bluuebunny/crossref_metadata_2025_split huggingface dataset:
#6812 ON THE TOP PHARMACOGENETICS STUDY EXTRACTED FROM EXOME SEQUENCING DONE FOR CHRONIC KIDNEY DISEASES OF UNKNOW ORIGIN
Authors: Ponce Fanny , Vanhoye Xavier , Mesnard Laurent , Hatz Karl-Dietrich , Raymond Laure 
Published: June 2023

Abstract

Background and Aims
A recent study from a large cohort published by the Ubiquitous Pharmacogenomic Consortium demonstrates the interest of pre-emptive pharmacogenetic panel testing, with a 30% reduction rate of clinically detectable side-effects. Our laboratory routinely performs diagnostic exome sequencing (ES) for adult patient with kidney disease and more than 2000 patients have been analyzed to date. Patient with chronic kidney diseases (CKD) could benefit from pharmacogenetics information, since they are often polymedicated and efficacy or safety of their medications are known to be influenced by the genetic background. We studied if meaningful pharmacogenetics information could be delivered from exome sequencing data provided for CKD, either retrospectively or prospectively.

Method
We selected 214 variants of pharmacogenetics relevance, based on evidence and frequency criteria. We evaluated their depth of coverage on 300 patients randomly selected in our CKD cohort.

Results
Eleven of those 214 variants were not covered by ES. Three of 11 variants were in UGT1A1 and were excluded from analysis since this information is only relevant for Irinotecan treatment. The remaining 8 variants fall in CYP2C19, CYP3A5, CYP3A4, CYP2D6, HLA B (B15:02), HLA A (A31:01), IFNL3, VKORC1 genes: we completed exome data by targeted sanger sequencing for these variants. One challenging region is CYP2D6 given high sequence homology with CYP2D7 and CYP2D8: to assess if we could reliably call variants in this region, we used 7 additional Coriell samples, as 8 others were also assessed with an orthogonal technique. We were able to properly detect variants in these complex regions in all cases, including hybrid genes.

Conclusion
Our preliminary data show that exome sequencing, initially ordered for CKD, could also be used to deliver pharmacogenetic meaningful information, by adding a few targeted genotyping assays. We currently evaluate the clinical utility and impact of pharmacogenetics in our CKD cohort prospectively.
#6839 MULTIDISCIPLINARY APPROACH TO STUDY THE BIOLOGICAL FUNCTION OF BBS10 IN THE PATHOGENESIS OF BARDET-BIEDL SYNDROME (BBS)
Authors: Gupta Neha , Capasso Giovambattista , Zacchia Miriam 
Published: June 2023

Abstract

Background and Aims
Bardet-Biedl Syndrome (BBS) is a rare inherited ciliopathy resulting in multiple organ dysfunctions, including chronic kidney disease (CKD). Although BBS is highly heterogenous at genetic level, BBS10 is one of the significant causative genes, accounting for almost 30% of cases of BBS cases in western countries. Despite the recent progress in the ciliopathy field, there is still little information on the mechanisms underlying renal disease. To elucidate the pathomechanisms, we have broadened the study's criteria into a combination of the in silico-in vitro approach.

Method
This study integrates the molecular dynamics (MD) simulations with the results of nine distinct (SIFT, SNAP2, PROVEAN, Align-GVGD, ConSurf, I Mutant, MuPro, PremPS, and Dynamut) in silico pathogenicity prediction tools. For in vitro studies we have used the inner medulla renal epithelial cells lacking Bbs10 (IMCD3-Bbs10-/-cells). MTT assay, Colony formation assay, Real time PCR, Western Blot and other experiments were performed using the cultured wild-type and IMCD3-Bbs-/-cells. BBS10 interactors have been studied using Mass Spec, after pulling down BBS10-FLAG in renal epithelial cells expressing the protein, after transfection.

Results
Our in-silico results showed that six BBS10 missense variants (Ser191Leu, Cys19Gly, Ile342Thr, Cys371Ser, Ala417Glu, and Tyr613Cys) could be potentially deleterious. IMCD3-BBS10-/-cells showed hyperproliferation, increased aerobic glycolysis and sings of mitochondrial dysfunction. Additionally, among BBS10 interactors in vitro, we found several proteins involved in cellular metabolism and mitochondrial-related function. Interestingly, Bbs10 depletion affected PINK1/PARKIN signalling, leading to the disruption of mitochondria quality control.

