated tubulin in podocytes(P&lt;0.05). Phosopho-YAP1 was also observed in the TPPP3 knockdown HPCs(P&lt;0.05). Apoptosis was increased in the TPPP3 knockdown HPCs, suggesting TPPP3 may be related to the podocytes injury and apoptosis.

Conclusion
TPPP3 is involved with the apoptosis of podocytes by regulates nuclear recruitment of YAP which was promoted by microtubule acetylation.
#5081 THE VALUE OF ANTI-C1Q ANTIBODIES IN PREDICTING THE CLINICAL-HISTOLOGICAL FEATURES OF LUPUS NEPHRITIS PATIENTS AT TIME OF KIDNEY BIOPSY
Authors: Calatroni Marta , Conte Emanuele , Reggiani Francesco , de Liso Federica , Moroni Gabriella Luisa 
Published: June 2023

Abstract

Background and Aims
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with renal involvement in around 50% of patients. Delayed diagnosis of lupus nephritis (LN) is associated with higher risk of end-stage kidney disease (ESKD) and mortality. Kidney biopsy remains the gold standard for diagnosis and management of LN, but in the last decades there is an interest for new serum biomarkers. Anti-C1q antibodies are autoantibodies associated with LN. Nevertheless, few studies have correlated the association of anti-C1q antibodies with active LN with focus on renal histology.

Method
We evaluated clinical and histological data of 59 patients with biopsy proven LN. Kidney biopsies were categorized following the ISN/RNP Classification. We evaluated the correlation of the main clinicopathologic features with values of antiC1q antibodies, measured by a commercial kit with a clinically validated ELISA test. Normal values of antiC1q were &lt; 20 UA, medium values were between 20 and 80 UA and high values were &gt; 80 UA. Demographic and clinical data were expressed as numbers or percentage for discrete variables and for continuous variables as mean and standard deviation. The correlation between antiC1q levels and clinicopathological characteristics have been analyzed with Fisher's test.

Results
At the presentation of 59 patients with LN, the mean age was 34 years and the time of SLE disease before the onset of LN was 73.2 months. 9 patients were male, mean serum creatinine was 1 mg/dl, glomerular filtration rate (eGFR) was 88.53 ml/min, proteinuria was 4.35 g/day and microscopic hematuria was present in 79% of pts. Kidney biopsies were classified as non-proliferative (class II and V) in 18.4% of patients and proliferative (class III and IV) in 77.6% of patients. We evaluated the correlation between all variables included in Table 1 with values of antiC1q antibodies and we found significant results for serum creatinine, active urinary sediment, C3 and C4 values, proliferative classes and the activity index at kidney biopsy (Table 2).

Conclusion
High titles of anti-C1q antibodies were significantly correlated with the main clinical and histological characteristics that identify active renal diseases in SLE. Kidney biopsy remains the gold standard for diagnosis and management of LN, but anti-c1q antibodies are strongly associated with active LN in SLE. In conclusion, anti-C1q monitoring should be helpful and might be a crucial serum biomarker for the diagnosis and follow-up of these patients.