bluuebunny/crossref_metadata_2025 huggingface dataset:
#4448 HUMORAL RESPONSE TO SARS-COV-2 AFTER FIVE SUCCESSIVE DOSES OF MRNA VACCINE AND PASSIVE IMMUNIZATION THERAPY IN STABLE KIDNEY TRANSPLANTATION PATIENTS
Authors: López Juan Manuel Cazorla , Fernández Florentino Villanego , Aguilera Aurora , Romero Ana Maria Gomez , Soto Teresa Trujillo , Garcia Teresa , Montiel Natalia , Orellana Cristhian , Mejía Carlos Narváez , Iglesias Manuel Antonio Rodríguez , Mazuecos Auxiliadora
Published: June 2023

Background and Aims

The poor humoral response after vaccination against SARS-CoV-2 in kidney transplant recipients (KT) led to the approval of new doses, the fifth being the last administered, and to the development of drugs for passive immunization. Our aim is to analyze the humoral immune response and the evolution of the antispike (antiS) antibody titer after 5 doses of mRNA vaccine against SARS-CoV-2 and the administration of pre-exposure prophylaxis.

Method

We performed a prospective cohort study of stable KT patients from our center who received 5 doses of a mRNA vaccine from March 2021 to December 2022. KT recipients with less than 6 months after transplantation and with active oncological or hematologic disease were excluded. We determined antiS titers (Abbott SARS-CoV-2 IgG chemiluminescent microparticle immunoassay) at baseline and one month after the second, third, fourth and fifth doses. We consider seroconversion if antiS titer was greater than 260 BAU/mL. We compared humoral response after 2, 3, 4 and 5 doses.

Results

We included 18 KT. Mean age was 59.8 years and 72.2% were male. The median time from KT to the first vaccine dose was 45 months, between the second and third 4 months and 6 months between the third and fourth and fourth and fifth doses. Seroconversion rate was 11.1% after 2 doses, 50% after the third, 72% after the fourth, and 94.4% after the fifth (p < 0.001). One TR did not develop antibodies after 5 doses. Two KT that had not seroconverted after the fourth also received passive immunization (tixagevimab-cilgavimab), maintaining high antiS titers 3 and 5 months after administration. The KT who seroconverted after 2 doses doubled the antiS titer after the third (1070 vs. 2168 BAU/mL; p = 0.180), in those who seroconverted after 3 doses it increased by 380% after the fourth (802 [587-2563] BAU/mL vs. 3116 [1004-5680] BAU/mL; p = 0.028) and in those who seroconverted after 4 doses, the antiS titer increased by 60% (1067 [100-2896] BAU/mL vs. 1762 [639-2684] BAU/mL) after the fifth (p = 0.213). No patients had neither acute rejection nor serious adverse effects.

Conclusion

Successive doses of vaccination increased the development and titer of antibodies against SARS-CoV-2 in KT. However the administration of new doses is necessary, especially bivalent vaccines, which increase protection against new variants of the virus. We should identify those patients who do not generate an adequate humoral response in order to offer them other prevention strategies.
#4450 ASSOCIATION OF DEMENTIA AND EXPOSURE OF PROTON PUMP INHIBITORS IN DIABETIC PATIENTS
Authors: Chen Yi-Hsin
Published: June 2023

Background and Aims

Dementia is characterized by a decline in cognition and an increasing inability to live independently. Proton pump inhibitors (PPI) are commonly used to treat gastric or duodenal ulcers. Recently, concern about the risk of dementia and exposure to PPI was noted. However, no known association has previously been reported in patients with diabetes.

Method

We analyzed data from the Taiwan National Health Insurance Research Database between January 1st, 2002 and December 31st, 2013. A total of 526920 diabetic patients were selected as the study cohort. A 1 to 4 propensity score was used for matching.

Results

During the follow-up period, 169 (2.2%) patients experienced newly diagnosed dementia compared to 1.7% of the control group. According to univariate analysis, the hazard ratio of dementia when exposed to PPI was 1.98(p = 0.0007). In multivariate analysis, the hazard ratio of exposure to PPI was 1.11 (p = 0.0008). In the sensitivity test, greater than 180 cDDDs were associated with a hazard ratio of 1.5 (p = 0.0006).

Conclusion

The association between PPI use and dementia was significant in diabetic patients. Therefore, PPI use should be cautious in this population. Further study is needed to clarify the mechanism.
#4456 HEALTHY PLANT-BASED DIET IN CHRONIC KIDNEY DISEASE THROUGH USE OF SODIUM ZIRCONIUM CYCLOSILICATE (HELPFUL TRIAL): RESULTS OF DIETARY INTAKE
Authors: Sallstrom Torsten , Heimbürger Olof , Rubin Charlotta , Danielsson Awa , Irving Gerd Faxen , Lindholm Bengt , Stenvinkel Peter , Avesani Carla Maria
Published: June 2023

Background and Aims

The dietary restriction of healthy food sources of potassium (K) counselled to patients with chronic kidney disease (CKD) and hyperkalemia (HK) contributes to a diet with poor dietary quality. The K lowering medication sodium zirconium cyclosilicate (SZC) has the potential to treat HK, thereby allowing a healthy plant-based diet (PBD). We designed a clinical trial to explore the safety and feasibility of prescribing a healthy PBD to CKD patients with HK with the concomitant use of SZC.

Method

The HELPFUL trial is an ongoing single-arm study with CKD stage 4-5 patients not on dialysis and with plasma K (pK) between 5.1-6.5 mmol/L at inclusion. Patients are followed for six weeks. In the first three weeks, SZC is prescribed to normalize pK while patients ingest a low protein diet with low K content. In the subsequent three weeks, a healthy PBD with a target K intake of 3700 mg/day is prescribed while maintaining the use of SZC. A food basket with PBD is delivered to participants weekly. A weekly monitoring of pK and titration of SZC to keep normokalemia is performed. Two dietary quality scores were calculated using the 24-hour food record (24h-FR) at baseline, week three and six. The first index is the Swedish version of Nutrient rich food index (S-NRF11.3) that measures the density of 11 beneficial nutrients (fiber, folate, iron, calcium, potassium, protein and vitamins A, C, D and E) and three non-beneficial nutrients (saturated fat, sodium and added sugars). The second index is the mean adequacy ratio (MAR) with the average intake of the same 11 beneficial nutrients as a proportion of the recommended daily intake (RDI). Data was analyzed by repeated measures-ANOVA or by Friedman test for related samples, as appropriate. Registered at www.clinicaltrials.gov (identifier NCT04207203).

