bluuebunny/crossref_metadata_2025 huggingface dataset:
#4186 FEASIBILITY OF NEPHROLOGY-TAILORED GERIATRIC ASSESSMENT: AN IMPLEMENTATION STUDY
Authors: Voorend Carlijn , Berkhout-Byrne Noeleen , van Bodegom-Vos Leti , Diepenbroek Adry , Franssen Casper , Joosten Hanneke , Mooijaart Simon , Bos Willem Jan W , van Buren Marjolijn
Published: June 2023

Background and Aims

Geriatric evaluation of older patients with progressive chronic kidney disease is recommended in guidelines to enhance decision-making for kidney replacement choices. Although frailty, physical and cognitive impairments, and depression are prevalent, routine identification of geriatric impairments is lacking. Therefore, we aimed to study feasibility and determinants of successful implementation of a novel approach: nephrology-tailored geriatric assessment.

Method

In a mixed-methods implementation study, we investigated the feasibility of implementation of a consensus-based geriatric assessment [1] in Dutch nephrology centers. Feasibility was assessed through hospital participation and patient inclusion (among patients aged 70+ years with eGFR≤20mL/min/1.73 m2). We also evaluated determinants of successful implementation with a post-implementation survey among healthcare professionals covering (i) perceived enablers and barriers of implementation, (ii) perceived integration in work routines (Normalization MeAsure Development tool), and (iii) perceived relevance of the instruments. In addition, patients were asked if the geriatric assessment provided them with new insights for their future treatment decision for kidney failure.

Results

Feasibility was substantiated in implementation of geriatric assessment in 10 hospitals among 191 patients, i.e. 100% and 96% of our aimed goals. According to participating healthcare professionals (n = 71), determinants that facilitated implementation were: collaboration with the geriatric department, multidisciplinary meetings and reports, and execution of assessments by nurses. Most frequently mentioned barriers to implementation were: patient illiteracy or language barrier, lack of time, and burden for patients. Professionals considered geriatric assessment sufficiently integrated into work routines (mean 6.7 of 10, SD 2.0), but also subject to improvement (Figure 1). Implementation of geriatric assessment was considered sufficiently relevant for routine care (mean score 7.8 of 10, SD 1.2). Half of the patients (n = 42/82) stated that the geriatric assessment provided them with new insights, whereas 27% (n = 22) responded not to have gained new insights from the tests.

Conclusion

Multicenter implementation of nephrology-tailored geriatric assessment seems feasible and relevant. For future implementation we recommend involving the geriatric department, using multidisciplinary teams and -meetings, acknowledging the pivotal role of nurse practitioners, and using a flexible approach matching local resources.
#4200 INTERACTIONS BETWEEN INTRADIALYTIC CENTRAL VENOUS OXYGEN SATURATION, RELATIVE BLOOD VOLUME, AND ALL-CAUSE MORTALITY IN HEMODIALYSIS PATIENTS
Authors: Zhang Hanjie , Rojas Priscila Preciado , Merlo Laura Rosales , Kooman Jeroen , Van Der Sande Frank , Kotanko Peter
Published: June 2023

Background and Aims

In maintenance hemodialysis patients, low central venous oxygen saturation (ScvO2) and small decline in relative blood volume (RBV) have been associated with adverse outcomes [1,2]. Here we explore the interactions between ScvO2 and RBV change in relation to all-cause mortality.

Method

We conducted a retrospective study in maintenance hemodialysis patients with central venous catheters as vascular access. During a 6-month baseline period, Crit-Line (Fresenius Medical Care, Waltham, MA) was used to measure continuously intradialytic ScvO2 and hematocrit-based RBV. We defined four groups per median change of RBV and median ScvO2. Patients with ScvO2 above median and RBV change below median were defined as reference. The follow up period was 3-years. We constructed a Cox proportional hazards model with adjustment for age, diabetes, and dialysis vintage to assess the association between ScvO2 and RBV and all-cause mortality during follow-up.

Results

Baseline comprised 5,231 dialysis sessions in 216 patients. The median RBV change was –5.5% and median ScvO2 was 58.8%. During follow-up, 44 patients (20.4%) died. Kaplan-Meier analysis is shown in Figure 1. In the adjusted model, all-cause mortality was highest in patients with ScvO2 below median and RBV change above median (HR 6.32; 95% confidence interval [CI] 1.37 to 29.06), followed by patients with ScvO2 below median and RBV change below median (HR 5.04; 95% CI 1.14 to 22.35) and ScvO2 above median and RBV change above median (HR 4.52; 95% CI 0.95 to 21.36).

Conclusion

Concurrent combined monitoring of intradialytic ScvO2 and RBV change may provide additional insights into a patient's circulatory status. Patients with low ScvO2 and small changes in RBV may represent a specifically vulnerable group of patients at particularly high risk for adverse outcomes, possibly related to poor cardiac reserve and fluid overload.
#4208 CRP EXACERBATES SARS-COV-2-NUCLEOCAPSID PROTEIN-INDUCED ACUTE KIDNEY INJURY
Authors: Chen Junzhe , Wang Wenbiao , Tang Ying , Lan Xiaoru , Lan Hui Yao
Published: June 2023

Background and Aims

COVID-19, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), is a progressive viral pneumonia with a broad spectrum of clinical manifestations involving multiple organs. Acute kidney injury (AKI) is common in COVID-19, especially the critically ill patients. Our previous study proved that kidney-specifically overexpressing SARS-CoV-2 N protein induces AKI, which become worsen in mice under ischemic condition. Clinically, CRP is a risk factor for AKI in COVID-19 patients. Recent clinical study showed that CRP Apheresis is able to effectively remove the plasma CRP and thus improve the clinical outcome in critically ill COVID-19 patients. We thus hypothesize that CRP may not only be a biomarker or risk factor, but also a potential mediator or novel therapeutic target for COVID-19 AKI.

