bluuebunny/crossref_metadata_2025 huggingface dataset:
#5134 THE REDS/MEWS SCALE USED FOR ASSESSMENT OF ESKD PATIENTS DIALYSED WITH CENTRAL CATHETER MAY REDUCE A NUMBER OF INFECTIVE ACCESS-RELATED COMPLICATIONS
Authors: Lachowski Michal , Ostrowska Aleksandra , Benc Krzysztof , Porazko Tomasz
Published: June 2023

Background and Aims

Central tunnelled catheter (CVC)-related infections are a leading cause of catheter lost and being the source of significant morbidity and mortality of end stage kidneys disease (ESKD) patients. The study aimed to evaluate the impact of the implementation of the own REDS/MEWS scale for combined assessment of ESKD patients dialysed with the CTC on the frequency of infective complication.

Method

A group of 52 ESKD patients dialysed through a CTC were evaluated, pre dialysis on every session, using the REDS/MEWS scale for 24 months years and results as well as follow up of participants were compared with a two years period of time before the tool was introduced.

Results

Two-years cumulative incidence of CTC exit site infection (ESI) has dropped significantly (log-rank p < 0.001) from 0.87 episode per 1000 catheter days (52.3%, CI95 [34.2%; 67.3%]) in time before REDS/MEWS was used to 0.28 episode per 1000 catheter days (19.3%, CI95 [7.3%; 30.1%]) in REDS/MEWS time. There were also significantly less episodes of ESI complicated with catheter related blood stream infection (CRBSI) requiring CTC removal (0.8 episode per 1000 catheter days; 20.6%, CI95 [8.4%; 33.2%] vs. 0.4 episode per 1000 catheter days; 5.4%, CI95 [1.1; 8.7%]; log-rank p = 0.05, in pre – REDS and REDS time respectively). There was no serious complications as infective endocarditis, vertebral discs abscess among patients due to early detection and treatment of possible CTC related infection.

Conclusion

The REDS/MEWS scale appears to be a simple, cost-effective tool reducing frequency of the CTC related infective complication and the type of vascular access loss.
#5171 MODIFIED, NON-INVASIVE, TUNNELLED CATHETER REPOSITION (NTCR), SIMPLE AND SAFE TO RESTORE FUNCTION OF CENTRAL TUNNELLED CATHETER FOR HAEMODIALYSIS
Authors: Lachowski Michal , Ostrowska Aleksandra , Benc Krzysztof , Porazko Tomasz
Published: June 2023

Background and Aims

Still many end stage kidney disease (ESKD) patients are dialysed using central tunnelled catheters (CTC) as vascular access. Catheter thrombosis and is a dominant, non-infectious CTC complication. There are a number protocols established, to resolve the problem, all are not always effective, time as well as cost consuming.

Method

The modified maneuver of non-invasive tunnelled catheter reposition (mNTCR) was introduced and studied, to obtain an immediate haemodialysis start, in case of CTC dysfunction. The NTCR is based on gentle movements of CTC or its part, with CTC lines flushing which resulted with quick CTC's tip reposition. The study was a continuation of previously published with modification including mandatory CTC lines flushing and locking lines with antithrombotic agent after the dialysis session.

Results

A number of 205 mNTCR were performed in 110 patients with CTC. Effective blood flow CTC was obtained after 115 procedures (56%), partial function followed 73 procedures (35,6%), and 17 attempts (8%) failed. Over 90% interventions improved a CTC patency allowing start of effective haemodialysis. The procedure could be successfully repeated with similar effect after the first, and the second attempt (28 vs 22 hemodialyses performed respectively). In the group of 50 elderly patients (median age 74 years) with CTC as the only vascular access, mNTCR was successful in 31 patients allowing dialysis continuation for median period 54 months. The mNTCR is safe as minor complications were observed after 5,1% of all procedures.

Conclusion

The novel mNTCR manoeuvre was safe and effective in a majority cases of CTC dysfunction. It permitted immediate dialysis without time consuming fibrinolytic agents usage protocols before the dialysis session, saving costs and nursing staff time.
#5213 RELATIONSHIP BETWEEN CYTOKINE RELEASE SYNDROME AND ACUTE KIDNEY INJURY AFTER CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY IN HEMATOLOGIC NEOPLASMS
Authors: Román Juan León , Iacoboni Gloria , Garcia Sheila Bermejo , Carpio Cecilia , Arana Ander Vergara , Matamoros Oriol Bestard , Barba Pere , Romeo Maria José Soler
Published: June 2023

Background and Aims

CAR-T cell therapy is a promising new immunotherapy to treat refractory hematologic malignancies (RHM). Despite the potential benefits, high rates of treatment related toxicity have been reported after CAR-T infusion. AKI occurs between 20-30% after treatment. The purpose of this study was to identify the relationship between the proinflammatory status (CRS, ICANs, and febrile neutropenia) and AKI development.

Method

Medical records of 115 patients treated with CD19-targeted CAR-T cells for refractory hematologic malignancies at HUVH between July 2018 and May 2021 were reviewed. Clinical data was reviewed within 30 days after CAR-T cells therapy. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria: grade 1, 1.5 to <2-fold of baseline; grade 2, 2- to <3-fold of baseline; grade 3, ≥3-fold of baseline We performed statistically analysis to identify risk factors for AKI development.

Results

A total of 24/115 patients presented AKI after CAR-T infusion. AKI Akin stage 1 was diagnosed in 17 (15%) patients, AKI Akin stage 2 was diagnosed in 4 (3.5%) patients, and AKI Akin stage 3 was diagnosed in 3 (2.6%) patients. 4/17 patients died in the AKI Akin stage 1 group while 2/3 patients in the AKI Akin stage 3 group. Renal function was recovered in 19/24 (79%) patients within the first month. Chronic kidney disease was present in 13% patients. Among types of CAR-T cell infusion, “investigational product” was infused in 27.8%, tisagenlecleucel in 49.6%, axicabtagen ciloleucelin in 20%, and brexucabtagene autoleucel in 2.6%. The most frequent complications were cytokine release syndrome (81.9%), febrile neutropenia (67%) and neurotoxicity (28.7%). Tocilizumab was given in 31 (27%) patients for CRS grade ≥2, and 5% of patients were admitted to the intensive care unit 3/36 patients died after CAR-T infusion. Male sex, CAR T-cell construct, ICANs, CRS, and death by any cause were associated with AKI. Only CRS ≥2(p=0.001) was identified as independent risk factor for AKI.

