bluuebunny/crossref_metadata_2025 huggingface dataset:
#6440 C1Q-BINDING ANTI-HLA DONOR-SPECIFIC ANTIBODIES AND LONG-TERM KIDNEY GRAFT OUTCOMES
Authors: Gniewkiewicz Michal , Czerwinska Katarzyna , Zielniok Katarzyna , Durlik Magdalena
Published: June 2023

Background and Aims

Immunological response mediated by anti-HLA donor specific antibodies plays an important role in renal allograft injury in kidney transplant recipients. Several characteristics of donor-specific antibodies such as HLA class, specificity, mean fluorescence intensity, IgG subclass and C1q-binding capacity can be assessed. The aim of this study was to determine the impact of circulating anti-HLA donor-specific and their characteristics, including C1q-binding capacity, on long-term kidney graft outcomes.

Method

One hundred eight patients from our transplant center, who underwent kidney allograft biopsy within three to twenty-four months after renal transplantation from brain-dead deceased donor between 2018 and 2020, were included in the study. At the time of biopsy patients’ sera were collected and stored for analysis. Samples were tested for anti-HLA donor-specific antibodies and their characteristics. Antibodies with mean fluorescence intensity > 500 were considered positive.

Results

Median time of follow-up of patients was thirty-nine months. Out of nineteen patients with detected donor-specific antibodies, ten patients were identified with immunodominant donor-specific antibodies with C1q-binding capacity (out of them, six patients had anti-HLA donor-specific antibodies detected also before transplantation). C1q-binding antibodies were IgG1 (six patients), IgG3 (three patients) and IgG1+IgG3 (one patient). Presence at the time of biopsy of donor-specific antibodies and their C1q-binding capacity were independent predictors (HR = 5.13, p < 0.001 and HR = 14.64, p < 0.001; respectively) of inferior kidney graft outcomes (composite of 30% reduction from eGFR at biopsy or death-censored graft loss).

Conclusion

Detection of donor-specific antibodies and their C1q-binding capacity might provide prognostic information in post-transplant monitoring in kidney transplant recipients.
#6456 DSA-NEGATIVE MICROVASCULAR INFLAMMATION IN KIDNEY TRANSPLANT BIOPSIES: GENE EXPRESSION COMPARISON WITH NATIVE AND TRANSPLANT KIDNEY CONTROLS
Authors: Buxeda Anna , Fixsen Ivy , Gibson Ian , Wiebe Chris , Nickerson Peter , Campbell Patricia , Fernandez Natalia Inmaculada Polanco , Crespo Marta , Mengel Michael , Adam Benjamin
Published: June 2023

Background and Aims

Microvascular inflammation (MVI) in kidney transplant (KT) biopsies from patients without detectable anti-HLA donor-specific antibodies (DSA) presents a diagnostic and therapeutic dilemma. This study aimed to further understand the significance of these changes by characterizing their molecular phenotype compared to other native and transplant kidney biopsies.

Method

The NanoString B-HOT panel (770 genes) was used to measure the expression of six literature-derived gene sets in 195 archival FFPE kidney biopsies from four centers, including transplant biopsies with MVI (g+ptc>1) but no detectable DSA (MVI, n = 47), antibody-mediated rejection with DSA (ABMR, n = 42), pure T-cell mediated rejection without DSA (TCMR, n = 25), mixed MVI and TCMR without DSA (MVI+TCMR, n = 47), normal implant biopsies (Normal, n = 11), and native kidney biopsies with either endocapillary proliferative glomerulonephritis (GN, n = 12) or minimal change disease (MCD, n = 11). The evaluated gene sets included transcripts previously associated with ABMR, DSA (DSAST), endothelial injury (ENDAT), TCMR, early injury, and late injury. Gene expression was compared between groups using principal component and class comparison analyses.

Results

Principal component analysis demonstrated significant molecular overlap between sample groups (Fig. 1A). However, gene set analysis showed lower expression of ABMR-related, DSAST (Fig. 1B), and ENDAT gene sets in DSA-negative MVI compared to ABMR. DSAST and ENDAT gene set expression was similar between MVI, MVI+TCMR, and TCMR groups; but higher than native biopsies (p ≤ 0.002). TCMR and early injury gene set expression was higher in TCMR than all other groups (p ≤ 0.002), except MVI+TCMR. Late injury gene set expression was lower in MVI compared to ABMR, MVI+TCMR, and TCMR groups (p ≤ 0.031); but higher than the Normal and MCD groups (p ≥ 0.016).

Conclusion

These results suggest that DSA-negative MVI displays a lower expression of ABMR-related genes than ABMR, but similar to MVI+TCMR and higher than native kidney biopsies with or without glomerulonephritis. Further work is underway to evaluate the potential role of non-HLA DSA and recognition of missing self in these cases.
#6489 UNI-494 DOES NOT SIGNIFICANTLY AFFECT RAT RESPIRATORY FUNCTION
Authors: Reddy Guru , Gupta Pramod , Khare Atul , Gupta Shalabh
Published: June 2023

Background and Aims

Nicorandil, a selective mitochondrial ATP-sensitive potassium channel activator, may be beneficial for several disease states, including acute kidney injury. However, its clinical use is limited by serious gastrointestinal side effects and rapid absorption and elimination. UNI-494, a novel nicorandil prodrug designed to improve its pharmacologic properties, may increase the short half-life and improve the safety profile of nicorandil. We present safety results from a safety pharmacology study evaluating the effects of UNI-494 on respiratory function in a rat model.