Method

The role of CRP in COVID-19 AKI was investigated in a mouse model of AKI induced by ultrasound-microbubble-mediated kidney-specifically transferring SARS-CoV-2 N-expressing plasmids in CRP wide-type (WT) and Transgenic (Tg) mice. We also developed a novel therapy for SARS-CoV-2 N-induced by targeting CRP signaling with a neutralizing anti-CD32 antibody both in vivo and in vitro.

Results

In COVID-19 patients with AKI, serum levels of CRP were significantly elevated when compared with non-AKI group. In mice, kidney-specifically overexpressing SARS-CoV-2 N protein caused AKI including tubular necrosis and elevated levels of serum creatinine and BUN in CRP WT mice, which became more severe in CRP Tg mice. Importantly, targeting CRP-CD32 signaling with a neutralizing antibody to CD32 significantly inhibited SARS-CoV-2 N protein-induced AKI in CRP Tg mice. Mechanistically, we uncovered that CRP promoted SARS-CoV-2-N protein-induced AKI via the Smad3-p21-dependent G1 cell cycle arrest and NF-κB/p-p65-driven renal inflammation, which was blocked by anti-CD32 antibody in vivo and in vitro.

Conclusion

CRP is not only a biomarker or risk factor, but also a mediator in SARS-CoV-2 N protein-induced AKI. CRP signals through CD32 mediate SARS-CoV-2 N-induced AKI via mechanisms associated with the Smad3-p21-dependent G1 cell-cycle arrest and NF-κB/p-p65-driven renal inflammation. Targeting CRP-CD32 signaling may represent as a novel therapy for COVID-19-associated AKI.
#4211 PULSE WAVE VELOCITY AND ERECTILE DYSFUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Bratsiakou Adamantia , Georgopoulou Georgia Andriana , Trivyza Maria , Ntrinias Theodoros , Goumenos Dimitrios , Giannitsas Konstantinos , Papachristou Evangelos , Papasotiriou Marios
Published: June 2023

Background and Aims

Erectile dysfunction is a frequent problem and adversely affects quality of life. In recent years, it has been shown to be an early indicator of cardiovascular disease and endothelial damage. For patients with chronic kidney disease, the incidence of cardiovascular events is increased, while erectile dysfunction is also more frequent. In this study we evaluated in patients with chronic kidney disease the incidence and the association of erectile dysfunction with pulse wave velocity (PWV) and reflection wave parameters.

Method

The incidence of erectile dysfunction was examined with the use of IIEF (5) Sexual Health Questionnaire in adult male patients aged less than 65 years with chronic kidney disease stage I-V or a history of kidney transplantation that were actively monitored or treated as outpatients. Peripheral blood pressure, central blood pressure, PWV and reflection wave parameters (augmentation pressure and augmentation index) were evaluated using the Mobil-o-graph device in office measurements.

Results

Overall, 69 men with a mean age of 46.5 ± 11.79 years were included in the study. Chronic kidney disease (CKD) classification according to baseline eGFR calculation was as follows: 12 patients with CKD-I, 27 with CKD-II, 12 with CKD-III, 6 with CKD-IV and 12 with CKD-V on maintenance hemodialysis. Erectile dysfunction of all degrees (mild to severe) was detected in 52% of patients. From the correlation of the various parameters assessed with the degree of erectile function, as calculated by the IIEF questionnaires, it was found that renal function as expressed by eGFR showed a positive correlation (r = 0.24, p = 0.047), while age and PWV showed a negative correlation (r = -0.384, p = 0.002 and r = -0.474, p<0.001 respectively). Moreover, pulse wave velocity was the only parameter which could predict erectile dysfunction (β = -0.995, 95% CI -0.465 to -10.074, p = 0.032).

Conclusion

The results of the study showed that worsening kidney function is associated with an increase in arterial stiffness and an increase in the incidence of erectile dysfunction. Moreover, erectile dysfunction was more common in patients with increased PWV.
#4233 FIXED LOW DOSE VERSUS CONCENTRATION-CONTROLLED INITIAL TACROLIMUS DOSING: RESULTS FROM A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL (SLOW&LOW STUDY)
Authors: Stumpf Julian , Budde Klemens , Witzke Oliver , Sommerer Claudia , Thomas Vogel , Schenker Peter , Woitas Rainer , Opgenoorth Mirian , Trips Evelyn , Schrezenmeier Eva , Hugo Christian
Published: June 2023

Background and Aims

Optimal initial tacrolimus dosing and early exposure of tacrolimus after renal transplantation is not well studied. Based on the assumption that current treatment protocols using frequent trough level determinations in the first week after transplantation may cause overexposure related nephrotoxic side effects and frequent monitoring is costly and not supported by basic pharmacokinetic principles, we had the hypothesis that early low and fixed tacrolimus dosing may be a safe and practical alternative.

Method

In this open-label, multicenter, randomized controlled, non-inferiority study, we randomly assigned 432 renal allograft recipients to receive basiliximab induction, mycophenolate and steroids and either standard prolonged-release tacrolimus (trough levels: 7-9 ng/ml; arm A), or an initial 7-day fixed 5 mg/day dose of prolonged-release tacrolimus followed by lower tacrolimus predose levels (trough levels: 5-7 ng/ml; arm B, see Figure 1). The primary end point was the combined incidence rate of biopsy-proven acute rejections (BPAR; including borderline), graft failure or death at 6 months with a non-inferiority margin of 12.5 %.