Results

22 patients were included; 59±13 years; 13 men, eGFR 18±4 mL/min/1,73m2 (Table 1). The total intake of energy, fibre, folate and K increased significantly in week 6. Nutrient density did not change, but the MAR-score increased significantly. The intake of servings of fruits, vegetables and nuts increased significantly throughout the PBD. Regarding animal protein, there was a tendency to decrease the intake of servings of red meat and a significant increase in poultry and fish. The mean pK normalized in week three and six. After the start of PBD, three patients (13.6%) had pK between 5.1-5.3 mmol/L.

Conclusion

The strategy of PBD food baskets with concomitant use of SZC improved the dietary quality and increased the intake of servings of healthy foods. The K intake increased but not to target value. The pK was kept within normal values for most patients.
#4494 DRUG UTILIZATION FOLLOWING INCIDENT CHRONIC KIDNEY DISEASE: AN OBSERVATIONAL STUDY IN THE UNITED STATES AND JAPAN
Authors: Tangri Navdeep , Bodegard Johan , Hong Lai San (Corinna) , Nan Cassandra , Sofue Tadashi
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) affects >840 million individuals worldwide and is a leading cause of morbidity and mortality. Complications include cardiorenal outcomes (e.g. end stage kidney disease and heart failure (HF)) and premature death, which may be preventable with early identification and appropriate treatment of CKD. Treatment of CKD with renin-angiotensin-system inhibitors (RASi) has been the main recommendation of guidelines in the past 20 years, but prescribing rates remain low and discontinuation rates remain high, particularly after adverse events like hyperkalaemia episodes. This study aims to describe RASi utilization following incident CKD.

Method

Adult patients with incident CKD in the United States (US; OPTUM Market Clarity until 31 March 2022) and Japan (Medical Data Vision until 28 February 2022) from 1 January 2016 onwards were included. CKD was defined as any of the following: a UACR measure of ≥30 mg/g, two estimated glomerular filtration rate (eGFR) ≥90 days apart of which the second was ≤75 ml/min/1.73 m2, or a CKD diagnosis code. Patients were included if they had an eGFR ≤60 ml/min/1.73 m2. Patients with ongoing RASi treatment at index, a history of diabetes, heart failure or dialysis were excluded.

Results

A total of 66,375 incident CKD patients were identified in the US (n = 32,158) and Japan (n = 34,217). Mean age was 66 and 78 years in the US and Japan, respectively, and about half of the patients were female. Mean eGFR was 48 and 40 ml/min/1.73 m2 in the US and Japan, respectively. Approximately 30% of patients had cardiovascular disease, but only 13% (US) and less than 5% (Japan) were prescribed cardiovascular preventive drugs (e.g. statins and low dose aspirin). During a 1-year follow-up after the incident CKD index date, only 15% and 5% had been initiated on RASi in the US and Japan, respectively (Figure 1). Time to RASi initiation was shorter among those with a CKD diagnosis vs those without a diagnosis (US: 15 vs 19 months, Japan: 6 vs 11 months). Of those who initiated treatment, approximately 50% discontinued within one year (Figure 1). Results for initiation and discontinuation were similar across CKD stages in both countries.

Conclusion

In the US and Japan, initiation of RASi was remarkably low among newly identified CKD patients, and discontinuation of initiated treatment was substantial. Given that most patients with CKD benefit from multi-drug therapy (RASi + SGLT2i) for slowing CKD progression and reduction of adverse events, efforts to increase prescribing and adherence are needed.
#4511 TOLVAPTAN DOSE ADJUSTMENT IN ADPKD BASED ON URINARY OSMOLALITY: SIMILAR EFFICACY AND LOW DROPOUT RATE
Authors: Oporto Francisco Roca , Gómez Cristina Andrades , Cosano Gema Montilla , Aguilera Alicia Luna , Castilla José Luis Rocha
Published: June 2023

Background and Aims

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease. Tolvaptan is the only treatment that has been shown to slow disease progression. The current recommendation is to reach the maximum tolerated dose while controlling side effects such as hepatotoxicity. There are data suggesting a marked decrease in tolerability at high doses of the drug. We explored the possibility of an individualized tolvaptan dose adjustment, based on urinary osmolality (Uosm), as an indirect indicator of treatment efficacy.

Method

Single-center prospective cohort study of tolvaptan in patients with ADPKD and rapid progression, with dose adjustment according to Uosm, with dose increase if Uosm > 200 mOsm/kg. Glomerular filtration rate (GFR) estimated by CKD-EPI, Uosm, adverse effects and dropouts were analyzed.

Results

40 patients: 35 patients with more than 2 years treatment, mean follow-up 30± 6 months. Mean age 45± 7 years, 82% hypertensive and 47% male.

Evolution: mean annual fall in GFR during the previous 3 years without treatment -7.24 ± 1.5 ml/min/year. Baseline GFR 51.05±12.5 mL/min and baseline Uosm 391±87 mOsm/kg. Average annual drop in GFR over 3 years with treatment -3.18±1.3 mL/min/year. Average Uosm achieved during treatment 171 ± 47 mOsm/kg. Maximum tolvaptan dose reached 60 mg (90%) and 90 mg (10%).