Conclusion

AKI development is mainly transient and associated with the proinflammatory status after CAR-T cell infusion.
#5216 DIALYSIS MODALITIES, URAEMIC TOXINS AND MICROINFLAMMATION: CAN WE DO MORE?
Authors: López Raquel Ojeda , Pavón Fátima Guerrero , López-López Isabel , Peregrín Cayetana Moyano , Carmona Andres , Martin-Malo Alejandro , Soriano Sagrario
Published: June 2023

Background

Patients on hemodialysis (HD) have a high morbidity and mortality from cardiovascular disease (CVD). Despite advances in HD -new membranes, such as medium cut-off (MCO) or techniques that combine diffusion+convection+adsorption such as hemofiltration with ultrafiltrate regeneration- (HFR)-, only online hemodiafiltration (OL-HDF) has been shown to improve survival in these patients. It is important to investigate whether the new HD filters/techniques help to improve the clearance of uremic toxins that are difficult to eliminate (those bound to proteins) and molecules associated with microinflammation in uremic patients, due to the important role they play in the development of CVD.

Aim

To study whether different HD membrane-techniques improve the clearance of uremic toxins and/or parameters associated with the microinflammation present in these patients.

Method

12 stable patients on HD were included, with a minimum time on HD of 3 months. Each patient underwent 4 random HD sessions in which only the dialysis membrane and/or the modality were changed. They underwent an HD session with a high-flux polyphenylene membrane, another session with this same filter in OL-HDF, another with MCO membrane, and another with HFR-H. All sessions were held in a short period. In all of them, pre- and post-dialysis blood samples were taken to assess the clearance of both conventional uremic toxins and protein-bound toxins (indoxyl-sultate and p-cresol), as well as molecules associated with the microinflammation process (proinflammatory monocytes: CD14+/CD16++ and proinflammatory cytokines).

Results

When evaluating the effect of the different HD techniques on the percentage of proinflammatory monocytes, a relevant, although not significant, decrease was observed in the OL-HDF and HFR-H techniques. Likewise, when evaluating the profile of markers of inflammatory activity, such as IL-12B, IL-17C, CD8A or TNFRSF9, a significant decrease was observed after the dialysis session in HFR-H compared to the rest of the techniques analyzed.

Conclusion

After analyzing the results of our study, the HD technique that combines convection+adsorption+diffusion (with a novelty high permeability filter), HFR-H, is the only one that has shown significantly greater clearance of proinflammatory cytokines, as well as a greater elimination of activated monocytes and protein-bound toxins, although without reaching statistical significance. These results, although preliminary, are promising and open up a new line of research to improve CVD in HD patients.
#5217 PROTOCOL AND PRELIMINARY RESULTS OF DAPAGLIFLOZIN IN INACTIVE LUPUS NEPHRITIS CROSS-OVER RANDOMIZED TRIAL
Authors: Vajgel Gisele , Filho Carlos Miranda , Oliveira Camila , Costa Denise Maria , Cavalcante Maria Alina , Junior Braziliano Silva , Lima Camilla , Sandrin-Garcia Paula , Valente Lucila
Published: June 2023

Background and Aims

Sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) with and without type 2 diabetes. Lupus nephritis (LN) patients under immunosuppression were excluded from the most important trials with SGLT2 inhibitors. Thus, efficacy and tolerance of these drugs are unknown in such patients. The present trial will assess the effect of Dapagliflozin in patients with inactive Lupus Nephritis with residual proteinuria.

Method

For this cross-over randomized trial, we will include adult patients with LN class III, IV (+/-V) without active nephritis but with proteinuria > 500mg/24h or UPC > 200mg/g and eGFR ≥ 20ml/min, in the maintenance treatment. RAAS inhibition should be stable for at least four weeks before the randomization. We will exclude patients with other etiologies of CKD, those with active LN lesions on the recent biopsy (AI>2), use of induction therapy in the last 12 months (Cyclophosphamide, Mycophenolate Mofetil >2 g/day and Calcineurin inhibitors) and prednisone dose ≥ 20 mg/day. Due to safety issues, we will exclude patients with recurrent urinary infections (>3 times/year). They will be randomized to receive Dapagliflozin 10mg on top of standard of care therapy or not. After 24 weeks the groups will be switched and those without Dapagliflozin will receive it for the next 24 weeks. Primary endpoint will be reduction of proteinuria compared to baseline at 6 and 12 months. Secondary endpoints will include sustained reduction of eGFR > 30%; changes in weight and blood pressure compared to baseline; and number of infections on Dapagliflozin treatment versus exclusive standard of care therapy. The sample size was calculated for 28 patients enrolled providing 80% power to detect a 25% relative risk reduction in proteinuria (α level of 0.05).

Results

From 85 screened class III, IV (+/- V) LN patients under maintenance therapy, we excluded 65 due to active nephritis, low proteinuria or low eGFR. Until now we included 17 patients that were randomized 1:1 to start the treatment with Dapagliflozin on top of standard care or remain with the usual therapy for 24 weeks. Patients’ baseline characteristics are described in Table 1. All patients randomized were using Mycophenolate Mofetil ≤2 g/day and RAAS inhibition and 14 of them were receiving Hydroxychloroquine.

Conclusion

We expect that the present trial will determine whether the SGLT2 inhibitor Dapagliflozin, added to LN maintenance therapy, could safely reduce the residual proteinuria of inactive LN patients.
#5267 INITIAL EMERGENCY ROOM 6-HOUR URINE VOLUME IS AN IMPORTANT FACTOR FOR THE SURVIVAL OF CRITICALLY ILL PATIENTS UNDERGOING CRRT
Authors: Choi Dae Eun , Park Heyrim , Lee Eu Jin , Ham Young Rok , Kim Hae Ri , Na Ki Ryang , Hwang Yunkyeong , Park Heewon , Lee Kang Wook , Jeon Jae Wan , Shin Jin Ah , Jeong Jin Young
Published: June 2023

Background and Aims

It has been little known whether initial emergency room factors affect survival or renal function in critically ill patients undergoing continuous renal replacement therapy. We examined whether initial factors in ER impact survival and renal recovery in critically ill patients undergoing continuous renal replacement therapy.