Conclusion
This multi-disciplinary approach could open new avenues to study the extra-ciliary biological function of BBS10 in renal epithelial cells and providing novel clues into our understanding of disease pathomechanisms.
#6844 MONITOR SWITCHING-INDUCED VARIATIONS IN CONDUCTIVITY AND PLASMA SODIUM DURING HEMODIALYSIS SESSIONS
Authors: Monzo Jose Jesus Broseta , Rodríguez Diana , Cuadrado Elena , Casals Joaquim , Rodas Lida , Baldellou Néstor Fontsere , Guillen Marta Arias , Vera Manel , Gomez Miquel , Maduell Francisco 
Published: June 2023

Abstract

Background and Aims
Until the advent of the new monitors with sodium modules, the differences between prescribed and actual sodium have been little studied. And most dialysis centers have a fixed sodium prescription. However, the sodium gradient during sessions is one of the key factors in its balance in hemodialysis patients. Predialysis plasma sodium has an important interindividual but not intraindividual variability, which supports the hypothesis of reference sodium (setpoint). This work aimed to compare the impact of switching from the 5008 Cordiax monitor to the new 6008 Cordiax monitor on the actually measured conductivity and initial and final plasma sodium.

Method
A total of 106 hemodialysis patients were included. Each patient received two dialysis sessions in which only the monitor was varied. The variables collected were: concentrate, prescribed sodium and bicarbonate, real conductivity, initial and final plasma sodium measured by ionic dialysance, and the change in plasma sodium concentration during treatment (ΔPNa), which has been related to mortality when it exceeds 4 mmol/L, was calculated. The clinical research ethics committee of Hospital Clínic de Barcelona approved the present study.

Results
The change of dialysis monitor showed small, although significant, differences in initial (138.14 mmol/L with 5008 vs. 138.81 mmol/L with 6008) and final plasma sodium (139.58 mmol/L vs. 140.97 mmol/L), as well as in the actual conductivity obtained (13.97 vs. 14.1 mS/cm). The ΔPNa also increased significantly, with the percentage of patients with a ΔPNa greater than 4 mmol/L going from 6 to 22% with the monitor change. All these differences were statistically significant regardless of the concentrate used. All sessions were performed without notable clinical incidents, hypotension, cramps or thirst episodes.

Conclusion
The ultimate goal of hemodialysis should be to achieve isonatremia that allows complete elimination of interdialytic sodium gain and avoid intradialytic sodium loading. The change from 5008 to 6008 monitor is associated with an increase in conductivity, higher plasma sodium, and an increase in ΔPNa. Knowing and confirming this change will allow us to individualize the sodium prescription to find adequate isonatremic dialysis and, thus, avoid possible adverse effects.
#6849 CLINICOPATHOLOGIC CHARACTERISTICS IN RENAL THROMBOTIC MICROANGIOPATHY
Authors: van Doorn Daan , Timmermans Sjoerd , Hamid Myrurgia Abdul , Van Paassen Pieter 
Published: June 2023

Abstract

Background and Aims
Thrombotic microangiopathy (TMA) is a life-threatening condition that can be caused on the background of various mechanisms, converging to a severe endotheliopathy that often affects the kidneys. Morphologic features of TMA on kidney biopsy have not been systematically studied. We studied the diagnostic and prognostic role of a kidney biopsy in patients with TMA, either linked to a coexisting condition (i.e., secondary TMA) or not (i.e., complement-mediated [C-]TMA).

Method
Patients with TMA on kidney biopsy and an enzymatic activity of ADAMTS13 &gt;10% were recruited from the Limburg Renal Registry. C-TMA was defined as massive ex vivo C5b9 formation on the endothelium and/or rare variants in complement genes [1]; secondary TMA was defined as the presence of a coexisting condition and normal complement regulation. Kidney tissue sections were studied for activity and chronicity; also, C3d staining was performed.

