bluuebunny/crossref_metadata_2025 huggingface dataset:
#6650 SGLT2-INHIBITION IMPROVES VASCULAR FUNCTION IN TYPE 2 DIABETES: A DOUBLE BLIND, RANDOMIZED, PLACEBO CONTROLLED CROSSOVER TRIAL
Authors: Kristensen Didde Kidmose , Nielsen Steffen Flindt , Buus Niels Henrik , Duus Camilla , Mårup Frederik , Bech Jesper , Mose Frank
Published: June 2023

Background and Aims

Sodium glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular events and protects kidney function in type 2 diabetes (DM2) patients. These benefits may partly be related to improvement of vascular function. In this study we examined the effects of SGLT2i treatment on vasodilatory capacity in patients with DM2.

Method

Using a double-blind, randomized, placebo-controlled cross-over study design, we included 15 patients with DM2 and preserved kidney function (eGFR > 60 ml/min/1.73 m2). Each participant received four weeks of SGLT2i treatment (empagliflozin 10 mg once daily) or matching placebo. After a two-week wash-out period, each participant was crossed over to four weeks of the opposite treatment. At the end of each treatment period, vascular function was evaluated by venous occlusion plethysmography. Forearm blood flow (FBF) was measured during intra-arterial infusion of increasing concentrations of acetylcholine (ACh) and sodium nitroprusside (SNP), assessing endothelium-dependent and independent vasodilation, respectively. Repeated measures two-way ANOVA was performed to compare absolute FBF between groups.

Results

11/15 (73%) of participants were male. Mean age was 68±9 (SD) years (range 49-82), eGFR was 81±10 ml/min/1.73 m2 and duration of diabetes was 15.8±9 years. 11/15 (73%) had hypertension and 9/15 (60%) received treatment with an ACE-inhibitor or Angiotensin-II blocker. 4/15 (27%) had cardiovascular disease. The median albumin-to-creatinine ratio was 29 mg/g (range: 4-1293). Both ACh and SNP dose-dependently increased FBF (Figure 1 and 2). FBF during SNP infusion was significantly higher during empagliflozin treatment as compared to placebo (p = 0.004), whereas there was no difference between empagliflozin and placebo in FBF during ACh infusion (P = 0.399).

Conclusion

Empagliflozin improves endothelium-independent vasodilatation in patients with DM2, whereas no changes could be observed in endothelium-dependent vasodilation. These results suggest that SGLT2i positively affects vascular function and that the effect is not related to nitric oxide from the endothelium.
#6679 ANALYSIS OF MACROPHAGE POPULATIONS IN THE KIDNEY WITH RENAL TUBULAR CELL-SPECIFIC SENESCENCE INDUCTION
Authors: Campbell Ross , Docherty Marie-Helena , Baird David , Ferenbach David , Mylonas Katie
Published: June 2023

Background and Aims

Ageing is a risk factor for multiple diseases, including kidney disease. To improve quality of life, pharmaceutical treatments are given to ageing patients, often with side-effects and cross-reactions. Research is needed into the effects and mechanisms of ageing in order to identify new druggable targets to improve quality of life. Cells can become senescent with age and are seen at sites of tissue injury. Senescent cells (SCs) undergo irreversible cell-cycle arrest, but remain metabolically active, producing a range of signalling molecules called the senescence associated secretory phenotype (SASP, made up of pro-inflammatory/fibrotic elements). Senescent cells within the kidney post-acute kidney injury (AKI) may be involved in ongoing damage, leading in some cases to chronic kidney disease (CKD), possibly due to interactions with macrophages. We hypothesise that the recruitment of monocytes/macrophages by senescent cells is due to the signalling components present in their SASP.

Method

Pax8 is renal tubule marker. We use Pax8-creERT2;mdm2 fl/fl mice to study kidney-specific senescence induction in absence of age/injury. Upon administration of tamoxifen, the mdm2 alleles are floxxed out by cre recombinase, allowing p53 to stabilise and activate the p21CIP1 cell-cycle inhibitor, inducing senescence in Pax8+ kidney-specific cells. The use of an endogenous tdTomato reporter allows visualisation of cells undergoing successful recombination upon the administration of tamoxifen (TAM).

