bluuebunny/crossref_metadata_2025 huggingface dataset:
#4161 DELETION OF PROTEIN TYROSINE KINASES 4A1 AMELIORATE RENAL FIBROSIS INDUCED BY UUO IN MICE
Authors: Choi Dae Eun , Park Heyrim , Shin Jin Ah , Chang Yoon-Kyung , Lee Eu Jin , Ham Young Rok , Na Ki Ryang , Lee Kang Wook , Kim Hae Ri , Jeon Jae Wan
Published: June 2023

Background and Aims

Inhibitors of protein tyrosine kinases has been investigated as potential anti-fibrotic agents. protein tyrosine kinases 4A1 belongs to a sub-class of three prenylated protein tyrosine kinases. protein tyrosine kinases 4A1 has known as promoting growth and migration of tumor cells. The role protein tyrosine kinases 4A1 has little known in kidney. We evaluated whether the protein tyrosine kinases 4A1 could be target of renal fibrosis.

Method

10 weeks old male background protein tyrosine kinases 4A1 KO mice and wild type mice were divided into 4 groups; wild, protein tyrosine kinases 4A1 KO, wild with unilateral ureteral obstruction, and protein tyrosine kinases 4A1 KO with unilateral ureteral obstruction. Mice were sacrificed at 7 days after surgery and kidney tissue were collected. Molecular study and Histologic examination were performed.

Results

Protein tyrosine kinases 4A1 KO with unilateral ureteral obstruction mice showed decrease of renal tubule-interstitial damage and fibrosis compared to wild type unilateral ureteral obstruction mice. protein tyrosine kinases 4A1 KO with unilateral ureteral obstruction reduced the renal expression of α-SMA and TGF-β in unilateral ureteral obstruction kidney, compared to wild type with unilateral ureteral obstruction mice. Wild type with unilateral ureteral obstruction kidney showed decrease of renal expression of E-cadherin, compared to sham mice. However, protein tyrosine kinases 4A1 KO unilateral ureteral obstruction showed increase of renal expression of E-cadherin, compared to Wild type unilateral ureteral obstruction mice. In vitro, silencing of protein tyrosine kinases 4A1 in TGF-β treated HK2 cell showed increase of E-cadherin and decrease of phosphorylation of AKT and GSK3ß.

Conclusion

Protein tyrosine kinases 4A1 KO ameliorate renal fibrosis in unilateral ureteral obstruction kidney.
#4168 RISK FACTORS FOR POST-CONTRAST AKI IN PATIENTS MIXEDLY ADMINISTERED BOTH IODINE- AND GADOLINIUM-BASED CONTRAST MEDIA ON VISITING EMERGENCY ROOM
Authors: Choi Dae Eun , Park Heyrim , Lee Eu Jin , Ham Young Rok , Kim Hae Ri , Na Ki Ryang , Hwang Yunkyeong , Jeon Jae Wan , Park Heewon , Shin Jin Ah , Lee Kang Wook , Jeong Jin Young
Published: June 2023

Background and Aims

This study aimed to investigate the incidence of post-contrast acute kidney injury (PC-AKI) and its risk factor in patients administered iodine-based contrast media alone and mixed use of iodine-based contrast media and gadolinium-based contrast media.

Method

This retrospective study analyzed the data from 2016 to 2021. Patients who had end-stage of renal disease or missing data for estimating renal function were excluded. The primary outcome was the development of PC-AKI, i.e., an increase in creatinine of ≥25% or 0.5 mg/dL over the baseline or reduction in eGFR of ≥25% within 72 h. We compared the primary outcomes between the iodine-based contrast media alone and Mixed groups using a propensity score matching (PSM) analysis, and its risk factors were assessed from multivariable logistic regression.

Results

Of the 29,635 patients administrated iodine-based contrast media, 6,318 were included. There were 139 patients who mixedly administered iodine-based contrast media and GBCA. Mixed group showed significant higher rate of development of PC-AKI compared with iodine-based contrast media alone group in total cohort (adjusted OR, 3.09 [95% CI, 2.09 – 4.58]) and PSM cohort (adjusted OR, 2.38 [95% CI, 1.25 – 4.55]). On multivariate analysis to investigate risk factors in Mixed group, osmolality (adjusted aOR, 1.05 [95% CI, 1.01–1.10]) and eGFR (adjusted OR, 0.931; 95% CI, 0.883–0.983) were associated with PC-AKI.

Conclusion

Mixed administration of iodine-based contrast media and GBCA on same day at ED visit may be a risk factor for PC-AKI compared with single administration of iodine-based contrast media alone. Osmolality and eGFR may be independently associated with PC-AKI after mixed administration of iodine-based contrast media and GBCA
#4203 PREDICTION OF BLEEDING AND THROMBOSIS IN PATIENTS ON CHRONIC HEMODIALYSIS WITH THE TOTAL THROMBUS-FORMATION ANALYSIS SYSTEM
Authors: Dimitrijevic Zorica , Ågren Anna , Mitic Branka , Tasic Danijela , Cvetkovic Tatjana , Hosokawa Kazuya , Wallen Håkan
Published: June 2023

Background

End-stage renal disease patients receiving hemodialysis (HD) are at increased risk of both bleeding and thrombotic complications. There are, however, few tools to help clinicians with risk stratification of the individual patient.

Aims and Method

To study if the Total Thrombus-formation Analysis System (T-TAS01), which measures thrombus formation in flowing whole blood inside a microchip [1], can be used to predict bleeding and thrombotic complications in patients on HD. Odds-ratios were calculated using the median split procedure. ROC curve analyses were performed to calculate the ability of T-TAS measurements performed at baseline to distinguish between patients with and without future bleeding or thrombotic complications.

