bluuebunny/crossref_metadata_2025 huggingface dataset:
#5781 DRUG-INDUCED ACUTE INTERSTITIAL NEPHRITIS (D-AIN): HOW TO IDENTIFY THE RESPONSIBLE DRUG?
Authors: Moreno Javier Azores , Rivas Begoña , Cabrera Cristina Vega , Cabañas Rosario , Fernández Eugenia García , Yébenes Laura , Barceló Sara Aldana , Raso Irene Vázquez , Juarez Gema Maria Fernandez
Published: June 2023

Background and Aims

The mainstay of D-AIN treatment is the removal of the responsible drug. However, it is not always easy to identify the culprit drug as this entity mainly affects elderly patients on multiple medications, they rarely associate systemic symptoms (rash, fever), and the timeline regarding the diagnosis and the associated drug is not always clear. Therefore, the diagnosis and treatment are delayed, making full renal function recovery less likely. The lymphocyte transformation test (LTT) has demonstrated to be useful in the identification of the involved drug in other hypersensitivity-mediated lymphocyte T diseases such as Stevens-Johnson Syndrome or Dress Syndrome. For this reason, we wonder if this test could be relevant in identifying the responsible drug in D-AIN. The aim of this study is to test LTT in patients with clinical and histological diagnosis of D-AIN.

Method

We have conducted a retrospective observational study in which we have collected data from 2019 to 2022 from our electronic databases.

Results: We have registered 9 cases of D-AIN diagnosed with histological confirmation in whom the LTT had been performed. 22.2% of these patients were men. The mean age was 48.1 years (standard deviation of 15.8). None of them had previous chronic kidney disease (CKD). Mean peak creatinine at diagnosis was 4.66 mg/dl (standard deviation of 1.95). Regarding the typical symptoms of the D-AIN, three patients (33%) presented with fever and none of them suffered from rash. 6 patients had sterile pyuria (66%). All of them received steroid treatment. Concerning the LTT results, 7 cases were positive for one of the drugs the patient was taking, and 2 were negative. Among the positive cases, the identified drugs were 1 case of beta lactams (piperacillin), 1 case of PPIs (omeprazole), 1 case of metamizole, 1 case of paracetamol, 1 case of eslicarbazepine and 2 cases of NSAIDs (dexketoprofen), while the negative cases have not been suspected of taking any culprit drug.

Conclusion

LTT may be a useful test to identify the responsible drug for D-AIN, especially in patients taking multiple medications in which may be included some of great importance like immunotherapy (typical cause of D-AIN) in oncological treatments. In negative cases, it could be expected that the patient had taken medications difficult to be identified in the clinical history or, in some situations, the drug hapten responsible for kidney damage might be a drug metabolite and not the drug itself, which cannot be detected by the test.
#5785 ACUTE KIDNEY INJURY AS A RISK FACTOR FOR THE DEVELOPMENT OF CHRONIC KIDNEY DISEASE AND MORTALITY IN HOSPITALIZED PATIENTS
Authors: García Julio Francisco Colina , García-Galán Lucía Cordero , Martínez Marta Rivero , Hernández Paúl , González-García Celia , Lozano Sergio Huerga , Pérez Justo César Sandino , Auñón Pilar , Gutiérrez Eduardo , Morales Enrique
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is a complication that affects more than 5% of all hospital admissions and up to one third of patients admitted to critical care units. This entity, whose incidence is on the rise, remains a major cause of morbidity and mortality. In addition, AKI has been linked as an independent risk factor for mortality, especially in severe forms, and of those patients who survive, a percentage will develop chronic kidney disease (CKD) during follow-up. We conducted this study to analyse the incidence of CKD at 6 and 12 months follow-up in hospitalized patients with AKI, to identify possible risk factors leading to its development and to determine mortality in this group of patients.

Method

This is a retrospective study of a cohort of cases with AKI (baseline eGFR >60 mL/min/1.73 m2 without previous structural damage) from our hospital, taking place from June 2020 to February 2021. Regarding the evolution of the AKI, four possibilities were considered: recovery of normal kidney function, development of CKD at 6 months, development of CKD at 12 months or death during follow-up.

Results

We studied 148 patients (55% male), with a median age of 83 years (74-87). Thirty-six patients (24.3%) developed CKD at 6 months follow-up and 30 patients (20.3%) at 12 months. Forty-one patients (27.7%) died within the first 12 months following de episode of AKI. The risk factors identified for development of CKD at 12 months were older age (85 vs 77; p = 0.03), higher serum lactate dehydrogenase levels at admission (246 U/L vs 201 U/L; p = 0.04) and at 3 months (252 U/L vs 192,5 U/L; p = 0.039), and eGFR < 60 mL/min/1.73 m2 at 1 week (74,5 vs 57; p = 0.004) and at 3 months (79 vs 50; p < 0.001) of follow-up. Identified risk factors and predictors of AKI-associated mortality were older age (84 vs 80,5; p = 0.018), concomitant oncological pathology (10,8% vs 7,4%; p = 0,018), higher Charlson index (6 vs 5, p <0.001), higher AKI stage (p = 0.042), lower serum albumin levels at first (3.35 g/dL vs 3.90 g/dL; p = 0.014) and at third month (3,2 g/dL vs 4 g/dL; p < 0.001) of follow-up.