Results
C-TMA and secondary TMA was diagnosed in 35 and 39 patients, respectively. The diagnosis TMA was based on a kidney biopsy in 52 (70%) out of 74 patients as systemic hemolysis, that is, microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, was lacking. Morphologic activity, such as, glomerular thrombosis and mesangiolysis, was not associated with MAHA (p = 0.116) and/or thrombocytopenia (p = 0.380). Morphologic activity, however, was associated with C-TMA, as was lower age and higher serum creatinine. C3d staining did not differentiate C-TMA from secondary TMA. A Mayo Clinic Chronicity Score (MCCS) of ≥4 was associated with an increased partial- (p = 0.023) and complete renal remission rate (p = 0.030), and decreased end-stage kidney disease (p = 0.050).

Conclusions
Only a small proportion of patients with TMA on kidney biopsy initially present with systemic hemolysis, suggesting an essential role of histologic examination to prevent underdiagnosing. Glomerular thrombosis and mesangiolysis were associated with C-TMA, however there is no role for staining of C3d in differentiating C-TMA from secondary TMA. An increased MCCS indicates worse renal outcome in patients with TMA.
#6864 IMMUNE RESPONSES OF PATIENTS ON MAINTENANCE HEMODIALYSIS AFTER INFECTION BY SARS-COV-2: A PROSPECTIVE OBSERVATIONAL COHORT STUDY
Authors: Bacharaki Dimitra , Karagiannis Minas , Papachristou Evangelos , Divanis Dimitrios , Bratsiakou Adamantia , Giannakopoulos Panagiotis , Damoraki Georgia , Liakopoulos Vassilios , Goumenos Dimitrios , Giamarellos Evangelos 
Published: June 2023

Abstract

Background and Aims
We aimed to study the immune response of maintenance hemodialysis (HD) patients to Corona Virus Disease-19 (COVID-19) since it is not fully elucidated.

Method
In this prospective study, hospitalized HD patients with moderate-to-severe COVID-19 and matched non diseased HD comparators were analyzed for their absolute counts of lymphoid cells (flow cytometry) and circulating inflammatory mediators (ELISA). Blood samples were collected at the start and at of the end of the first in hospital HD session; dialysate samples at the end of the first half hour session.

Results
59 HD patients with acute COVID-19 HD and 20 comparators were enrolled. Circulating median (range) of interferon-gamma (IFNγ) at the start of HD was 125 (125-1777) pg/ml in comparators and 810 (125-4000) pg/ml in SARS-CoV-2 (p&lt;0.00001) and 125 (125-1278) pg/ml and 738 (125-4000) pg/ml at the end of HD (p&lt;0.0001). Respective concentrations of platelet derived growth factor-A were 8286 (4600-28150) and 27938 (8285-99256) pg/ml (p&lt;0.0001) and 7779 (5055-28128) and 27410 (6836-87887) pg/ml respectively. Similar increases were found for tumor necrosis factor-alpha (TNFα) only at the start of the HD whereas no differences were found for interleukin (IL)-6, IL-10 and IL-38. Respective mean (SD) CD4-counts were 881.3 (407.6) and 461.6 (365.4) per microliter (p&lt;0.0001) and 839.4 (509.7) and 483.6 (329.9) per microliter (p&lt;0.0001). Respective mean (SD) CD19-counts were 199.0 (154.5) and 76.4 (78.6) per microliter (p&lt;0.0001) and 144.9 (110.3) and 98.3 (70.8) per microliter (p&lt;0.0001). The respective mean (SD) MFI expression of HLA-DR on CD14-monocytes was 97.2 (28.2) and 67.4 (44.7) (p: 0.013) and 87.3 (26.7) and 63.3 (36.3) (p: 0.009). MFI of HLA-DR on CD14-monocytes before the first HD session less than 44 was associated with 100% sensitivity for unfavorable outcome (defined as respiratory failure or death) after 28 days. An absolute CD19-count more than 40 per microliter before the first HD session was associated with 8.70 odds ratio for cure favorable outcome after 28 days.

