bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1613 Gadolinium and gadoteric acid's short-term impact on kidney function and lipid profile
Authors: Belo Luís , Coimbra Susana , Rocha Susana , Viana Sofia D , Rebelo Rute , Rocha-Pereira Petronila , Valente Maria João , Catarino Cristina , Bronze-Da-Rocha Elsa , Reis Flávio , Santos-Silva Alice 
Published: May 2024

Abstract

Background and Aims
Concerns regarding the safety of gadolinium-based contrast agents (GBCA), which are often employed in medical imaging, have been raised in light of reports of free gadolinium's [Gd (III)] cytotoxicity. It appears that GBCAs having macrocyclic structures, like gadoteric acid (Gd-DOTA), are more stable and less toxic.
Previous work from our group found that Gd (III) promotes inflammation and fibrosis in proximal tubular cells cultures. A disturbance of lipid metabolism was also reported, accompanied by the build-up of lipid droplets, lipid peroxidation and the overexpression of genes linked to lipogenesis and lipolysis.
The aim of this study was to evaluate the short-term effects of Gd (III) and of Gd-DOTA on renal function and lipid metabolism biomarkers, using an animal model.

Method
Male Wistar rats were exposed to a single dose of Gd (III) or Gd-DOTA (groups A and B, respectively); a control group was also included (C). Blood was collected after 48h of exposure to compounds. We evaluated circulating levels of renal function biomarkers—creatinine and cystatin—using a routine automated assay and ELISA, respectively. The lipid profile was also determined including triglycerides (TG), total cholesterol, HDL-cholesterol, LDL-cholesterol, and oxidized LDL (oxLDL) levels.

Results
Gd (III) group (A) presented significantly higher circulating cholesterol (P=0.006) and LDL-cholesterol (P&lt;0.001) and lower TG (P&lt;0.001) levels than the control group (C); a non-significant increment in cystatin was also observed for group A. The Gd-DOTA group (B) only presented lower TG levels (P=0.002) compared to the control group (C), being similar to those presented by group A. Both exposed groups (A and B) presented non-significantly higher oxLDL levels compared to the control group.

Conclusion
Single exposition to free Gd (III) induced prompt changes in lipid profile, with little short-term influence in traditional kidney biomarkers. The exposition to Gd-DOTA was associated with lower disturbance in lipids and lipoproteins (only lower TG levels) and imperceptible renal changes. Despite the significantly safer profile for Gd-DOTA, further studies are necessary, testing different biomarkers, to clarify the short-term, and even the long-term impacts, of these molecules.

Acknowledgements
This work was financed by FCT through the project 2022.08400.PTDC; FCT, in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.
#2705 Hypertension as a risk factor for mortality and the development of chronic kidney disease after an episode of acute kidney injury in the elderly
Authors: Mahmoud Nouha Ben , Hamouda Mouna , Salah Manel Ben , Salem Meriem Ben , Bchir Sirine , Letaief Ahmed , Sabra Aloui , Skhiri Habib 
Published: May 2024

Abstract

Background and Aims
Acute kidney injury (AKI) is a real public health problem due to its severity and its consequences in the short, medium and long term. Hypertension is a very common disease in our country. The association between hypertension and acute and chronic renal failure is not well studied in our country, and given the lack of data, we proposed to carry out this study and even more so the elderly, who are fragile subjects with multiple illnesses.

Method
We undergone a retrospective study which was carried out in the nephrology department of Fattouma Bourguiba hospital in Monastir. We included patients aged &gt; 65 years, who had an AKI with full recovery who had been hospitalized between January 2002 and December 2015. Our study aimed to assess the impact of hypertension on mortality and the development of chronic kidney disease (CKD) after an episode of AKI.

Results
Our population was made up of 67 men and 60 women, 30.1% had multiple comorbidities. Pre renal Aki represented the predominant mechanism of AKI which was retained in our study with a rate of 40% and dehydration as the main aetiology in 70 patients.
In the short term, 15 patients had progressed to CKD. The mean overall survival in our study was 159 months with a high risk of mortality in elderly (patients aged &gt;65 years), who had multiple comorbidities, hypertensive, diabetics, with vascular disease, Charlson Comorbidity index &gt;5, who presented with hyperkalaemia &gt;5.5 and pre renal mechanism of the AKI episode.
In the medium term and the long term, 4 and 2 patients developed CKD respectively. Hypertension was a factor in poor prognosis and mortality in elderly subjects after an episode of acute kidney injury (p=0.005).