Conclusion

Our study showed a high incidence of CKD in patients who have had an episode of AKI. Several risk factors for development of CKD were identified, being the older age and the greater length of recovery period from AKI the most useful predictors in the clinical practice. AKI-associated mortality was very high in those older patients with higher comorbidity and persistence of AKI. Despite advances, we need non-classical biomarkers for early diagnosis and more effective therapeutic measures to avoid this high prevalence of CKD and mortality.
#5790 IMPAIRED FATTY ACID METABOLISM PERPETUATES LIPOTOXICITY ALONG THE TRANSITION TO CHRONIC KIDNEY INJURY
Authors: Rinaldi Anna , Lazareth Helene , Poindessous Virginie , Nemazanyy Ivan , Lopes-Sampaio Julio , Malpetti Daniele , Bignon Yohan , Naesens Maarten , Rabant Marion , Anglicheau Dany , Cippà Pietro , Pallet Nicolas
Published: June 2023

Background and Aims

Understanding the cell-intrinsic mechanisms contributing to the maintenance of a dysfunctional cellular state in chronic kidney disease (CKD) and identifying therapeutic targets are research priorities in renal medicine. A key contributor to chronic kidney histological damage is acute kidney injury, especially ischemia-reperfusion injury (IRI). Persistent cell-extrinsic perturbations generated upon IRI, for example hypoxia, impair the energetic metabolism of Proximal Tubular Cells (PTC) participating in the process of transition from acute to chronic kidney injury. Here, we propose to investigate the PTC intrinsic factors involved in the perpetuation of an impaired cellular state which contribute to CKD progression

Method

We combined single nucleus transcriptomic, metabolomic and lipidomic approaches in experimental models and patient cohorts to investigate the molecular bases of the progression to chronic kidney allograft injury initiated by IRI.

Results

The urinary metabolome of kidney transplant recipients with chronic allograft injury and who experienced severe IRI was significantly enriched with long chain fatty acids (FA). We identified a renal FA-related gene signature with low levels of Cpt2 and Acsm5 and high levels of Acsl4 and Acsm5 associated with IRI, transition to chronic injury, and established CKD in mouse models and kidney transplant recipients. The findings were consistent with the presence of Cpt2-, Acsl4+, Acsl5+, Acsm5- PTC failing to recover from IRI as identified by single nucleus RNA sequencing. In vitro experiments indicated that endoplasmic reticulum (ER) stress contributes to CPT2 repression, which, in turn, promotes lipids accumulation, drives profibrogenic epithelial phenotypic changes, and activates the unfolded protein response.

Conclusion

ER stress through CPT2 inhibition and lipid accumulation, engages an auto-amplification loop leading to lipotoxicity and self-sustained cellular stress. Thus, IRI imprints a persistent FA metabolism disturbance in the proximal tubule sustaining the progression to chronic kidney allograft injury.
#5802 ASSESSMENT OF THE INTERNATIONAL IGA NEPHROPATHY PREDICTION TOOL AFTER IGAN TREATMENT: A CASE-SERIES STUDY
Authors: DI Maso Vittorio , Perencin Brigitta , Yazbek Ahmad , Marcantoni Carmelita , Zacchi Alberto , Zanconati Fabrizio , Bianco Francesco
Published: June 2023

Background and Aims

IgAN have a variable clinical course and a considerable risk of ESKD. The 2021 KDIGO guidelines recognize the International IgAN Prediction Tool (IIgAN-PT) as a quantifier of progression risk at the time of kidney biopsy. The possible application of the IIgAN-PT to re-evaluate the risk after treatment and during follow-up is debated. We analyzed the possible association between treatment response and changes of IIgAN-PT risk estimation.

Method

Retrospective study including patients with IgAN undergone kidney biopsy from Jan 2010 to Dec 2020. Inclusion criteria: treatment with glucocorticoids, age>18, follow-up at 3-6-12-24 months, availability of risk

assessment. Progression risk evaluated by IIgAN-PT at time 0 (biopsy) and after 6-12 months. Two risk groups were identified based on the IIgAN-PT at time 0: Low-Intermediate risk group (Low-risk, IIgAN-PT<23%) and High-risk group (High-risk; IIgAN-PT risk≥23%).

Results

A total of 22 patients were included (59% Low-risk; 31% High-risk). Patients at low- risk had significantly higher eGFR with respect to high-risk group (78 vs 40 ml/min/1.73 m² respectively) (p<0.001). Age, MAP, and RASi use at biopsy did not differ significantly. Proteinuria was comparable among groups: 3.14 g/24 h in High-risk and 2.49 g/24h in Low-risk (p = 0.17). In the Low-risk group the median proteinuria swiftly decays below 1.0 g/day already at three months, and below 0.5 g/day after six. Conversely, in the high-risk group, it remained above 1 g/day until 12 months (Fig. 1). Regarding risk progression assessment: 89% of patients at higher risk at baseline became at lower risk at 6 months (Fig 2; Table 1).

Conclusion

Treatment response was associated with a reduction in the IgAN progression risk as demonstrated by changing of IIgAN-PT already after 6 months. These data suggest a possible dynamic use of IIgAN-PT for IgAN progression risk re-evaluation even in the short follow-up period.
#5811 URINARY CXCL9 AND CXCL10 CONCENTRATIONS AND KIDNEY TRANSPLANT INJURY
Authors: Macioniene Ernesta , Miglinas Marius , Simanavicius Martynas , Vitkauskaite Monika
Published: June 2023

Background and Aims

Kidney transplant rejection is diagnosed by the kidney biopsy which is an invasive diagnostic method, however, non-invasive biomarkers, distinguishing normal kidney transplant from transplant rejection would be prefered but are lacking. CXC chemokine ligand 9 (CXCL9) and CXC chemokine ligand 10 (CXCL10) are gamma interferon inducible small cytokines. The aim of this study was to evaluate urinary CXCL9 and CXCL10 as potential biomarkers of allograft rejection.

Method

117 kidney transplant recipients undergoing kidney transplant biopsy (surveillance or indication) were included into this study. Spot urine samples were collected before kidney biopsy for urinary creatinine, CXCL9 and CXCL10 measurement. The ratios of CXCL9 over urinary creatinine and CXCL10 over urinary creatinine were calculated. Kidney biopsies were analyzed according to Banff criteria by an experienced pathologist.