Results

The combined primary endpoint in arm B was non-inferior compared to the control arm A (22.1 % versus 20.2 %; difference 95 % CI: 1.9- 8.8 %). While overall rate of BPAR including borderlines were similar (B: 17.4 % versus A: 16.1 % (see Figure 2), a statistically significant difference of higher than borderline graded BPAR was noted (B: 11.6 % vs. A: 5.2 %; p = 0.027). Safety parameters such as delayed graft function, kidney function, infections or post-transplantation diabetes mellitus did not differ.

Conclusion

An initial fixed low prolonged release tacrolimus dose of 5 mg/day followed by lower tacrolimus exposure is non-inferior compared to standard tacrolimus therapy and equally efficient and safe within 6 months after renal transplantation. (EudraCT-Nr: 2013-001770-19).
#4297 AN ALTERNATIVE METHOD FOR SCREENING FABRY DISEASE IN WOMEN - PARTIAL RESULTS OF A BRAZILIAN STUDY
Authors: Silva Cassiano Augusto , Ribeiro Marcia Gonçalves , Silva Artur Quintiliano , Gueiros Ana Paula Santana , Petruccelli Karla Cristina Silva , Pascotto Roberta Correa , DE Souza Boger Marta Vaz Dias , Carvalho Luiz Roberto , Lucca Leandro Júnior , Sevignani Gabriela , Neto Osvaldo Merege Vieira , Barretto Carolina Teles , Gordon Gina Moreno , Veloso Valeria Soares Pigozzi , Vieira Fernando Antônio Freitas , Ennes Gelzie Sorrentino , Da Silva Montenegro Malaguti DE Souza Eduarda Morgana , Guedes Felipe Leite , Barreto Fellype , de Andrade Luis Gustavo Modelli
Published: June 2023

Background and Aims

Fabry disease (FD) is a rare X-linked lysosomal storage disease that can affect multiple organs, including the kidneys. The main objective of this study was to evaluate the effectiveness of a combination of α-GAL enzyme activity and plasma levels of lyso-GL3 for screening FD in women with chronic kidney disease (CKD).

Method

Women with CKD, stages 3 to 5, in regular nephrological follow-up were selected from renal centers in all regions of Brazil. Exclusion criteria: under 18 years old and known diagnosis of CKD. Patients underwent biochemical analysis of α-GAL enzyme activity and plasma levels of lyso-GL3. GLA gene sequencing was performed if α-GAL enzyme activity was below and/or lyso-GL3 levels were above the reference range. Sensitivity and specificity analyzes were performed to evaluate the performance of the combined biochemical approach for the diagnosis of FD.

Results

From October 2020 to December 2022 1,647 collections were carried out. Low α-GAL activity was found in 44 (2.6%) of the cases and increased lyso-GL3 was found in 101 (6.1%) of the cases. The mean age was 53 [42 – 64] years. All cases of low α-GAL and/or increased lyso-GL3 were submitted to genetic analysis, and 6 positive cases were found. As for genetic variants, four patients have R118C, one A143T and other with T430G, all considered variants of uncertain significance (VUS). The sensitivity and specificity of α-GAL reduction for the detection of FD was 83.3% and 97.6%, respectively. As for the increase in lyso-GL3, the values were 16.6% and 93.9%, respectively. There were no cases that presented a concomitant increase in lyso-GL3 and a reduction in enzymatic activity.

Conclusion

Preliminary results suggest that the combination of α-GAL enzymatic activity with lyso-GL3 measurement may be a good alternative for screening FD in women with CKD. A thorough medical evaluation is required to determine the pathogenicity of variants in these patients.
#4318 ASSOCIATION OF PLANT PROTEIN INTAKE AND RISK OF INCIDENT CHRONIC KIDNEY DISEASE: THE UK BIOBANK STUDY
Authors: Heo Ga Young , Koh Hee Byung , Kim Hyo Jeong , Kim Kyung Won , Jung Chan-Young , Kim Hyung Woo , Park Jung Tak , Chang Tae Ik , Yoo Tae-Hyun , Kang Shin-Wook , Han Seung Hyeok
Published: June 2023

Background and Aims

Dietary intake from various protein sources can affect health differently. However, the association between plant protein intake and incident chronic kidney disease (CKD) is uncertain.

Method

Using the UK Biobank prospective cohort, we included 117,809 participants who completed more than one dietary questionnaire and had an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2, urinary albumin-to-creatinine ratio (UACR) <30 mg/g, and no prior history of CKD. The main predictor was the daily plant protein intake, assessed with a web-based 24-hour recall questionnaire. The primary outcome was incident CKD, based on the International Classification of Diseases, 10th Revision (ICD-10) or Office of Population Censuses and Surveys Classification of Interventions and Procedures, version 4 (OPCS-4) codes. We additionally analyzed this association in 37,955 participants with primary care-linked data for eGFR and UACR. We used strictly defined CKD based on ICD-10 and OPCS-4 codes or two consecutive measures of eGFR <60 ml/min/1.73 m2 or UACR >30 mg/g.

Results

During the median follow-up of 9.9 years, incident CKD occurred in 3745 (3.2%) participants (incidence rate, 3.2 per 1,000 person-years). In a multivariable cause-specific model, the adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for the second, third, and highest quartiles were 0.91 (0.83-0.99), 0.79 (0.71-0.87), and 0.75 (0.64-0.85), respectively, compared with the lowest quartile. In a continuous model, the aHR (95% CIs) per 0.1 g/kg/day increase in plant protein intake was 0.91 (0.88-0.94). This beneficial association was also consistent in the secondary analysis with strictly defined CKD and various sensitivity analyses.

