bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1731 Clinico-epidemiological characteristics of early versus late onset cytomegalovirus disease among renal transplant recipients: two decade experience
Authors: Kaul Anupma , Roy Shuvam , Prasad Narayan 
Published: May 2024

Abstract

Background and Aims
The epidemiology of the Cytomegalo virus (CMV) disease among renal transplant recipients has changed with the advent of effective antiviral prophylaxis usually occurs in the later part of the post transplant period. To study the difference between CMV infections occurring in early versus late post renal transplant period with respect to nature of immunosuppressive medications (induction agents, maintenance agents and heightening of immunosuppression), type of CMV infection and occurrence of biopsy proven rejection post CMV infection.

Method
A single centre retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between 1st January, 2002 and 31st December, 2021. CMV disease was classified as early or late depending on detection before or after 90 days post transplant. The differences in clinical presentation between early and late onset CMV disease, use of immunosuppression, and the impact on graft outcomes were studied.

Results
Total number of recipients with CMV disease was 156 (7.2%) out of total 2164 renal transplant recipients. Twenty-five (16%) patients had early CMV while one hundred and thirty one (84%) had late CMV. The two groups did not differ with respect to induction or use of maintenance immunosuppressive agents. Proportion of CMV syndrome was more among early CMV group (56.0% vs 26.7%, p = 0.01) while tissue invasive disease was more frequent among late CMV group (44.0% vs. 73.3%, p = 0.01). Diarrhoea was more frequent in late (63.4%) versus early CMV (36%) (p = 0.01). Graft loss occurred in 4.0% of early and 25.2% of late CMV cases (p = 0.03). However, both groups did not differ with respect to occurrence of biopsy proven rejection post infection.

Conclusion
Early CMV presents more frequently as CMV syndrome while late CMV usually manifests as tissue invasive disease. Graft loss is more common in patients with late onset disease.
#2867 Is there an interrelationship between the SARS-CoV-2 virus and the BK polyomavirus in kidney transplant recipients?
Authors: Alonso Marta , Villanego Florentino , Vigara Luis Alberto , Orellana Cristhian , García Ana , Lopez Juan Manuel Cazorla , Amaro José Manuel , Montiel Natalia , Garcia Teresa , Rodriguez-Iglesias Manuel , Mazuecos Auxiliadora 
Published: May 2024

Abstract

Background and Aims
Several viral co-infections following SARS-CoV-2 infection have been described. However, there is very limited and inconclusive data on the relationship between COVID-19 and BK polyomavirus (BKV) in kidney transplant (KT) recipients.

Method
Retrospective analysis of KT recipients with BK infection (BKi) in our centre from March 2020 (first cases of COVID-19) to March 2023. BK viremia is periodically determined prospectively in all KTs performed in our hospital. We carried out a case-control study, choosing two controls without BKi for each case (closest transplant date and similar donor and recipient age). We analyzed clinical characteristics and evolution, as well as previous history of COVID-19 in both groups. A composite outcome including de novo BKi and/or significant increase in BK viremia (increase &gt; 50% in at least 2 consecutive samples) was analyzed. Multivariate analysis was performed using logistic regression for de novo BKi and/or significant increase in BK viremia risk factors.

Results
During this period 235 KTs were performed in our center, of which 37 were diagnosed with BKi (16.1%). The median time from the date of KT to BKi was 73 days.
When comparing cases versus controls, demographic characteristics and donor type were similar in both groups, except for a higher proportion of males in the BKi group (76.3% vs. 55.3%; p = 0.029). The incidence of SARS-CoV-2 infection was significantly higher in patients with de novo/increased viremia BKi than in the control group (44.7% vs. 26.3% p = 0.048). During follow-up, one patient in the BKi group died and one patient in the control group lost the graft due to causes other than viral infections.
In multivariate analysis, male gender and SARS-CoV-2 infection were risk factors for the composite outcome.