Results

176 patients on chronic HD were included and followed for one year; 11.4% were on antiplatelet drugs and 8.0% on continuous anticoagulation. Venous blood samples were taken at inclusion before dialysis procedure, and platelet-thrombus formation (PL-AUC; higher value reflects increased thrombogenicity) and platelet-fibrin thrombus formation (AR-OT; higher value reflects reduced thrombogenicity) were registered. Fifty-seven patients (32%) developed a bleeding complication, whereof 12 (6.8%) were ISTH major bleedings. The Odds-Ratio (OR; 95% CI) to develop any bleeding for patients with T-TAS01 measurements below (PL-AUC) or above (AR-OT) median were 7.67 (3.59-16.36) and 8.94 (4.10-19.51), respectively. ROC analyses to predict bleeding with T-TAS01 showed AUCs of 0.85 for all bleeding and 0.83 for ISTH major bleed (PL-AUC and AR-OT data combined). Furthermore, thirty-one patients (17.6%) developed a thrombotic complication, whereof 13 (7.4%) were acute coronary syndrome (ACS) or ischemic stroke (IS). The Odds-Ratio (OR; 95% CI) to develop any thrombosis for patients with T-TAS01 measurements below (PL-AUC) or above (AR-OT) median were 0.14 (0.05-0.40) and 0.28 (0.12-0.67), respectively. ROC analyses to predict thrombosis with T-TAS01 showed AUCs of 0.78 for all thrombosis and 0.62 for ACS/IS (PL-AUC and AR-OT data combined).

Conclusion

T-TAS01 is a promising tool to aid in the prediction of bleeding and thrombosis in HD patients.
#4204 MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING BIOMARKERS OUTPERFORM LAB BIOMARKERS FOR PREDICTING PROGRESSION OF DIABETIC KIDNEY DISEASE
Authors: Hockings Paul , Makvandi Kianoush , Hulthe Johannes , Baid-Agrawal Seema
Published: June 2023

Background and Aims

We recently showed that comprehensive non-contrast multiparametric Magnetic Resonance Imaging (mpMRI) allowed functional and structural assessment of diabetic kidney disease (DKD) and that an imaging endpoint, R1 cortex, showed significant predictive property for progression of DKD. We further investigated the performance of other MRI and lab biomarkers for predicting disease progression.

Method

In this prospective study, 38 DKD subjects aged 18–79 years and 20 age- and gender-matched healthy volunteers (HV) were included at baseline. 31 DKD subjects (2 stage 2, 13 stage 3, 14 stage 4, and 2 stage 5) and 17 HV were re-examined at 2 years ± 6 months. Clinical and lab examination, iohexol clearance for measured glomerular filtration rate (mGFR), urine albumin:creatinine ratio (UACR) and mpMRI were performed at both visits.

A wide range of MRI biomarkers associated with kidney hemodynamics, oxygenation and macro/microstructure were included for evaluation. Disease progression was defined by at least one of the following at 2 years: decrease in mGFR slope of >5 mL/year/1.73 m2; worsening UACR category; or any major adverse kidney event defined as sustained decrease in eGFR of >40%; doubling of serum creatinine from baseline; development of kidney failure with mGFR <15 ml/min/1.73 m2; or death from renal cause. Univariable logistic regression analyses were performed to discriminate between progressors and non-progressors using each relevant lab and imaging endpoint as a predictor variable.

Results

Mean 2-year mGFR decline (ml/min/1.73 m2) in DKD patients was -2.7± 5.4 and in HV -1.9 ± 10.7. 13/31 (42%) DKD subjects and 4/17 (24%) HV progressed. Key lab biomarkers are shown in Table 1 and MRI biomarkers in Table 2.

Conclusion

Of all analyzed biomarkers, only the imaging biomarker R1 cortex, which reflects molecular environment viscosity, fibrosis, and inflammation (interstitial oedema, cellular swelling) showed significant predictive property for progression of DKD. UACR trended towards significance but was not statistically significant. R1 cortex outperformed all other imaging and lab biomarkers, but further studies with R1 cortex as a pre-specified endpoint are required to confirm these results.
#4209 A COMPARATIVE RETROSPECTIVE STUDY OF PATIENTS WITH ADPKD: FIRST RESULTS RELATING TO THE USE OF TOLVAPTAN
Authors: Oikonomaki Theodora , Liatsos Alexandros Nikolaos , Paikopoulou Angeliki , Avgikos Dimitris , Choulitoudi Vasiliki , Christodoulidou Christallenia
Published: June 2023

Background and Aims

Autosomal Dominant Polycystic Disease (APKD) is the fourth leading cause of End Stage Renal Failure (ESRD). Since 2015, the administration of Tolvaptan has been approved in patients with APKD at high risk of progression to ESRD (Mayo classification system, classes 1C-D).

Method

In this study we compare the characteristics of APKD patients who received Tolvaptan (45/15 mg) in relation to those who did not receive but followed the periodic check-up. These are 33 people with an average age of 44.17± 13.6 years. Tolvaptan was administered to 9 (27.3%) patients who met the Mayo classification criteria for its administration. The mean follow-up time for all the patients was 11.41±7.4 months and for those taking tolvaptan it was 10.6±3.9 months. Values ​​of urea, creatinine, plasma sodium, specific gravity and urine osmolarity were determined at the start of follow-up and compared with those at the last visit.

Results

A significant reduction was observed in the values ​​of urea, osmolality and specific gravity of urine after one year of tolvaptan use compared to the group that did not receive the treatment and thus no titration of the drug dose was needed. In the same group, marginally higher values ​​of the plasma sodium were observed, but within normal limits. The indicators of renal function in both groups did not show any change.