Results

As expected, cell-cycle inhibitor/SC marker, Cdkn1a was upregulated by qPCR in TAM-treated young murine whole kidneys 10-fold compared to controls (p = 0.0173) (Figure 1). Ccl2 (monocyte chemoattractant) was up-regulated 20-fold in young (p = 0.0405) TAM-treated TG mice vs controls (Figure 1). In agreement with an increase of Ccl2 transcripts, there was a significant increase of renal macrophages as quantified by flow cytometry of kidney digests (p = 0.0141) in TAM treated young TG mice. Immunofluorescence staining of transgenic mice revealed an increase of Iba1 positive macrophages, correlated with staining of tdTomato tubules, suggesting that increase in macrophage numbers was in response to senescence induction (Figure 2). Iba1-p21 co-stains show a increases in p21 positive cells in TAM-treated transgenic mice, evidently a result of construct activation and appear in proximity to the macrophages (Figure 2).

Conclusion

Apparent increases in macrophages due to the presence of senescent cells may indicate one of the mechanisms by which AKI progresses to CKD, particularly if inflammatory macrophage phenotypes are present and persist. Macrophage and monocyte populations fluctuate with age and the use of this model allows analysis of macrophage recruitment/polarisation due to senescent cell burden in the absence of age/injury and possible confounding factors, in young mice.
#6691 COMPREHENSIVE TWO-DAY IN-HOSPITAL ASSESSMENT MODE IS ASSOCIATED WITH THREE-YEAR AND FIVE-YEAR MORTALITY IN PERITONEAL DIALYSIS PATIENTS
Authors: MA Dengyan , LI Xing , Zhong Hui , Pu LI , Zhou Xueli , Duan Difei , Liao Ruoxi , Fu Ping
Published: June 2023

Background and Aims

The study aims to explore the relationship between a "comprehensive 2-day in-hospital assessment management mode” (C2IAMM) and survival and technical survival rates of patients undergoing peritoneal dialysis (PD).

Method

Eight hundred and thirty PD patients were retrospectively analyzed from January 1, 2011, to October 31, 2017. The “C2IAMM” includes admitting patients undergoing PD to the hospital for 2 days for various assessments. Based on these results, comprehensive interventions was provided. The 1-year, 3-year and 5-year survival and technical survival rates of patients following the C2IAMM were analyzed, and subgroup analysis were further performed.

Results

The 830 PD patients following C2IAMM achieved 1-year, 3-year and 5-year survival rates of 98.0%, 91.4% and 84.3%, respectively; the corresponding technical survival rates were 97.1%, 87.1% and 80.5%. The subgroup analysis showed that age ≥ 60 years, diabetes mellitus, cardiovascular and cerebrovascular diseases, and respiratory diseases (all P < 0.001) were associated with survival.

Conclusion

This article implies that the C2IAMM may be associated with higher survival and technical survival.
#6713 THE INTERACTION EFFECT OF PHASE ANGLE AND AGE ON FEMORAL NECK BONE MINERAL DENSITY IN PATIENTS WITH NON-DIALYSIS CHRONIC KIDNEY DISEASE STAGE 5
Authors: Han Byoung Geun , Kim Jae Seok , Yang Jae Won
Published: June 2023

Background and Aims

Low bone mass is common in malnourished patients with chronic kidney disease (CKD) and can lead to higher risk of fractures. Elderly and CKD patients have the same risk factors for protein energy wasting, sarcopenia, and osteoporosis. We attempted to investigate an association between phase angle (PhA) and bone mineral density (BMD) in dialysis naïve patients with stage 5 CKD, and to identify a statistical relationship between PhA and age that affects bone density.

Method

Bio-impedance spectroscopy for evaluating body composition and PhA and dual energy X-ray absorptiometry for determining the BMD were simultaneously performed in 167 consecutive patients (age: 59.65 ± 13.98 years; women: 40.1%). Two-way analysis of variance (ANOVA) was conducted to assess the potential interaction effect of PhA and two age group (young and elderly group) on femoral neck BMD (FN-BMD).

Results

Our results showed that PhA and age were independently associated with both FN-BMD and the T-score in multiple linear regressions analyses. A significant interaction effect of PhA and age on FN-BMD was found in the two-way ANOVA (P = 0.028). Average BMD values for first and second tertiles of PhA were higher in the young group than the elderly group, whereas patients in the elderly group had higher BMD in third tertiles on average.

Conclusion

A relationship between PhA and BMD in patients with advanced-stage CKD was identified in current study. The effect of PhA level on FN-BMD was different between elderly and young patients. Higher PhA levels may have protective effects on bone health in the elderly patients with stage 5 CKD and seem to be an important determinant for BMD.
#6717 IS PERITONEAL DIALYSIS RELATED PERITONITIS A MAJOR RISK FACTOR FOR CARDIOVASCULAR EVENTS?
Authors: Almeida Catarina , de Faria Maria Victoria Vaz Da Rocha Paes , Dias Joana Pereira , Lopes Daniela , Carmo Rute , Fernandes João Carlos , Almeida Maria Clara , Gomes Ana Marta
Published: June 2023

Background and Aims

Cardiovascular (CV) disease remains the leading cause of death in peritoneal dialysis (PD) patients and traditional CV risk factors are unable to fully account for this high incidence. The aim of our study was to establish the incidence of CV events such as acute myocardial infarction (AMI) in the PD population and assess possible risk factors for its occurrence.