The adverse events recorded highlight that there were no cases of hepatotoxicity (0%). The most frequent alterations were hyperuricemia (18%) and hypernatremia (11%), but in all cases asymptomatic. Polyuria was recorded in all our patients (100%), with a median diuresis 6000 ml/day (7000-5500), but the dropout rate due to aquaretic effects was minimal, only 2 patients (5%).

Conclusion

In our series of patients, treatment with tolvaptan at a dose adjusted to Uosm, seems to show similar efficacy to the reference studies in the annual fall of GFR, with a low rate of adverse events and very low dropout rate.
#4535 CLINICAL CHARACTERISTICS AND OUTCOMES IN PATIENTS ABOVE THE AGE OF 65 WITH ANCA-ASSOCIATED VASCULITIS: A SINGLE CENTRE EXPERIENCE.
Authors: Spanos Georgios , Atalla Alexandros , Bakou Marianna , Paschou Styliani , Fragidis Stylianos , Bantis Christos , Armetzoiou Livia Karmen , Bamichas Gerasimos
Published: June 2023

Background and Aims

ANCA-associated vasculitis (AAV) is common in patients above the age of 65 but there are limited data about the clinical characteristics and patient outcomes. This study intents to investigate the demographic features, treatment and outcomes in patients ≥ 65 years of age with AAV in Greece.

Method

In this retrospective observational study, we analyzed medical records of patients with ANCA positive AAV in a nephrology unit over the past 20 years. Patients with secondary causes of AAV were excluded. In total 37 patients were included in the study. Data are presented as median and interquartile range (IQR).

Results

Thirteen patients (35.1%) were above the age of 65 and 24 patients (64,9%) below the age of 65. The median age of diagnosis was 71.3 (67.5/75.1) vs 54.9 (40.4/57.3) and estimated glomerular filtration rate CKD-EPI was 30 (21.5/48) vs 17 (12.3/29.8) respectively. The Birmingham vasculitis activity score and organ involvement did not differ between the two groups. The median follow-up duration was 44.2 (15/108) months. Immunosuppressive therapy was similar in both groups, including glucocorticoids, cyclophosphamide or rituximab as induction and azathioprine or rituximab as maintenance therapy. The overall survival was significantly lower in the older group (69.2%) compared to the younger (95.8%) and renal survival was 69.2% and 91.2% respectively. Older age and elevated serum creatinine were related to increased mortality. Elevated creatinine at diagnosis was the only significant predictive factor of renal survival.

Conclusion

AAV is a disease with significant morbidity and mortality in patients above the age of 65. This study showed that the typical immunosuppressive therapy might not improve outcomes in the older patients.
#4566 PREDICTIVE ADMISSION RISK FACTORS, CLINICAL FEATURES AND KIDNEY OUTCOMES IN COVID-19 HOSPITALISED PATIENTS WITH ACUTE KIDNEY INJURY
Authors: Taneska Aleksandra Canevska , Bushljetik Irena Rambabova- , Markovska Zhaklina Shterjova- , Milenkova Mimoza , Vasilova Adrijana Spasovska , Pushevski Vladimir , Trajcheska Lada , Spasovski Goce
Published: June 2023

Background and Aims

Kidneys in COVID-19 patients demonstrate high vulnerability and acute kidney injury (AKI) is recognized as a cause of poor outcome and high mortality, in those requiring hospitalisation. The aim of our study was to assess the predictors and rate of AKI involvement among COVID-19 hospitalised patients at the day of admission, and to see the impact of AKI on patient's prognosis and life expectancy.

Method

We analysed admission data of COVID-19 patients, hospitalized in a tertiary nephrology hospital, during the first pandemic wave. Outcome data were recorded, including the need for renal replacement therapy (RRT) and inpatient mortality at 30 days.

Results

Out of 115 admitted patients included into the final analysis, 62(53.9%) presented with AKI, 21(33.9%) met KDIGO criteria for stage 1, 7(11.3%) for stage 2 and 34(54.8%) for stage 3 of AKI. RRT was required in 26 patients (22.6% of total, 41.9% of all AKI). From the discharged patients, AKI has been resolved in 76% and no need of RRT following hospital discharge was noted. Pre-existing CKD was associated with a 13-fold risk of AKI (OR 13.04; 95% CI:3.85–44.06, p < 0.0001) adjusted for demographics and comorbidities, low albumin (OR 0.895; 95% CI: 0.797–0.970, p  =  0.017), thrombocytopenia (OR 0.994; 95% CI:0.988–0.999, p  =  0.022) and increase of CK over 350UI (OR 3.60; 95% CI:1.184–10.95, p  =  0.024) were all independently associated with a higher risk for AKI. Mortality rates were significantly higher among patients who developed AKI compared to those without (59.6% vs 30.2%, p < 0.003). The low oxygen blood saturation at admission and albumin were presented as powerful independent predictors of mortality (OR 0.937; 95%CI: 0.917 – 0.958, p  =  0.000; OR 0.987; 95%CI: 0.885–0.991, p < 0.024, respectively). The Kaplan-Meier curve illustrated longer survival in patients without AKI compared to patients with AKI (22.01± 1.703 vs 16.69 ± 1.54, log rank p = 0.009).

Conclusion

Renal impairment in COVID-19 patients occurs in significant percentage, and it is a factor of poor prognosis. The severity of the disease itself is emphasized as main contributing mechanism in the occurrence of AKI, and the lower blood saturation at admission is the strongest mortality predictor, outreaching the significance of the AKI itself.
#4577 RENAL SAFETY OF FLOT REGIMEN FOR GASTROESOPHAGEAL CANCER
Authors: Trevisani Francesco , Floris Matteo , Angioi Andrea , Liscia Nicole , Cinque Alessandra , Pani Antonello , Puzzoni Marco , Scartozzi Mario , Dettori Manuela , Mazza Elena , Cascinu Stefano
Published: June 2023

Background and Aims

Currently, peri-operative docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) chemotherapy is the gold standard treatment for patients with locally advanced gastric cancer (LAGC), who undergo peri-operative chemotherapy and surgery. The known nephrotoxicity of both docetaxel and oxaliplatin compounds may limit the its application in CKD population. Nevertheless, limited evidence is available regarding the effects of FLOT regimen on renal function. In our analysis we evaluated the renal safety of FLOT regimen in LAGC population.