Method

The study was a single-center, retrospective study of 332 patients for critically ill patients admitted to ICUs for continuous renal replacement therapy via emergency room from March 1, 2018 to May 31, 2021. Clinical parameters including urine output, eGFR, and serum NGAL were identified. The primary outcomes were the 30-day and 90-day mortality. Secondary outcomes were the 30-, and 90-day dialysis-free duration.

Results

Low urine output (LUO, defined as < 0.5 mL/kg/hr x 6 hours) group was significantly associated with 30-day mortality and 90-day mortality. Multivariable Cox regression analysis showed that LUO group was significantly more associated with the increased risk of 30-day mortality and 90-day mortality (hazard ratio, 1.935 and 2.141, respectively) compared to high urine output (HUO, defined as ≥ 0.5 mL/kg/hr x 6 hours) group. There was no significant association between 30-day or 90-day mortality and initial estimated glomerular filtration rate (eGFR) plasma neutrophil gelatinase-associated lipocalin (NGAL) levels. In critically ill patients undergoing continuous renal replacement therapy, HUO group and initial eGFR ≥ 30 ml/min/1.73m2 groups was associated with decreased 30-, and 90-day dialysis-free duration. However, serum NGAL had no significant relation with 30-, and 90-days RRT free durations.

Conclusion

During admission to emergency room, the initial low urine output is an important factor for 30-day and 90-day mortality in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.
#5277 THE EVALUATION OF FLUID VOLUME AND PROGNOSIS IN HEMODIALYSIS PATIENTS UTILIZING PLASMA HUMAN ATRIAL NATRIURETIC PEPTIDE
Authors: Suzuki Yuya , Otsuka Tadashi , Yoshioka Yuki , Iida Tomomichi , Watanabe Hirofumi , Kaseda Ryohei , Yamamoto Suguru , Kaneko Yoshikatsu , Goto Shin , Aoyagi Ryuzi , Narita Ichiei
Published: June 2023

Background and Aims

Volume overload leads to the development of heart failure, which contributes to the high mortality in patients on hemodialysis. The post-dialysis plasma level of human atrial natriuretic peptide (hANP) reflects the fluid volume in patients on hemodialysis. The threshold hANP level is reportedly 100 pg/mL; however, the clinical usefulness of the threshold hANP level for volume control has not been sufficiently studied.

Method

We conducted a single-center, retrospective, observational study that included 156 hemodialysis patients without atrial fibrillation. First, we examined the usefulness of the threshold hANP level (100 pg/mL) for predicting hypoxemia due to congestion in a short-term observational study from December 30, 2015 to January 5, 2016. Subsequently, we conducted a 5-year follow-up study wherein the outcomes were hospitalization due to acute heart failure (AHF), development of cardiovascular diseases (CVD), and all-cause death. Finally, we collected echocardiography data to investigate the relationship between cardiac function and hANP.

Results

Our short-term observational study showed that patients with an hANP level ≥ 100 pg/mL developed hypoxemia due to congestion (odds ratio, 3.52; 95% confidence interval, 1.06–11.71; P = 0.040). At the 5-year follow-up, patients with an hANP level ≥ 100 pg/mL had significantly higher rates of hospitalization due to AHF, CVD, and all-cause death based on the log-rank test (P = 0.003, P = 0.019, P < 0.001, respectively). Analysis of echocardiography data showed that the presence of reduced left ventricular ejection fraction and left ventricular diastolic disfunction were significantly associated with high plasma hANP levels. However, the threshold hANP level (100 pg/mL) remained independently associated with hospitalization due to AHF after adjusting for cardiac disfunctions in the multivariable model.

Conclusion

The hANP level is indicative of both fluid volume and cardiac dysfunction. In clinical practice, we suggest utilizing hANP as an easily accessible measure to identify high-risk patients for developing AHF initially. If the hANP level exceeds 100 mg/dL, we propose to perform echocardiography and consider reducing the DW. In clinical practice, the plasma hANP level could serve as a valuable indicator for assessing the risk of developing AHF and managing fluid volume.
#5289 INTRARENAL RENIN-ANGIOTENSIN SYSTEM ACTIVATION ALTERS RELATIONSHIP BETWEEN SYSTOLIC BLOOD PRESSURE AND PROGRESSION OF CHRONIC KIDNEY DISEASE
Authors: Kang Dong Hoon , Park Cheol Ho , Kim Hyung Woo , Park Jung Tak , Chang Tae-Ik , Yoo Tae-Hyun , Kang Shin-Wook , Han Seung Hyeok
Published: June 2023

Background and Aims

Elevated blood pressure (BP) and intrarenal renin-angiotensin system (RAS) activity are closely related to chronic kidney disease (CKD) progression. However, interrelationship between BP and intrarenal RAS activity on the risk of CKD progression is unknown.

Method

We analyzed 2,076 participants from the Korean Cohort Study for Outcomes in Patients With CKD. The main exposure was systolic BP (SBP). The urinary angiotensinogen-to-creatinine (u-AGT/Cr) ratio was stratified according to the median value (3.65 μg/gCr). The primary outcome was a composite kidney outcome of a ≥50% decline in estimated glomerular filtration rate from baseline measurement or initiation of kidney replacement therapy.