Conclusion

This large prospective cohort study showed that increased dietary plant protein intake was associated with a lower risk of CKD.
#4322 MEDIATION ANALYSIS OF THE RELATIONSHIP BETWEEN INFLAMMATION AND CONTRAST INDUCED ACUTE KIDNEY INJURY IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Jung Ji Yong , Chang Jae Hyun , Oh Yun Jung , Lee Chung Sik
Published: June 2023

Background and Aims

Decreased kidney function is a risk factor for the development of contrast-associated acute kidney injury (CA-AKI) in chronic kidney disease (CKD). Although the relationship between CKD and CA-AKI is well established, the mechanistic link between the two, particularly the extent to which this interaction is mediated by inflammation, remains poorly understood. We examined the association between CKD and CA-AKI, as well as potential mediators, including serum albumin and high-sensitivity C-reactive protein (hs-CRP) levels.

Method

A total of 3,738 patients were enrolled for analysis from 5,299 patients and fulfilled the inclusion criteria among 12,742 patients who underwent coronary angiography (CAG) between 1 January 2007, and 31 December 2016. Multivariable logistic regression and mediation analyses were performed. In addition to the effect as risk factors, direct and indirect effects were also estimated.

Results

Among 3,738 subjects, 414 developed AKI (11.1%). Pre-procedural albumin and Lnhs-CRP (log-transformed) were independently associated with CA-AKI (odds ratio [OR], 95% confidence interval [CI]): 0.320 (0.272–0.3787), P <0.001 and 1.211 (1.132-1.296), P<0.001, respectively. Direct, and indirect effects were also estimated. Patients with CKD were found to be more likely to exhibit lower serum albumin and higher serum hs-CRP levels. Simple mediation analyses showed that 33.8% and 52.3% of the relationship between CKD and CA-AKI was mediated by the serum albumin and hs-CRP levels, respectively with co-mediation being 13.9%.

Conclusion

These results represent that, in addition to reduced kidney function, inflammatory parameters are also risk factors and mediators of CA-AKI in patients with CKD.
#4331 UPREGULATION OF ADIPOSE TISSUE FATTY ACID-BINDING PROTEIN 4 IN PATIENTS WITH CHRONIC KIDNEY DISEASE: IMPLICATIONS FOR DYSFUNCTIONAL VASCULAR CELLS
Authors: Noh Hyunjin , Kim Hyoungnae , Hong Moonju , Yu MI Ra , Lee Haekyung , Kwon Soon Hyo , Jeon Jin Seok , Song Dan , Yun Sangchul , Yu Byung Chul , Cho Nam-Jun , Park Samel , Park Mooyong , Choi Soo Jeong , Kim Jin Kuk , Gil Hyo-Wook , Lee Eun Young , Lee Jongsoon
Published: June 2023

Background and Aims

FABP4, a fatty acid-binding protein, is predominantly expressed in adipose tissue (AT) and has been shown to be elevated in patients with chronic kidney disease (CKD). Although elevated levels of FABP4 have been linked to cardiovascular disease in end-stage renal disease (ESRD) patients, the cause of this increase is unclear. The aim of this study was to evaluate the expression of AT FABP4 under uremic conditions and its impact on the function of macrophages and vascular smooth muscle cells (VSMC).

Method

We measured the levels of FABP4 in the blood and urine of CKD patients. The expression of AT FABP4 under uremic conditions was analyzed using omental AT obtained from healthy kidney donors and patients with ESRD who received peritoneal catheter insertion. The effect of FABP4 on the function of macrophages and VSMC was also assessed.

Results

The levels of FABP4 in the blood and urine of CKD patients were inversely correlated with their estimated glomerular filtration rate (eGFR). An increase in FABP4 in the blood was detected before its increase in the urine. FABP4 expression was found to be higher in mature adipocytes in visceral AT compared to the stromal vascular fraction (SVF). Adipocytes treated with p-cresol and adipocytes isolated from CKD patients showed higher levels of FABP4 expression compared to healthy individuals. Single-cell RNA sequencing of SVF showed increased FABP4 expression in progenitor cells and macrophages from CKD patients. In THP-1 cells, FABP4 induced more foam cells and increased levels of inflammatory mediators in the presence of palmitic acid. VSMC treated with p-cresol or VSMC isolated from CKD mice induced by an adenine diet showed a pro-calcific phenotype, as indicated by increased calcium content and bone-related gene expression, which was further enhanced by FABP4.

Conclusion

The elevated levels of FABP4 in CKD patients are not solely a result of decreased renal clearance but also due to increased production in AT. These higher levels of circulating FABP4 may be associated with dysfunction in vascular cells.
#4339 CARDIORENAL SYNDROME TYPE 1 IN CHILDREN AFTER SURGICAL TREATMENT OF CONGENITAL HEART DISEASE USING CARDIOPULMONARY BYPASS
Authors: Amanzholova Ainamkoz , Ivanova-Razumova Tatyana , Bekishev Bolat , Morenko Marina , Jabayeva Nilufar
Published: June 2023

Background and Aims

According to recent data, acute kidney injury (AKI) after pediatric cardiac surgery is a significant postoperative complication that occurs in 35-64% of children (1,2) and is associated with increased hospital mortality and unfavorable short-term outcomes. The problem of acute kidney injury in children after cardiac surgery remains relevant, despite the development of modern technologies and methods. Complications after pediatric cardiac surgery have serious negative consequences, prolonging the days of stay in the pediatric intensive care unit (PICU) and increasing mortality (3). The aim of the study is to analyze the frequency of AKI in children after open-heart surgery for congenital heart defects (CHD) using cardiopulmonary bypass (CBP).

Method

We conducted a retrospective analysis of 402 medical records of patients hospitalized in the ICU of JSC NRCSC Astana, Kazakhstan, from January 2018 to December 2022. Inclusion criteria: Children under 18 with CHD who underwent open-heart surgery with the following diagnosis - transposition of the great vessels, total anomalous pulmonary venous connection, interrupted aortic arch, coarctation of the aorta, ventricular septal defect. Exclusion criteria: The presence of AKI and terminal chronic kidney failure.