Conclusion
Hypertension is a real public health problem impacting the short, medium and long term prognosis of patients who have had an episode of AKI with full recovery.
#2781 Renal cortical necrosis—a rare cause of acute kidney injury
Authors: Jaryal Ajay , Vikrant Sanjay , Yadav Riti 
Published: May 2024

Abstract

Background and Aims
Renal cortical necrosis (RCN) is a rare and catastrophic cause of acute kidney injury (AKI). It is characterized by ischemic destruction of all the elements of renal cortex due to marked reduction in renal arterial perfusion of renal cortex due to vascular spasm and microvascular injury. It can be patchy or diffuse depending upon the cause and extent of hypoperfusion. Snake bite is rare cause of RCN. Incidence of RCN following snake bite has been reported to be as high as in 25% of the bitten patients to &lt;1%. Lack or delay in receiving anti snake venom (ASV) has been observed to be a contributing factor in development of RCN following snake bite.

Method
A 45-year-old female had an unknown bite on foot while returning to home at twilight. She had intense pain at site of bite with slight ooze of blood. Overnight she had vomiting and pain abdomen. Subsequently she developed progressive fall in urine output and dyspnoea. After about 36 hours of bite at the time of admission in hospital she had anuria, prolonged whole blood clotting time, tachypnoea, hypoxemia and required oxygen (O2) to maintain normal O2 saturation. She was given two doses of polyvalent ASV 6 hours apart which corrected her coagulation defect. Investigations showed: haemoglobin—9 gm/dl, total leucocyte count—18700/mcl, platelet—1.15 lakh/mcl, blood urea—88 mg/dl and serum creatinine—10.5 mg/dl. She was managed with haemodialysis and supportive care. Even after 3 weeks of onset of AKI, she had anuria so a kidney biopsy was done.

Results
kidney biopsy on light microscopy examination showed 9 glomeruli; 8 revealing global tuft necrosis along with necrosis of adjacent tubules and vasculature and necrotic process affected around 60% of sampled cortical area consistent with cortical necrosis (Fig. 1). She was continued with haemodialysis support and urine output and pre-dialysis serum creatinine were monitored. Her urine output after 3 months of onset of AKI is around one litre per day but her pre-dialysis serum creatinine stays in the range of 9-10 mg/dl and so she continues to receive biweekly haemodialysis.

Conclusion
In our index case, there was delay in getting ASV which may have contributed to development of RCN. So, early treatment of snake bite is important to prevent this catastrophic complication.
#2875 Experience in the use of plasmapheresis as a therapeutic tool in acute pathologies in a tertiary level hospital
Authors: Fernández Maria Paz Castro , Valverde Daniel Campos , Fernández Sara Anaya , Saponara Luis Guillermo Piccone , Conejo Gloria García , Conforme Roger Abduvar Cox , Escudero Patricia Sanchez , Del Carmen Vozmediano Poyatos Maria 
Published: May 2024

Abstract

Background and Aims
Apheresis is a therapeutic modality which purpose is the elimination from plasma of the pathogenic components of a disease or its clinical manifestations. Plasmapheresis is an apheresis technique used in the treatment of various diseases with varying degrees of proven clinical efficacy. The aim of our work is to describe the experience in the use of plasmapheresis in different acute pathologies in our center, and if there are factors that favor the clinical response to treatment.

Method
Retrospective cohort study. We included plasmapheresis performed in the years 2017-2022. Variables such as age, sex, etiology, type of replacement performed, number of sessions, and American Society for Apheresis (ASFA) classification, among others, were collected. We defined response to treatment as partial or total clinical remission.

Results
We included 72 patients who received plasmapheresis during 2017-2022. Mean age 54 ± 18 years. 56.9% male. Disease etiology was neurological in 56.9%, nephrological in 36.1% and hematological in 6.9%. Between 2017-2019, 39.7% of the plasmapheresis were performed, while the remaining 60.3% were between 2020-2022. The number of sessions was 5.3 ± 2. 59.6% were performed with albumin, 29.2% with fresh frozen plasma and 13.9% with albumin and fresh frozen plasma. The ASFA indication was category I in 68.1%. 23.6% presented some complication, the most frequent being febrile in 6.9%, systemic infection and allergic reaction in 5.6%. A response to treatment was observed in 75%. Antibodies were positive before starting plasmapheresis in 29.2%, decreasing to 16.7% 3 months after treatment. There was recurrence in 19.4%, 16.7% received more cycles of plasmapheresis and there was 11.1% mortality due to disease. In patients with response to treatment, a higher percentage of response was observed in those diseases of non-nephrological origin (70.4% vs. 29.6%, p 0.04), lower percentage of complications (16.7% vs. 83.3%, p 0.01) and lower mortality associated with the disease (3.7% vs. 96.3%, p 0.001).