Results

26 (22.2%) of kidney biopsies were defined as normal histology, 24 (20.5%) – antibody mediated rejection, 9 (7.7%) – T cell mediated rejection, 10 (8.6%) mixed rejection, 5 (4.3%) BK virus nephopathy and 43 (36.8%) were defined as other histological lesions. Average CXCL9/creatinine was 0.39 ng/mmol in normal histology group and 12.1 ng/mmol in allograft rejection groups (p<0.01). Average CXCL10/creatinine was 0.26 ng/mmol in normal histology and 4.55 ng/mmol in allograft rejection group (p<0.01). CXCL9/creatinine and CXCL10 moderately correlated to proteinuria at the time of kidney biopsy (accordingly r = 0.595, p<0.01 and r = 0.408, p<0.01). ROC curve for CXCL9/creatinine detecting antibody mediated rejection was 0.79, CI 0.67 to 0.90, p<0.01. ROC curve for CXCL10/creatinine detecting antibody mediated rejection was 0.79, CI 0.64 to 0.94, p<0.01.

Conclusion

Urinary biomarkers CXCL9/creatinine and CXCL10/creatinine has a potential to distinguish normal renal histology from allograft rejection and correlates to proteinuria at the time of the biopsy.
#5821 CLINICALLY MEANINGFUL IMPROVEMENT IN QUALITY OF LIFE ACCOMPANIES ITCH RELIEF IN PATIENTS WITH CHRONIC KIDNEY DISEASE ASSOCIATED PRURITUS
Authors: Kraft Leonie , Schaufler Thilo , Ruessmann Despina , Morin Isabelle , Menzaghi Frederique , Wen Warren , Krüger Thilo
Published: June 2023

Background and Aims

The impairing effect of chronic kidney disease-associated pruritus (CKD-aP) on the quality of life (QoL) of patients undergoing haemodialysis (HD) is well-established. The aim of this post-hoc analysis was to assess the impact of itch relief on QoL, as measured by the 5-D itch scale, in patients with CKD-aP enrolled in the Phase 3 KALM-1 and -2 clinical trials. This study also aimed to confirm the use of ≥5-point reduction in 5-D itch scale total score as a threshold for clinically meaningful improvement in itch-related QoL, by comparing to notable improvement on the Patients’ Global Impression of Change (PGI-C) scale.

Method

Data were pooled from 851 patients with moderate-to-severe CKD-aP undergoing HD in the KALM-1 and -2 trials testing difelikefalin vs placebo. Sustained responders were defined as patients who achieved a ≥3-point improvement in the weekly mean 24-hour Worst Itching Intensity Numerical Rating Scale [WI-NRS] score at Week 12 of the study, whereas non-sustained responders were defined as patients that reported a ≥3-point improvement in any week of the study but not at Week 12. Improvements in QoL, as measured by the mean change in 5-D itch scale total score from baseline to Week 12, were compared in sustained responders vs non-sustained responders. Data were analysed by ANCOVA multiple imputation, with a missing-at-random assumption. The mean change in 5-D itch scale total score was analysed in relation to patients’ reporting on the five categories of the PGI-C scale.

Results

In pooled analysis, 305 patients undergoing HD with CKD-aP qualified as sustained responders, whereas 128 patients were non-responders. Reduction in 5-D itch scale total score over 12 weeks was significantly higher in sustained responders compared with non-sustained responders (least squares [LS] mean ±standard error; –7.1±0.2 vs –4.0±0.3, LS mean difference –3.0±0.3, p<0.001) (Figure 1). Greater reductions in 5-D itch scale total score were observed in patients reporting more substantial improvements in PGI-C. Specifically, patients reporting much, or very much, improvement in PGI-C scored ≥5-point reduction on the 5-D itch scale (mean ±standard error; –5.3±0.2 and –8.2±0.3, respectively) (Figure 2).

Conclusion

This study observed a greater improvement in QoL, as measured by the 5-D itch scale total score, in patients with CKD-aP who reported a clinically meaningful reduction in itch, as measured by WI-NRS, at Week 12. These results also support the use of ≥5-point reduction in the 5-D itch scale total score as a threshold for clinically meaningful improvement in the QoL of patients with CKD-aP. As only sustained responders exceeded this threshold, these data suggest that continued treatment of itch may be necessary to maximally improve QoL in these patients.
#5825 REAL WORLD EVALUATION OF SGLT2 INHIBITORS IN PATIENTS WITH DIABETIC NEPHROPATHY AND HEART FAILURE: THE EFFECT ON THE DIASTOLIC DYSFUNCTION
Authors: Xydakis Dimitris , Antonaki Ergini , Tzali Eleni , Liaka Fanouria , Petra Christina , Kostakis Konstantinos , Vardaki Eleftheria
Published: June 2023

Background and Aims

In patients with diabetes mellitus and diabetic nephropathy, a high incidence of left ventricular diastolic dysfunction has been reported by various studies. The objective of this study was to the real world evaluation of the impact of sodium glucose cotransporter type 2 (SGLT2) inhibitors on left ventricular (LV) diastolic function of type 2 diabetes mellitus (T2DM) patients with diabetic nephropathy and heart failure (HF).

Method

We studied patients with Diabetes Mellitus type 2, diabetic nephropathy (eGFR> 30 ml/min/1.73 m2) and stable (at least for 3 months) Heart Failure with reduced ejection fraction. We excluded patients treated with iSGLT2 before the study initiation. Laboratory and Echocardiographic studies (Left Ventricular Ejection Fraction LVEF%, the ratio (E/A), Early diastolic velocity (Em), LV mass index (LVMI)), were performed in all patients at baseline and after 12 months of treatment with dapagliflozin 10 mg/day.

Results

67 patents were included (38/29 M/F, age 68±14.2years), with eGFR 72.5±9.2 ml/min/1.72 m2) at baseline. Mean duration of diabetes was 14.2 ± 7.9 years, and mean HbA1c was 7.9 ± 1.1%. There was a significant increase of LVEF (38.5±8.1% to 43.7±7.4%; p = 0.02). LV Mass Index was decreased from 78 g/m2 to 67 g/m2 (p = 0.01) and there was a significant decrease in E/e′ (11.8 to 9.6 cm/s (p = 0.01). Urinary albumin excretion rate at baseline was 526±233 mg/24H and there was a reduction of 32% at the end of the follow up. Multiple regression analysis showed that reduction in albuminuria was an independent predictive factor for E/e′ changes.