Method

The effects of UNI-494 on respiratory function (peak inspiratory and expiratory flow, inspiratory and expiratory time, minute volume, and respiratory rate) were evaluated using whole body plethysmography test in 4 groups of male Wistar Han rats (n = 8 per group). In addition to a control group, 3 test groups were administered doses of 2, 20, or 200 mg UNI-494/kg. Airway function parameter data generated were acquired using specialized EMKA Technologies software (IOX version 2.9.5; DATANLYST version 2.6.1) connected to Emka plethysmographic equipment. Recordings were taken 3 hours before and 4 hours after administration of the control and test items. Effects were reported at 0, 10, 15, 20, 30, 60, 90, 120, 180, and 240 minutes after administration.

Results

UNI-494 had no relevant effects on rat respiratory function over the 240-minute test period at any dose (2, 20, or 200 mg UNI-494/kg). There were small but insignificant differences in peak inspiratory and expiratory flow (Figure 1, 2), minute volume, respiratory rate, and inspiratory and expiratory time between the control group and the 200 mg UNI-494/kg group.

Conclusion

Rat respiratory function was not significantly affected by UNI-494. Future studies should continue to evaluate the safety and efficacy of this novel drug.
#6499 The CIRCRNA–MIRNA–MRNA REGULATORY NETWORK AND THE POTENTIAL ASSOCIATIONS WITH THE PATHOGENESIS OF SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Fengping Zheng , Tan Lishan , Yang Guang , Lai Zhiwei , LI Sanmu , Xiong Zibo
Published: June 2023

Background and Aims

This study aimed to explore the possible role of plasma and PBMCs circular RNA (circRNA) in systemic lupus erythematosus (SLE).

Method

Total RNA was extracted from blood plasma samples obtained from 10 patients with SLE and 10 healthy controls and subjected to microarray analysis to define the profile of circRNA expression. The quantitative reverse transcription-polymerase chain reaction amplification (qRT-PCR) was conducted. The overlapped circRNA between PBMCs and plasma was performed, the interactions with microRNAs were predicted, the miRNA target mRNA was predicted, and the GEO database was used. The Gene ontology and pathway analysis was performed.

Results

131 upregulated and 314 significantly downregulated circRNAs were identified in the plasma of patients with SLE by the Fold change criteria (≥2.0) and P < 0.05. The qRT-PCR results showed that the expression of has-circRNA-102531, has-circRNA-103984, and has-circRNA-104262 was increased in plasma of SLE, and the expression of has-circRNA-102972, has-circRNA-102006, has-circRNA-104313 was decreased in plasma of SLE. 28 upregulated circRNAs and 119 downregulated circRNAs were overlapped from PBMCs and plasma, and ubiquitination was enriched. Furthermore, the circRNA-miRNA-mRNA network was constructed in SLE after analyzing dataset GSE61635 from GEO. The circRNA-miRNA-mRNA network comprises 54 circRNAs, 41 miRNAs, and 580 mRNAs. In addition, the TNF signaling pathway and the MAPK pathway were enriched from the mRNA of the miRNA target.

Conclusion

We described differentially expressed circRNAs in plasma and PBMCs, and the circRNA-miRNA-mRNA network was constructed. The network's circRNAs could be a potential diagnostic biomarker and potentially play an important role in the pathogenesis and development of SLE.
#6508 THE EFFECTS AND MECHANISM OF BRAIN-TARGETING DRUG-LOADED EXOSOMES ON ADRIAMYCIN NEPHROPATHY MODEL
Authors: Tan Lishan , Yang Guang , Fengping Zheng , Lai Zhiwei , LI Sanmu , Xiong Zibo
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is a common clinical syndrome, and the current clinical efficacy is still limited. Our previous study confirmed that a small amount of losartan injected into the central lateral ventricle can effectively protect the kidneys, but the route of administration limits its clinical application. As a drug carrier, exosomes have several advantages and are expected to support drug delivery. Therefore, this study aims to develop a brain-targeting exosome complex to provide a new idea for the treatment of CKD.

Method

In this study, the brain-targeting exosome complex (ExoACP) was synthesized by co-cultivation. The markers of ExoACP were detected by immunoblotting. The structure and particle size distribution were observed by TEM and NTA. Angiotensin II receptor antagonist losartan (ExoACP@Los) was loaded on ExoACP by electroporation. The mice of Adriamycin (ADR)-induced nephropathy were divided into 5 groups: Control, ADR, ADR + Los (IG), ADR + ExoACP (iv.), ADR + ExoACP@Los (iv.). Corresponding treatment was given every other day from the 3rd week after modeling, and all mice were sacrificed at the 5th week, serum and renal tissue was collected for the following experiments.

Results

This study found that the exosome markers of ExoACP were highly expressed. The Exo and Ang-CP05-Exo were disc-like structures, and the size of the latter was larger than that of the former, suggesting that ExoACP was successfully modified on the surface of Exo. The modification efficiency of ExoACP on Exo was as high as 96.1%. Compared with free Exo, the distribution of ExoACP in brain was increased. Blood biochemical results showed that ExoACP and ExoACP@Los had no apparent side-effects on mice (Figure 1). In-vivo, ExoACP@Los treatment significantly improved the levels of kidney function in mice with ADR nephropathy. ExoACP@Los could significantly reduce renal tubular damage, interstitial fibrosis area and degree of glomerular sclerosis, suggesting that ExoACP@Los could improve the injury of renal tissue (Figure 2).