Conclusion
HD patients develop an inflammatory reaction to Severe Acute Respiratory Syndrome Coronavirus 2 characterized by increase of the inflammatory mediators IFN-γ, PDGF-A and TNF-a and decrease of circulating T helper lymphocytes. Decreased expression of HLA-DR on CD14-monocytes is a hallmark of unfavorable prognosis.
#6873 HEPATOCYTE GROWTH FACTOR CORRELATES WITH SERUM GLUCOSE LEVELS IN HYPERTENSIVE SUBJECTS
Authors: Prlic Margareta Fistrek , Brinar Ivana Vukovic , Ivandic Ema , Knezevic Tamara , Ivkovic Vanja , Jelakovic Bojan 
Published: June 2023

Abstract

Background and Aims
Hepatocyte growth factor (HGF) is a pleiotropic factor derived from mesenchymal cells and is considered a humoral mediator in the interaction of epithelium and mesenchyme. The concentration of HGF in the serum is related to blood pressure (BP), but also to serum glucose concentration. Patients with type 1 and 2 diabetes have significantly higher HGF values, especially those with developed atherosclerotic disease and diabetic retinopathy. Moreover, the concentration of serum HGF in patients with diabetes is higher than that in healthy subjects, regardless of their blood pressure (BP) levels. Our aim was to determine the correlation between serum HGF levels and serum glucose levels in subjects with optimal blood pressure and untreated hypertensives.

Method
The subjects were divided into two groups based on the BP values. There were 295 subjects with optimal blood pressure (OBP, BP&lt;120/80 mmHg) and 268 subjects with untreated arterial hypertension (AH, BP&gt;140/90 mmHg). Blood pressure was measured according to ESH/ESC guidelines. Fasting blood samples were drawn, serum glucose and HGF levels were measured using commercial tests.

Results
The average blood pressure was 110/72 mmHg in the OBP group vs 151/92 mmHg in the AH group (p&lt;0,001). Subjects with AH had significantly higher glucose levels than subjects with OBP (4,8±0,5 mmol/l vs. 5,7±1,6 mmol/l, respectively, p&lt;0,001). Serum HGF concentration showed a significant positive correlation to serum glucose levels in the AH group (correlation coefficient = 0,195, p&lt;0,05), but not in the OBP group (correlation coefficient = 0,045, p = 0,06). Serum HGF concentration did not show a significant correlation to blood pressure levels in both groups (all p&gt;0,05).

Conclusion
Serum HGF concentration is associated with glucose levels in subjects with untreated arterial hypertension.
#6875 COMPLICATIONS AND TREATMENT OF HYPERCALCIURIA IN FAMILIAL HYPERKALAEMIC HYPERTENSION (FHHT)
Authors: D’ambrosio Viola , Mcknight Olivia , Wan Elizabeth , Speller Robert , Moss Robert , Siew Keith , Walsh Stephen 
Published: June 2023

Abstract

Background and Aims
Hypertension is frequently associated with hypercalciuria1, nephrolithiasis2 and low bone mineral density. Familial Hyperkalaemic Hypertension (FHHt) causes hypercalciuria3, although complications of this are not reported.

Method
We examined a cohort of 9 patients with genetically confirmed FHHt. Biochemical, radiological, and clinical data was obtained in patients before and after thiazide treatment. All patients gave informed consent. The study had ethics committee approval. Data were compared using paired t tests.

Results
5 of the 9 patients were female (median age 41.7 years). The genetic diagnosis was confirmed in all patients, 5 patients had variants in KLHL3, 3 patients had variants of WNK4, and one had a variant of WNK1 (Table 1). Pre-treatment potassium was high (median 5.6 IQR 5.2-6.2 mmol/L). Pre-treatment calcium was in the normal range (2.34 IQR 2.29-2.38 mmol/L). There was significant hypercalciuria with a raised urinary calcium/creatinine ratio (0.69 IQR 0.41-1.13). However, PTH (4 IQR 3.95-4.35 pmol/L), phosphate (1.15 IQR 1.25mmol/L) and alkaline phosphatase (57 IQR 45-84 mmol/L) were all in the normal range. Thiazide treatment significantly reduced hypercalciuria (calcium/creatinine ratio 0.15 IQR 0.05-0.29 p = 0.04) as well as the serum potassium (3.9 IQR 3.5-4.4 mmol/L p = 0.0167) (Table 1). Patients also developed complications of hypercalciuria. 3 patients had kidney stones demonstrated on cross-sectional imaging (Figure 1). One of these patients (male, 30 years old) had DXA criteria for osteoporosis (T score Femoral neck -1.5, lumbar spine -2.4).