Method

We retrospectively studied patients on PD in our unit with a minimum 3-years dialysis vintage, between January 1st 2015 and April 30th 2022. Patients with previous CV disease were excluded. Demographic and clinical data were collected, such as traditional CV risk factors, AMI, peripheral artery disease, cerebrovascular events, as well as dialysis efficiency, hydration status obtained by Body Composition Monitor (Fresenius Medical Care) and PD-related infections before AMI or end of follow-up. Univariate analysis was performed and logistic regression was applied to access predictors of AMI.

Results

Of the 43 patients recruited, 53.5% were male, with a mean age of 56.4 ± 11.8 years. About 98% of patients were hypertensive, 21% were diabetic, 19% were obese, and 54% had dyslipidemia. Five (11.6%) patients had a CV event while on PD, 4 suffered AMI and 1 patient had an ischemic stroke. Patients’ characteristics are presented in Table 1. In the follow-up, peripheral arterial disease (p = 0.037), hyperphosphatemia (p = 0.035) and the cumulative number of peritonitis (p = 0.018) were associated with the occurrence of AMI. In our population we found a higher frequency of peritonitis in the year prior to the AMI (p = 0.024). In logistic regression, the cumulative number of peritonitis was a predictor of AMI (OR 4.918, CI 95%:1.093-22.132). In the mean follow-up time of 4.7 ± 1.4 years, the overall mortality was 21,7%, with CV disease accounting for 60% of the observed deaths. AMI and peritonitis were associated with higher mortality in PD patients (p = 0.016 and p = 0.009, respectively).

Conclusion

PD-related peritonitis was a predictor of AMI in these population. The risk is higher in the year following a peritonitis episode. This may be due to a chronic inflammatory state that persists after successful treatment of peritonitis which may predispose to enhanced CV risk. Similar to previous studies, we found that cumulative episodes of peritonitis were associated with increased mortality in PD population.
#6728 ALCOHOL LOCK FOR PROPHYLAXIS AGAINST PERMCATH CRBSI: IS IT A BOON?
Authors: Varma Prem , Singla Mahak
Published: June 2023

Background and Aims

Introduction: Catheter related blood stream infection (CRBSI) is a dreaded complication in patients with tunneled dialysis catheter and often results in catheter loss. Antibiotic lock, a preventive strategy, is not followed for fear of emergence of resistant strains. We have reported usefulness of 70% alcohol lock in cases of established CRBSI. The present study was aimed to find usefulness of alcohol lock for CRBSI prophylaxis.

Method

This is a single centre observational pilot study. Dialysis patients with Permcath as vascular access were randomised into two groups. Both groups were similar in age, sex and comorbidities. Both groups received routine heparin lock after each dialysis session. Group A in addition also received 70% alcohol lock, once a fortnight. Patients with minimum follow up of 60 days were included in the study. Diagnosis of CRBSI was made by IDSA criteria.

Results

Forty five patients with permcath were divided in Group A (29 patients) and Group B (16 patients). In Group A, 21 and in Group B, 12 patients completed the study. In Group A, during a mean follow up of 2988 catheter days, 5 patients (23%,1/600 days) developed CRBSI (2 pseudomonas, two staphylococcus aureus and 1 Klebsiella) and in group B, 4 patients (33%) with mean follow up of 1611 catheter days (1 in 403 catheter days) developed CRBSI (p = 0.69) (2 klebsiella, two staphylococcus). There was no case of catheter leak, crack or block in either group. Results showed a trend towards better outcome in alcohol lock group though because of small number, statistical significance couldn't be reached.

Conclusion

This pilot study found usefulness of alcohol lock in preventing CRBSI. Alcohol lock is cheap and there was no apparent catheter damage with alcohol over 6 months period. A larger study can confirm our findings.
#6738 ALCOHOL LOCK IN CRBSI: A PANACEA
Authors: Varma Prem , Singla Mahak
Published: June 2023

Background and Aims

CRBSI is a dreaded complication of permcath, with a reported incidence of 1.1 – 5.5 episodes/1000 days. Many of these patients especially those infected with Staphylococcus aureus, Pseudomonas aeruginosa or fungal growth require catheter removal. 70% alcohol possibly breaks the biofilm in the catheter and exposes hidden bacteria to antibiotics. This study was done to find the usefulness of 70% alcohol lock in patients with established CRBSI.