Method

Retrospective data on patient with resectable gastric cancer in four tertiary referral hospital between jan/2018 to jan/2022 have been analyzed. Patient have been treated with docetaxel (60 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2), and 5-fluorouracil (2,600 mg/m2 as a 24 hr infusion), all given on day 1 and administered every 2 weeks in 4 administrations before surgery. Serum creatinine, hemoglobin, lymphocytes and CKD-EPI eGFR were detected at baseline and before each cycle. AKI and CKD onset/prevalence were determined according to K-DIGO criteria.

Results

A consecutive cohort of 90 patients was enrolled. At baseline CKD was present in 16 pts (21.9%). Median eGFR was 84,9 ml/min. In terms of eGFR decay and CKD onset during the treatment cycle, the result of ANOVA indicated no significant differences or relationship with FLOT; Wilks’ Lambda = 0.94, p = 0.354 (Table 1 and Figure 1). AKI incidence was very low with one episode of stage 2 AKI (0,7%) between the 2nd and the 4th treatment cycle. New onset anemia between the 1st and the 2nd cycle was the only significant adverse event observed (p = 0.003).

Conclusion

According to our results, the pre-operative FLOT regimen seems to have a negligible impact on renal function with very low rate of renal toxicity suggesting the possibility to extend its use even in patient with advanced CKD.
#4597 REDUCED VO2PEAK IN PATIENTS WITH END-STAGE RENAL DISEASE: UNVEILING THE HIDDEN IMPLICATION OF CEREBRAL AND MUSCULAR HEMODYNAMICS
Authors: Machfer Amal , Tagougui Semah , Hassen Hayfa Hadj , Fekih Nadia , Amor Hassen Ibn Hadj , Bouzid Mohamed Amine , Chtourou Hamdi
Published: June 2023

Background and Aims

Aerobic fitness, as reflected by maximal oxygen (O2) uptake (VO2peak), is impaired in chronic kidney disease (CKD) patients. The mechanisms underlying this impairment remain to be explored. This study aimed to investigate whether CKD influence O2 supply including O2 delivery and release to the brain and active muscles during maximal physical exercise.

Method

Twenty three male undergoing dialysis therapy (HD group) and twenty three healthy males (CTR group) performed exhaustive incremental exercise to determine VO2peak. Throughout the exercise, near-infrared spectroscopy allowed investigation of changes oxyhemoglobin (∆O2Hb), deoxyhemoglobin (∆HHb), and total hemoglobin (∆THb) in the prefrontal cortex and in the vastus lateralis muscle.

Results

VO2peak was significantly lower in HD group compared to CTR. Muscular ∆HHb changes was impaired in HD patients (Figure 1). Increase in ∆THb (i.e., muscle blood volume) was significantly blunted in HD in both muscular and cerebral side (Figure 1 and 2). Also, HD patients had impaired changes in ∆O2Hb during the exercise compared to CTR group (Figure 1 and 2). A positive correlation has been observed between VO2peak and muscular blood colume (∆THb) for both groups.

Conclusion

HD patients displayed lower VO2peak that could be linked, in part, to impaired muscular hemodynamics responses during the exercise. Furthermore, reduced exercise muscle and brain blood volume may warm clinicians of brain endothelial or microcirculation dysfunction in HD population occurring even before overt microangiopathy.
#4609 ASSOCIATION BETWEEN THE SERUM CREATININE-TO-CYSTATIN-C RATIO AND RAPID PROGRESSION OF CHRONIC KIDNEY DISEASE
Authors: Lee Jiwon , Jeong Saeyoung , Han Sang-Woong , Yu MI-Yeon
Published: June 2023

Background and Aims

Chronic Kidney Disease (CKD) is a common and progressive condition that affects a significant portion of the global population. It is a leading cause of death and requires timely evaluation and monitoring to ensure proper management. Cystatin C has been shown to be an effective marker of kidney function and a predictive marker of CKD progression. However, there is limited research evaluating the relationship between the serum creatinine-to-cystatin-C (Cr/cysC) ratio and the rapid progression of CKD. This study aims to investigate the effectiveness of the Cr/cysC ratio in predicting rapid progression of CKD.

Method

A retrospective study was conducted on 1,104 patients with CKD who were treated at the Nephrology Outpatient Clinic of Hanyang University Guri Hospital between December 2020 and November 2022. Eligible patients had at least two simultaneous measurements of serum creatinine and cystatin C, with a minimum interval of 6 months. The definition of rapid progression of CKD was a decrease in creatinine-based estimated glomerular filtration rate (eGFR) of more than 4 mL/min/1.73 m2 over a 1-year period or initiation of renal replacement therapy (RRT). In addition, considering the short duration of the study, initiation of RRT was considered as a secondary outcome only in CKD stages 3b, 4, and 5.

Results

The study population consisted of patients with CKD stages 1 to 5, with a mean age of 69.7 years and 57.7% of the population being male. The mean baseline body mass index was 25.8 kg/ m2, and the mean initial eGFR was 46.7 mL/min/1.73 m2. 38.4% of the total patients showed rapid progression of CKD. The analysis showed that a lower Cr/cysC ratio was significantly associated with an increased risk of rapid progression of CKD (OR: 0.812, 95% CI: 0.761-0.867, p<0.001). After adjusting for age, sex, body mass index, and initial eGFR, a lower Cr/cysC ratio remained a significant risk factor for rapid progression of CKD (OR: 0.760, 95% CI: 0.685-0.844, p<0.001). The initiation of RRT increased with the advancement of CKD stage, with 11 patients with CKD stage 3b, 30 patients with CKD stage 4, and 41 patients with CKD stage 5 initiating dialysis treatment. After adjusting for all variables, the OR was 0.774 (95% CI: 0.667-0.898, p = 0.001), indicating that as the Cr/cysC ratio increased, the progression of dialysis significantly decreased by 22.6%.