Results

During 10,550 person-years of follow-up (median, 5.2 years), the composite outcome occurred in 800 (38.5%) participants. In the multivariable cause-specific hazard model, higher SBP was associated with an increased risk of CKD progression. There was a significant interaction between SBP and u-AGT/Cr ratio on the risk of the primary outcome (P-for-interaction = 0.019). In patients with u-AGT/Cr <3.65 μg/gCr, the hazard ratios (HRs) (95% confidence intervals [CIs]) for SBP 120–129, 130–139, and ≥140 mmHg were 1.47 (1.08-2.01), 1.74 (1.26-2.39), and 2.43 (1.76-3.37), respectively, compared with SBP <120 mmHg. In addition, each 10 mmHg increase in SBP was associated with an 18% higher risk of CKD progression. Moreover, there was a greater decline in the estimated glomerular filtration rate among the higher SBP categories. However, these associations were not observed in patients with u-AGT/Cr ≥3.65 μg/gCr.

Conclusion

Urinary angiotensinogen levels may modify the association between SBP and adverse kidney outcomes.
#5322 RENAL AEROBIC GLYCOLYSIS AND LOCAL LACTATE PRODUCTION IN AKI
Authors: LI Jiaying , Shi Xiaoxiao , Chen Zhixin , Xu Jiatong , Chen Limeng
Published: June 2023

Background and Aims

Kidney is a high energy-consuming organ depending on fatty acid β-oxidation (FAO) to fulfil energy supply. During various biological stresses in AKI, FAO shuts down, and the aerobic glycolysis is enhanced. In this study, we aimed to investigate the effect of aerobic glycolysis and local lactate production in AKI.

Methods & Results

A maleic acid (MA) induced AKI model (MA-AKI) was established by MA intraperitoneally (i.p.) in C57BL/6J mice and sacrificed after 24h. The renal function in MA-AKI mice was damaged, accompanied by proximal tubular injury and mitochondrial dysfunction. RNA sequencing revealed a relative increase in glycolytic enzymes (HK1, PKM and PFKP) mRNA levels in the AKI phase. The protein level of glycolysis-related enzymes was also elevated with increased urinary lactate significantly (0.25±0.10 versus 8.60±0.74 mmol/L, P<0.0001) in MA-AKI. Furthermore, glycolysis inhibitor 2-DG was administrated after 2h of MA injection, which improved the renal function (indicated by decreased serum creatinine (Scr), 33.52±2.78 versus 57.15±4.81 μmol/L, P<0.001), proximal tubular histopathological injuries and mitochondrial dysfunction in MA-AKI. Mechanistically, we observed a significant positive correlation between the Scr and urinary lactate levels (R2 = 0.78, P < 0.0001). In order to examine the role of lactate in AKI, the mice were pretreated with oxamate, an inhibitor of lactate dehydrogenase A (LDHA), and the level of Scr (59.18±5.83 versus 28.82±3.41 μmol/L, P<0.0001) was mitigated, with the reduction of urinary lactate (8.60±0.74 versus 4.90±0.98 mmol/L, P<0.01).

Conclusion

Our study demonstrated that inhibition of aerobic glycolysis to protect kidney function in MA-AKI might be via reducing lactate accumulation.
#5333 IMPROVING AUTOPHAGY FLUX BY TFEB ACTIVATION WITH CERIA NANOPARTICLES ATTENUATED CHRONIC KIDNEY INJURY IN CELLULAR AND ANIMAL MODELS OF FABRY DISEASE
Authors: Yun Sung-Ro , Hwang Won-Min , Yoon Kuk Ro , Park Yohan , Lee Ji-Won , Kim Eun Kyung , Yoon Se-Hee
Published: June 2023

Background and Aims

Fabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid–polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We accessed the action mechanisms of PEG-CZNPs in autophagy regulation and checked the effect on chronic kidney injury in cellular and animal models of FD.

Method

PEG-CZNPs were synthesized using a non-hydrolytic sol-gel reaction method. HK-2 cells were transfected with α-galactosidase A (α-GLA) shRNA for permanent cellular model of FD. For in-vivo study 4-week-old male B6;129-Glatm1Kul/J mice were treated for 48 weeks with 10mg/kg of PEG-CZNPs twice per week via intraperitoneal injection. PCR, immunoblotting, immunoflouresce assay, electron microscopy analysis, ICP-MS, biochemical and histological analysis were done

Results

TFEB tanslocated to the nucleus by treatment with PEG-CZNPs. Autophagy flux was evaluated with chloroquine. Autophagy flux was enhanced by PEG-CZNPs treatment. To show whether TFEB plays the important role in autophagy flux, we transfected HK-2 cells with siTFEB. Autophagy flux significantly decreased after knockdown of TFEB with PEG-CZNPs treatment. We next assessed upper signaling pathway of TFEB by PEG-CZNPs. TFEB dephosphorylation was independent of both mTOR and ERK but GSK3ß signaling pathway showed massive impact on TFEB dephosphoryation by PEG-CZNPs. PEG-CZNPs decrease intracellular globotriaosyceramide (Gb3) accumulation and decreased the levels of Collagen type IV, αSMA and MMP9 expression in cellular model of FD. Gb3 levels were significantly reduced in the kidney tissues and the levels of Fibronectin, Collagen type 4 and αSMA was decreased by PEG-CZNPs in animal model of FD.

Conclusion

These results suggested PEG-CZNPs promote autophagy flux through GSK3ß -TFEB signaling pathways, showed the beneficial effect on renal fibrosis in cellular and animal models of FD. It thus provided a new insights of the potential therapeutics on FD.
#5341 EFFECTS OF URIC ACID-LOWERING THERAPY ON RENAL OUTCOMES IN CKD PATIENTS WITH ASYMPTOMATIC HYPERURICEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Luo Yuxin , Song Qirong , Fu Sha , Wang Honglei , Shao Xiaofei , Chen Junzhe , Tang Ying
Published: June 2023

Background and Aims

It is well known that hyperuricemia and gout play an important role in the adverse cardiovascular and renal events both in patients with and without renal disease. However, the effect of uric acid-lowering therapy (ULT) on renal outcomes of CKD patients with asymptomatic hyperuricemia remains controversial. Therefore, our study summarized reliable results draw from published randomized controlled trials (RCTs) to evaluate the effects of ULT on renal and cardiovascular outcomes in CKD patients with asymptomatic hyperuricemia.