Conclusion

At one year of follow-up, APKD patients who received Tolvaptan did not exhibit worsening of the kidney function. We observed changes in the values of urea, urine specific gravity and urine osmolarity associated with our instructions to drink more water, showing good compliance with the treatment.
#4251 KIDNEY TRANSPLANTATION WITH DONOR-SPECIFIC ANTIBODIES: A GROWING NEED
Authors: Aristoy Emma Calatayud , Kanter Julia , Gavela Eva , Alonso Cristina Castro , Marín María Montesa , Antón Alejandro Valero , Beltrán Sandra , Calabuig Maria Asuncion Sancho
Published: June 2023

Background and Aims

Preformed donor specific antibodies in kidney transplant (KT) recipients are associated with higher risk of antibody mediated rejection (ABMR) and poorer graft survival. However, remaining a long time on the waiting list is strongly related to worse patient outcomes. We aimed to analyze KT recipients with preformed DSA with mean intensity fluorescence (MFI) who received induction therapy adapted to their higher immunological risk.

Method

We conducted a cohort retrospective study. All KT with preformed DSA performed in our center since May 2010 until March 2021 were included in the analysis. The presence of DSA was evaluated through Luminex Single Antigen (SA®) technology. All KT were performed with cadaveric kidney donor and with previous negative test by CDC crossmatch. The induction therapy in the presence of DSA included steroids, thymoglobulin, rituximab, plasmapheresis and standard treatment with tacrolimus and mycophenolate.

Results

During the study period 27 KT with preformed DSA were carried out. Recipient median age was 49 (IQR 40-62) years and 70,2% were women. Dialysis vintage was 5.8 (IQR 2.3-10.2) years. 63% were blood group A and 29,5% blood group 0. 29.6% were also included in the Hypersensitized National Programme (PATHI). The main causes of sensitization were previous KT (55.6%), pregnancy (29.6%) and blood transfusions (3.7%). 63% received KT with preformed DSA class I (median MFI 2218) and 37% with preformed DSA class II (median MFI 1900). Median calculated PRA was 90.5% (IQR 80.6-98.3). Median follow up time was 32.5 (IQR 12.3-61.2) months. Seventeen kidney biopsies were carried out. The most frequent findings were acute tubular necrosis (35.3%) and active ABMR (23.5%). DSA disappeared in most of the cases in successive analysis (81%) without any differences between both DSA classes. Median serum creatinine was 1.25 (IQR 0.97-1.75) mg/dl at 12 months and 1.65 (IQR 1.1-1.81) mg/dl at 24 months. In the post-transplantation period 2 patients were diagnosed with malignant solid organ tumors, 3 developed BK nephropathy, 5 CMV asymptomatic reinfection, and 9 recurrent urinary tract infections. During the observation time, 8 grafts were lost (29.6%): 3 due to patient deaths with functioning grafts and 5 due to graft failure (3 chronic ABMR, 1 active ABMR and 1 BKV nephropathy). Graft survival was 98% and 12 months and 92% at 24 months, respectively.

Conclusion

DSA with MFI low levels must be considered as a risk factor of ABMR and not as a contraindication to perform KT. A reinforced induction immunosuppression therapy enables KT to patients with high immunological risk and avoid prolonged time on the waiting list.
#4279 ATTENTION AND EMOTIONAL COGNITIVE DEFICITS IN HEMODIALYSIS PATIENTS WITH NORMAL NEUROCOGNITIVE SCREENING TEST RESULTS: AN EGYPTIAN TRIPLE CENTER STUDY
Authors: Awad Ahmed , Abdelsalam Adel L , Ibrahim Ibtihal , Samaan Emad
Published: June 2023

Background and Aims

Cognitive impairment (CI) is common in hemodialysis (HD) patients. St. Louis University Mental Status (SLUMS) examination is a traditional cognitive assessment method that relies on a pen-and-paper format. SLUMS test is known to be one of the most sensitive tests to detect early CI. Its questions cover many functions, including memory, attention, orientation, and overall executive function. This study aimed to compare its results with computerized neurocognitive battery assessment for attention and emotional orientation functions.

Method

One hundred twenty HD patients from three different in-hospital HD centers in Dakhlia governorate, Egypt, were subjected to the 10-minute Arabic-validated version of the SLUMS test for early CI (11 questions- 30 points). The patients were below 60 years old with no previous functional or structural neurological disease history. According to the stated test interpretation scores, fifty patients were defined to have no CI. Those patients underwent computerized neurocognitive battery assessment for attention and emotional cognition accuracy and response times; their results were analyzed compared to another fifty age, gender, and educational level-matched healthy controls.

Results

Of the 120 SLUMS-tested patients, 50 patients (41.6%) had no CI, 43 with mild to moderate CI (36%), and 27 with severe CI (22.4%). The classified 50 HD patients with no CI results within the computerized neurocognitive battery assessment revealed significantly reduced scores than matched healthy controls in the number of true positive answers of continuous number performance test for attention (90.46±26.61 vs. 109.15±14.56, respectively, p <0.001), emotion recognition correct answers (29.44±5.54 vs. 31.41±4.65, respectively, p 0.02), emotional recognition response times by m.seconds (3482.76±2907.62 vs. 2907.62±732.98, respectively, p <0.001), and correct answers of emotion differentiation test (19.82±5.88 vs.23.77±3.63, respectively, p <0.001). HD patients' age was the only clinical correlate to emotional recognition and differentiation accurateness (rho = 0.442, p <0.001 and rho = 0.3, p 0.02, respectively).