Conclusion
This is the first case series to demonstrate complications of hypercalciuria (i.e. kidney stones) in patients with FHHt. We demonstrate that thiazide treatment normalises urinary calcium excretion. Thiazide treatment may have clinical utility in FHHt even if hypertension or hyperkalaemia are not problematic in order to avoid the complications of hypercalciuria.
#6888 COMPARISON OF COMBINATION OF RITUXIMAB WITH LOW DOSE THYMOGLOBULIN VERSUS LOW DOSE THYMOGLOBULIN ALONE AS INDUCTION AGENT IN RENAL TRANSPLANTATION
Authors: Parthasarathy Rajeevalochana , Selvanathan Deepak , Veena S 
Published: June 2023

Abstract

Background and Aims
Current immunosuppressive therapies and protocols have led to significant improvements in early patient and graft survival rates following kidney transplantation. However full dose rATG induction therapy (7-10 mg/kg) has been associated with increased morbidity. There is not much data available on the use of single dose low dose rATG and rituximab, a Anti CD 20 chimeric antibody in low sensitized Indian transplant recipients. To compare the efficacy of low dose single dose rATG(1–1.2mg/kg) versus combination of rituximab with low dose single dose rATG in ABO compatible low sensitization renal transplant recipients.

Method
Retrospective analysis of all renal transplant recipients between 2010 and 2022 in our center who received low dose rATG(1-1.2mg/kg) or a combination of single dose rituximab(375mg/m2) and low dose thymoglobulin were studied. Demographic data, donor characterstics, HLA matches, infections,rejections was collected Graft function at 3,6 and 12 months post transplant if available was collected. Data was analysed using SPSS 16.

Results
Of 86 patients studied, 58(67.4%) received single dose of low dose rATG(1-1.2 mg/kg/day) (Grp1) and 28 received a combination of single low dose rATG & Rituximab(375mg/m2)(Grp 2)(32.5%). There was no significant difference between the Grp 1 and Grp 2 in terms of age,gender,vintage of dialysis, PRA status prior to transplant, no of HLA Matches, donor age and Donor GFR. There were 9(15%) of Acute cellular rejections (ACR) in Group1 when compared to 8 (28%) in-group 2(p = 0.263). The number of steroid resistant ACR were 2 (3%)in Grp 1 when compared to 3 (10%)in grp 2(p = 0.365) The number of ABMR were 5(8.6%) in group 1 when compared to 1(3.5%)in grp 2(p = 0.658) 15.5% had graft loss by 1 year in group 1 compared to none in grp 2(p = 0.322)CMV and BKV infections were seen in 1 and no pts and 1 patient in each group respectively.Overall infection rate was 24% when compared to 46.4% in grp 2(p = 0.03). The mean egfr(ml/min/1.73m2) at the end of 3 months, 6 months and 1 year was &95.6,93,95 respectively in grp 1 when compared to 92, 89.4 & 84.3 in grp 2.

Conclusion
The % of steroid resistant ACR and the number of infections were higher in the 1 year in the Single low dose rATG+Rituximab induction when compared to low single dose rATG alone. However ABMR was lower in the combination grp. Further prospective RCT s are required to establish the role of Rituximab in ABO Compatible transplants.
#6894 KIDNEY TRANSPLANTATION IN PATIENTS WITH AA AMYLOIDOSIS: A FRENCH MULTI-CENTER MATCHED COHORT STUDY IN THE ERA OF BIOTHERAPIES
Authors: Schwarz Chloe , Lavialle Sophie Georgin , Marion Olivier , Jambon Frédéric , Legendre Christophe , Marx David , Levi Charlène , Toure Fatouma , Quintrec Moglie Le , Bobot Mickaël , Matignon Marie , Dujardin Amaury , Maanaoui Mehdi , Cuozzo Sébastien , Jalal-Eddine Arwa , Louis Kevin , Mohamadou Inna , Brazier François , De Nattes Tristan , Geneste Claire , Thervet Eric , Ducloux Didier , Mayet Valentin , Kormann Raphaël , Lanot Antoine , Duveau Agnès , Zaidan Mohamad , Mesnard Laurent , Ouali Nacera , Rondeau Eric , Petit-Hoang Camille , Audard Vincent , Deshayes Aurélie , Moktefi Anissa , Rabant Marion , Buob David , Francois Helene , Luque Yosu 
Published: June 2023