Conclusion
Plasmapheresis is a therapeutic plasma exchange technique that is increasingly used in our hospital, with a greater increase in recent years. It is a therapeutic option that should be considered in many occasions as first line or adjuvant treatment, with a low rate of complications and clinical improvement in most patients. Despite this, studies with a larger number of patients are required to increase and consolidate the existing evidence on the use of these procedures.
#815 Maternal and fetal outcomes in kidney transplant recipients: a single-center observational study
Authors: Artan Ayse Serra , Mirioglu Safak , Sivrikoz Tuğba Saraç , Ünal Elif , Hocaoglu Rabia Hacer , Suleymanova Vafa , Doksan Müge , Oto Ozgur Akin , Ozturk Savas , Yazici Halil , Turkmen Aydin 
Published: May 2024

Abstract

Background and Aims
Pregnancy poses a high risk for adverse maternal and fetal outcomes in kidney transplant recipients (KTRs), and data on long-term allograft functions compared to healthy population are still limited. Therefore, we aimed to conduct a comparative analysis of maternal and fetal outcomes in KTRs with age-matched non-transplanted controls.

Method
In this retrospective single-center study, KTRs who experienced at least one pregnancy after transplantation between 1984 and 2016 were evaluated (study group). In order to create an age-matched control group, healthy women who had one pregnancy each and received prenatal care were included. Maternal and fetal outcomes were gestational age, preterm birth, newborn mortality, admittance to neonatal intensive care unit (NICU), Apgar scores, birth weight, and obstetric complications (preeclampsia, peripartum hemorrhage, duration of maternal hospitalization) in all pregnancies, and composite kidney outcome of KTRs which was defined as progression to graft failure necessitating dialysis or re-transplantation or doubling of serum creatinine at the end of follow-up.

Results
In 53 KTRs, 68 pregnancies occurred. Mean age at birth was 31.6 ± 5.2 for KTRs and 30.5 ± 5.8 for controls (p = 0.288). Preeclampsia (29.4% vs. 2.9%, p &lt; 0.001) and preterm birth (57.4% vs. 32.4%, p = 0.003) were significantly higher in KTRs. KTR pregnancies had lower mean birth weight (2354 ± 814 vs. 2856 ± 729 mg, p = 0.001) and longer durations of maternal hospitalization (3 vs. 2 days, p = 0.001), as well. However, neonatal mortality, admittance to NICU, and peripartum hemorrhage rates and Apgar scores were similar (Table 1). Baseline serum creatinine and eGFR levels of KTRs were 1 (0.8-1.2) mg/dl and 76.6 (59.9-91.5) ml/min/1.73 m2, respectively. Follow-up for a median of 105 months after the index birth showed higher serum creatinine levels at postpartum visits (p &lt; 0.001) and last follow-up (p = 0.001) compared to baseline, with a tendency for increased proteinuria during pregnancies (Table 2). Six KTRs (11.3%) experienced composite kidney outcomes, including 5 patients with graft failure and 1 with doubling of serum creatinine.

Conclusion
KTRs exhibit comparable neonatal mortality and NICU rates but higher rates of preeclampsia and preterm birth. Notably, graft functions worsen significantly during postpartum follow-up.
#2599 Adam17 inhibition moderates interstitial fibrosis and macrophage infiltration in TD1 mouse model
Authors: Riera Marta , Palau Vanesa , Galdon Eric , Martyn Claudia , Cervera Cristina , Silva David , Amador Ana , Romeo Maria Jose Soler , Crespo Marta , Barrios-Barrera Clara 
Published: May 2024

Abstract

Background and Aims
ADAM17 participates in the release into circulation of inflammatory and fibrotic molecules, such as TNF-α actively involved in the progression of Diabetic Nephropathy. We studied the effect of specific deletion of ADAM17 in the endothelium and renal tubule in a T1 diabetic mouse model demonstrating its participation in the progression of kidney damage. As ADAM17 is also expressed in other cell types we wanted to study the effect of the complete deletion of Adam17 in type 1 diabetic mouse.