Conclusion

Early detection of CI in HD patients is an important target to improve the patient's quality of life and functionality. The complete dependence on the known simple screening assessment may miss a significant portion of the early-affected personnel.
#4298 DOES STARTING RENAL REPLACEMENT THERAPY WITH INCREMENTAL HAEMODIALYSIS WORSEN OUTCOMES?
Authors: Lorenzo Javier Deira , Rodrigues André Rocha , Mayor Elena Jiménez , Aguilar José Carlos Aguilar , Carrero María Elena Davín , Montalban José María Sánchez , Sanchidrián Silvia Gonz-Lez , Santisteban Miguel Angel Suárez , Funes Vanesa García-Bernalt , Casino Francesco
Published: June 2023

Background and Aims

Most patients start maintenance haemodialysis (HD) with a fixed dose of 3 HD sessions per week (3HD/Wk), regardless of their residual kidney function (RKF). This intense schedule is considered the “standard” or “conventional” modality (cHD). It is widely accepted, and no randomised controlled trial (RCT) has examined whether other less frequent schedules are inappropriate or harmful. Thus, the optimal modality for incident patients is currently unknown. Incremental HD (iHD), on the other hand, adjusts the frequency of sessions to the RKF, increasing their number to compensate for any subsequent reduction in RKF. While iHD approaches precision medicine by customising the number of sessions, it raises concerns about long intersession periods and the risk of under-dialysis. Pending ongoing RCTs [1], our aim is to analyse the efficacy and safety of iHD in our incident patients.

Method

The policy of our Centre is to try to start with iHD in incident patients who are clinically stable and with RKF. We start with 1 session (1HD/Wk) if the RKF is above 4 ml/min/1.73 m2 and with 2 sessions (2HD/Wk) if the RKF is between 4 and 2.5 ml/min/1.73 m2. We progress from 1HD/Wk to 2HD/Wk and from 2 to 3HD/Wk depending on the RKF and ultrafiltration rates required, which are assessed at least monthly. Since 2012, we have treated 186 incident patients with iHD, of whom 168 had a follow up ≥ 90 days. 72% (128 patients) started with 1HD/Wk and the remaining 28% (40 patients) with 2HD/Wk. We compared the results with 410 incident patients who from baseline receive 3 sessions/Wk (cHD) and with 80 incident patients on Peritoneal Dialysis (PD). We also analysed 27 iHD patients who after 60 days were already dialysed with 3 sessions (3HD/Wk/60d group). We calculated the mortality rate (deaths/365 days in %) in each group and survival in the iHD technique (sessions not performed).

Results

The mean age in the iHD group was higher than in cHD or PD (Table 1). Mortality in iHD patients was similar to cHD patients, although the latter were younger. Patients who stayed less time in iHD (3HD/Wk/60d group) had the highest mortality rate (Table 1). Survival in technique (time in which 50% of patients remain on iHD) was 12 months, avoiding 86 sessions/patient. The cost reduction was €17,200/patient (session + transport = €200).

Conclusion

iHD is efficient, as it considerably reduces the number of sessions performed and thus costs, thereby improving quality of life. It is safe, as it has a similar mortality rate to cHD. Being on iHD for more than 60 days does not worsen the results. On the contrary, requiring 3 weekly sessions at the beginning of HD treatment may be associated with a poor prognosis.
#4308 EVOLUTION OF HYPONATREMIA IN PATIENTS WITH CHRONIC SIADH TREATED FOR 1 YEAR WITH ORAL UREA
Authors: Amézquita Yésika , Hernández Yolanda , Diaz Raquel , Ruisánchez Sílvia Caldés , Ledesma Gabriel , Valdivia Verónica Ruth Mercado , Carrillo R Echarri , Andreu Cristina , Thuissard Israel , Villalobos Ángel Gallegos , Ojanguren María Covadonga Hevia , Cirugeda Antonio
Published: June 2023

Background and Aims

Hyponatremia (<135mEq/L) is the most common electrolyte disorder observed in clinical practice, associated with increased hospital admissions and mortality. One of its causes is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In chronic SIADH, urea is considered as a therapeutic possibility among other measures; however, its use is not widespread due to few studies on its efficacy.

Objects

To evaluate sodium levels in patients with chronic SIADH who received oral urea for at least 12 months.

Method

Observational, descriptive and retrospective study. Population: 13 patients with SIADH under treatment with urea for 12 months. The relationship between natremia and the rest of the clinical variables was analyzed using Chi-square, Student's T test, and ANOVA or their corresponding non-parametric tests.

Results

Mean age: 64 years +/-15. Men: 61% (n = 8). Comorbidities: hypertension (50%, n = 6), CKD (30.7%, n = 4), diabetes (15.3%, n = 2). SIADH etiology: Antiepileptics (n = 4), idiopathic (n = 3), intracranial pathologies (n = 5) and cancer (n = 1). 61% required admission for SIADH. Median of 10 ± 26 months from diagnosis to start of treatment. The initial dose was: 15 grams/day (53%, n = 7), 15 grams every 48 hours (30%, n = 4) and 15 grams every 72-96 hours (17%, n = 2). At one year, 61% of patients maintained the same dose (n = 8) and 39% of patients required an increase in the dose (n = 5) and of these 3 patients they increased to 30 grams/day. The treatment was well tolerated, only 1 patient out of 13 (7.6%) reported nausea and dysgeusia, no patient presented hypernatremia (Na >145meq/L), hospital admissions due to SIADH, or adverse effects that led them to discontinue urea.

Conclusion

After a year of treatment, urea increases and maintains plasma sodium in the normal range safely in chronic SIADH. Treatment with urea is well tolerated, avoids hospitalizations, and is not associated with complications from its use.
#4314 IMPACT OF ACUTE KIDNEY INJURY ON OUTCOME OF SEVERE FEVER WITH THROMBOCYTOPENIA SYNDROME
Authors: Lee Kim Hae , MI Lee Jin , Nam Lim Myoung- , Min Son Seong , Jin Hwang Duck- , Lee Sunhwa , Hyunjeong Baek , Park Ji In
Published: June 2023

Background and Aims

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high case-fatality rate in East Asia. In addition, acute kidney injury (AKI) has been reported in 14∼36% of the SFTS virus-infected patients. However, the risk factor for AKI and the clinical outcome of AKI in patients with SFTS has not been well understood.