Abstract

Background and Aims
Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high allograft recurrence. However, recent advances in biotherapies, especially anti-IL-1 treatments, may have improved patients’ outcome in the transplantation setting.

Method
We conducted a retrospective multicenter matched cohort study in 26 French centers reporting all patients with AA amyloidosis who received a kidney transplant between 2008 and 2018, and compared them to matched control patients (ratio 1:2 controls) who received a kidney transplant for other causes

Results
Eighty-six AA amyloidosis transplants and 157 control transplants were included. Median age was 49.4 years (interquartile range 39.7-61.1), and the main cause of amyloidosis was Familial Mediterranean Fever (37 cases, 43%). Sixteen (18.6%) patients received a biotherapy after transplantation. At 5 years, patient survival was 85.5% (95% confidence interval 77.8-94.0) and 86.2% (80.5-92.2) for cases and controls, respectively (p = 0.5). Death censored graft survival was 78.2% (78.2-93.5) and 91.7% (87.0-96.6), respectively (p = 0.05). Histologically proven AA amyloidosis recurrence was found in 5 patients (5.8%). 55.8% of amyloid patients had at least one infection requiring hospitalization and 27.9% an episode of acute graft rejection. In this group, multivariable analysis showed that CRP concentration at time of transplantation was associated with patient survival (HR 1.01, p = 0.01).

Conclusion
In this recent cohort, patient survival was comparable to controls and recurrence rates were lower than previously reported. Provided the underlying inflammatory disease is well controlled, patients with AA amyloidosis may be transplanted with similar patient and graft outcomes than that of matched controls.
#6919 CARDIORESPIRATORY FITNESS AND MORTALITY RISK IN PATIENTS RECEIVING HEMODIALYSIS: A PROSPECTIVE COHORT
Authors: Andrade Francini Porcher , Ferraro Carolina , Benvenutti Heloíse , Ribeiro Heitor , Rovedder Paula 
Published: June 2023

Abstract

Background and Aims
Kidney failure reduces life expectancy by one-third compared with the general population, and cardiovascular complications and poor cardiorespiratory fitness (CRF) are the main causes. We aimed to evaluate the association between severe CRF and all-cause mortality risk in HD patients.

Method
This observational prospective cohort study followed-up patients receiving HD from August 2015 until March 2022. Cardiorespiratory fitness was evaluated through the cardiopulmonary exercise test and the peak of oxygen uptake (VO2peak) value was used to determine severe CRF (&lt;15 mL·kg−1·min−1). Cox regression and Univariate Kaplan-Meier evaluated its association with mortality risk and survival rate.

Results
Forty-eight patients were followed-up for a median of 33.0 [14.3 – 49.3] months. A total of 26 patients had severe CRF. During the follow-up period, 11 patients (22.92%) experienced all-cause mortality. From these, eight (30.8%) had severe CRF. Even so, severe CRF was not associated with crude death rates for patients stratified by CRF levels (p = 0.189), neither in unadjusted (HR 2.35; CI 95% 0.61−9.15) and adjusted (HR 1.29; CI 95% 0.30−5.56) Cox proportional hazard models. As a continuous variable, each mL·kg−1·min−1 increase in VO2peak was not associated with mortality risk (HR 0.94; CI 95% 0.79−1.11). Univariate Kaplan-Meier analysis showed that severe CRF patients did not have significantly worse survival rates than those with mild-moderate CRF (p = 0.186).

Conclusion
Our findings indicated that severe CRF was not associated with all-cause mortality in patients receiving HD. Despite severe CRF being prevalent, larger cohort studies are needed to establish strong conclusions on its association with all-cause mortality.