Conclusion

Data from this study showed LV diastolic function as assessed in terms of E/e′ and LVMI had significantly improved 12 months after the initiation of dapagliflozin. Reduction of albuminuria by SGLT2i, is an independent predictive factor for improvement of LV function.
#5879 PILOT MONITORING STUDY IN PATIENTS WITH DIABETIC KIDNEY DISEASE USING NORA APPLICATION
Authors: Gaibor Néstor Toapanta , Sánchez Ester , Guirao Cristina , Román Juan Carlos León , Terrada Natalia Ramos , Vergara Ander , Azancot María A , Agraz Irene , Bermejo Sheila , Montiel Estefania , Molina Carlos , Ribó Marc , Romeo Maria Jose Soler
Published: June 2023

Background and Aims

Diabetic Kidney Disease (DKD) is the most common cause of end-stage chronic kidney disease (CKD), conditioning these patients to a worse renal prognosis and higher cardiovascular mortality and/or requirement for renal replacement therapy. The use of novel information and communication technologies (ICTs) focused on the field of health, may facilitates a better quality of life and disease control in these patients. Our objective is to evaluate the effect of monitoring DKD patients using NORA-app.

Method

Prospective feasibility/validation study of NORA-app in patients with DKD stage G3bA3 or higher, followed in outpatient clinics of a tertiary care hospital. NORA-app is an application for smartphones designed to control risk factors, share educational medical information, communicate via chat with health professionals, increase treatment compliance (Morisky-Green), and collect patient reported outcomes such as anxiety and depression using HADs scale. Clinical-laboratory variables were collected at 3 months and compared to control patients who declined using NORA-app.

Results

From 01/01/2021 to 03/03/2022 the use of NORA-app was offered to 118 patients, 82 accepted and 36 declined (controls). After a mean follow-up period of 6,04 months and at the time of data extraction 71(86.6%) NORA-app patients remain active users, 2 have completed the follow-up at one year and 9 are inactive (3 due to death and 6 due to non-locatable). There were no differences in baseline characteristics including Creatinine [2.1 (1.6-2.4) vs. 1.9 (1.5-2.5)] mg/dL and alb/creat [962 (475-1784) vs. 1036 (560-2183)] mg/gr between Nora and control patients respectively. The therapeutic compliance rate in the NORA-app group was 77%, improving at 90 days to 91%. Patients in the NORA-group showed significantly lower levels of alb/creat than controls (768(411-1971) mg/g Vs 2039 (974-3214) p = 0.047) at 90-day follow-up.

Conclusions

In patients with DKD the use of NORA-app was maintained in the long-term, leading to high levels of treatment compliance, and achieving a better disease control. Our study suggests that the generalized use of ICTs may help in the personalized monitoring of these patients to delay the progression of kidney disease.
#5882 BENEFIT OF LONG-TERM TOLVAPTAN ADMINISTRATION ON KIDNEY DISEASE PROGRESSION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: A SINGLE-CENTRE EXPERIENCE
Authors: Filiopoulos Vassilis , Melexopoulou Christina , Kofotolios Ioannis , Stroppou Persia , Vallianou Kalliopi , Athanasopoulou Diamanto , Karavasilis Efstratios , Ntounas Georgios , Efstathopoulos Efstathios , Boletis Ioannis , Marinaki Smaragdi
Published: June 2023

Background and Aims

Tolvaptan introduction in autosomal dominant polycystic kidney disease (ADPKD) treatment has significantly modified kidney disease progression in these patients. The efficacy and safety of tolvaptan in the management of ADPKD has already been demonstrated by TEMPO and REPRISE trials, however studies examining the long-term outcomes are limited. The aim of our study was to evaluate the long-term administration of tolvaptan in patients with ADPKD in our center.

Method

ADPKD patients treated with tolvaptan for at least one year were included in the study. Demographic, laboratory, and total kidney volume (TKV) data were collected. Kidney disease progression was assessed by comparing observed and predicted glomerular filtration rate (eGFR), based on the Mayo Clinic prediction model, at the last visit.

Results

Forty-one patients, 22 males, with ADPKD were studied. Median age at initial visit was 35 years (IQR 27-42), and median time on tolvaptan treatment was 24 months (IQR 18-33). Six (14.6%) patients discontinued tolvaptan after at least one year on treatment. Patients were classified according to the Mayo Clinic imaging classification into 1C (n = 8), 1D (n = 16) and 1E (n = 17). Those who received tolvaptan showed a lower eGFR decline from baseline compared to predicted (eGFR 66.7±32.7 vs 61.5±29.1, p<0.001), while a greater benefit was observed in Class 1E (eGFR 60.1±36.5 vs 52.4±29.5, p = 0.003) and in patients with eGFR>45ml/min (eGFR 79.4±28.8 vs 73±25.2, p = 0.001).

Conclusion

Our initial experience from long-term administration of tolvaptan in patients with ADPKD demonstrates benefit on kidney disease progression. The widespread use of tolvaptan in a larger number of patients and their long-term follow up are necessary to draw more secure conclusions.
#5890 THE IMPACT OF CKD STATUS BEFORE KIDNEY TRANSPLANTION ON ALPHATORQUEVIRUS DNA LEVELS
Authors: Lozano Claudia Yuste , González-García Celia , Espada Paula Jara Caro , Hernandez-Velasco Paul , Gayo Lucia Rodriguez , Fernandez Natalia Inmaculada Polanco , Belmonte Amado Andrés , Morales Enrique , Fernandez Mario
Published: June 2023

Background and Aims

Torque teno virus (TTV) is a non-pathogenic anellovirus whose replication kinetics reflects the overall state of immunosuppression. Although chronic kidney disease (CKD) induces a well-stabilised dysfunction of the immune system, long-term use of renal replacement therapies (RRT) itself could also modify the immune response.