Method

Patients who confirmed SFTS virus infection during five years from 2016 to 2020 in Kangwon national university hospital were retrospectively reviewed. Their laboratory data and medical records, such as comorbidity, complications, and mortality, were obtained from the electronic medical record. AKI was defined according to KDIGO criteria. The risk factors for death were assessed by Cox proportional hazards regression analysis.

Results

Of the 53 patients, 29 (54.7%) were male, and the mean age was 66.5 years. Twenty-seven (50.9%) patients were defined as AKI; 17 patients were AKI stage 1, 5 patients were AKI stage 2, and 5 patients were AKI stage 3. Of these, 5 patients underwent dialysis and all of them needed continuous renal replacement therapy. Patients with AKI were significantly older and had a higher proportion of diabetes (p = 0.041 and p = 0.019, respectively). In baseline laboratory tests, levels of aspartate aminotransferase, alanine aminotransferase and c-reactive protein were higher in AKI group (p = 0.011, p = 0.019, and p = 0.012, respectively). Among 53 patients, nine died due to SFTS, and the fatality rate was 15.1%. The AKI group (29.6%) had a higher mortality rate than the no AKI group (3.8%). In univariate analysis, higher levels of white blood cells, blood urea nitrogen, creatinine, and alkaline phosphatase were risk factors for death. In multivariate analysis, leukocytosis and AKI stage 3 were independent risk factors for death.

Conclusion

AKI frequently occurs among patients with SFTS. In patients with AKI stage 3, the mortality rate is significantly higher than no or mild AKI, so special attention should be paid when it occurs.
#4319 ASSOCIATION BETWEEN INTRADIALYTIC HYPERTENSION FREQUENCY AND SHORT-TERM CLINICAL OUTCOMES AMONG ESRD PATIENTS RECEIVING HEMODIALYSIS
Authors: De Castro Jeanmar , Manalaysay Trisha Michelle
Published: June 2023

Background and Aims

Systolic blood pressure (SBP) pattern in hemodialysis (HD) is typically characterized by a rapid decrease during the start of HD and followed by a more gradual decline in the latter part of the treatment. Deviation from the typical BP trend with a paradoxical rise in BP during HD, has been associated with increased mortality and morbidity and therefore, could be a modifiable risk marker for short-term adverse events in this population. Physicians may usually pay more attention to the more common complication that is hypotension during dialysis than the pattern of BP rise, hence overlooking a significant marker for poor prognosis. This study aims to investigate the association of intradialytic hypertension with short-term 30-day clinical outcomes including hospitalizations and mortality. Previous observational studies have suggested that changes in blood pressure during dialysis is associated with mortality and morbidity, however, the exact mechanism is still unclear.

Method

This study is a prospective cohort study of ESRD patients receiving in-center maintenance hemodialysis in a tertiary hospital in Davao City. All patients who were more than 18 years old and at least 1-year hemodialysis vintage were included. The study collected data from patients within a 30-day observation period and recorded the occurrence of events within the next 30-day follow-up period. Data collection was done from July 2022 to August 2022.

Results

In this study, patients had an average age of 49.18 years, majority of 55.56% were male and the most common cause of ESRD was glomerular disease. This study demonstrates that the incidence of intradialytic hypertension in this institution is high at 49.38%. Among the 81 enrolled patients, 16% had short term outcomes. Among the patients, 13.5% were hospitalized within the follow-up period and majority of 63.6% of them had IDH. All of the 2.47% of patients who expired during the follow-up period had IDH. Patients who had concomitant heart failure (p-value <0.001), has non-tunneled catheter as vascular access (p-value 0.004), high intradialytic frequency of 50–87.5% (p-value <0.001), and interdialytic weight gain of at least 2 kilograms (p-value 0.029) were significantly associated with hospitalization and mortality within 30 days.

Conclusion

The results of this study recommends that prompt attention should be given to ESRD patients who exhibit IDH as this may be a risk marker for adverse short term events within 30 days. In line with this, setting of dry weight, screening for heart failure, conversion to permanent AVF access, and tailoring of anti-hypertensive medications for better BP control should be assessed with vigilance in the dialysis unit.
#4326 STATIN INITIATION AND RISK OF INCIDENT KIDNEY DISEASE IN PATIENTS WITH DIABETES
Authors: Zhou Shiyu , Nie Sheng , Xin Xu
Published: June 2023

Background and Aims

The role of statin therapy in the development of kidney disease in patients with type 2 diabetes mellitus (T2DM) remains uncertain. We aim to determine the relationships between statin initiation and kidney outcomes in patients with T2DM.

Method

Using deidentified electronic health record data and new-user design, we conducted a nationwide retrospective cohort of patients with T2DM aged 40 years or older across China. The study outcomes included the development of diabetic kidney disease (DKD) and a sustained ≥40% decline in estimated glomerular filtration rate (eGFR). Cox proportional hazards regression was used to evaluate the relationships between statin initiation and kidney outcomes Analyses were conducted using propensity overlap weighting to balance the characteristics.

Results

Among 7272 statin initiators and 12 586 noninitiators in the weighted cohort, statin initiation was associated with lower risks of incident DKD (hazard ratio [HR], 0.72; 95% confidence interval [CI] 0.62-0.83), new-onset eGFR <60 ml/min/1.73 m2 (HR 0.63, 95% CI 0.50-0.79), new-onset proteinuria (HR, 0.70; 95% CI 0.59-0.84) and kidney function decline (HR 0.60, 95% CI 0.44-0.81). Among statin initiators, intensive control of LDL-C (<1.8 mmol/L) had a lower risk of incident DKD (HR 0.51, 95% CI 0.32-0.81) than that in non-control group (LDL-C ≥ 3.4 mmol/L). Similar results were obtained for participants with differing patterns of dyslipidemia, those using different statins, and after stratification according to the characteristics of the participants.