Conclusion

This study synthesized a drug-loaded exosome complex with brain targeting and good biocompatibility, and significantly improved renal function, renal tissue damage and collagen fiber deposition in the ADR model.
#6547 ON104, A NOVEL BIOENGINEERED ANTIBODY TARGETING OXIDIZED MACROPHAGE MIGRATION INHIBITORY FACTOR (OXMIF) AMELIORATES EXPERIMENTAL GLOMERULONEPHRITIS
Authors: Ferhat Maroua , Kerschbaumer Randolf , Tam Frederick , Prendecki Maria , Costa Lyndon , Thiele Michael , Landlinger Christine
Published: June 2023

Background and Aims

Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic inflammatory cytokine and a primary counter-regulator of glucocorticoids (GCs) that emerged as a pivotal regulator of immune-mediated disorders including glomerulonephritis (GN). MIF occurs in two immunologically distinct, conformational isoforms: reduced MIF, ubiquitously present in various tissues and the circulation of healthy subjects, and oxidized MIF (oxMIF), described as the pathogenic and druggable isoform of MIF [1]. We previously reported a positive correlation between disease severity and urinary oxMIF levels in patients with acute lupus nephritis, suggesting oxMIF contribution to kidney damage [2]. In this study we evaluated the anti-inflammatory effects of oxMIF neutralization using ON104 antibody during crescentic GN.

Method

By advanced antibody engineering we generated the fully human antibody ON104 that is specific and highly affine for human oxMIF and its orthologs. ON104 was tested for its therapeutic potential in a rodent model of GN. Nephritis was induced in male WKY rats by a single intravenous (i.v.) injection of rabbit anti-rat GBM (glomerular basement membrane) serum. On day 4 and day 6 after GN induction, ON104 was administrated intraperitoneally (i.p.). Body weight, proteinuria, and hematuria were assessed to evaluate GN severity. On day 8, kidneys were harvested for immuno-histological examinations by HE, PAS-staining and IHC staining.

Results

Treatment with ON104 substantially attenuated clinical signs of GN by preserving kidney function demonstrated by reduced proteinuria, and reduced hematuria. Furthermore, ON104 significantly reduced tissue injury, reduced crescentic glomerulus formation, and increased the percentage of normal glomeruli. On the cellular level, oxMIF neutralization by ON104 reduced CD68+ macrophage accumulation within the inflamed kidneys compared to untreated and isotype Ig-treated rats.

Conclusion

Our findings substantiate the role of oxMIF in the pathogenesis of experimental GN. Thus, targeting oxMIF may represent a new and promising treatment option for kidney diseases.
#6562 ITGAM PROMOTES MACROPHAGE ALTERNATIVE ACTIVATION IN HYPERURICEMIA-RELATED CHRONIC KIDNEY DISEASE
Authors: Liu Jing , Guo Fan , MA Liang , Fu Ping
Published: June 2023

Background and Aims

Hyperuricemia is an essential risk factor in chronic kidney disease (CKD), while urate-lowering therapy to prevent or delay CKD progression is controversial. Alternatively activated macrophages in response to local microenvironment play diverse roles in kidney injury, repair, and fibrosis. Here, we aim to investigate whether and how macrophage ITGAM contributes to hyperuricemia-related CKD.

Method

In vivo, we explored dynamic characteristics of renal tissue in hyperuricemia-related CKD. By incorporating mRNA and protein sequencing data, we analyzed gene expression profile, hub genes and potential pathways responsible for disease development, which was further confirmed using qPCR, western blotting, and immunofluorescent stainings. In vitro, we validated bioinformatic findings under different conditions of macrophages with interventions corresponding to core nodes in pathway.

Results

Hyperuricemia-related CKD was characterized by the rise in serum uric acid, decline in renal function, macrophage alternative (M2) polarization, and kidney fibrosis. Integrated bioinformatic analyses revealed ITGAM as the potential core gene mediating disease progression which was associated with FAK/Akt1/β-catenin signaling. Notably, we confirmed the upregulated macrophage ITGAM, activated pathway, and macrophage M2 polarization in injured kidneys and Raw 264.7 macrophages. In vitro, we verified ITGAM/FAK/Akt1/β-catenin pathway participated in promoting macrophage M2 polarization through silencing Itgam and inhibiting FAK or Akt1 phosphorylation, where the expression of M2 phenotype macrophage markers and downstream molecules in pathway were down-regulated.

Conclusion

In hyperuricemia-related CKD, ITGAM promotes macrophage M2 polarization contributing to renal fibrosis through FAK/Akt1/β-catenin signaling pathway. Targeting macrophage ITGAM might be a promising therapeutic approach for preventing or delaying CKD.
#6648 LONG TERM EFFECT OF MEDIUM CUT-OFF DIALYZER ON MIDDLE UREMIC TOXINS
Authors: Bushljetik Irena Rambabova- , Markovska Zhaklina Shterjova- , Taneska Aleksandra Canevska , Janevski Zoran , Filipovski Stefan , Nikolov Igor , Andreevska Galina Severova- , Bushljetikj Oliver , Gjorgjievski Nikola , Pushevski Vladimir , Spasovski Goce , Trajcheska Lada
Published: June 2023

Background and Aims

Better removal capacities for middle and large middle molecules in hemodialysis was achieved in (HD) treatment with the new medium cut-off (MCO) membranes. The aim of this study was to evaluate the long term removal efficacy of Theranova® in standard HD in comparison with standard high-flux HD.

Method

11 patients were assigned to high flux and 11 to MCO membranes in 12-months observational study. Each patient was assessed every three months from T0 with high-flux dialyzers, T1 to T5 with MCO at first, third, sixth, nineth and twelfth month by measuring pre- and post-HD samples of β2-microglobilin (β2M), myoglobin, albumin, free light chains kappa (FLC-k), and free light chains lambda (FLC-λ). The cumulative change from as RR from T0 to T5 was defined as long term outcome.