Method

Pubmed, EMBASE, China National Knowledge Internet (CNKI) and the Cochrane Library were searched systematically for trials up to October 2021. RCTs assessing the effects of uric acid-lowering agents on renal and/or cardiovascular outcomes in CKD patients complicated with asymptomatic hyperuricemia were included. Both the fixed-effect and the random-effect models were used.

Results

A total of 17 RCTs (one trial1 divided patients into two groups according to CKD stages). including CKD patients with asymptomatic hyperuricemia were included in this meta-analysis. Compared with placebo or no treatment group, ULT group showed a higher estimated glomerular filtration rate (eGFR) with a weighted mean difference (WMD) of 3.679 mL/min/1.73 m2, 95%CI [1.592, 5.766] (p = 0.001) and a lower serum creatinine (Scr) with a WMD of -46.131umol/L, 95% CI [-65.643, -26.619] (p<0.0001). Subgroup analysis demonstrated a significant benefit from ULT in patients with CKD stage 1-3 (p = 0.035), from Asian countries (p = 0.005) and those younger than 60 years (p = 0.002). At the same time, ULT was associated with lower incidence of events of doubling of Scr without dialysis (relative risk (RR) 0.314[0.203, 0.485] (p< 0.0001)). However, no difference was found for all-cause mortality, incidence of AKI, progression to end-stage kidney disease (ESKD), and cardiovascular events. In addition, ULT with allopurinol was associated with lower cardiovascular events (RR 0.678[0.473, 0.971] (p = 0.034)).

Conclusion

ULT could slow down the progression of renal impairment in CKD patients complicated with asymptomatic hyperuricemia, especially for patients under 60 years old, early CKD stage(1-3) and the Asian descent.
#5342 ASSOCIATION BETWEEN LONGITUDINAL GFR TRAJECTORIES AND BMD DECLINE RATE IN PATIENTS WITH CKD STAGE 2­–4
Authors: Kang Dong Hoon , Kim Hyung Woo , Park Jung Tak , Han Seung Hyeok , Kang Shin-Wook , Yoo Tae-Hyun
Published: June 2023

Background and Aims

Bone mineral density (BMD) predicts fracture risk in patients with chronic kidney disease (CKD). However, there are few studies regarding BMD decline rates in CKD population. In this study, we investigated whether BMD decline rate is associated with baseline estimated glomerular filtration rate (eGFR) and further evaluated with longitudinal eGFR trajectories.

Method

A prospective cohort study of 1,006 patients with CKD stages 2 through 4 who enrolled in the KoreaN Cohort Study for Outcome in Patients With CKD between 2011 and 2016. BMD was measured using dual-energy X-ray absorptiometry at baseline and year 4. Estimated GFR was measured 2–5 times during 4 years of follow-up. Mixed linear regression model was used for the longitudinal analysis and trajectory analysis was performed using semiparametric group-based modeling using maximum likelihood.

Results

Declined renal function was associated with increased rate of decline in total hip BMD (Stage 2: −0.23, Stage 3A: −0.39, Stage 3B: −0.80, Stage 4: −1.20 in men; −0.86, −1.19, −1.20, −1.58% change/year respectively in women). Trajectory analysis revealed two distinct trajectories of eGFR for each CKD Stages 2 through 4: Class 1, stable group; Class 2, rapid decline group. Trajectory group that represented rapid eGFR decline showed consistent trends of increased rate of decline in total hip BMD. There was significant difference between stable and rapid decline group in Stage 3A, 3B (Stage 3A: −0.18 vs. −0.67 [p = 0.009], Stage 3B: −0.36 vs. −1.10 [p = 0.031] in men; Stage 3A: −0.79 vs. −1.67 [p = 0.006], Stage 3B: −0.60 vs. −1.52% change/year [p = 0.001] in women; p for interaction).

Conclusion

Declined renal function and faster GFR decline is associated with rapid BMD decline in CKD stage 2–4.
#5348 THE EFFECTS OF RITUXIMAB IN NON-HCV-RELATED MIXED CRYOGLOBULINEMIC VASCULITIS
Authors: Guarino Annalisa , Caruso Nunziante , Geraci Giovanni , Longo Roberta , Amore Giorgio , Rabajoli Gianluca , Fenoglio Roberta , Sciascia Savino , Roccatello Dario
Published: June 2023

Background and Aims

Remarkable results in severe HCV-related cryoglobulinemic vasculitis have been obtained with Rituximab. Details of the clinical characteristics and effective treatment of non HCV-related cryogloulinemic syndromes are presently lacking.

Method

This paper reports on a prospective single-Center open study aimed at evaluating the clinical presentation and effects of Rituximab administered alone in patients with severe non HCV-related cryoglobulinemic syndrome

Results

The study group included 11 patients followed for at least 6 months. Three patients had type I cryoglobulinemia, 6 had type II and the remaining 2 patients had type III. Mean cryocrit was 2.5%. Four out of 11 patients had symptomatic sicca complex with anti-SSA (Ro)/anti SSB (La) antibodies. All 11 patients presented with biopsy-proven renal involvement, 4 out of 11 with leukocytoclastic vasculitis, and 8 with involvement of the peripheral nervous system. Renal biopsy revealed diffuse membranoproliferative glomerulonephritis (MPGN) in 9 out of 11 patients. Extracapillary proliferation and necrosis of the glomerular tuft was observed in 1 of these 9 cases. Interstitial nephritis together with mesangial expansion and capillary immune deposits were observed in 1 patient. Prevalent interstitial fibrosis and glomerular sclerosis were detected in the remaining case. Patients underwent treatment with rituximab alone. After 6 months we observed a remarkable improvement in the necrotizing skin ulcers and a substantial amelioration of the electrophysiological parameters of motor and sensory peripheral neuropathy. Improvement in both renal function (from 2.8 to 1.4 mg/dl, p < 0.001) and proteinuria (from 4.2 g/24 to 0.4 g/24 h, p < 0.001) was found in 10 out of 11 patients, while 1 could not be fully treated because of a severe infusion reaction and sudden development of anti-Rituximab antibodies. Good renal response was confirmed at the end of follow-up (38.4 months). Three patients had a relapse at 6, 12, and 48 months, respectively.