Conclusion

Statin initiation is significantly associated with a lower risk of kidney disease development in patients with diabetes. This reno-protective effect was more prominent in patients with intensive control of LDL-C.
#4364 LEUCOPENIA AFTER KIDNEY TRANSPLANTATION: SWITCHING MYCOPHENOLATE TO MTOR INHIBITOR APPEARS SAFE AND FEASIBLE TO REDUCE THE RISK OF ALLOSENSITIZATION
Authors: Rho Elena , Bohraus Pascal , Mueller Thomas , Schachtner Thomas
Published: June 2023

Background and Aims

Mycophenolate acid (MPA) is a standard component of maintenance immunosuppression after kidney transplantation. MPA, however, increases the risk of leucopenia. In the past, mTOR inhibitors (mTOR-I) in combination with calcineurin inhibitors (CNI), were considered immunologically safe but showed higher mortality in the long term.

Method

We conducted a retrospective single-center study analyzing 98 kidney transplant recipients (KTRs) under standard triple maintenance immunosuppression between 2020 and 2022 who developed leucopenia. We compared patient and kidney allograft outcomes between 31 KTRs who were temporarily switched from MPA to mTOR-I and 67 KTRs who underwent a reduction of MPA dose.

Results

A switch to mTOR-I was performed more often in case of a CMV high-risk status (50% vs. 21%, p = 0.009), CMV primary infection (68.2% vs. 22%, p<0.001), and more severe leucopenia (median nadir of neutropenia: 0.52 G/L vs. 0.86 G/L, p = 0.023). The median duration of leucopenia was comparable between the two groups (69 vs. 80 days). 9 of 67 KTRs (13%) developed de novo donor-specific antibodies (dnDSA) under reduced MPA compared to 1 of 31 KTRs (3%) under mTOR-I (p = 0.17). Biopsy-proven rejections were comparable between the two groups (1 in each). There was a slight but insignificant improvement of eGFR under mTOR-I compared to MPA (ΔeGFR +17 vs. +7 ml/min/1.73m2, p = 0.13) and no difference in proteinuria.

Conclusion

A temporary switch from MPA to mTOR-I is a feasible and safe strategy to overcome leucopenia, especially in cases of CMV high-risk status and CMV primary infection. No significant adverse effects on kidney allograft outcomes were observed. Development of dnDSA tended to be lower in the mTOR-I group, suggesting that this strategy may have the potential to reduce the risk of allosensitization.
#4401 IMPACT OF POLYPHARMACY ON QUALITY OF LIFE IN DUTCH DIALYSIS PATIENTS: A QUALITATIVE STUDY
Authors: Colombijn Julia Mt , Colombijn Freek , van Berkom Lideweij , van Dijk Lia A , Tierolf Charlotte , Senders Dionne , Abrahams Alferso C , Van Jaarsveld Brigit
Published: June 2023

Background and Aims

Almost all dialysis patients have polypharmacy but little is known about their experiences with medication and perception towards it. In this study, we aim to gain insight in dialysis patients’ experiences with polypharmacy the ways they integrate their medication in their daily lives and how it affects their quality of life.

Method

We conducted a qualitative study among dialysis patients from two Dutch university hospitals and affiliated dialysis clinics. Participants were interviewed in semi-structured interviews based on a pre-selected topic list. Interviews were transcribed verbatim and analysed independently by two researchers through thematic content analysis.

Results

Overall, 28 participants were interviewed (29% women, mean age 63±16 years, median dialysis vintage 25.5 [IQR 15-48] months, mean number of medications 14±3). Important themes were (1) participants’ own definition of what constitutes ‘medication’, (2) their perception of medication, (3) medication routines and its impact on daily life, and (4) interactions with healthcare professionals and others regarding medication. Participants generally perceived medication as burdensome but less burdensome than dialysis. Medication was accepted as an essential condition for their health even though participants could not always directly notice these health benefits and often relied on their physicians to determine the effectiveness of medication. Medication routines and other coping mechanisms helped participants to reduce the perceived negative effects of medication. In fact, for some participants, medication increased their freedom. Participants generally had constructive relationships with their physicians discussing their medication.

Conclusion

Polypharmacy negatively affected dialysis patients’ quality of life. These effects were, however, overshadowed by the burden of dialysis. Patients’ realization that medication is of importance for their health and effective coping strategies mitigated the negative impact of polypharmacy on quality of life. Physicians should continuously work together with their patients to evaluate the impact of treatments, not only on health but also on other aspects of patients’ daily lives.
#4421 CHALLENGES TO DIALYSIS TREATMENT DURING THE COVID-19 PANDEMIC: A QUALITATIVE STUDY OF PATIENTS’ AND EXPERTS’ PERSPECTIVES
Authors: Flores Krystell Oviedo , Stamm Tanja , Alper Seth , Ritschl Valentin , Vychytil Andreas
Published: June 2023

Background and Aims

The substantial health challenges faced by patients on peritoneal dialysis (PD) or hemodialysis (HD) have increased considerably during the ongoing COVID-19 pandemic, but remain inadequately investigated. We therefore decided to compare the perspectives of PD and in-center HD patients on their needs and challenges through this period with those of their healthcare professionals through interviews with both groups.

Method

Qualitative study of 7 in-center HD patients, 7 PD patients, 7 dialysis nurses and 7 physicians at the Division of Nephrology and Dialysis, Medical University of Vienna between March 2020 and February 2021, involving content analysis of semi-structured interviews supported by a natural language processing technique.