Conclusion

In this study, a lower Cr/cysC ratio was significantly associated with an increased risk of rapid progression of CKD and initiation of RRT. The results of this study suggest that monitoring the Cr/cysC ratio may provide valuable information for the management of CKD patients.
#4610 LACK OF EFFICACY AND SAFETY OF ECULIZUMAB FOR TREATMENT OF ANTIBODY-MEDIATED REJECTION FOLLOWING RENAL TRANSPLANTATION
Authors: Park Byung Hwa , Kim Ye Na , Shin Ho Sik , Jung Yeonsoon , Rim Hark
Published: June 2023

Background and Aims

We evaluated the efficacy and safety of eculizumab in comparison with plasmapheresis and intravenous immunoglobulin therapy in renal transplant recipients diagnosed with antibody-mediated rejection (AMR).

Method

This was a multicenter, open-label, prospective, randomized analysis. The patients were randomized by therapy type (eg, eculizumab infusions or standard of care [SOC]: plasmapheresis/intravenous immunoglobulin). The patients (ie, eculizumab arm: 7 patients, SOC arm: 4 patients) were evaluated for the continued presence of donor-specific antibodies (DSAs) and C4d (staining on biopsy), as well as histologic evidence, using repeat renal biopsy after treatment.

Results

The allograft biopsies revealed that eculizumab did not prevent the progression to transplant glomerulopathy. Cases of AMR were diagnosed in the early post-transplantation period in 2 patients (eculizumab arm: 1 patient, SOC arm: 1 patient) and in the late period in 9 patients. Most of the reports show that eculizumab, in combination with other therapeutic measures such as PP and/or IVIG, effectively reversed rejection. However, eculizumab alone could not treat AMR effectively. Only 2 patients in the SOC arm experienced rejection reversal, and no graft losses occurred in either group. After AMR treatment, the DSA titers generally decreased compared to titers taken at the time of AMR diagnosis. There were no serious adverse effects in the eculizumab arm.

Conclusion

Eculizumab alone cannot treat AMR effectively and does not prevent acute AMR from progressing to chronic AMR or transplant glomerulopathy. However, it should be considered as a potential alternative therapy because it may be associated with decreased DSA levels.
#4626 EFFECTS OF HEMODYNAMIC PARAMETERS OF THE BRACHIAL ARTERY ON AVF FLOW
Authors: Gnjidic Nadezda Zec , Milicevic Jovana Kusic , Apostolovic Marija Andjelkovic , Lazic Aleksandar , Lekovski Vladan , Jemcov Tamara
Published: June 2023

Background and Aims

Arteriovenous fistula (AVF) remains the preferred form of vascular access for hemodialysis, although dealing with the high rate of maturation failure. Many factors are found to be influencing the AVF outcome, however the diameter of the blood vessels, both arteries and veins, is recognized as the most important predictor. Aim of this study was to evaluate hemodynamic parameters of the brachial artery (Ab) on the change of volume flow (VF) during AVF maturation.

Method

This single-centre observational study included patients in whom AVF was created between September 2021 and December 2022. All patients underwent pre-operative physical and Color Doppler Ultrasound (CDU) measurements of the radial artery (Ar), brachial artery and cephalic vein (Vc). AVF maturation was evaluated by CDU consecutively 1, 14 and 28 days after AVF creation. As the hemodynamic parameters of the arteries, peak systolic volume (PSV), end-diastolic volume (EDV) and resistance index (RI) were measured.

Results

Study included 33 patients (81.8% male, mean age 64±10). VF was 346.55±126.86, 491.26±183.51, and 608.28±275.10 at day 1, 14 and 28, respectively (p = 0,000). Univariate regression analysis showed PSV (Beta = 0,456; p = 0,008) and EDV (Beta = 0,551; p = 0,001), both measured on Ab at day 1 post-AVF creation, are statistically significant predictors of flow change during 28 days of maturation. In the linear regression model EDV measured on Ab at day 1 post-AVF creation (Beta = 0,683; p = 0,003) and diameter of Ab (Beta = 0,441; p = 0,004) remained significant (Fig. 1 and 2). The vast majority of the study population undergone the first AVF puncture between 15-30th day post-creation (48.5%), while 12 (36.4%) and 5 (15.1%) experienced AVF puncture after more than 30 days and at the 14th day, respectively

Conclusion

Hemodynamic parametres of the brachial artery, precisely peak systolic volume and end-diastolic volume at the first day post-AVF creation, play a significant role in AVF maturation. CDU measurements of those hemodynamic parameters at day 1 may be useful for an early identification of AVF maturation outcomes.
#4663 BLOOD AND URINARY CYTOKINE PROFILES AND CLINICAL OUTCOME IN PRIMARY MEMBRANOUS NEPHROPATHY AND DIABETIC KIDNEY DISEASES
Authors: Rivera Jorge Enrique Rojas , Fernandez-Fernandez Beatriz , Saruta Yuko , Hasegawa Takehiro , Juarez Gema Maria Fernandez , Ortiz Alberto
Published: June 2023

Background and Aims

Primary membranous nephropathy (MN) is an autoimmune, immune complex-mediated primary glomerulopathy causing podocyte injury and nephrotic syndrome. The results of therapy may be suboptimal and biomarkers are needed that predict the need for immune suppression and the response to different immunosuppression regimens. Diabetic kidney disease (DKD) is the most common cause of kidney failure. It is characterized by non-immune podocyte injury that may lead to nephrotic syndrome. We evaluated the circulating and urine cytokine pattern and pathophysiologic difference between both conditions. For MN, we further aimed at identifying the biomarkers of immunosuppressive treatment response.