Method

We analyzed TTV DNA loads at baseline (in the pre-transplant assessment), day 7 and months 1, 3,6 and 12 after kidney transplantation (KT). Recipients were categorized according to their RRT status: pre-emptive KT (pre-KT), hemodialysis (HD) and peritoneal dialysis (PD). TTV DNA load was measured by real-time polymerase chain reaction.

Results

A total of 221 CKD patients were analyzed. The mean age was 53.9 ± 15.7 years, 72.4% were males, and hypertension (85.1%) and diabetes (30.1%) were the most common comorbidities. According to the pre-transplant TTR status, 159 (72.0%) were on HD, 35 (15.8%) on PD and 27 (12.2%) received pre-KT. There were no differences in baseline comorbidities or age between patients according to their RRT status, except for residual diuresis (P <0.01). HD patients had higher serum albumin levels than patients receiving pre-KT or PD (4.4 ± 0.5 vs. 4.1 ± 0.6 vs. 3.9 ± 0.4 g/dL, respectively, P <0.01). PD patients exhibited higher TTV DNA load (3.4 ±1.2 log10 copies/mL) than HD (2.8 ± 1.6 log10 copies/mL) or pre-KT patients (2.4 ± 2.1 log10 copies/mL), although the differences were not statistically significant. PD patients had lower time on dialysis than HD patients (18.4± 16.2 vs. 37.5± 53.6 months, respectively; P = 0.038). Although PD patients had higher TTV DNA load during the post-transplant follow-up than HD and pre-KT patients, viral kinetics were comparable across these three groups by month 12 after transplantation. Time on dialysis was not associated with TTV DNA load (P = 0.18). RRT status was not associated with the incidence of post-transplant infection or a composite of opportunistic infection and/or de novo malignancy.

Conclusion

TTV DNA load could be useful identifying KT recipients at high risk of immunosuppression-related complications. Although PD patients presented a non-significant higher TTV DNA load, we did not find differences according to the modality of prior RRT or the time on dialysis.
#5895 HOSPITAL-ACQUIRED INFECTIONS IN HOSPITALIZED PATIENTS WITH ACUTE KIDNEY INJURY: A RETROSPECTIVE COHORT STUDY
Authors: Reggiani Francesco , Calatroni Marta , Angelini Claudio , Badalamenti Salvatore
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is recognized as a systemic disease that leads to several complications, including infections. However, only few studies have investigated the relationship between AKI and subsequent development of hospital-acquired infections (HAI). The aim of this study was to evaluate this relationship.

Method

Retrospective cohort study, analyzing data of 413 hospitalized adult patients. Immunosuppressed patients have been excluded. Descriptive analysis was done with t-test, Mann-Whitney and Fisher test. Mediation analysis was done modelling time-to-HAI through a Cox regression, including AKI as the exposure of interest, the use of medical devices as mediator, and age, diabetes and multimorbidity as confounders.

Results

Clinical characteristics of patients are shown in Table 1. AKI patients resulted more fragile and with a higher frequency of HAI (10.8% vs 5.9%, p = 0.07). Univariate logistic regression showed that the presence of urinary catheter (OR 5.053, 95% CI 2.040-12.520) and a longer hospital stay (OR 1.115, 95% CI 1.075-1.157) were risk factors for the development of HAI. Compared to other AKI etiologies, intrinsic AKI had a significantly higher frequency of HAI (38.5%, p<0.01) (Fig. 1). HAI frequency also increased progressively with increasing AKI stage (15.2% in stage I-II and 6.4% patients without AKI or stage I, p = 0.01) (Fig. 1). From the Cox regression model, none of the variables showed an independent association with HAI (Table 2). The total effect of AKI on HAI development was estimated in a HR of 0.970 (95% CI 0.438-3.016). Part of this effect was found to be mediated by the medical devices (HR 1.155, 95% CI 0.982-1.393), while the direct effect of AKI was a HR of 0.840 (95% CI 0.352-2.411).

Conclusion

AKI patients are more fragile and have a higher frequency of HAIs, especially in intrinsic and stage II-III AKI. However, we didn't observe an independent effect of AKI on the development of HAIs. Further research is needed.
#5906 THE PROGNOSTIC VALUE OF DIFFERENT HISTOPATHOLOGIC MODELS OF ANCA-ASSOCIATED VASCULITIDES: A PROSPECTIVE STUDY
Authors: Christodoulou Michalis , Moysidou Eleni , Lioulios Georgios , Stai Stamatia , Bantis Konstantinos , Nikolaidou Christina , Fylaktou Asimina , Papagianni Aikaterini , Stangou Maria
Published: June 2023

Background and Aims

Renal histology in ANCA-associated vasculitides-glomerulonephritis (AAV/GN) is characterized by active (inflammation, necrosis, crescents) and chronic lesions (sclerosis, fibrosis), and lately classified by Berden Classification (BC), ANCA renal risk (RRS) and Mayo Chronicity score (MCCS). We aimed to prospectively compare predictive ability of the three classification models in AVV.

Method

27 AVV/GN patients, 17 females, were estimated at time of diagnosis (T0), based on renal biopsy, commenced on the same treatment protocol, cyclophosphamide+steroids, and followed for 6 months. BC, RRS and MCCS Classification models were initially applied on renal biopsies and results were correlated to renal function at T0, and accordingly, 3 (T3) and 6 (T6) months.