Results

The data showed a higher average removal rate (RR) for all the uremic toxins with Theranova® dialyzers for β2M, myoglobin, FLC-k, and FLC-λ (66.1, 53.2, 59.2.5, and 60.9%, respectively) compared to high flux (57.1, 10.8, 29.9 and 37.4%, respectively). The analyses on the cumulative RR from T0 to T5 found significant decrement of β2M, myoglobin, FLC-λ in MCO vs high flux group where those values significantly raised (14.9 vs −6.1, p = 0.043; 27.7 vs −7.8, p = 0.001; 21.9 vs −4.2, p = 0.017, respectively). The FLC-k showed borderline significantly better removal with MCO (17.8 vs 8.4. p = 0.067). The distribution of patients with 12 month middle molecules reduction was much better in the MCO group. Albumin retention was better in MCO group and did not change between T0 and T5 (p = 0.824).

Conclusion

Compared to high-flux membranes, MCO membranes show greater permeability for middle molecules and albumin stability in long-term report. Their use in HD standard setting is effective and safe.
#6681 MT-TL1 M.3243A>G MITOCHONDRIAL DNA VARIANT DETECTED FROM WHOLE EXOME SEQUENCING CAN EXPLAIN CASES OF ADULT UNKNOWN NEPHROPATHIES
Authors: Bensouna Ilias , Dancer Marine , Lebre Anne-Sophie , Raymond Laure , Doreille Alice , Lauteri-Badin Florence , Mesnard Laurent
Published: June 2023

Background and Aims

In a population-based study, mainly constituted of unknown nephropathies (cohort Sorbonne University, Paris, France N = 1197 patients), beyond reporting the diagnostic yield of nuclear genes, we also investigated the incidence of the mtDNA pathogenic variant MT-TL1 m.3243A>G. This variation was systematically searched from whole exome sequencing (WES) data. In retrospect, we described the renal phenotype and studied the heteroplasmy level of the mtDNA variation in urine or kidney tissues compared to its blood fraction. The prevalence of m.3243A>G has been estimated ranging from 0.08% to up to 0.25%.

Method

From September 2018, to February 2023, WES has been prospectively performed, as a first exploration of adult's nephropathies of unknown origin or when a genetic renal disease was clinically suggested. As off-target result, we retrieved m.3243A>G variation in blood DNA and then determined the mtDNA heteroplasmic level respective from urine sample or kidney tissue when available with an orthogonal method.

Results

We report a molecular diagnosis in 294 over 1197 adult patients sequenced (diagnostic yield: 24%, Age 43 y/o in average). Among these 294 patients with molecular diagnoses, 48 were distinct monogenic disorders, out of which 8 accounted for 52% of the genetic diagnoses. MT-TL1 m.3243A>G pathogenic variant was detected in 1,7% of the patients (20 patients over 1197 patients). An orthogonal method confirmed the presence of m.3243A>G variant in 10 patients supporting the possibility to diagnose from blood DNA analysed by WES. In all cases, the presence of m.3243A>G had major clinical implications for the patients and their families: living related donor aborted for two patients, a molecular diagnosis in three patients with unknown nephropathies and in three patients with histological diagnosis of focal segmental glomerulosclerosis. Other mitochondrial diseases appeared less likely involved in our adult cohort (only one patient with COQ2 pathogenic variants).

Conclusion

This population-based study reinforces the place of WES as first-tier exploration for adult patients with chronic kidney disease in whom phenotypes are often poor and/or atypical. The mitochondrial genome analysis with the same assay allowed the detection of yet unsuspected MT-TL1 m.3243A>G variant in 1,7% of patients suggesting enrichment compared to current prevalence observed in other population. Our data suggest that the entity “mitochondrial nephropathy” can represent a significant part of adult unknown nephropathies.
#6698 THROMBOPROPHYLAXIS IN PEDIATRIC KIDNEY TRANSPLANTATION: A META-ANALYSIS
Authors: Azharuddin MD , Sharma Manju
Published: June 2023

Background and Aims

Kidney transplant patients are at higher risk for developing renal graft thrombosis, especially in pediatric patients. Renal graft thrombosis mainly causes graft failure leading to high morbidity, mortality, and a significant impact on quality of life. To minimize the risk of renal graft thrombosis, antithrombotic prophylaxis is widely used. However, the effect of antithrombotic prophylaxis for kidney transplantation is still a matter of discussion. Therefore, we carried out a meta-analytic synthesis to determine the effect of antithrombotic prophylaxis in pediatric kidney transplantation patients.

Method

We systematically searched MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Web of Science. The eligible studies were identifying the incidence of renal graft thrombosis, hemorrhagic complication (bleeding and bleeding severity), and adverse outcomes related to antithrombotic prophylaxis compared with control group (placebo, active treatment, and no antithrombotic prophylaxis). Meta-analysis was carried out using Review Manager 5.3. The random-effects model was used to compute the pooled estimates of risk ratio (RR) and 95% confidence intervals (CI).