Method
We studied total inducible (by TAM) Adam17 knockout male mice (ADAM17KO) and their control littermates. Animals were rendered diabetic by STZ injection (DB group). Blood glucose, mesangial index (PAS staining), number of podocytes and positive area of α-SMA (by immunohistochemistry) were determined. We also studied the protein expression of the cytokine MCP-1 in renal cortex by Western Blot.

Results
The mesangial index value observed in the 20wk-DB group was compared with the diabetic ADAM17KO group. In the latter, the value significantly decreased. Podocyte loss detected in DB group was not observed in the KO-DB group. For interstitial fibrosis, the intensity and location of α-SMA was significantly lower in the ADAM17KO group. In addition, complete deletion of Adam17 partly prevented the infiltration of macrophages assessed by the expression of MCP-1 in the protein extract of the renal cortex.

Conclusion
Complete inhibition of Adam17 expression in T1DM mice prevents fibrosis progression and protects the glomerulus from hypertrophy. At the same time, it reduces macrophage infiltration, limiting the inflammatory response induced by diabetes. We demonstrate the influence of Adam17 on macrophages to reduce the expression of TNF-a partly responsible for the progression of diabetic nephropathy.
#1448 Regulation of renal phosphate excretion independent of FGF23 and PTH
Authors: Leifheit-Nestler Maren , Walter Stefanie , Walles Franziska , Richter Beatrice , Haffner Dieter 
Published: May 2024

Abstract

Background and Aims
The phosphaturic hormones fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) promote renal phosphate excretion through FGFR1/Klotho and PTH1R-mediated ERK1/2 activation, respectively, leading to inhibition of the sodium-phosphate cotransporters NPT2a (SLC34A1) and NPT2c (SLC34A3) in proximal tubule (PT) cells. In bone cells, high extracellular phosphate can directly activate ERK1/2 via the sodium-phosphate cotransporters PiT-1 (SLC20A1) and PiT-2 (SLC20A2). To date, it is unclear to what extent phosphate can also regulate its own excretion in the kidney independently of FGF23 and PTH.

Method
To further investigate the role of phosphate in the regulation of renal phosphate homeostasis, male C57BL/6 mice were placed on a 0.8% control phosphate diet (CPD) or a 2% high phosphate diet (HPD) for 6 months. After four months, one HPD group was additionally treated with a calcimimetic (etelcalcetide) to lower FGF23 and PTH. In vitro, PT cells were stimulated with phosphate, FGF23 or PTH ± the phosphate transporter inhibitor foscarnet.

Results
HPD resulted in increased plasma concentrations of FGF23 and PTH, which were associated with reduced tubular phosphate reabsorption and increased fractional phosphate excretion. RNAseq analyses from isolated PT cells showed a reduction of Fgfr1, Kl, Slc34a1 and Slc34a3 and an induction of Slc20a2 in the HPD group compared to CPD. qPCR and immunoblot analyses of whole kidney tissue confirmed the reduction of the FGF23 co-receptor Klotho in the HPD group, while Fgfr1 was not significantly altered. Protein expression of NPT2a was decreased in isolated brush border membrane vesicles from HPD-fed mice, and immunofluorescence staining showed internalization of NPT2a from the apical brush border membrane. Treatment with etelcalcetide resulted in a reduction of circulating FGF23 and PTH, whereas urinary phosphate excretion in HPD mice remained elevated. In cultured PT cells, high phosphate induced phosphorylation of ERK1/2 and mRNA expression of Slc20a2, while Slc34a1 was suppressed. Phosphate-mediated PiT-2/ERK1/2 activation could be blocked by simultaneous treatment with foscarnet.

Conclusion
Our data suggest that high phosphate leads to internalization of NPT2a via direct activation of the PiT-2/ERK1/2 signaling cascade, independent of FGF23 and PTH, resulting in increased renal phosphate excretion.
#111 RNAseq of microdissected collecting ducts revealing the early signaling mediating the loss of aquaporin 2 after K+ deprivation
Authors: Sung Chih-Chien , Chen Min-Hsiu , Lin Shih-Hua 
Published: May 2024

Abstract

Background and Aims
Potassium (K+) deficiency could cause a reduction in urinary concentrating ability, resulting in nephrogenic diabetes insipidus (NDI), but the detailed mechanism remains unclear. Recently, transcriptomic and proteomic data from acquired NDI models reveal that oxidative stress, apoptosis, and inflammatory signaling are associated with AQP2 loss. We aim to explore the early signaling after K+ deprivation in collecting ducts.