Method

192 MN data-points from the STARMEN trial and 92 DKD from the biobank of IIS-FJD-UAM were included. We analyzed the blood and urine samples by HISCL (Sysmex Inc. Kobe, Japan), a chemiluminescence immunoassay that can afford a high-throughput multiplex cytokine analysis. Sixteen biomarkers were measured and evaluated for the correlation with the clinical outcome (eGFR, uPCR, 24-hour proteinuria). Also, the biomarkers’ concentration at baseline was compared with the treatment response during 6-9 months and the disease status after treatment until 24 months. The treatments evaluated STARMEN were Tacrolimus-Rituximab (TacRt) and alternating therapy with corticosteroids-cyclophosphamide. Box plot and Mann Whitney U test were used to assess subgroup differences and Spearman's rank correlation to assess correlation between variables.

Results

Median age, baseline eGFR and proteinuria for the MN and DKD cohorts were 53 and 66 years, 74 and 52 ml/min/1.73 m2, and 8.8 and 0.2 g/24h, respectively. Five cytokine markers in blood and 5 in urine from MN and 2 in blood and 2 in urine from DKD showed a significant correlation with proteinuria (Table). Circulating TNFa had been previously related to both MN and DKD pathophysiology and we confirmed its correlation with clinical outcomes in both. CCL20 is one of blood biomarkers correlated with anti-PLA2R (rS = 0.151, p = 0.036) and proteinuria in MN but not DKD. We identified a baseline urinary Protein A whose concentration differed between responders and non-responders to TacRt.

Conclusion

MN and DKD displayed characteristic cytokine patterns. Protein A is related to the progression of chronic inflammation and B cells. Its presence in urine and the differences between TacRt responders and non-responders suggest that high inflammatory progression activities may offset the treatment response. In conclusion, protein A could be the potential prognostic marker of TacRt response. However, additional investigation is needed to confirm and evaluate the possible application to other glomerular diseases.
#4666 ASSOCIATION BETWEEN URINARY ALBUMIN CREATININE RATIO AND CARDIOVASCULAR DISEASE
Authors: Lee Jun Young , Shin Dong Hui , Choi Soo Yeon , Kim Jae Seok , Yang Jae Won , Han Byoung Geun
Published: June 2023

Background and Aims

The association between microalbuminuria and cardiovascular disease (CVD) is accumulating in various patient populations. However, when stratified by sex, the relationship between microalbuminuria and CVD remains unclear.

Method

We obtained data from the 2011–2014 and 2019–2020 Korea National Health and Nutrition Examination Survey (KNHANES). Microalbuminuria was measured based on spot urine albumin-creatinine ratio (UACR). The Framingham risk score (FRS) model was implemented to evaluate the CVD risk. Linear and logistic regression models were used to identify the associations of microalbuminuria status with cardiometabolic predictors and CVD status determined by the FRS score.

Results

Among 19,340 representative Korean participants, the (UACR) in Korean women and men with history of CVD was higher than in those without history of CVD. Among patients without history of CVD, multivariate regression analysis showed that a high UACR was related to older age, lower high-density lipoprotein cholesterol level, higher total cholesterol level, higher systolic blood pressure, higher prevalence of current smoking, higher prevalence of diabetes, and higher anti-hypertensive medication use in both women and men. The UACR showed a positive linear correlation with the Framingham risk score in both women and men.

Conclusion

The presence of microalbuminuria was significantly associated with the cardiometabolic risk factors and the increased risk of CVD evaluated by FRS model in both women and men in a nationally representative sample of Korea.
#4677 EARLY MARKERS OF POSTOPERATIVE ACUTE KIDNEY INJURY
Authors: Cocchini Lorenzo , Filippo Marta De , Lanzani Chiara Livia , Vezzoli Giuseppe , Citterio Lorena , Zagato Laura , Raimondo Davide , Manunta Paolo , Simonini Marco
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is a common clinical condition among patients who undergo cardiac surgery, significantly affecting morbidity and mortality[1]. To date, preoperative biomarkers and solid predictive models for AKI are not yet currently available in clinical practice. Recent studies reported endogenous ouabain (EO), a stress hormone secreted by the adrenal glands, as associated to worse kidney outcomes after cardiac surgery[2]. The aim was to validate the use of EO as biomarker of individual susceptibility for AKI after cardiac surgery and to create a new powerful score for postoperative AKI risk.

Method

1174 patients undergoing elective cardiac surgery were enrolled in the study. Preoperative biological samples were collected and analysed. The primary outcome was AKI development, according to KDIGO 2012 guidelines.

Results

21.6% of patients developed AKI (9% developed severe AKI, stage≥2). AKI confirmed strong correlation to postoperative death: all patients dead within 90 days for postsurgical complication developed AKI and each AKI stage was associated to a 10 times higher mortality risk (p < 0.001). Different preoperative clinical variables were analyzed, identifying five independent risk factors significantly correlated to AKI and severe AKI: age, FE, NYHA class, reoperation and complex surgical intervention (p < 0.001 for all of them). Preoperative EO levels turned out significantly associated to the incidence of AKI (p < 0.001) and clinical complications. Specifically, patients with higher EO levels had greater incidence of AKI (p < 0.001) and worse cardiac and kidney basal function (p = 0.005 and p = 0.003, respectively). Finally, a simple score was developed on the base of those preoperative clinical values significantly associated to AKI (AUC for severe AKI = 0.79, p <0,001). Adding preoperative EO to the model significantly improved the predictive capability (AUC for severe AKI = 0.82, p < 0.001; Δ-AUC +0.0229, p = 0.026).

Conclusion

We confirmed in a large population the role of preoperative plasma level of EO as an important early predictor for post-surgical AKI and we built a powerful clinical model for postoperative AKI risk, exclusively using few simple preoperative clinical factors and a single biohumoral marker.
#4694 AUTOMATIC SEGMENTATION OF GLOMERULAR SUBSTRUCTURES BY DEEP LEARNING
Authors: Dendooven Amélie , Styanidis Aristotelis , Raes Louis , Van Craenenbroeck Amaryllis , Maeyens Matthias , Kotras Konstantinos , De Vos Maarten
Published: June 2023

Background and Aims

Electron microscopy (EM) complements light microscopy (LM) evaluation of the kidney biopsy. Foot process effacement, as assessed by EM, helps in diagnosing podocytopathies. However, human interpretation of EM images is time-intensive and often subjective. In this pilot, we investigate how deep learning techniques can help in adequate segmentation of the glomerular basement membranes (GBM) and podocytes in EM images. The ultimate goal would be to design an automatic tool for reliable and fast assessment of foot process effacement.