Results

A total of seven studies with 10,51 patients were included in the meta-analytic synthesis. Heparin was used across all the studies as the preferred antithrombotic prophylaxis. Results from the pooled meta-analysis reported that the overall risk for developing renal graft thrombosis was significantly lower in the antithrombotic prophylaxis group compared with the control group (RR = 0.81, 95% CI = 0.06-0.56, p = 0.003). There is no significant difference was found in incidence of hemorrhagic complications between antithrombotic prophylaxis and control group (RR = 0.81, 95% CI = 0.43-1.54). Similarly, there were no significant deaths were found in antithrombotic prophylaxis group compared with the control group (RR = 0.33, 95% CI = 0.01-22.45)

Conclusion

The results showed that antithrombotic prophylaxis significantly reduced the risk of renal graft thrombosis in pediatric kidney transplantation. However, due to limited outcomes, further real-world studies with long-term follow-up are required to generate sufficient data on the use of antithrombotic prophylaxis in pediatric kidney transplantation patients.
#6706 ACUTE KIDNEY DISEASE FOLLOWING COVID-19 VACCINATION: A RETROSPECTIVE, SINGLE- CENTER STUDY
Authors: Chen Chien-Chou , Yang Sung-Sen , Hsu Yu-Juei , Sung Chih-Chien , Chu Pauling , Wu Chia-Chao , Hsu Shun-Neng , Wang Han-En , Lin Shih-Hua
Published: June 2023

Background and Aims

The rare de novo or relapsed kidney diseases associated with coronavirus disease 2019 (COVID-19) vaccination have been increasingly reported. The aim of the study was to investigate the incidence, characteristics, and outcome of acute kidney disease (AKD) following COVID-19 vaccination.

Method

This retrospective study scrutinized the data from renal registry in a single academic medical center from Jan. 1st, 2020, to Apr. 30th, 2022. Patients who developed AKD within 90 days after COVID-19 vaccination were first included. Naranjo score as a causality assessment tool for adverse vaccination reaction and charts review by peer nephrologists were utilized for the exclusion of other causes. The etiologies of AKD, their characteristics, treatment, and outcome attributing to the COVID-19 vaccines were examined (Fig. 1).

Results

Twenty-seven aged 23 to 80 patients with AKD were identified from 1897 patients (incidence of 6.3 per 1000 patient-years). Their Naranjo score was 7.7± 1.5, and 14 of 27 patients (51.9%) had definite diagnosis (Naranjo score ≥ 9). They incorporated both glomerular disease (n = 16) including IgA nephropathy (n = 7), anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis (AAN) (n = 4), membranous glomerulonephritis (n = 3), minimal change disease (MCD) (n = 2), and chronic kidney disease (CKD) with acute deterioration (n = 11). The majority (21 of 27, 77.8%) of COVID-19 vaccination was messenger RNA (mRNA)-based regimen. Four patients (14.8%) rapidly progressed to end stage kidney disease (ESKD) requiring dialysis despite aggressive management. Extra-renal features such as pulmonary hemorrhage, myopericarditis and hepatitis/pancreatitis were observed in 4 patients.

Conclusion

In summary, AKD after COVID-19 vaccination may occur with more alarm in this renal registry. In addition to GN, patients with pre-existing moderate to severe CKD should also receive more intensive evaluation before vaccination despite the established benefits of vaccination in this vulnerable population likely outweigh the risk.
#6732 EPICARDIAL ADIPOSE TISSUE AND REVERSE EPIDEMIOLOGY IN DIALYSIS PATIENTS
Authors: D'marco Luis , Checa-Ros Ana , Karohl Cristina , Soto Carlos , Bermudez Valmore , Raggi Paolo
Published: June 2023

Background and Aims

Conventional risk factors of cardiovascular disease and mortality in the general population such as body mass is relate to adverse outcome in dialysis patients, but often in an opposite direction (reverse epidemiology). On the contrary, epicardial adipose tissue (EAT) has reported to have a local inflammatory and proatherogenic effect. Thus, the association of EAT as direct measures of region specific adipose tissue in chronic kidney disease (CKD) has been studied.

Method

The study evaluated 37 CKD-5 patients in hemodialysis (mean dialysis duration 26±30 months, 70% males, 57% African-American, 48% diabetic) that underwent MSCT to measure EAT and coronary artery calcium (CAC) score. CAC distribution in quartiles of EAT was assessed. Finally, we measured patients’ body mass index (BMI) and categorized them as normal (BMI 18.5-25 kg/m2) and abnormal BMI (BMI >25 kg/m2).

Results

The mean BMI was 28.6±5.7 kg/m2, and the mean EAT volume was 66±29 ml and 102±69 ml for normal and abnormal BMI groups. There was a direct correlation between dialysis vintage and EAT while BMI showed an inverse relationship with dialysis vintage (p = 0.05). In this small sample size, the association of CAC and EAT was only marginally significant (p = 0.7). EAT was significantly correlated with age (p = 0.02), history of cardiovascular disease (p = 0.03) and diabetes (p = 0.001).

Conclusion

The direct association of EAT with dialysis vintage in the face of an inverse association of BMI with dialysis duration appear to support the notion that chronic hemodialysis is a state of chronic inflammation and malnutrition.
#6733 THE PREDICTORS OF CARDIO-RENAL SYNDROME AMONG PATIENTS WITH COVID-19 INFECTION
Authors: Attallaha Aber , Mansour Hazem , Khouly Ahmed Tareq El , Farrag Osama , Tanagho Bishoy Abd El Maseeh
Published: June 2023

Background and Aims

Several reports showed that some Covid-19 patients tend to have serious and fatal complications related to the kidney and heart. Rationale and mechanisms inducing this pathogenesis is unclear, but it's more common to happen in patients with hemodynamic instability and refractory severe hypotension related to cytokine storm. It represents an irreversible stage of a sepsis-like illness that induces simultaneous damage to various organs as the myocardium and renal tubules alike the cardio-renal syndrome. The predictors for this injurious effect of COVID-19 on both myocardium and renal tissues might be related to the co-morbidities, late presentation and other factors which need further evaluation.The aim of this article is to study the predictors of cardio-renal syndrome in COVID-19 patients

Method

Our study is a prospective observational study conducted upon confirmed 160 COVID-19 ICU patients admitted from 15th March till 20th May 2020. All patients were subjected to clinical assessment, full laboratory evaluation including PCR for COVID-19 from nasopharyngeal swab and full radiological evaluation

Results

As regards the predictors for cardio-renal syndrome [15-17]; Age showed high statistically significance (P <0.0004). Furthermore, serum creatinine and serum K were statistically significant in patients with cardio-renal affection (P= 0.015, 0.021) whereas GFR, D-dimer, need for mechanical ventilation and vasopressors were highly statistically significant with cardio-renal affected patients (P <0.001).