Results

Main themes brought up by patients included: 1) Concerns about being a ‘high risk patient’; 2) Having reduced fear of COVID-19 as an HD patient; 3) Whether home dialysis might be better than in-center dialysis during COVID-19; 4) Changes in clinical routine; 5) Positive psychological elements to overcome stress. Main themes emerging from interviews with physicians and nurses included: 1) Fear of COVID-19 infection; 2) Anxiety, sadness, loneliness of PD patients; 3) Negative impact of changes in clinical routine on patients' well-being; 4) Telehealth as a new care modality.

Conclusion

Physicians did not perceive the full extent of patients’ psychological burdens. Positive psychological constructs were more evident in survivors of previous serious health crises. Patients' concerns related to COVID-19 need to be addressed proactively. Implementation of measures to prevent COVID-19 transmission, introduction of telemedicine, and increased use of home-dialysis have led to communication barriers and reduced contact between healthcare providers and patients. Selection or modification of dialysis modality should include analysis of the patient's support network as well as periodic psychological assessment of patients in anticipation of future surges of COVID-19 or of currently unforeseen pandemics.
#4463 JAPANESE AND WHITES SHARE SIMILAR IPTACOPAN PHARMACOKINETICS AND PHARMACODYNAMICS
Authors: Schmouder Robert , Junge Guido , Nidamarthy Prasanna , Kulmatycki Kenneth
Published: June 2023

Background and Aims

Iptacopan (LNP023) is a first-in-class, oral, proximal complement inhibitor that specifically binds to Factor B and inhibits the alternative complement pathway (AP). Current Phase III studies of iptacopan focus on diseases associated with AP activation, such as paroxysmal nocturnal hemoglobinuria, C3 glomerulonephritis, IgA nephropathy, and atypical hemolytic uremic syndrome. These studies are enrolling patients across geographical regions and ethnicities, including those from Japan. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of iptacopan in Japanese patients.

Method

CLNP023 × 1102 was a randomized, subject-blinded, placebo-controlled, single-dose Phase I study conducted in Japan in healthy Japanese male subjects to assess safety, tolerability, PK, and AP blood biomarkers (Wieslab, Bb) in three dose cohorts, 25, 100, and 400 mg (8 active/2 placebo per cohort). Subjects were dosed on day 1 and observed for 96 hours post-dose. PK and PD data from this study was compared to White data from the similarly designed, previous CLNP023 × 2101 first-in-human study.

Results

Iptacopan was well tolerated in both Japanese and White subjects. White subjects were on average 15.7 years older and 19.5 kg heavier than Japanese subjects. Iptacopan mean (±SD) Cmax and AUCinf as well as mean (±SD) % change from baseline at 12 hours post-dose for Wieslab and Bb by dose are shown in the table below. All three dose groups manifested a general trend of increased systemic exposure and increased AP biomarker inhibition with increasing dose in both Japanese and White subjects.

Conclusion

Japanese and White healthy subjects had similar PK and PD results at all dose levels. The slightly higher Cmax and AUCinf in Japanese subjects may be explained in part by the lower average weight of these subjects. This study provides reassurance that there are no clinically meaningful differences in the human pharmacology of iptacopan between these ethnic groups.
#4482 PREGNANCY AND RENAL OUTCOMES IN WOMEN WITH CHRONIC KIDNEY DISEASE: A POPULATION STUDY
Authors: Ralston Elizabeth , Wang Yanzhong , Farmer Chris , Childs Steve , Akolekar Ranjit , Bramham Kate
Published: June 2023

Background and Aims

Women with CKD stages 3-5 are at higher risk of adverse pregnancy outcomes, including preterm delivery and low birthweight and progression of kidney disease. However, data describing outcomes of women with less severe kidney disease are limited, and few compare with women normal renal function. Furthermore, most studies report cohorts recruited from specialist clinics and may not be representative. This study aimed to describe pregnancy outcomes in a UK population cohort according to pre-conception eGFR <90 ml/min/1.73 m2 compared with women with eGFR ≥90 ml/min/1.73 m2.

Method

Routinely collected pregnancy data from three NHS Trust hospitals in Kent (UK) between 2010 and 2020 were extracted with Research Ethics Committee approval (19/LO/1242 and 18/SC/0158). Local laboratory and clinical data were linked to identify women with eGFR measured within two years of conception. Women without preconception creatinine were excluded from analysis. Baseline characteristics were described and comparisons between eGFR and adverse pregnancy and renal outcomes were tested.

Results

A total of 14,243 pregnancies with confirmed pre-pregnancy creatinine were included, of which 1,405/14,243 (9.9%) had CKD stages 1-4 (stage 1: 221/14,243 (1.6%), stage 2: 1,170/14,243 (8.2%), stage 3: 12/14,243 (0.1%), stage 4: 2/14,243 (0.01%) (Table 1). Women with pre-pregnancy eGFR 60-89 ml/min/1.73 m2 (stage 2) were significantly older at conception than women without CKD (eGFR ≥90 ml/min/1.73 m2) but there were no significant differences in live birth rates, small for gestational age, gestation at delivery, and preterm birth. In pregnancies with CKD (1,405, stages 1-4), pre-pregnancy eGFR was weakly correlated with birthweight (rs = 0.05, p = 0.05), and gestational age (rs = 0.06, p = 0.05).