Results

Patients’ median age at presentation was 61.9(18-82) years, ratio of MPO/PR3/ANCA- was 17/7/3, eGFR was 19(19)mg/ml/1.73m2, and 11/27(40.7%) patients were hemodialysis-dependent (HD) at T0. Based to BC model, 5(18,5%), 9(33,3%), 8(29,7%), 5(18,5%) were classified as Focal, Crescentic, Mixed, Sclerotic, respectively, while according to RRS 7(26%), 10(37%), 10(37%) as Low, Medium, High, respectively and to MCCS 3(11%), 13(48%), 6(22%), 5(19%) as Minimal, Mild, Moderate, Severe, respectively. During follow up eGFR significantly increased from T0 towards T3 and T6, 19(19), 34(21), 38.5(26)mg/ml/1.73m2, respectively, p<0.0001. In RRS model, significant improvement was noticed in patients classified as low, eGFR from 37.5(55) vs. 57.5(39) vs. 57(22)mg/ml/1.73m2, p = 0.019) or medium risk group, 31(24) vs. 39(18) vs. 40(10)mg/ml/1.73m2, p = 0.047), at T0, T3, T6, respectively. In BC, a significant increase of eGFR was evident in sclerotic class, 18(9) vs. 32(17) vs. 38(21)mg/ml/1.73m2, respectively p = 0.05. RRS showed important results regarding HD dependence. At T0, from the 11 HD patients 1/3/7 were classified as low/medium/high risk, p = 0.04, the ratio changed to 0/1/5, respectively, p = 0.02 at T3 and 0/1/4, p = 0.04 at T6. No patient with low risk RRS remained on HD, while, 7/10 patients with high RRS, were still on HD at T6. BC and MCCS could not predict end stage renal function either at 3 or 6 months of follow up.

Conclusion

In the short term follow up, ANCA renal risk could better predict renal function outcome compared to Berden Classification and Mayo Chronicity Score, with high RRS frequently leading to HD. Instead, the sclerotic class in BC was not predictive of poor outcome.
#5922 CINACALCET IMPACT ON ESTIMATED GLOMERULAR FILTRATION RATE AMONG KIDNEY TRANSPLANT RECIPIENTS WITH SECONDARY HYPERPARATHYROIDISM: A CASE-CONTROL STUDY
Authors: Yu Jerome Han Yee , Goronflot Thomas , Kerleau Clarisse , Giral Magali , Frey Samuel , Figueres Lucile
Published: June 2023

Background and Aims

Secondary hyperparathyroidism (sHPT) is common in kidney transplant recipients. It remains unknown if Calcimimetic agents (as cinacalcet), oftenly used in this context, have an impact on mortality or morbidity. The objective of this work was to compare the renal and cardiovascular outcome of kidney transplanted patients with sHPT.

Method

Data from January 2008 to December 2019 were retrospectively extracted from the DIVAT database. 575 kidney transplant recipients with sHPT (PTH > 100 pg/ml) followed in Nantes University Hospital, were separated into two groups: Treated (cinacalcet) and sHPT Controls (no cinacalcet). A propensity score was used to match the patients (age, sex, first transplant, transplantation before/after 2015, time on dialysis, history of cardiovascular disease, initial condition, anti-HLA class I and II immunization, corticosteroids, serum parathormone level). Biological data (including estimated glomerular filtration rate by CKD-Epi formula), cardiovascular events (coronaropathy, obliterating arteriopathy of the lower limbs, stroke), return in dialysis or related death were extracted from one year of transplantation to the last follow-up. Time-varying exposure Cox PH model was used.

Results

292 patients were included after matching (146 Treated, 146 sHPT Controls). After one year of transplantation, serum parathormone was significantly higher in Treated patients compared to sHPT Controls (152 pg/mL vs 111 pg/mL respectively, p < 0.001), suggesting a more severe sHPT in Treated patients. 7% of Treated and 10% of sHPT Controls suffered from a cardiovascular event or related death during the follow up (HR = 1.28 [0.52; 3.14], p = 0.6). Return to dialysis or related death were more frequent in the Treated patients (HR: 1.90 [0.97 - 3.75, p = 0.06]. At 48 months post-transplantation, estimated glomerular filtration rate was significantly decreased in Treated patients compared to sHPT controls (52.3 mL/min/1.73 m2 vs 44.1, p = 0.006).

Conclusion

Our study highlights that kidney transplant recipients with sHPT treated with cinacalcet have a worse kidney graft outcome than non-treated sHPT patients. It remains to be assessed if this reflects an underlying more severe sHPT condition or a direct effect of cinacalcet on the graft function. This study needs to be completed by the assessment of bone mineralization. Parathyroidectomy for sHPT should be discussed in kidney transplant recipients with impaired glomerular filtration rate and/or cardiovascular events.
#5950 MAJOR HLA ALLELE AND HAPLOTYPE FREQUENCIES IN THE MALTESE KIDNEY TRANSPLANT REGISTRY
Authors: Micallef Sarah , Buttigieg Jesmar
Published: June 2023

Background and Aims

The human leukocyte antigens (HLA) are the most diverse and polymorphic genes in the human genome and matching them is of vital importance for maximising the survival of kidney transplants. The Maltese archipelago consists of three inhabited islands in the Mediterranean Sea, with a total population of just over half a million people. HLA polymorphisms in Malta have never been described. The aim of this study was to investigate allelic frequencies and determine the most common haplotypes for major HLA Class I and Class II groups in the Maltese kidney transplant registry. This will hopefully facilitate organ sharing with other European countries and improve the HLA matching for kidney transplant recipients.

Method

All patients of Maltese ethnicity on the national kidney transplant list between 2018 and 2022 were analysed retrospectively. HLA typing is routinely performed at medium to high resolution using polymerase chain reaction sequence specific oligonucleotide probes and Luminex technology at the HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ and HLA-DP loci. Allele and haplotype frequencies were calculated by direct counting and simple percentages.

Results

A total of 191 patient samples were analysed yielding the following allele types: 16 HLA-A, 31 HLA-B, 17 HLA-C, 15 HLA-DRB1, 6 HLA-DP, 7 HLA-DQ, 5 HLA-DRB3, one HLA-DRB4 and one HLA DRB5. The most frequent allele groups for the HLA-A locus were HLA-A*02 (30.9%), HLA-A*24 (12.0%) and HLA-A*01 (11.8%) whilst for the HLA-B locus these were HLA-B*35 (16.2%), HLA-B*18 (11.5%) and HLA-B*51 (7.1%). The most prevalent allele groups for the HLA-DRB1 locus were HLA-DRB1*11 (24.1%), HLA-DRB1*04 (13.1%) and HLA-DRB1*07 (11.3%). The commonest allele group for each of HLA-C, HLA-DP and HLA-DR loci were HLA-C*07 (23.6%), HLA-DP4 (5.8%), HLA-DQ7 (31.2%) respectively. The five most frequently encountered haplotypes were HLA-A*02-B*13-DRB1*07 (2.1%), HLA-A*02-B*35-DRB1*04 (1.6%), HLA-A*02-B*18-DRB1*10 (1.3%), HLA-A*02-B*35-DRB1*11 (1.3%), HLA-A*24-B*35-DRB1*11 (1.3%).