Conclusion

Cardio-renal syndrome was common in COVID-19 ICU patients. Hypokalemia, lower GFR on admission, mechanical ventilation, vasopressors, age and D-dimer were significant independent predictors for CRS. Moreover,CRS during hospitalization was associated with an increased risk of in-hospital death.
#6760 EFFICACY OF HEMOSORPTION IN REMOVAL OF HIGH MOLECULAR WEIGHT UREMIC TOXINS IN CHRONIC HEMODIALYSIS PATIENTS
Authors: Karpov Pavel , Vishnevskii Konstantin , Gerasimchuk Roman
Published: June 2023

Background and Aims

Symptoms associated with the accumulation of large uremic toxins (the development of chronic inflammation, accelerated progression of cardiovascular diseases and an increase in the incidence of protein-energy malnutrition) are common for patients who get chronic hemodialysis (HD) for a long time. HD effectively removes small and medium molecules (up to 15 kDa), while convection techniques, which are not always available, are used to remove substances of higher molecular weight. An alternative strategy for removing uremic toxins, especially large medium molecules, is the use of sorption techniques. The aim of the study was to compare the removal efficiency of substances with a molecular weight from 11.8 to 45 kDa using HD on a high-flux membrane and a combination of a high-flux membrane with hemosorption.

Method

The study included patients with a duration of hemodialysis therapy for more than 5 years. Blood sampling was carried out before and after the procedures, in the average RRT session per week. The following indicators were determined: β-2-microglobulin, leptin, free light chains (FLC) κ and λ, Il-6. The first HD session was performed on a Fresenius Fx-80 high-flux membrane. The second procedure (one week after) was carried out using the same filter, but with the connection of a Jafron HA130 sorption column (HD+HP). The duration of the both procedures was 4 hours. Blood flow did not exceed 300 ml/min.

Results

Total 10 patients were included in the study. Mean duration of renal replacement therapy was 12±5 years. The ratio of men and women was equal. Mean age 54±12 years. All patients used AV fistulas as vascular access. When determining and comparing the concentrations of β-2-microglobulin, leptin, Il-6, a comparable significant decrease in concentrations was noted after both procedures without significant statistical differences between the methods. At the same time, the efficiency of FLC removal on HD and HD+GP was convincingly different:

- average kappa-FLC concentration change after HD was +1.8±9.1 mcg/ml, after HD+GP:

-9.4±7.5 mcg/ml, p = 0.04.

- average lambda -FLC concentration change after HD/HD+GP was +3.2±16.3 and -12.9±4.4 mcg/ml, respectively. p = 0.02.

Conclusion

The use of sorption techniques as an adjunct to standard HD therapy can increase the excretion of medium-large molecular substances, such as FLC kappa/lambda, which may help reduce the severity of symptoms associated with the accumulation of these uremic toxins. Additional studies are required to evaluate the clinical effectiveness of the new sorption method in chronic HD.
#6768 TIO2/TI3C2 NANOCOMPOSITES FOR BILIRUBIN CLEARANCE FROM BLOOD
Authors: Chang Kaixi , Su Baihai
Published: June 2023

Background and Aims

The artificial liver treatment based on blood purification is an important and commonly used treatment for liver failure. Aggressive management of hyperbilirubinemia is one of the key steps to reduce mortality in patients with liver failure. Herein, targeting bilirubin in nano-sized, we synthesized a TiO2/Ti3C2 nanocomposite from Ti3C2 MXenes via hydrothermal oxidation for bilirubin clearance from whole blood.

Method

Firstly, Ti3C2 MXene was prepared by hydrofluoric acid etching method reported in our previous work [1]. Then, it was transferred into Teflon-lined stainless-steel autoclaves (2 mg/ml, 30 ml) and was undergone the hydrothermal process at 180 °C for 6 h and 12 h. TiO2/Ti3C2 nanocomposites were obtained after lyophilization. Hemocompatibility evaluation assays include hemolysis ratio test, complement activation (human complement fragment 5a (C5a)), contact activation (Thrombin–anti-thrombin (TAT) complex) and platelet activation (platelet factor 4 (PF 4)) were systemically conducted in vitro to evaluate the feasibility of the novel nanocomposites (0.5 mg/ml) in contact with blood. We evaluated the bilirubin adsorption capacity of original Ti3C2 (0 h) and TiO2/Ti3C2 (6 h and 12 h) at the concentration of 0.5 mg/ml, respectively, in bilirubin solution (250 mg/l, 10 ml) for 2 h at 37 °C in an air bath away from light. The sphere-forming properties of TiO2/Ti3C2 with polyethersulfone (PES), a commonly used blood purification material, were first verified using a liquid-liquid inversion method.