Conclusion

In our cohort the administration of 4 once-weekly infusions of Rituximab followed by 2 more infusions after 1 and 2 months proved to be effective in the management of these rare patients.
#5359 DETECTING NEONATAL AKI BY SERUM CYSTATIN-C
Authors: Xin Xu , Nie Sheng , Hou Fan Fan
Published: June 2023

Background and Aims

Serum creatinine is not a sensitive biomarker for acute kidney injury (AKI) in neonates. Unlike creatinine, cystatin-C (Cys-C) does not cross the blood placental barrier and the serum level in the neonates is not significantly impacted by the gestation age, birthweight, and the age during the first four weeks after birth. Therefore, serum Cys-C may be a better marker neonatal AKI than serum creatinine. We aimed to assess the performance of serum Cys-C as an alternative biomarker for detecting neonatal AKI.

Method

This is a large multicenter cohort study including 52,333 hospitalized neonates. First, we assess the impacts of gestational age, birthweight, and days after birth on the level of Cys-C, and estimated the upper normal limit (UNL) and the reference change value RCV of serum Cys-C in neonates. Then, we proposed a Cys-C based criteria (CyNA) for detecting neonatal AKI based on both Cys-C level and the change in Cys-C using UNL and RCV as the cutoffs, respectively. Finally, we assessed the performance of CyNA in detecting neonatal AKI and the association of CyNA-detected AKI with the risk of in-hospital death, and compared the performance with that using the KDIGO creatinine criteria.

Results

Cys-C level in neonates did not vary with gestational age and birthweight, and remained relatively stable during the neonatal period (Figure 1). The UNL of Cys-C was 2.2 mg/L and the RCV (for Cys-C ratio) was 1.25. CyNA criteria defines AKI by a serum Cys-C of ≥2.2 mg/L (UNL) or an increase in Cys-C of ≥25% (RCV) during the neonatal period. Among 52,333 neonates 6,336 (12.1%) AKI cases were detected by CyNA criteria, of whom 96 (1.5%) died. In comparison, 202 (0.44%) death events occurred in 45,997 neonates who did not have AKI. After adjusting all comorbidities, CYNA-detected AKI was associated with a significantly increased risk of in-hospital mortality (adjusted HR 2.91, 95% confidence interval, 2.24 to 3.78). Among 45,839 neonates that had measurement of both Cys-C and SCr, 4,513 (9.8%) had AKI detected by CyNA only, 373 (0.8%) by KDIGO only, and 381 (0.8%) by both criteria (Table 1). After adjusting admission to ICU and comorbidities, AKI detected by CyNA only (C+/K-) was associated with a significantly increased risk of in-hospital mortality compared with those without AKI by both criteria (C-/K-), with an adjusted hazard ratio of 2.86 (95% CI, 2.02 to 4.04). In comparison, the HR for those detected by KDIGO only (C-/K+) was lower at 2.15 (95% CI, 0.96 to 4.81). Neonates with AKI detected by both criteria (C+/K+) had the highest risk of in-hospital mortality (HR 4.86, 95% confidence interval, 2.84 to 8.29).

Conclusion

Serum Cys-C is a robust and sensitive biomarker for detecting neonatal AKI. CyNA is 5.5 times more sensitive than the modified KDIGO in detecting neonates who are at an elevated risk of in-hospital mortality.
#5363 LONG-TERM CLINICAL OUTCOMES OF PATIENTS WITH LUPUS NEPHRITIS TREATED WITH AN INTENSIFIED B-CELL DEPLETION PROTOCOL WITHOUT MAINTENANCE THERAPY
Authors: Ceruti Cecilia , Amore Giorgio , Caruso Nunziante , Guarino Annalisa , Longo Roberta , Fenoglio Roberta , Sciascia Savino , Roccatello Dario
Published: June 2023

Background and Aims

The aim of this prospective study is to investigate the long term safety and efficacy of intesified B-cell depletion therapy (IBCDT) in patients with active lupus nephritis (LN), in comparison to a conventional immunosuppresant therapy, followed by a 3 year maintenence micophenolate mofetil (MMF) regimen.

Method

Thirty patients were administered an IBCDT (4 weekly rituximab [RTX] 375 mg/m2 and 2 more doses after 1 and 2 months; 2 infusions of 10 mg/kg cyclophosphamide [CYC], 3 methylprednisolone pulses), followed by oral prednisone (tapered to 5 mg/d by the third month). No immunosuppressive maintenance therapy was given. Thirty patients matched for LN class and age were selected as controls: 20 received 3 methylprednisolone pulses days followed by oral prednisone and mycophenolate mofetil (MMF) 2 to 3 g/d, whereas 10 were given the Euro Lupus CYC. MMF (1-2 g/daily) or azathioprine (AZA, 1-2 mg/kg/day) were given for > 3 years as a maintenance therapy.

Results

At 12 months, complete renal remission was observed in 93% of patients on IBCDT, in 62.7% on MMF, and in 75% on CYC (P = 0.03); the dose of oral prednisone was lower in the IBCDT group (mean ± SD 2.9 ± 5.0 mg/dl) than MMF (10.5 ± 8.0 mg/d, P < 0.01) or CYC group (7.5 ± 9.0 mg/d, P < 0.01). Mean follow-up after treatment was 44.5 months (interquartile range [IQR] 36-120 months), 48.6 months (IQR 36-120 months), and 45.3 (IQR 36-120 months) for IBCDT, MMF, and CYC, respectively. At their last follow-up visit, we observed no significant differences in proteinuria and serum creatinine, nor in the frequency of new flares among the 3 groups.

Conclusion

In biopsy-proven LN, the IBCDT without further immunosuppressive maintenance therapy was shown to be as effective as conventional regimen of MMF or CYC followed by >3-year maintenance either MMF or AZA regimen. Moreover, the use of IBCDT was associated with a marked reduction of glucocorticoid cumulative dose.
#5365 T2DM MODIFIES THE RELATIONSHIP BETWEEN CAC AND ADVERSE KIDNEY OUTCOME IN PATIENTS WITH CKD
Authors: Yun Hae-Ryong , Han Seung Hyeok
Published: June 2023

Background and Aims

Kidney function decline faster in patients with type 2 diabetes mellitus (T2DM) than in those without. We previously showed that coronary artery calcification (CAC) is a strong risk of adverse kidney outcome. Here, we examined whether T2DM could modify the relationship between CAC and the progression of chronic kidney disease (CKD).