Conclusion

This study provides the first data on the Major HLA allele and haplotype frequencies in Maltese kidney transplant candidates. Such data may be crucial in setting up international kidney exchange programmes.
#5958 VALUE OF EXOME SEQUENCING “FIRST” FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Authors: Dancer Marine , Bensouna Ilias , Robert Thomas , Mesnard Laurent
Published: June 2023

Background and Aims

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common Mendelian kidney diseases, that can progress to end-stage kidney failure. Pathological variants in PKD1 or PKD2 genes are found in about 78% and 15% respectively. Additional variants in genes such as GANAB, DNAJB11, and ALG8/5 have been identified in ADPKD. The sequencing of PKD1 by short read sequencing technics with exome capture such as Exome sequencing (ES) has been describe as technically challenging given 6 pseudogenes with more than 98% homology in PKD1 exonic regions 1 to 33. Moreover, the presence of repeated motifs and GC-rich in PKD1/2 add difficulties. We study the relevance of exome sequencing (ES) “first-hand” during autosomal dominant polycystic kidney disease.

Method

ES was performed in 684 unrelated adult patients with kidney disease from the department of Nephrology of Sorbonne University, Paris, France. Genomic DNA was extracted and exonic coding regions (37 megabases) were enriched with the Twist Human Core Exome kit, and paired-end sequenced on NextSeq500 (Illumina) machine. Sequences were analyzed with in-house and the SeqOne v1.3,2019 pipelines according to GATK4 best practices. If necessary, co-segregation of pathological variants was studied by Sanger sequencing in relatives.

Results

Of the 684 patients, 143 had renal cysts. Pathogenic or probably pathogenic variations in the PKD1, PKD2, and DNAJB11 genes have been identified in 26 patients, all with cystic disease; with respectively 17 variants in PKD1, 6 variants in PKD2 and 3 variants in DNAJB11. In this cohort, 18.2% of the 17 pathogenic variants are reported in PKD1, and 14 (82%) are included in exons 1 to 33. All variants were eventually confirmed by Sanger sequencing without false positive. Moreover, in 5 of the 26 patients diagnosed (19%), meaningful additional genetic data have been found, falling either in CFTR, DHCR7, HFE, F8, or ACTA2 gene.

Conclusion

ES highlights PKD1 and PKD2 pathogenic variants detection without false positive. This strategy allowed us to provide appropriate genetic counseling (CFTR, DHCR7), as management of yet unexpected additional genetic diseases that can affect ADPKD (F8, HFE, and ACTA2) phenotype. Given these preliminary data, ES appears effective for PKD1/PKD2 variant detection, providing additional information for ADPKD management in 20% of cases.
#5959 CONSIDERABLE HEPARIN SAVINGS DURING 48 WEEKS OF HEMODIALYSIS WITH CITRATE-BUFFERED DIALYSIS BATH
Authors: Woitas Rainer Peter , Haarhaus Mathias , Capin Dario , Macário Fernando
Published: June 2023

Background and Aims

There are research data suggesting a citrate-buffered dialysis bath being superior to conventional acetate-buffered dialysis. Since Heparin may lead to bleeding complications and increased costs we focused on potential Heparin savings in a cohort of 100 dialysis patients who systematically were examined in a 48 weeks comprising timeframe using a citrate-buffered dialysis bath.

Method

Stable dialysis patients (n = 100, 30 females, mean age 70.7 yrs.) who were treated by high flux dialysis were switched from conventional acetate-buffered dialysis (3mmol/l acetate) to a citrate-buffered dialysis bath (0.8 mmol/l citrate, 0.3 mmol/l acetate; MTN, Neubrandenburg, Germany). After a 4 weeks run-in phase on the new dialysis bath the heparin-dosing was systematically reduced. Heparin was given as a single shot prior to the start of dialysis, the dialysate flow was set on 500 mL/min constantly. Heparin-dosing in the time course was assessed on the basis of the run-in phase.

Results

Average treatment time was 256 minutes per session and the average blood flow at baseline 361 mL/min and 254 minutes and 369 ml/min at the end of follow-up. The average Heparin-dosing at start of the observation period was 5450 IU/session, which could be reduced to 3909 IU/ session (71% of the starting dose, p<0.01) after the first month of treatment and was further decreased to 3147 IU/session after 24 weeks treatment (58% of the initial dose, p<0.01). In the next 24 weeks of observation no further reductions of Heparin-dosing were achieved (average Heparin dose after 48 weeks 3115 IU/session). In the week before reduction of Heparin we observed 2.2% of clotting episodes and 1.6% at week 48, respectively.

Conclusion

Despite a reduction of the initial heparin dose by 42% the number of clotting episodes did not increase during the 48 weeks observation period. Our data indicate that long-term treatment with a citrate-buffered dialysis bath is feasible, irrespective of considerably reduced heparin-dosing which may be beneficial for the patient but also interesting from a commercial view point. Further long-term studies are ongoing to assess clinical effects like calcification, morbidity, and mortality.
#5960 MORBIDITY AND MORTALITY OF SARS-COV-2 POSITIVE HOSPITALISED HEMODIALYSIS PATIENTS IN CASE OF CENTRALIZED ORGANIZATIONAL STRUCTURE IN HEALTHCARE
Authors: Hazoyan Armenuhi
Published: June 2023

Background and Aims

During the COVID epidemic, hemodialysis patients were a very serious vulnerable group due to the underlying kidney disease, many other comorbid health problems commonly present, the need for regular hospital visits even during the lockdown, and the high risk of staying with other patients in hemodialysis rooms, getting infected and subsequently high mortality. There are about 1000 patients with chronic hemodialysis in Armenia. All SARS-CoV-2 positive hemodialysis patients, regardless of the severity of the infection, were hospitalized in the largest multidisciplinary hospital center in the country, as it was the only dedicated hemodialysis service for SARS-CoV-2 positive cases in the country during the pandemic.