Results

TiO2/Ti3C2 (6 h and 12 h) showed better hemocompatibility than the original Ti3C2 (0 h) (Figure 1). The bilirubin adsorption capacities by the original Ti3C2 (0 h) and TiO2/Ti3C2 (6 h and 12 h) were 354.11 mg/g, 492.83 mg/g and 492.52 mg/g, respectively. From the original Ti3C2 (0 h) to TiO2/Ti3C2 (6 h), the clearance rate of bilirubin improved from 70.82% to 98.57%. Therefore, we chose TiO2/Ti3C2 (6 h) to verify the sphere-forming properties of TiO2/Ti3C2 with PES. TiO2/Ti3C2-PES spheres were constructed successfully by a liquid-liquid inversion method. More 3D porous structure on the surface and uniform distribution of TiO2/Ti3C2 (Ti element) in the substrate were observed via a scanning electron microscope (SEM) images and energy dispersive spectroscopy (EDS) mapping images (Figure 2).

Conclusion

The TiO2/Ti3C2 nanocomposite showed excellent bilirubin clearance capability, superior hemocompatibility, and the great application potential in the form of spheres for hemoperfusion, which may provide a promising choice in the performance enhancement of artificial liver characterized by bilirubin clearance. Importantly, the above properties are adjustable by the heating temperature and the time period, other application forms and strategies of the TiO2/Ti3C2 nanocomposite to target bilirubin in nano-sized are worth being explored and expected.
#6779 EXPERIENCE IN A GERIATRIC NEPHROLOGY CONSULTATION
Authors: Morales Orlando Siverio , Davila Maria Adela , Izquierdo Edduin Miguel Martín , Reguera María José , Garcia Patricia , Bethencourt Alejandro Alonso , Rodríguez Carla , Aragao Ana , Perez Rosa , Dominguez Virginia , Macia Manuel
Published: June 2023

Background and Aims

In the last two decades, the Spanish population over 65 years of age has increased by more than two million people. This has made the coexistence of comorbidities such as arterial hypertension (AHT) and diabetes (DM) more frequent, which act as risk factors in the onset of chronic kidney disease (CKD). This circumstance is conditioned by the presence of other factors associated with aging that condition greater frailty and a greater degree of dependency. Due to this, the application of the comprehensive geriatric assessment could be useful for its adequate stratification, obtaining a better evaluation of kidney disease and, with it, trying to improve the functionality of the patient.

Method

To analyze the parameters associated with CKD and their possible relationship with the degree of frailty and/or functionality in patients older than 75 years referred to a specific Nephrology consultation.

Material and methods: descriptive and observational epidemiological study corresponding to a series of cases, which includes patients from the southern area of Tenerife who were referred for evaluation by the HUNSC Nephrology Service over a period of 8 months.

Results

It was obtained that, of 1263 patients referred, 41.1% of patients were older than 75 years. Of these, 19.1% of patients required face-to-face assessment in the Nephrogeriatrics consultation. When analyzing the relationship between frailty and functionality, we observed that the groups with greater frailty had both older ages and lower hemoglobin and albumin values. Likewise, it was observed that patients classified as frail had a higher risk of mortality than those who were not frail. Regarding functionality, when comparing the means of the parameters associated with CKD in relation to the degree of functionality (Barthel), it was obtained that age, creatinine, hemoglobin and albumin presented statistical significance.

Conclusion

The geriatric population represents a significant number of all consultations referred to Nephrology. The high prevalence of associated diseases that affect renal function (HBP and DM) together with the physiological changes that occur in aging make CKD an important public health problem. Carrying out adequate frailty and functionality scales may constitute one of the most important parameters to assess in nephrogeriatric patients, since it would allow us to improve the efficiency of the care process in CKD.
#6786 ADTKD DUE TO MUC-1 GENE MUTATION: A MAJOR DIAGNOSTIC CHALLENGE, NOT IDENTIFIED BY EXOME SEQUENCING
Authors: Sossai Giulia , Moscato Marco , Gandolfini Ilaria , Delsante Marco , Mellone Simona , Giordano Mara , Cirami Calogero , Allinovi Marco
Published: June 2023

Background and Aims

Autosomal dominant tubulointerstitial renal disease (ADTKD) is a rare cause of end-stage renal disease (ESKD) in adulthood. In addition to its rarity, ADTKD is probably underdiagnosed due to the very non-specific and heterogeneous clinical-laboratory-histopathological-instrumental picture and because of the diagnostic need to use specific methods of genetic investigation in order to highlight the mutations within the VNTR sequences of the MUC1 gene, not recognized by the most common exome sequencing. Mutations in the MUC1 gene, together with those in the UMOD gene, are the main mutations implicated in the pathogenesis of ADTKD.

Method

We analyzed the clinical, laboratory and histopathological characteristics of four families followed by our center with suspected diagnosis of ADTKD and detection of mutation of the MUC1 gene.

Results

Our data (Table 1) revealed a marked phenotypic variability, even within members of the same family (Fig. 1), and in particular as regards the age of disease onset and the different rate of progression towards ESKD (range 16 – 88 years). From a laboratory point of view, in 10 out of 13 patients the sediment was negative, and only in 3 patients proteinuria >1 g/24h was highlighted. In 6/13 the onset occurred at the age of less than 35 years and among these, 4 of them presented ESKD early. In the few cases in which renal biopsy was performed (4/17), representing 0.4% of all biopsies in our centre, the most frequent finding was the presence of tubular atrophy and interstitial fibrosis (3/4), with cystic ectasia of the tubular lumen at the cortical-medullary level in half of the cases. Among the 10 patients subjected to genetic analysis, only in one case the mutation was highlighted by exome sequencing.