Method

2067 participants from the KoreaN Cohort Study for Outcome in Patients With CKD were enrolled. The main exposures were T2DM and CAC. The primary outcome was CKD progression defined as a composite of a 50% decline in estimated glomerular filtration rate or kidney failure with replacement therapy. Multivariable cause-specific hazard function was employed to determine the association between the main exposures and the primary outcome.

Results

During 8633 person-years of follow-up, the primary outcome occurred in 565 (27.3%) participants. In the multivariable cause-specific hazard model, both T2DM and CAC Agatston score (CACS) >0 were associated with a 1.80- and a 1.41-fold increased risk of CKD progression compared with counterparts. There was a significant interaction between T2DM and CAC for the primary outcome. In patients without T2DM, CACS >0 was not associated with the primary outcome compared with CACS of 0. However, in patients with T2DM, CACS >0 was associated with a significantly higher risk of CKD progression (adjusted hazard ratio, 2.12; 95% confidence interval, 1.64-2.75). In addition, a 1-SD increase in CACS was associated with 1.11-fold higher risk of CKD progression. Notably, this association was also significant in patients with T2DM who had CACS of 0. The slope of eGFR decline was steeper in patients with T2DM and the magnitude of decline was greater when CACS >0.

Conclusion

CAC were more strongly associated with risk of CKD progression in patients with T2DM than in those without. Thus, clinical implication of CAC may differ depending on the presence of T2DM.
#5383 THE PREDICTIVE VALUE OF URINARY CONGOPHILIA AS A BIOMARKER IN PREGNANT AND NON-PREGNANT WOMEN WITH LUPUS NEPHRITIS
Authors: Younis Dalia , Shemies Rasha Samir , El-Kannishy Ghada , Mosbah Alaa , Zakaria Mahmoud , Awadalla Amira , Elnagar Sherouk
Published: June 2023

Background and Aims

Endoplasmic reticulum (ER) stress with protein misfolding has been introduced as a key pathogenetic mechanism in patients with lupus nephritis (LN). Pregnancy is thought to exaggerate ER stress in conjunction with autophagy inhibition. This probably explains disease flares during pregnancy; however, this is not fully addressed. The detection of the abnormally misfolded proteins is made using the Congo red stain, which is referred to as congophilia. This study aimed to assess the predictive value of urinary congophilia as a marker of protein misfolding in pregnant and non-pregnant women with lupus nephritis.

Method

Urine samples from non-pregnant lupus nephritis patients (n = 45) and pregnant women with lupus nephritis (n = 12), as well as pregnant healthy controls (n = 38) were collected. Urinary congophilia was assessed by Congo Red Dot Blot assay. The disease activity was defined according to SLE Disease Activity Index (SLEDAI) criteria. Renal biopsy was done for 26 adults of non-pregnant lupus nephritis patients at time of urine sampling as it was clinically indicated and modified NIH activity index was assessed.

Results

The median and range values for SLEDAI score were 14(4-34) for non-pregnant LN patients, and 4(0-6) for pregnant women with LN (Table 1). Congo red retention (CRR) was significantly higher for non-pregnant LN patients (24.18%(0.75-126.29%)), in comparison with pregnant LN patients (0.67%(0.31-27.69%), P = 0.001), and healthy controls (0.33%(0.18-2.7%), P≤0.001). There was a significant positive correlation between CRR on one hand, and anti-ds-DNA (r = 0.791, P≤0.001), as well as SLEDAI score (r = 0.623, P≤0.001) on the other hand. However, no significant correlation has been found between CRR with renal histopathological activity index (r = 0.2, P = 0.425). CRR at a cut point ≥ 21.85% had 83% sensitivity, and 58% specificity to capture high LN activity status (NIH-AI >10) versus lower LN activity status (Fig. 1).

Conclusion

Urinary congophilia may add a diagnostic value in patients with lupus nephritis and can be a reliable marker of disease activity. CRR is related to disease activity rather than pregnancy.
#5402 ASSOCIATION BETWEEN URINARY N-ACETYL-β-D-GLUCOSAMINIDASE AND BISPHENOL AND ITS SUBSTITUTE EXPOSURE IN TAIWANESE ADULTS
Authors: Huang Po-Chin , Lin Yu-Jung , Chang Wan-Ting , Chen Hsinchang , Chang Jung-Wei
Published: June 2023

Background and Aims

Urinary N-acetyl-β-D-glucosaminidase (NAG) is a sensitive and reliable indicator of renal damage, like proximal tubular cell injury. Bisphenol A (BPA), a known endocrine disruptor, or its substitute has been reported as a risk factor that caused kidney damage in experimental studies. We aimed to investigate the correlation between urinary NAG and Bisphenol and its Substitute Exposure in Taiwanese Adults.

Method

We collected urine samples including 271 adults (145 female and 126 men) from Taiwan Environmental Survey for Toxicants 2013, and analyzed for three urinary BPA, BPS and BPF by using ultraperformance liquid chromatography–tandem mass spectrometry. The bisphenol and their substitutes in the human urine samples were converted into daily intake (DI) values. We measured by the indicators of renal function, included urine creatinine (crea, mg/dL), microalbumin (mg/dL), NAG (IU/L), etc. We used logistic regression analysis to elucidate their correlations and adjustment for significant covariate.

Results

We found the median levels were 7.96 for BPA, 7.89 for BPF, and 1.96 (μg/L) for BPS, respectively, and yielded a median estimate daily intakes were 3.01 (BPA), 2.99 (BPF), and 0.76 (BPS) (ng/kg/day) in the Taiwanese adults. We found that the ratio of urinary NAG and creatinine (NAG/crea) was a significantly increased trend with exposure doses of BPA, BPF and BPS whereas no similar trend for ACR. After adjustment for age, sex, BMI and other covariate, we found that DI of BPA increased the risk of NAG/crea by 5.8 times (ORAdj: 5.8, p<0.01, 2nd tertile) and 9.6 times (ORAdj: 9.6, p<0.01, 3rd tertile).