Results

The analysis included the total number of patients - 402 patients. The frequency of AKI was 15.6% (63 out of 402). Among the patients who developed AKI: boys - 45 (71.4%), girls - 18 (28.5%). The age distribution is as follows: children under 1 month among AKI - 50 (79.3%), under 6 months among AKI – 13 (20.6%), under 1 year among AKI – 5 (7.9%). According to the statistical analysis results, the complication depends on the type of operation, as there is a statistical significance of the differences in the groups (p = 0.046). However, the type of operation (p = 0.35) does not matter for the outcome. Also, the children's weight (p = 0.082) has no statistical significance on the number of complications and the outcome. The sex of children has a statistical significance for complications; in boys, it is significantly higher (p = 0.05). In addition, the lethal outcome in male children is higher than in girls (p = 0.000). The total number of patients with peritoneal dialysis is 63 (15.6%). The total mortality was 80 patients (19.9%). Mortality in the intensive care unit in patients with AKI after open-heart surgery for CHD was 43 (68.2%).

Conclusion

According to our data, the frequency of AKI developed in 15.6% of patients after surgical treatment of CHD using CBP. The overall mortality rate is 19.9%, with boys having a higher risk. Thus, the frequency of AKI is influenced by many factors before, during and after surgery. Therefore, developing preventive measures is a priority for improving the cardiac surgery results in children.
#4355 THE INFLUENCE OF ANTIRETROVIRAL DRUGS AND HIV RESISTANCE MUTATIONS ON THE SHEDDING OF HIV-1 INTO PERITONEAL DIALYSIS EFFLUENT
Authors: Mooko Teboho , Bisiwe Busiswa , Chikobvu Perpetual , Morobadi Daniel , Nyaga Martin , Bester Phillip , Kemp Gabre , Goedhals Dominique , Mofokeng Thabiso , Ndlovu Kwazi
Published: June 2023

Background and Aims

Antiretroviral therapy (ART) is effective HIV management even in HIV-positive patients with end-stage kidney failure (ESKF). However, drug resistance mutations are important determinants of therapeutic effects. The study aimed to determine the prevalence of HIV resistance mutations and ART drug penetration in the peritoneal compartment and their effect on the shedding of HIV-1 into continuous ambulatory peritoneal dialysis (CAPD) effluents.

Method

This prospective cross-sectional study of HIV-positive ESKF patients managed with ART and CAPD at Universitas Academic Hospital collected enrolled patients' background information and clinical and laboratory data. HIV-1 was detected using quantitative polymerase chain reaction (qPCR) and sequenced by the Sanger method, while ART levels were quantified using LC-MS/MS.

Results

There were 38 patients recruited with a median age of 41.8 (IQR, 36.15–48.0) years and were predominantly on abacavir (89.5%), lamivudine (100%) and efavirenz (76.3%) for a median duration of 8 (IQR, 6–11) years. Among participants with detectable HIV in CAPD effluents, the prevalence of ARV-drug resistance mutations was 71.4% (5/7) compared to 12.9% (4/31) among those with undetectable HIV-1 (p = 0.004) with NNRTI resistance mutations predominating. Participants with detectable HIV-1 had lower abacavir (0.00182 vs 5.68 ng/µl; p = 0.021), lamivudine (0.0152 vs 1.09 ng/µl; p = 0.001) and efavirenz (3,605 vs. 57,8 ng/µl; p = 0.004) plasma levels compared to those with undetectable HIV-1. Measured lamivudine (0.455 vs 0.342 ng/µl; p = 0.007) and efavirenz (46.5 vs 2.34 ng/µl; p<0.001) drug levels are significantly higher in plasma than CAPD effluents.

Conclusion

ART resistance mutations, lower drug levels and poor compartment penetration are suggested significant factors for HIV-1 shedding into CAPD effluents.
#4356 DYNAMIC EFFECT OF PROTEINURIA ON ADVERSE KIDNEY OUTCOMES WITH TARGETED MAXIMUM LIKELIHOOD ESTIMATION METHOD: RESULT FROM THE KNOW-CKD STUDY
Authors: Oh Yun Jung , Oh Kook-Hwan , Chung Wookyung , Jung Ji Yong
Published: June 2023

Background and Aims

Proteinuria is a risk factor for the progression of chronic kidney disease (CKD), but its causal inference may be challenging due to time varying exposure and confounding, the changing its degree, and loss to follow up.

Method

A total of 1,223 patients enrolled as part of The Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) were analyzed at 3 observational points (baseline, 3-year; early, and 7-year; late) at which spot urine protein creatinine ratio (UPCR) was measured. We used longitudinal targeted minimum loss-based estimation (TMLE) and marginal structural models (MSM) to estimate the cumulative incidence of adverse kidney outcomes (eGFR halving and kidney failure requiring replacement therapy) of dynamic exposure to high proteinuria (UPCR≥1g/g) comparing counterfactuals (UPCR<1g/g) adjusted for time varying confounding (systolic blood pressure, estimated glomerular filtration rate, and renin-angiotensin-aldosterone blockers) and baseline covariates (age, sex, diabetes, cardiovascular disease, and smoking).

Results

Patients with sustained high proteinuria throughout 7-year follow-up had significant higher risk of renal events than those with counterfactuals (relative risk [RR], 3.120; 95% confidence interval, 2.150-4.528; P < 0.001). The RR were 0.168 (0.055-0.517; P = 0.002) and 0.613 (0.337-1.114; P = 0.108) for early and late proteinuria reduction comparing sustained high proteinuria, respectively. In MSM, hazard ratio (HR) of accumulative high proteinuria frequency were 1.612 (1.463-1.844; P <0.001) up to 3 years and 1.102 (0.877-1.387; P = 0.404) up to 7 years, respectively.