Method

All dialysis patients in our centre with permcath as vascular access were the subjects of the study. All patients were given heparin lock after each dialysis session. CRBSI was diagnosed as per CDC/IDSA criteria. All patients with CRBSI in addition to antibiotics were also given 70% alcohol lock (2 ml in each port) for 3 consecutive days. Outcome of these patients in term of clinical response and need for catheter removal was studied. The catheter outcome of this group was compared with our patients (retrospective controls) who were given only antibiotics and not given alcohol lock.

Results

Over last two years 166 permcaths were placed in our institution. Eighty nine of them continued dialysis in our centre. Their total follow up period was 12028 days (30-720 days). There were 18 episodes of CRBSI in 14 of these patients (1.5 episodes per 1000 catheter days). Three of these patients (16.67%) required catheter removal, rest all improved with antibiotics and alcohol lock. Over a follow up of 150 days (30 -420 days), these patients have been doing well and there has been no episode of catheter leak or break or block. On comparing with our retrospective control of 22 patients with CRBSI, who were not given alcohol lock, 15 (68.18%) required catheter removal (P = 0.001).

Conclusion

The present study though on small numbers, shows that alcohol lock works as a boon in the setting of established CRBSI. It avoids catheter removal in majority of patients.
#6747 ACTIVATION OF GPR120 IMPROVES THE SENESCENCE OF TUBULAR EPITHELIAL CELLS IN SEPTIC ACUTE KIDNEY INJURY
Authors: Yang Letian , Wang Bo , MA Liang , Fu Ping
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is a serious clinical complication that has high morbidity and mortality. Although there have been substantial advances in understanding AKI mechanisms, at present, there are no effective therapies to treat or prevent it.

Method

We had formerly found that TUG891, a GPR120 (a member of the G protein-coupled receptor (GPCR) family) agonist, alleviated tubular damage as well as renal dysfunction in mice with AKI. Nevertheless, the multifunctional effects of FFAR4 in the kidney have not been well described.

Results

In the current research, the GPR120 expression was abnormally reduced in tubular epithelial cells (TECs) of cecal ligation/perforation induced AKI mice, respectively. Systemic and conditional TEC-specific knockout of GPR120 aggravated renal function and pathological damage, whereas GPR120 activation by TUG-891 alleviated the severity of disease in AKI mice induced with cisplatin. Notably, GPR120, as a key determinant, was firstly explored to regulate the cellular senescence in TECs and AKI mice injured kidneys, as represented through the activity of senescence associated β-galactosidase (SA-β-gal), marker protein p21, p53, Lamin B1, phospho-histone H2A.X, phospho-Rb expression, and secretory phenotype IL-6 level. Mechanistically, pharmacological activation and overexpression of FFAR4 reversed the decrease of aging-related SirT3 protein, where GPR120 regulated SirT3 expression to exhibit anti-senescent effect via Gq subunit-mediated CaMKKβ/AMPK signaling in cisplatin-induced mice and tubular epithelial cells.

Conclusion

These results underline the primordial role of renal tubular GPR120 in the cellular senescence through AMPK/SirT3 signaling and define GPR120 as a target for underlying drugs against septic AKI.
#6809 PULSE VERSUS DAILY ORAL CYCLOPHOSPHAMIDE IN ANCA-ASSOCIATED VASCULITIS WITH RENAL INVOLVEMENT: A SINGLE CENTER EXPERIENCE
Authors: Dias Joana Pereira , de Faria Maria Victoria Vaz Da Rocha Paes , Almeida Catarina , Alferes Daniela , Carmo Rute , Santos Maria Clara , Almeida Clara
Published: June 2023

Background and Aims

We aimed to compare the risk of death, relapse and infections requiring hospital admission of ANCA-associated vasculitis (AAV) patients according to the induction of remission scheme used: daily oral (PO) cyclophosphamide or pulse intravenous (IV) cyclophosphamide.

Method

We identified all newly diagnosed AAV patients treated with PO or IV cyclophosphamide between January 1998 and December 2022 admitted to the CHVNGE Nephrology Department. Data were analyzed with SPSS v28® using parametric and non-parametric tests and Kaplan Meyer survival analysis.