Conclusion

Our findings supported that the exposure of bisphenol and its substitute may increase the risk of renal tubular injury. Further large and longitudinal studies are warrant.
#5409 FACTORS ASSOCIATED WITH THE CIRCUIT LIFESPAN OF CONTINUOUS KIDNEY REPLACEMENT THERAPY (CKRT)
Authors: Hashimoto Yorikazu , Moromizato Takuhiro
Published: June 2023

Background and Aims

Approximately half of patients in intensive care unit (ICU) experienced acute kidney injury (AKI). ICU patients with severe AKI and hemodynamic instability sometimes require continuous kidney replacement therapy (CKRT). Termination of CKRT circuits leads to blood loss, attenuation of therapeutic effects of CKRT, and a heavy workload and resource burden for medical staff. Identification of the factors which can prolong the lifespan of CKRT circuits is clinically essential. We aimed to elucidate the factors affecting the lifespan of CKRT circuits in ICU patients.

Method

We evaluated the lifespans of 559 CKRT circuits used for 63 ICU patients at the Okinawa Prefectural Nanbu Medical Center and Children's Medical Center from April 1st, 2021 to March 31st, 2022. We enrolled all ICU patients who required CKRT. Our research team prospectively collected information on the patients' basal characteristics, CKRT prescription, activated clotting time (ACT) after the hemofilter, CKRT circuit lifespan, and causes of termination of circuits prospectively. Effects of ACT were examined by grouping patients into three with their ACT values: <140, 140≦ and <180, and ≧180 seconds. The primary outcome of this study was a termination of the CKRT circuit within 24 hours after the initiation of the CKRT circuit. The secondary outcome was the cause of terminating CKRT circuits. Primarily, we examined the impacts of factors associated with CKRT circuit lifespan using multivariable Cox-proportional hazards regression.

Results

Our cohort's median follow-up period of CKRT hemofilter was 18.5 hours. The total number of participants was 63, and 63.5% were male. In the multivariate Cox regression analysis, targeting ACT between 140 to 180 seconds was associated with a longer circuit lifespan (HR = 2.11(1.43-3.11), p<0.0001) than the group of CKRT circuits with ACT<140 seconds. Based on our results, targeting ACT between 140 to 180 seconds extended the median survival time of the circuit lifespan to 1.4 times longer than the group of circuits with ACT less than 140 (Fig. 1). There were no differences in the causes of hemofilter occlusion among the three ACT groups. Notably, COVID-19 was not significantly associated with a reduction in circuit lifespans (HR = 0.63(0.35-1.11), p = 0.110).

Conclusion

Appropriate monitoring of ACT during CKRT may help prolong circuit lifespan, and the optimal ACT range was 140 to 180 seconds. In contrast, COVID-19 was not a risk factor for an early occlusion of CKRT circuits.
#5417 EARLY MARKERS AND VASCULAR IMPAIRMENT IN THE PROGRESSION OF CHRONIC KIDNEY DISEASE (CKD)
Authors: Virgala Julia Martin , Martín-Carro Beatriz , Villabrille Sara Fernández , Bande Jose Joaquin , Fernandez-Mariño Belinda , López Teresa Naves , Faedo Mónica Llaneza , Andía Jorge Cannata , Diaz Manuel Naves , Carrillo-Lopez Natalia
Published: June 2023

Background and Aims

Soluble Klotho (sKlotho) is thought to decrease early in CKD, but its use as biomarker of the CKD progression is controversial. In addition, the use of newnon-invasive techniques to diagnose incipient vascular damage in CKD would be of clinical interest. The aims of this study were: to assess the utility of serum and urinary sKlotho as a useful biomarker of kidney impairment and; to analyse the value of carotid adventitial neovascularization and aortic stiffness in the course of CKD.

Method

Forty-three CKD patients were classified according to their estimated glomerular filtration rate (eGFR) into 4 groups (CKD-2/3a, CKD-3b, CKD-4 and CKD-5) and 38 sex and age matched controls were studied. Carotid and femoral adventitial neovascularization was assessed by ultrasensitive ultrasonography without contrast (Superb microvascular image, SMI). Aortic pulse wave velocity (PWV) was measured to determine stiffness.

Results

No differences in age and body mass index between control group and the four CKD stages were observed. The eGFR showed a significant and progressive decrease (Table 1). Serum PTH, FGF23 and proteinuria were significantly higher and serum calcitriol lower in CKD stages 3b to 5 (Table 1). No changes were observed in serum Ca and serum P increased only in CKD-5 (Table 1). Serum sKlotho displayed a progressive decrease from CKD-2/3a to CKD-5, before other CKD parameters, such as FGF23 and PTH changed. A significant correlation between serum sKlotho and serum creatinine was observed (r = -0.394, p = 0.0003). Urinary sKlotho increased in CKD-2/3a stage and remained similar up to CKD-5 (Table 1). The carotid artery of CKD patients stages 4 and 5 showed a higher number of adventitial vasa vasorum (CKD-4 = 2.09±2.26, p = 0.002; CKD-5 = 1.56±1.67, control = 0.90±2.37, p = 0.019) and a greater area of adventitial neovascularization (CKD-4 = 3.52±3.49, p = 0.0008; CKD-5 = 4.51±7.75, control = 0.84±2.18, p = 0.009) compared to controls. No differences in femoral neovascularization were found. PWV was significantly higher only in CKD-5 (CKD-5 = 12.91, control = 10.81, p = 0.045). A significant correlation was observed between PWV and the area of adventitial neovascularization (r = 0.360, p = 0.001) and the number of adventitial vasa vasorum in the carotid artery (r = 0.246, p = 0.028).

Conclusion

Serum sKlotho decreased before FGF23 levels begun to rise, indicating the sKlotho decrease as the earliest marker of CKD-MBD, although it remains with no changes throughout the CKD progression. Carotid adventitial neovascularization by SMI and PWV increased in advanced CKD stages, suggesting that they have a limited clinical utility as early markers of vascular damage in CKD.