Conclusion

The large phenotypic variability, in particular of age at achievement of ESKD, suggests that other factors (modifier or environmental genes) could also affect disease progression. Common gene sequencing methods (e.g. exome sequencing, Sanger) have proved unable, in most cases, to identify mutations within the VNTR sequences of the MUC1 gene.
#6795 DISSEMINATED STRONGYLOIDES INFECTION IN A PATIENT WITH IGA NEPHROPATHY ON IMMUNOSUPPRESSIVE MEDICATIONS
Authors: Parry Manzoor , Dogra Ajay , Yousuf Rayees
Published: June 2023

Background and Aims

Immunosuppressive medications such as high dose steroids and antimetabolites are frequently used in glomerulonephritis. However, use of these medications is usually associated with various adverse effects. Among the drawbacks of immunosuppressive therapy, the risk of reactivation of latent infections, including parasitic infestations, is to be considered.

Method

Case report.

Results

Our case is a 28 year old male patient who was diagnosed as a case of IgA nephropathy 7 months back with M1E1S1T1C0 lesions with a serum creatinine of 1.7 mg/dL and eGFR of 56 ml/min/1.73 m2. He was started on prednisolone (40mg daily) and mycophenolate mofetil (1000mg twice daily) for 1 month. He presented with us with diarrhea. He was treated with IV fluids and mycophenolate mofetil was stopped. After two weeks, he was readmitted with a 4-day history of fever, vomiting, and epigastric pain. On examination, he showed mild epigastric tenderness, normal vitals. The laboratory investigations on admission showed hemoglobin-15 g/dL, total leucocyte count-8600, eosinophilia with absolute eosinophil count 1900/ mm3, urea-92 mg/dL, creatinine-2 mg/dL. ECG showed sinus tachycardia, and HRCT chest revealed bilateral ground glass opacities and a calcified nodule in the left upper lobe. Liver function test was normal with normal amylase and calcium level. Blood culture was sterile. Ultrasound abdomen showed a bilateral raised Eco pattern in kidneys rest were normal. Upper GI endoscopy revealed diffuse edema, erythema, and superficial ulceration in duodenum and biopsy was taken. The duodenal biopsy showed features of strongyloidiasis stercoralis (Figure 1). Bronchoesophageal lavage was done which revealed strongyloidiasis stercoralis larvae. Meanwhile, the patient developed subacute small bowel obstruction with abdominal x ray showing multiple air fluid levels and CT scan showed features of small bowel obstruction with transition at mid-ileal level secondary to short segment thickening. Small bowel obstruction was relived with conservative mangement with ryles tube decompression and enemas. He was diagnosed with disseminated strongyloidiasis and treated with ivermectin for 14 days with full recovery

Conclusion

Our case signifies need of awareness among clinicians of the risk of disseminated strongyloidiasis as a complication of the treatment with immunosuppressive medications even in non-endemic areas.
#6797 EFFICACY OF DESENSITIZATION TREATMENT IN HYPERIMMUNIZED PATIENTS AWAITING A CADAVERIC KIDNEY TRANSPLANTATION
Authors: Garcia Maria Elena Gonzalez , Oliva Maria Ovidia Lopez , Mancebo Esther , Jimenez Carlos
Published: June 2023

Background and Aims

On all kidney waiting lists, patients who have antibodies against more than 80% of a panel reactive antibody (PRA) are difficult to transplant, even with national or regional programs. Desensitization treatment with high-dose intravenous immunoglobulin and rituximab could be offered to patients with a long waiting time for a cadaveric donor to improve their odds of finding a kidney.

Method

Retrospective, single-center study including all hyperimmunized patients on the waiting list for a cadaveric kidney donor who received a desensitization treatment between 2010-2020. To be considered to the desensitization protocol, all the patients must have a PRA above 75% and have been on the waiting list more than 3 years, without any offer. Our treatment was based on the modified Cedars-Sinai Medical Center protocol. Eight hyperimmunized patients on the waiting list for a cadaveric donor kidney transplant (50% male with a mean age of 41.5±16.4 years) received desensitization treatment with intravenous immunoglobulin and Rituximab. Six of the 8 patients (75%) were on renal replacement therapy with hemodialysis and two on peritoneal dialysis (mean time on dialysis 48±14 months). 75% had received a previous transplant. The median PRA calculated was 98%. The time between desensitization and kidney transplantation, the percentage of reactivity against panel cells (PRA) before and after therapy, graft and donor survival, as well as episodes of acute rejection and viral infections were analyzed. The mean follow-up time after transplantation was 67 months.

Results

No patient presented significant side effects to desensitization treatment. Seven of the 8 patients (87.5%) could be transplanted from a cadaveric donor (negative crossmatch test), in a median 8 months after desensitization. No significant changes were observed in the PRA levels. In the immediate post-transplant period, there were 2 graft losses (28.6%) due to non-immunological causes (1 venous thrombosis in a patient with a coagulation disorder and 1 primary graft failure). Creatinine at discharge was 1.6±0.4 mg/dl and 1.4±0.2 a year after the transplant. Five-year censored death graft survival was 100%. Three patients presented viral replication (1 due to cytomegalovirus (CMV), 1 due to polyomavirus (BK) and another CMV+BK), which became negative after switching to m-Tor therapy. There were no episodes of acute rejection. No patient developed cancer during the follow-up.

Conclusion

Desensitization treatment with immunoglobulin and rituximab on hyperimmunized patients on the cadaveric waiting list is a safe and effective treatment that increases the chances of achieving a kidney transplant in highly sensitized patients.