Method
Immunoblotting of kidney lysate were performed at 0, 12, 24, and 48 hours after K+ deprivation in rats. Serum and urine biochemistry were also recorded. Based on immunoblotting, cortical collecting ducts (CCDs) were microdissected from rats at 6 hrs after K+ deprivation versus time controls. Small samples RNA-Seq was carried out independently in K+ deprivation rats versus controls (n = 4).

Results
Immunoblotting of bulk kidney showed a decreased in AQP2 protein abundance at 12 hours of K+ deprivation diet, and urine osmolality was significantly decreased at 24 hours, confirming the animal model of K+ deprivation-induced NDI. Small samples RNA-Seq data of CCDs at 6 hrs after K+ deprivation showed Aqp2, Aqp3, and Atp1a1 were significantly downregulated. It also revealed that chemokine transcripts (Ccl20 and Ccl28) were increased significantly. We also carried out analysis of Gene Ontology Biological Process terms that are statistically over-represented in the list of 88 “Increased Transcripts” at 6 hrs of K+ deprivation in CCDs, and many of the terms are related to glutathione metabolic process, cell chemotaxis, cellular response to lipopolysaccharide, consistent with an inflammatory response.

Conclusion
Our small samples RNA-Seq from microdissected CCDs in rats showed early cellular signaling changes in activation of oxidative stress and inflammatory signaling causing loss of aquaporin-2 in K+ deficiency induced NDI.
#883 P-cresyl sulphate and Indoxyl sulphate: two uremic toxins stimulating colon cancer progression in patients with chronic renal failure
Authors: Simeoni Mariadelina , DI Paola Rossella , De Ananya , Izhar Raafiah , Abate Marianna , Zappavigna Silvia , Perna Alessandra , Capasso Anna , Capasso Giovambattista , Caraglia Michele 
Published: May 2024

Abstract

Background and Aims
Chronic kidney disease (CKD) leads to the accumulation and production of uremic toxins, such as Indoxyl Sulphate (IS) and P-cresyl sulphate (p-CS). These toxins have been found to activate various processes that promote tumor growth. The literature has reported a two-fold increase in the incidence of colon cancer (CRC) and a worse prognosis in CKD patients, although the specific mechanisms underlying this association have not been fully elucidated. Given the pro-oncogenic activities of p-CS and IS at both the systemic and intestinal levels, it is plausible that these toxins contribute to the heightened aggressiveness of CRC in CKD patients.

Method
In order to assess the impact of toxins detected in uremic patients, we conducted experiments using three different colorectal cancer (CRC) cell lines (HT29, Hct116, LoVo). We tested various concentrations of IS and p-CS and measured their effects on tumor cell proliferation through a colorimetric assay called WST-8. For further analysis of cell survival, we performed a clonogenic assay. To investigate the migratory abilities of tumor cells after toxins treatment, we conducted a wound healing assay. Additionally, we assessed the invasive capacities of the three CRC cell lines post treatment with IS and p-CS using an invasion assay. In order to identify the specific pathways affected by toxins exposure, we conducted Real Time PCR and Western blot analysis to evaluate the inflammatory pathway and the epithelial-mesenchymal transition (EMT), respectively.

Results
The results of this study are remarkable, as we observed a notable increase in cell growth after exposure of cultured cells to various concentrations of toxins, as compared to the control group. Furthermore, the concentrations of IS and p-CS induced a substantial enhancement in cell migration and invasion. In the case of HCT116 cells treated with uremic toxins, there was an up-regulation of Vimentin protein expression, while E-cadherin expression was down-regulated compared to the control group. These proteins are crucial in the process of Epithelial-Mesenchymal Transition (EMT). Additionally, we evaluated the expression of genes associated with the inflammatory process (TNF-alpha, INOS, and IL-6) in the HT-29 and LoVo cell lines. Interestingly, we observed an up-regulation of these genes. Of particular importance, in the LoVo cell line, IL-6 exhibited the most significant increase in expression.

Conclusion
Based on these preliminary results, it appears that IS and p-CS play a key role in the progression of CRC in patients with CKD.