Method

Podocytes and glomerular basement membranes (GBM) of 10 patients, 5 with podocyte disease and 5 without glomerular changes (where biopsy showed tubulointerstitial pathology on LM) were annotated with a combination of manual annotation and thresholding for providing ground truth. After data preprocessing including splitting, flipping, rotating and tiling, a modified U-net architecture was applied (‘baseline model’). This baseline model was compared to a combination of U-net and a self-supervised contrastive learning approach with pretraining on 100 additional images (SimCLR framework, ‘fine-tuned model’). Segmentation performance was measured by IoU score.

Results

Segmentation of the glomerular basement membrane was best achieved by the baseline model and resulted in an IoU score of 0.711±0.089 compared to a IoU score of 0.675 ±0.093 in the fine-tuned model Segmentation of the podocytes was most successful in the fine-tuned model, with a IoU score of 0.609±0.118 compared to a IoU score of 0.591 ±0.118 in the baseline model

Conclusion

This study pioneers in segmenting glomerular substructures on EM images by means of a modified U-net architecture. The next step is training and validation in larger datasets. Data annotation remains a challenge. Inclusion of more images is expected to greatly improve the performance of the model.

Guideline 1500-3600 characters
#4699 QUALITY OF LIFE AS REPRESENTED BY PHYSICAL ACTIVITY WAS IMPROVING AFTER FULL CORRECTION OF POST-TRANSPLANT ANEMIA
Authors: Alotaibi Torki , Halim Medhat MA , Nagib Ayman Maher , Aboatya Hasaneen Hasaneen Ahmed Aboatya , Mahmoud Tarek S H , Atta Ahmed , Reda Suzan , Fayad Zohair , Gheith Osama Ashry Ahmed
Published: June 2023

Background and Aims

Recent studies showed positive impact of correction of post-transplant anemia (PTA) on general health, exercise capacity, and physical scores. So we conducted this prospective randomized controlled trial (RCT) to assess quality of life after full correction of post-transplant anemia in renal recipients receiving erythropoietin stimulating agents.

Method

We recruited 247 kidney transplant recipients with stable graft function in this RCT with 2 groups according to their target hemoglobin (11-12 g/dl, group 1, n = 183) and (13:15 g/dl (group 2, n = 64) which was achieved using erythropoietin stimulating agents (ESA). Monthly clinical and laboratory evaluation of kidney graft function was carried out. Quality of life (QOL) was assessed –using 25 and 36 questionnaires-at the start and 12 months.

Results

We observed more females in group 1 and the original kidney disease was chronic glomerulonephritis was significantly higher in group 2 (37.5%) followed by diabetic nephropathy (15.7%) while in group 1 it came as 25.7% and 22.4% respectively (p<0.05).The studied groups were comparable regarding pre-transplant co-morbidities. Most patients received thymoglobulin as induction and most of them were maintained on cyclosporine. We did not find any significant difference between the two groups concerning post-transplant co-morbidities (p >0.05), however better graft function was observed in group 2 at 6 months (p< 0.05). At 12 months, the assessment of QoL using the Medical Outcomes Study 36-Item Short-Form Health Survey, group 1 showed better post-transplant physical features and higher emotional factors related inactivity at 12 month (p<0.05), while group 2 showed significantly higher basal and 12 months activity state (p = 0.05). Basal inactivity was comparable in group 2 with that at 12 months (p>0.05), emotional factors related inactivity was significantly higher at 12 months in group 1. Graft outcome was comparable between both groups (p = 0.125), (p = 0.005).

Conclusion

Quality of life as represented by physical activity was improving by full correction of PTA in renal transplant recipients receiving ESA.
#4710 CYCLOPHOSPHAMIDE INDUCTION TREATMENT IN ANCA-ASSOCIATED VASCULITIS WITH RENAL AND PULMONARY INVOLVEMENT: OUTCOMES AND SIDE EFFECTS
Authors: Vezzani Valeria , DI Vito Roberto , Orfeo Chiara Alessia , Capone Martina , Iarlori Luigia , Marra Pietro , Nolletti Lorenzo , Bonomini Mario
Published: June 2023

Background and Aims

ANCA associated vasculitis are necrotaizing vasculitis of small and medium vassels - which cause organ damage. They are relatively rare diseases with an estimated prevalence of 200–400 cases per million people [1]. Pauci-immune necrotizing and crescentic glomerulonephritis (GN) is a frequent component of ANCA-associated vasculitis that can cause rapidly progressive Acute Kidney Injury (AKI). Less frequently, it can cause low progressive Chronic Kidney Disease (CKD) [2]. Combination therapy of steroids and cyclophosphamide has improved 5-years survival up to 70-90% but it can cause serious side effects including infectious episodes [3], bone marrow suppression and myelodysplasia. We present a case highlighting treatment modalities and our decision making.

Method

Our retrospective study analyzes the case of a 63-year-old male presenting with progressive dyspnea and hemoptysis. A chest CT suggested diffuse alveolar hemorrhage. The blood tests showed onset of AKI with 7.68 mg/dl serum creatinine (normal values 0.72-1.25), mild proteinuria and hematuria. A kidney and pulmonary vasculitis was suspected and the c-ANCA serum value was elevated at >500 IU/ml. Three cycles of Plasma Exchange (PEX) were performed and methylprednisolone was given (500 mg for 3 days, 1 g on the 4th day) followed by cyclophosphamide boluses of 1 g/week for 4 weeks. Broad-spectrum antibiotics and antifungal therapy was administered to prevent secondary infections. Due to the further worsening of the renal function, three hemodialysis treatments and a cascade filtration were performed continuing with cyclophoshamide 1 g/day orally and methylprednisolone 60 mg/day. Cyclophosphamide therapy was discontinued due to thrombocytopenia and progressive leukopenia. Filgastrim 30MU/0.5 ml was administered for five days until the resolution of the pancytopenia when cyclophosphamide 50 mg 2cp+1cp was resumed.