Results

We identified 74 cases of de novo vasculitis, 50 of them received PO cyclophosphamide and 24 received IV cyclophosphamide. Median age at presentation was 68,50 ± 16,06 years PO and 68,00 ± 10,41 years IV. Median duration of follow-up was 3,8 years ± 2,98 for both groups, 6,21 years PO and 3,88 years IV. One-year survival was 84% in PO and 91,3% in IV patients; 15 (30%) PO and 5 (20,8%) pulse patients had at least one relapse. Neoplasms occurred in 3 (6%) patients in the PO group and 1 (4,2%) patient in the IV group. The number of patients admitted with one or more infections was 22 (44%) in the PO group and 9 (37,5%) in the IV group. Renal survival was 26 (52%) PO and 15 (62,5%) IV. There was no difference in survival (p = 0,176), renal survival (p = 0,113), risk of relapse (p = 0,283) and infection (p = 0,196) between the two groups.

Conclusion

There was no difference in renal or overall survival, confirming the previous published data. Contrasting with CYCLOPS, our analysis does not confirm an increased risk of relapse in the IV group. One particularly interesting data is that the number of infections in IV route was lower than PO, corroborating the data on lower cumulative doses and therefore lower risk of infection in previous studies. Potential bias of this study is the small sample of patients enrolled in the two groups and the duration of follow up. Despite the reduction in the cumulative dose of cyclophosphamide, we continue to have significant adverse effects, which can also be explained by the dose of corticosteroid previously used, therefore strategies to reduce the toxicity associated with treatment without compromising efficacy are important goals for future research. Treatments need to be optimized and customized according to the severity of the patient's disease and the risk of recurrence.
#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

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

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

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

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 >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

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<0.00001) and 125 (125-1278) pg/ml and 738 (125-4000) pg/ml at the end of HD (p<0.0001). Respective concentrations of platelet derived growth factor-A were 8286 (4600-28150) and 27938 (8285-99256) pg/ml (p<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<0.0001) and 839.4 (509.7) and 483.6 (329.9) per microliter (p<0.0001). Respective mean (SD) CD19-counts were 199.0 (154.5) and 76.4 (78.6) per microliter (p<0.0001) and 144.9 (110.3) and 98.3 (70.8) per microliter (p<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

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<120/80 mmHg) and 268 subjects with untreated arterial hypertension (AH, BP>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<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<0,001). Serum HGF concentration showed a significant positive correlation to serum glucose levels in the AH group (correlation coefficient = 0,195, p<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>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

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

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

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

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 (<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.
#6934 INFLAMMATORY STATUS PRIOR TO THE CREATION OF ARTERIOVENOUS FISTULAS FOR HEMODIALYSIS: IS IT DETERMINING?
Authors: Saponara Luis Guillermo Piccone , Heredia Nancy Giovanna Uribe , Garcia Guillermo Ferrer , Conejo Gloria García , Conforme Roger Abduvar Cox , Gutierrez Eliana Olazo , Fernández Maria Paz Castro , Fernandez Sara Anaya , Carreno Agustin , Poyatos Maria Del Carmen Vozmediano
Published: June 2023

Background and Aims

Clinical practice guidelines recommend an arteriovenous fistula (AVIF) as the preferred vascular access for hemodialysis and is associated with a lower incidence of morbidity and mortality. However, primary vascular access (VA) failure is not uncommon. Low-grade inflammation is present in ERCT. We identified the inflammatory parameters that influence the primary patency of the vascular access for hemodialysis.

Method

Cross-sectional study; We included all VAs made between October 2009 and April 2022. We evaluated the initial performance after the creation of the VAs. Demographic variables (age, sex), CKD etiology, and associated comorbidity were collected. Statistical analysis with SPSS 25.0. Categorical variables are expressed as percentages and compared using the Chi2 test. Quantitative variables are expressed as mean ± standard deviation and the t-student test was used to compare them. Statistical significance for a value of p<0.05.

Results

712 VA performed in 546 patients were reviewed between October 2009 and April 2022. 617 autologous VA (86.7%) and 95 prosthetic VA (13.3%) were performed. The mean age of the patients was 65.4 ± 14.1 years and 67.4% were male. The most frequent etiology of CKD was diabetic nephropathy (30.5%), followed by unknown (17.3%) and glomerulonephritis (16.4%). 91.4% of the patients presented arterial hypertension (HTA), diabetes mellitus (DM) 47.5%. 72.6% of the VA presented primary permeability. In the univariate analysis using Chi2 and T student, AHT (p<0.001), treatment with statins (p<0.001), antiaggregation (p<0.001), normal fibrinogen levels (p = 0.003), and CRP (p<0.001) reached statistical significance. = 0.039). When recoding the PCR in relation to its normal values, the pathological levels were associated with primary failure after the creation of AVFs.

Conclusion

In our study, inflammatory states with elevated CRP and ferritin were associated with primary failure in initial functioning after the creation of AVFs. On the contrary, arterial hypertension and treatment with statins prior to the creation of AVFs are associated with their primary permeability.