Conclusion

In CKD patients, sustained higher proteinuria is the main risk factor during the entire observation period. However, considering dynamic exposure, proteinuria reduction from the beginning has a protective effect on renal progression, but the effect weakens as the observation period becomes longer.
#4358 INCREASED RV PRESSURE AS A PREDICTOR OF ACUTE DECOMPENSATED HF IN ESRD PATIENTS ON MAINTENANCE HD
Authors: Kim Ye Na , Park Byung Hwa , Shin Ho Sik , Jung Yeonsoon , Rim Hark
Published: June 2023

Background and Aims

Many patients with end-stage renal disease (ESRD) on hemodialysis (HD) have reduced vascular compliance and are likely to develop heart failure (HF). This study aimed to determine the factors associated with acute decompensation events among ESRD patients undergoing HD.

Methods

We retrospectively investigated ESRD patients on HD using a medical record review. We divided the patients into those admitted to hospital due to acute decompensated heart failure (ADHF) and those who were not. We compared the medical histories, electrocardiograms, and echocardiographic and laboratory data between the two groups. The cut-off value of the TR jet velocity for predicting an ADHF with corresponding sensitivity and specificity was estimated using a receiving operator characteristic (ROC) curve analysis. A p value < 0.05 was considered to indicate statistical significance.

Results

Of the 188 ESRD patients on HD, 87 were excluded, and 101 were enrolled (mean age: 63.7 years; 52.1% male). Thirty patients (29.7%) were admitted due to ADHF. These patients exhibited similar left ventricular ejection fraction (LVEF), left ventricular (LV) mass index, and E/E′ values compared to the non-ADHF group. However, the ADHF group exhibited significantly higher tricuspid regurgitation (TR) jet velocity (2.9±0.6 vs. 2.5±0.4 m/s; p = 0.004) and right ventricular systolic pressure (RVSP) (43.5±17.2 vs. 34.2±9.9 mmHg; p = 0.009) than the non-ADHF group, respectively. A multivariate logistic regression analysis demonstrated that the TR jet velocity (odds ratio, 8.356; 95% confidence interval, 1.806–38.658; p = 0.007) was an independent predictor of ADHF after adjusting for age and sex, while the LVEF and E/E′ were not.

Conclusions

Our data showed that an increased TR jet velocity was an independent predictor of ADHF events in ESRD patients on HD, but the LVEF and E/E′ were not.
#4360 FACTORS ASSOCIATED TO RENAL REMISSION IN CRESCENTIC GLOMERULONEPHRITIS
Authors: Sánchez Loreto Mariscal de Gante , Morales Cristina , Giraldo Yohana Gil , Aranzábal María Alejandra Cortiñas , Ruano Pablo , Quiroga Borja
Published: June 2023

Background and Aims

Impaired renal function is one of the most relevant factors associated to crescentic glomerulonephritis (CGN) prognosis. However, renal remission has not yet been defined and clinicians are required to use systemic scores (such as BVAS) to predict severity. In this retrospective study, we aim to describe the associated factors to long-term chronic dialysis incidence and survival in CGN.

Method

We included all biopsy-proven CGN of our center between 2004 and 2022. At baseline, demographics, treatments and comorbidities were collected. Renal function was assessed by glomerular filtration rate (GFR) using CKD-EPI equation, quantification of proteinuria and demonstration of hematuria. During follow-up (median 1486, interquartile range [25-3082] days) renal and vital status was evaluated. Factors associated to dialysis requirement were assessed using Cox regression models. A combined endpoint of death and dialysis was established. Factors associated to the combined endpoint were assessed.

Results

We included 47 CGN (77% female, 67±15 years). Of them, 35 (75%) presented positive ANCA antibodies, 3 (6%) positive glomerular basement membrane (GBM) antibodies, 8 (17%) ANCA and GBM antibodies and one (2%) presented negative autoimmunity. Induction treatment was based on prednisone and cyclophosphamide in 43 patients (91%), prednisone and rituximab in 3 (6%) and prednisone alone in one (2%). At admission, median CKD-EPI was 11 (11-21) ml/min/1.73 m2, proteinuria was 1030 (552-1872) mg/g and 43 (91%) patients presented hematuria. Nineteen patients (40%) required dialysis at admission. Following the definition of KDIGO guidelines for renal remission, 28 (64%) patients achieve it at 6 months. During follow-up, fifteen patients (36%) started chronic dialysis. Factors associated to chronic dialysis were the type on CGN (dual ANCA and GBM and GBM (+) vs ANCA (+), p = 0.003), CKD-EPI at admission (p = 0.001), AKIN (p = 0.050), requirement of dialysis at admission (p<0.001), percentage of crescents (p = 0.037), proteinuria at admission (p = 0.046) and remission after induction treatment (p<0.001). Twenty-four patients (53%) died or needed dialysis during follow-up. Factors associated to this combined endpoint were CKD-EPI at admission (p = 0.017), type on CGN (dual ANCA and GBM vs others, p = 0.003) (Figure 1), debut in dialysis (p<0.001), remission after induction treatment (p<0.001). An adjusted Cox regression model demonstrated that the need for dialysis or death during follow-up was independently associated to not achieving remission after induction (i.e. 6 months) (HR 8.78, 95%CI (2.88-26.7), p<0.001) and requirement of dialysis at debut (HR 3.96, 95%CI [1.15-13.6], p = 0.029).