Results

A one-month follow-up CT showed reduction in hemorrhagic opacities and the c-ANCA level was significantly reduced. Steroid dosing was progressively reduced and the patient was discharged with methylprednisolone 16mg 2cp+1/2cp tapering over 6 months and cyclophosphamide 50 mg 2cp+1cp. Serum creatinine levels improved from 2.64 mg% at discharge to 1.6 mg% at follow up.

Conclusion

When treating c-ANCA vasculitis with corticosteroids and cyclophosphamide, routine evaluation of complete blood count parameters is necessary to prevent bone marrow toxicity. We continued methylprednisolone and cyclophosphamide for six months, obtaining a total clinical remission despite side effects induced by the state of immunosuppression (oral cavity mycosis, bone marrow toxicity and CMV reactivation).
#4725 INCIDENCE OF ACUTE KIDNEY INJURY IN PATIENTS WITH COVID-19 AND ITS IMPACT ON THE COURSE OF THE ACUTE INFECTION AND POST-COVID PERIOD
Authors: Arutyunov Alexander , Trubnikova Marina , Arutyunov Gregory , Batyushin Mikhail , Tarlovskaya Ekaterina , Bashkinov Roman , Melnikov Evgenii , Batluk Tatiana , Gordeychuk Elizaveta
Published: June 2023

Background and Aims

It is known that SARS-CoV-2 virus infection can contribute to kidney damage. In the literature, the incidence of acute kidney injury (AKI) during the acute period of COVID-19 is estimated to range from 5 to 36.6%. This complication significantly aggravates the course of both the acute phase and post-COVID period. However, the number of studies investigating these interactions is currently insufficient. To determine the incidence of AKI in the acute phase of COVID-19 and to assess the impact of this complication on the post-COVID period.

Method

The international register “Dynamics analysis of comorbidities in SAES-CoV-2 survivors” (ACTIV) (NCT04492384) was established to assess the course of COVID‑19 in the Eurasian region and involved specialists from 7 countries. ACTIV is a multicenter, non-interventional, real-world clinical practice register that included men and women over 18 years of age with a confirmed diagnosis of COVID-19. The analysis included 9206 patients with reported evidence of kidney damage or its absence. In the register, the presence of AKI was determined from the attending physician's notes in the medical records (according to modern diagnostic criteria) and the difference in serum creatinine levels ≥ 26.5 µmol/l during inpatient treatment for COVID-19. The post-COVID period was analyzed using telephone surveys of 3099 patients at 3 months, 2493 patients at 6 months and 1782 patients, at 12 months after recovery from COVID-19.

Results

AKI was detected in 11.6% (n = 1068) of cases during the inpatient treatment of the acute SARS-CoV-2 infection. Among markers of severe infection, AKI was more common (p<0.001) than cytokine storm (7.46% of patients) or sepsis (0.17% of patients). Analysis showed that AKI occurred in patients with higher average body mass index (BMI) (29.6 kg/m2 (25.1; 33.5) vs. 27.8 kg/m2 (24.8; 31.6) without AKI, p = 0.018) and serum glucose levels (6.0 (5.2; 8.55) mmol/l vs. (5.8 (5.0; 7.0) mmol/l without AKI, p = 0.011). AKI increased the odds of death in the acute period of COVID-19 by 3.94 times (95% confidence interval (CI) 3.24–4.78; p = 0.0001). Similar results were recorded 3 months after recovery (Table 1).

Conclusion

AKI was reported in 11.6% of patients with COVID-19 who were hospitalized for treatment of acute infection. Kidney damage occurred in patients with higher BMI and serum glucose levels. Patients with AKI during SARS-CoV-2 infection had a significantly higher risk of death in the first 3 months after recovery.
#4733 NEFROTOXICITY CAUSED BY COLISTIN USE: A SINGLE CENTER EXPERIENCE
Authors: Kilic İsa , Ayar Yavuz , Ceylan lkay , Kaya Pinar Kucukdemirci , Calıskan Gulbahar
Published: June 2023

Background and Aims

In resistant infections and septic patients, the choice of colistin in the selection of antibiotic therapy is important in the treatment response. Kidney damage is common after antibiotic use. In our study, we evaluated the clinical and laboratory data of the patients who developed nephrotoxicity after the use of colistin, followed in the intensive care unit of our hospital.

Method

The clinical and laboratory characteristics and treatment results of 148 patients (54 nephrotoxic patients) with infection who were followed up in the intensive care unit (ICU) of our hospital evaluated.

Results

The group that developed nephrotoxicity was older [70.5 (40-91), p<0.001]. The APACHE II score was higher in the nephrotoxicity group [20.5 (5-49), p = 0.004]. Positive inotrope use and mortality were higher in the nephrotoxicity group [32 (59.3%), p< 0.001 and 30 (55.6%), p = 0.004]. The duration of colistin use was longer in the nephrotoxicity group [13.5 (3-36), p = 0.045]. In the group that developed nephrotoxicity, the highest growth was detected in the tracheal aspirate (TAS) [49 (90.7%), p = 0.045]. Positive inotrope use and growth in TAS culture predisposed the development of nephrotoxicity in multivariate analysis [3.12 (1.38-7.02), CI 95%, p = 0.006, 5.70 (1.64-19.79), CI 95%, p = 0.006].

Conclusion

Consideration should be given to the use of colistin in resistant infections and septic patients in terms of nephrotoxicity and mortality. Antibiotic selection should be considered in critically ill patients, and patients should be closely monitored.