Method

Our prospective, observational study included about 1040 patients (Included re-infection) infected with the new coronavirus and hospitalized in one center between 01/04/2020 and 01/05/2022.

Results

The number of SARS-CoV-2 positive deaths was 183, which was 17.5% of those hospitalized. The number of re-infections was around 15%. A low level of vaccination of hemodialysis patients was recorded in the country, around 13,4%. During the first 6 months post-hospitalization, another 39 deaths were registered, which is 3.75% of those hospitalized. About 25,000 SARS-CoV-2 positive non-hemodialysis patients were hospitalized in the above period, and mortality in this population did not exceed 9% during peak epidemic and periods of maximum mortality.

Conclusion

Even with a centralized health care system, early hospitalization, close monitoring, and urgent access to multidisciplinary care, SARS-CoV-2 positive hemodialysis patients have a high mortality rate, the risk of which persists in the first 6 months of the post-hospital period and perhaps even longer, and this risk correlates also with low vaccination rates in this patients’ population.
#5993 KINETICS IN RENAL FUNCTIONAL RESERVE USING DTPA-CLEARANCE MEASUREMENTS
Authors: Valkova Kristyna , Figurek Andreja , Matter Laurenz , Lopez Kai Castrezana , Zitta Sabine , von Moos Seraina , Huellner Martin , Luyckx Valerie A , Schachtner Thomas , Mueller Thomas
Published: June 2023

Background and Aims

Kidneys have an intrinsic reserve capacity to respond to a higher workload by increasing filtration in their nephrons, called renal functional reserve (RFR). Despite the high clinical relevance of RFR, the necessary dynamic measurements are rarely done in the clinical routine, due to time- and workload as well as lack of standardized protocols.

Method

We developed a novel RFR protocol using 99mTc-DTPA (DTPA-Cl) before and after an oral protein load performed in an outpatient clinical setting within one day. Following a weak of low protein diet and using standardized hydration baseline and post-stimulation GFR were measured. 50 MBq activity were given i.v. at 0 and 240 mins, the plasma clearance was calculated based on the activity course at 13 time-points over 480 mins. RFR was expressed as the difference of post-protein stimulation peak mGFR to baseline mGFR in fasting state.

Results

In the pilot study we measured RFR in 7 healthy participants. The results showed a high heterogeneity. Therefore, we modified the study protocol for the next 16 patients by (a) extending the time of measurements to 330 min post-stimulation and (b) increasing the frequency of activity measurements to every 30 mins. In addition, we used a protein load of 1.5 g/kg bwt of beef protein. These standardized measurements showed inter-individual time differences in reaching the peak GFR values post-protein load, the peaks detectable between 150 to 270 mins after the protein meal. The mean RFR (±SD) was 14 (±13) ml/min/1.73 m2 corresponding to 16 (±15)% [Fig. 1]. All participants demonstrated a significant fall in DTPA-Cl 60 mins post-stimulation.

Conclusion

RFR can be measured with a same day pre- and post-stimulation DTPA-clearance protocol. Using a high oral load of beef protein and a long, post-stimulation period of measurements demonstrates inter-individual differences in reaching the hyperfiltration peak and a significant, previously not appreciated, post-prandial drop in GFR.
#6005 COMPARISON OF SEMAGLUTIDE ORAL VS SUBCUTANEOUS IN CHRONIC KIDNEY DISEASE (CKD)
Authors: Vidas Maria Marques , López Paula , Briales Paula Sanchez , Illazquez María Victoria López , Portoles Jose M
Published: June 2023

Background and Aims

The use of GLP-1 receptor agonist (ra) has become one of the cornerstones for CKD type 2 diabetic patients (T2DM) treatment. Oral formulation of semaglutide appeared as new therapeutical tool to increase the use of drugs with proved renal benefit. However, method of administration of the oral formulation and oral absorption limitations in CKD patients could adversely affect drug efficacy. The aim of this study was to compare the efficacy of semaglutide sbc vs oral in CKD patients

Method

Prospective, real-world study performed in T2DM-CKD patients with indication of initiation of GLP-1ra therapy in which semaglutide sbc or oral was initiated. Patients were assigned to sbc or oral formulation according to drug accessibility and patient preferences. Patients previously treated with any other GLP-1ra were excluded.

Results

70 patients were included, 50 with sbc and 20 with oral semaglutide with mean follow up time of 407 [180-753] and 154 [75.5-205] days respectively (mean, IQR) Basal characteristic of the patients are shown in the table. More male patients were included but age eGFR and UACR showed no significant differences between groups. 80% and 50% of the patients were on maximum semaglutide dose (1.0 mg sbc and 14 mg or respectively) and 12% and 45% were on the low dose (0.25 mg sbc and 3mg or respectively). We observed similar percentage of HbA1C reduction sbc: -6.2% [-10.8 a 0] and oral -6.2% [-11.5 a 0] (p 0.9). Differences on BMI and weight loss were slightly higher on sbc group though non-significant. We observed no significant effects on eGFR or UACr, nor on blood pressure during the observation period. and main side effect was gastrointestinal intolerance, similar in both groups (7 (14%) in subc and 3 (20%) in oral group, pv alue 0.9.

Conclusion

Oral formulation of semaglutide was equally effective in terms of glucose control and body weight in patients with T2DM and CKD even with more patients on the low-medium doses. Gi side effects were similar with both formulations though the lower number of patients on the higher oral dose does not allow further conclusions.