Conclusion

The requirement of dialysis at debut and not achieving remission after induction are independent predictors of death or need for chronic dialysis in CGN.
#4367 THE IMPACT OF QUALITY OF LIFE ON THE SURVIVAL IN THE ELDERLY END-STAGE RENAL DISEASE PATIENTS : A PROSPECTIVE MULTICENTER COHORT STUDY IN KOREA
Authors: Chung Yu-Kyung , Cho Jang-Hee , Lim Jeong-Hoon , Jeon You-Hyun , Kim Yong-Lim , Kim Chan Duck , Park Sun-Hee , Choi Ji-Young , Jung hee-Yeon , Lee Seong-Wook , Kim Yoon-Ju , Lee Young-Hwan
Published: June 2023

Background and Aims

Quality of life (QOL) are associated with mortality in dialysis patients. However, the impact of QOL index or score on elderly patients with end-stage renal disease (ESRD) is controversial. We analyzed the relationship between QOL items and survival in elderly ESRD patients.

Method

A total of 492 patients with ESKD aged > 65 who assessed for QOL items were included from a Korean nationwide prospective cohort study. QOL was evaluated using the Kidney Disease Quality of Life (KDQOL) instrument, and the effect of each QOL item on mortality was analyzed. Multivariable Cox regression analysis was performed to identify independent risk factors for death after adjusting for compounding factors.

Results

The low physical component scale (PCS) and short form-36 score were significantly associated with low survival rate (PCS: p<0.001 and short form-36: p = 0.017, respectively), while the mental component scale (MCS) and ESRD-targeted item score had no correlation with survival rate. Multivariable Cox regression analysis confirmed that only a high PCS score is associated with better survival (hazard ratio 0.71, 95% confidence intervals 0.52-0.97, P = 0.031). Linear regression analysis identified that age, sex, modified Charlson Comorbidity Index, albumin, and intact parathyroid hormone were factors to PCS. Among the four PCS components, only physical function score was significantly associated with mortality (p<0.001).

Conclusion

Among the KDQOL items, PCS was an independent risk factor for death in elderly ESRD patients. The higher physical function score of PCS components was associated with a better outcome, suggesting the importance of physical conditions in elderly dialysis patients.
#4389 CONSENSUS STATEMENTS FROM THE DIABETOLOGISTS AND ENDOCRINOLOGISTS ALLIANCE FOR THE MANAGEMENT OF PEOPLE WITH HYPERTENSION AND TYPE 2 DIABETES MELLITUS
Authors: Tong Peter , Chan Susanna , Chan Wb , Ho Kai Leung , Leung Godwin , Lo Hok King Stanley , Mak Gary , Tse Ts
Published: June 2023

Background and Aims

Hypertension and type 2 diabetes mellitus (T2DM) are important, intertwined issues in public health. People with both conditions face significantly elevated risks of complications, particularly albuminuria, which is an independent risk factor for cardiovascular (CV) events, kidney failure and all-cause mortality, and thus deserves more attention among physicians and patients. The purpose of this study is to describe the development of recommendations for the management of hypertension and T2DM by a multidisciplinary expert panel.

Method

The panel included eight specialists (three cardiologists, three endocrinologists and two nephrologists) experienced treating patients with hypertension or T2DM. The panel reviewed clinical trials, meta-analyses, observational studies and clinical guidelines that were obtained by searching PubMed for the publication period from January 2015 to June 2021, to address five discussion areas: (i) blood pressure (BP) targets based on CV/renal benefits; (ii) management of isolated systolic or diastolic hypertension; (iii) roles of angiotensin II receptor blockers (ARBs); (iv) implications of albuminuria for CV/renal events and treatment choices; and (v) roles and tools of screening for microalbuminuria. The panel held three virtual meetings using a modified Delphi method to discuss the literature and their experience regarding the discussion areas. After each meeting, consensus statements were derived and anonymously voted on by every panelist. A consensus statement was accepted only if ≥ 80% of the panelists selected ‘accept completely’ or ‘accept with some reservation’.

Results

A total of 17 consensus statements were formulated.

Conclusion

The key messages include: (i) home BP is considered as important as office BP in treatment decision-making; (ii) in patients with T2DM and hypertension on antihypertensive drug treatment, the targets should be < 130/80 mmHg for office BP and < 125/75 mmHg for home BP; (iii) albuminuria is an important therapeutic goal and should be screened for regularly in people with T2DM or hypertension; and (iv) an ARB with proven cardioprotective and renoprotective effects is the preferred drug treatment for patients with T2DM and hypertension.
#4400 QUALITY OF LIFE, PRURITUS BURDEN, AND TREATMENT SATISFACTION IN CHRONIC KIDNEY DISEASE PATIENTS IN GERMANY
Authors: Zavlin Dmitry , Weinreich Thomas , van Bentum Kai , Müller Berno , Koczor Martin
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) and its related symptoms significantly impact patients’ health-related quality of life (HRQoL). CKD-associated pruritus (CDK-aP) often affects patients with advanced CKD, particularly those on renal replacement therapy, and remains mostly underrecognized by both patients and medical providers. To explore the current patients’ impairment of HRQoL due to CKD-aP, we conducted a quantitative survey amongst members of a CKD patient association in Germany.

Methods

Our questionnaire was distributed via the channels of the German National Kidney Patients Association (Bundesverband Niere e.V.) from mid-June to mid-September 2022. Responses of 569 CKD-patients of a total of roughly 16,000 members were analysed regarding their general health, HRQoL, and general treatment satisfaction using multiple choice questions. Pruritus burden was assessed with a 0-10 numeric rating scale.