Conclusion

To our knowledge, this is the largest population cohort to describe pregnancy outcomes between women with eGFR 60-89 ml/min/1.73 m2 compared with eGFR ≥90 ml/min/1.73 m2. Women with eGFR 60-89 ml/min/1.73 m2 did not have worse renal or pregnancy outcomes compared to eGFR ≥90 ml/min/1.73 m2. Limitations include lack of proteinuria data and details of structural CKD (Class 1 CKD), and only one eGFR measurement prior to pregnancy may have led to some women with temporary reduction in function being included in the cohort. Overall, the findings suggest that women with eGFR 60-89 ml/min/1.73 m2 should not be discouraged from pregnancy.
#4484 EFFECT OF BROCCOLI SPROUT EXTRACT IN PATIENTS WITH TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE (INITIATE) - DESIGN AND BASELINE DATA
Authors: Avesani Carla Maria , Swartling Oskar , Svensson Maria Eriksson , Heimbürger Olof , Lundberg Sigrid , Guron Gregor , Jonsson P Andreas , Segelmark Marten , Evans Marie , Stenvinkel Peter
Published: June 2023

Background and Aims

In advanced stages of chronic kidney disease (CKD) some glucose-lowering agents, such as metformin, cannot be prescribed to patients with type 2 diabetes (T2D) due to the risk of accumulation and adverse events. Foods with bioactive components, “functional food”, can be an alternative to mitigate the metabolic disturbances in these patients. Previous research on experimental animals and patients with T2D has shown that sulforaphane, present in broccoli sprouts, improves insulin sensitivity and glucose control. We hypothesize that sulforaphane ingested as a broccoli sprout extract (BSE) can improve glucose control in patients with T2D and CKD.

Method

This is an ongoing multicentre randomized double-blinded controlled trial with glucose control as the primary outcome. Glucose control is evaluated by fasting serum glucose, serum insulin in all patients, and oral glucose tolerance test (OGTT) in patients not on insulin treatment. Moreover, as a secondary aim, we investigate the role of BSE in improving other signs of metabolic alterations, including oxidative stress, proteinuria, inflammation and production of uremic toxins from the gut microbiota. Patients: Adult patients with T2D and CKD (eGFR 15- 45 ml/min/1.73m2) are included and randomized 1:1 to receive BSE or placebo. Both groups are followed for 20 weeks. The first 12 weeks, patients receive BSE or placebo and are then followed for 8 weeks. Patients randomized to BSE receive an increasing dose of sulforaphane administered as BSE (Lantmännen®) starting with 50 µmmol/day in week 0 - 4; 100 µmmol/day in week 5 - 8 and 150 µmmol/day in week 9 - 12. The placebo consists of maltodextrin sprayed with copper-chlorophyllin. Blood and urine laboratory measurements and OGTT is performed at week 0, 12 and 20. Randomization is done using a computer-based block randomization algorithm. The protocol is registered at clinicaltrials.gov (NCT04858854).

Results

98 patients with T2D and CKD from 12 centers in Sweden were included and the recruiting phase has now been finalized but the follow up phase is still ongoing. We here present baseline characteristics of all study participants (Table 1). Median age is 75 years and a minority are women. Mean eGFR corresponds to CKD stage 4 and there are large variations in albumin/creatinine ratios. Most participants are on a combination of oral glucose-lowering agents and insulin. A history of cardiovascular disease is common, and 21% had a previously had myocardial infarction.

Conclusion

We are currently conducting a randomized clinical trial testing if BSE can be used as an alternative or add-on to improve glucose control in patients with T2D and CKD stages 3-4 type and to see if this ‘high risk’ patient group could benefit from treatment with BSE.
#4486 VALIDATION OF A CKD PROGRESSION RISK PREDICTION MODEL IN THE FIDELITY TRIAL POPULATION
Authors: Tangri Navdeep , Ferguson Thomas , Leon-Mantilla Silvia , Anker Stefan D , Pitt Bertram , Rossing Peter , Ruilope Luis , Farjat Alfredo , Farag Youssef , Lawatscheck Robert , Rohwedder Katja , Bakris George
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is often underrecognised until later stages when most of the kidney function is lost and the therapeutic window for disease-modifying therapy is narrow [1]. We previously developed a lab-based risk prediction model to accurately predict CKD progression in adults at all stages of CKD [2]. Here, we describe a validation of our model in the clinical trial population of FIDELITY, a prespecified pooled analysis of the phase III FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049) trials for the nonsteroidal mineralocorticoid receptor antagonist finerenone [3].

Method

We performed a post hoc analysis of all participants from the FIDELITY database, irrespective of estimated glomerular filtration rate (eGFR) or albuminuria stage. Baseline values for the underlying laboratory tests required for the model, Klinrisk, were extracted from the complete blood count, comprehensive metabolic panel and urine albumin-to-creatinine ratio (UACR). The predicted outcome was a ≥40% decline in eGFR or kidney failure. We calculated discrimination ability of the model and calibration using area under the curve (AUC), Brier scores and calibration plots in the overall population, and stratified by treatment assignment. Sensitivity analyses examined the accuracy of the models in predicting ≥57% decline in eGFR, as well as the change in risk score over time. Kidney Disease: Improving Global Outcomes (KDIGO) heat map categories were used as the reference standard.

Results

We included 13,026 participants with a mean age of 64.8 ± 9.5 years, mean eGFR of 57.6 ± 21.7 ml/min/1.73 m2, and median UACR of 58.2 mg/mmol (interquartile range 22.4–129.6). At time horizons of 2 and 4 years, 984 and 1795 patients experienced a primary outcome event, respectively. The Klinrisk model predicted progression accurately, with an AUC of 0.81 (95% confidence interval [CI] 0.79–0.82) at 2 years and 0.86 (95% CI 0.84–0.87) at 4 years, compared with the KDIGO heatmap categories (AUC of 0.59 [95% CI 0.58–0.60] at 2 years and 0.66 [95% CI 0.65–0.68] at 4 years). Calibration was appropriate (Brier score of 0.067 [95% CI 0.064–0.070] at 2 years and 0.115 [95% CI 0.109–0.120] at 4 years). Similar discrimination accuracy was seen for the ≥57% decline outcome (C-statistic 0.88, 95% CI 0.87–0.90) at 3 years.

Conclusion

Based on routinely collected lab data, our machine learning model (Klinrisk) accurately predicts CKD progression events in a well characterized global clinical trial population. Prospective implementation of the model in clinical trial enrolment as well as clinical care pathways is needed.