Results

The demographic details are displayed in Figure 1. Among the surveyed CKD patients, 33% were transplanted, 39% on hemodialysis, and 7% on peritoneal dialysis. We could confirm that most CKD patients (92 %) suffered from comorbidities. Initially, 12% reported dermatological comorbidities but when asked specifically about pruritus, 62% reported this symptom which was also associated with worse HRQoL (Figure 2). However, only one third was receiving antipruritic treatment by a physician. Furthermore, patients who were able to fully or at least partially participate in their medical decisions showed higher satisfaction and higher HRQoL (86% vs. 65% vs. 43% satisfaction, depending on full/partial/no participation, respectively) yet the patients did not always perceive that shared-decision-making was possible. Patients also showed high interest in topics outside of their primary CKD treatment, such as overall symptom control and additional psychological measures. They reported higher HRQoL when these areas were addressed by the medical team (87% vs. 55% satisfaction).

Conclusions

Our survey results emphasize the persisting need for shared or co-creative exchange between patient and physician. Improving patient education and the caregiver's awareness of the burden of pruritus – one of the many CKD-related symptoms – could be a first step towards higher patient satisfaction and HRQoL and higher treatment rates. CKD-aP appears underreported by patients via unprovoked questioning and should be screened frequently.
#4440 PREVALENCE OF GENES INVOLVED IN HEREDITARY KIDNEY DISEASE AS A TOOL FOR THE DEVELOPMENT OF A GENE PANEL
Authors: Gómez Cristina Andrades , Cosano Gema Montilla , Valdivia Miguel Ángel Pérez , Castilla José Luis Rocha , Prieto Francisco Javier Toro , Lopez-Mendoza Manuel
Published: June 2023

Background and Aims

Genetic study is the fundamental tool for the diagnosis of Hereditary Kidney Diseases (HKD). The proliferation of its use has led to an increase in diagnostic complexity due to phenotypic overlap and genotypic heterogeneity. The aim of this study is to evaluate the prevalence of genes in our series of adult patients with suspected monogenic kidney disease in order to develop the basis for the elaboration of a gene panel that will make its usefulness in our routine clinical practice profitable.

Method

A retrospective descriptive observational study was performed with the collection of all genetic studies that were positive in the period between October 2014 and December 2020 in our center. With a description of the causative genes involved, as well as the clinical data of the proband patients who turned out to be carriers of these variants. Descriptive results of continuous variables are expressed as mean and standard deviation (SD) or median and interquartile range (IQR) according to their distribution. For categorical data, frequency and percentage are reported.

Results

The results of a total of 77 genetic studies on probands were collected, of whom 51% were women with a mean age at diagnosis of 46 years (SD ± 13.4) and 64.9% had a family history of kidney disease. Renal function measured by mean estimated glomerular filtration rate (eGFR) using the CKD-EPI (CKD Epidemiology Collaboration) was 90.1 ml/min/1,73 m2 (SD ± 29.64) with a mean proteinuria quantified in 24-hour urine of 627.9 mg (SD ±43.7) and 7.7% were on renal replacement therapy. (Table 1) 40.25% of probands were carriers of a mutation for Alport syndrome, in this group the most frequent gene was COL4A3 in 50% of cases. The second most frequent entity was autosomal dominant polycystic kidney disease (ADPKD) with 37% of the studies and among these the great majority were carriers of a variant in the PKD1 gene with 96.5%. The remaining diagnostic entities in order of frequency were Fabry disease, autosomal dominant tubulointerstitial nephropathy (ADTKD), congenital anomalies of the kidney and urinary tract (CAKUT), nephrotic syndrome, hereditary angiopathy with nephropathy, aneurysm and cramps syndrome (HANAC) and tuberous sclerosis (Figure 1).

Conclusion

Alport syndrome was the most frequently identified entity in patients with suspected monogenic renal disease in whom the genetic study was performed. Based on the results of our series, a proposal has been made for the genes to be included in a panel for hereditary renal diseases in our center. The development of these panels increases the efficiency and increases the cost-effectiveness of genetic studies in the diagnosis of these patients.
#4446 THE CARE TRAJECTORY LEADING TO EMERGENCY DIALYSIS START: CROSSING PATIENTS’, GENERAL PRACTITIONERS’ AND NEPHROLOGISTS’ PERSPECTIVES
Authors: Raffray Maxime , Vigneau Cécile , Laude Laetitia , Arnaud Campeon , Bayat Sahar
Published: June 2023

Background and Aims

Emergency dialysis start (EDS) is an important issue to understand and tackle in CKD care. Late referral, absent previous nephrology care and higher comorbidity scores have been associated with EDS. However, how those quantitative risk factors happen and contribute to EDS remains unexplored. We conducted a qualitative study in France to identify and describe the mechanisms that shape the trajectories that lead to EDS, using patients, GPs and nephrologists perspectives.

Method

Three groups of participants were recruited in Brittany, north-west France: Patients who started dialysis in emergency between 2017 and 2019, GPs and nephrologists. Maximum variation sampling approach was used based on patients’ socio-economic profiles and GPs’ and nephrologists’ years and settings of practice. Semi-structured interviews were conducted between 2017 and 2020. A crossed thematic analysis between the 3 groups of transcripts was performed, informing how EDS trajectories come to be.

Results

Twenty patients, 12 GPs and 18 nephrologists were interviewed. Five main themes were identified: 1) Learning about dialysis, 2) Dialysis and nephrology care representations: a) an unacceptable biographical disruption, b) a dreadful invasive machinery, c) a straw that breaks the camel's back, 3) The gap between the “illness” perceived and the “disease” treated, 4) Slipping through the primary care prevention net, 5) the unavoidable unpredictability of CKD course.

Conclusion

This study shows how quantitative risk factors of EDS such as low or absent previous nephrology care are, in part, the results of an interplay between patients’ constructed representations of dialysis, relation with the medical sphere and CKD physiopathology. The results suggests a need for evaluation of kidney replacement therapy education programs and reinforcement of psychological care. Finally, results also support ambitious mass prevention campaign focused on kidney health to counter the persistent negative representation of dialysis and seal off prevention cracks younger patients slip through.