Conclusion
As has been described with other viruses, there may be an interrelationship between SARS-CoV-2 and BKV. Our experience suggests that close monitoring for BKV after episodes of COVID-19 may be appropriate.
#3087 Phenotype of extracellular vesicles in diabetic kidney disease with albuminuria
Authors: Mora-Gutiérrez José María , Fernández Alfonso Jiménez , Andueza Saioa Echeverria , Fernandez-Seara Maria A , Garcia-Fernandez Nuria 
Published: May 2024

Abstract

Background and Aims
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) and affects more than 40% of patients with type 2 diabetes mellitus (T2D). The pathogenesis of CKD is multifactorial and leads to a clinical presentation with diverse phenotypes characterised by proteinuria and/or progressive deterioration of renal function, thus urging the search for new non-invasive biomarkers that allow early diagnosis and the development of new therapeutic targets. Urinary extracellular vesicles (EVs) have emerged as an alternative, as changes in their number and composition have been described in clinical conditions associated with DM and kidney disease. EVs are able to interact with neighbouring and/or distant cells by transferring their cargo, rich in proteins, lipids or nucleic acids, from progenitor cells to recipient cells, thus participating in cell-to-cell communication processes. The aim of the present study was to analyse the different phenotypes of EVs in T2D patients with different degrees of albuminuria compared to healthy controls, as well as their correlation with the degree of albuminuria.

Method
A cohort of 69 subjects (49 patients with T2DM and 20 healthy volunteers) was analysed. The phenotype of EVu present between the two groups was assessed, as well as the association between the different cell lines and the presence of albuminuria. Statistical analysis was performed using Spearman correlations. Analyses were performed with R software.

Results
A positive correlation was observed between EVu from podocytes (PODO+) and those from macrophagocytes (R = 0.3180, p-value = 0.0082), as well as a positive association between PODO+ and neutrophil EVu, both in the whole cohort and when analysing only patients with diabetes (R = 0.3225, p-value:0.0254). When assessing the association of EVu with the degree of albuminuria, we observed a direct association with proximal tubule EVu (R: 0.3158, p-value 0.0271) both in all subjects (T2D and HV) and only in those with T2D (R = 0.4200, p-value = 0.0056). When stratifying according to the degree of albuminuria (A1, A2 and A3), we still observed a dependent association of the degree of glomerular involvement with the number of EVu of TCP (A1: mean 5.5 (SD 4.1); A2: mean 12.3 (SD 30.9); A3: mean 132.5 (SD 322.8)) p-value: 0.0609.

Conclusion
The results presented suggest a relevant role of TCP in the glomerular involvement of patients with DKD, in line with the emergence of new therapeutic lines such as iSGLT2. The study suggests new lines of research aimed at developing therapeutic targets that assess the cellular expression of EVu.
#993 The molecular effects of SGLT2i (Empagliflozin) on α-Klotho and Nephrin/Podocin proteins in type II diabetic mice model
Authors: Ertracht Offir , Nakhoul Farid 
Published: May 2024

Abstract

Background and Aims
Type 2 diabetes mellitus (T2DM), especially hyperglycemia, is associated with increased glucose cell toxicity and oxidative stress that can lead to irreversible damage in the kidney such as diabetic nephropathy (DN). DN is one of the most common microvascular complications of diabetes and is the leading cause of end-stage renal disease (ESRD) and replacement therapy. Several works in the setting of early experimental diabetic nephropathy using the recent anti-diabetic drugs such as sodium-glucose transporter type 2 inhibitors in the prevention, development or amelioration of renal injury. The exact mechanisms, by which these drugs ameliorate glomerular injury from hyperglycemia, had not been clarified well.
Klotho and Podocin-Nephrin proteins are an important proteins involved in the tubule-glomerular injury. The Klotho is a circulating anti-ageing hormone with anti-oxidative and anti-inflammatory properties with vascular protective effects in animal studies. Podocin & Nephrin are important component of the glomerular foot-process membrane, the slit-diaphragm. Recently, several experimental reports showed decreased α-Klotho, Nephrin and Podocin expression in different models of diabetic nephropathy.

Method
We used BTBR mouse strain with the ob/ob leptin-deficiency mutation, which develops T2DM with hyperglycemia and DN; C57/BL mice were the control (CON). EMPA was administrated to T2DM mice (T2DM+EMPA) via drinking water for 12 weeks. Blood parameters were measured repeatedly, and at sacrifice, mice kidneys were harvested for histological and biochemical analyses. We evaluated renal glomerular structure of Nephrin, Podocin and α-Klotho proteins expression.

Results
EMPA treatment reduced T2DM blood glucose vs C57 group (P &lt; 0:01), and increase urine glucose in EMPA+DM group (P &lt; 0:001) EMPA vs. C57BL/6 and DM). Histological analyses in kidney sections, revealed decreased α-Klotho expression in glomeruli of DM mice vs Control mice (15.95 ± 0.64 vs 36 ± 2.42, (P &lt; 0:01), and restored back in DM+ EMPA mice vs control mice (27.64 ± 0.94 vs 15.95 ± 0.64, P &lt; 0:01). Podocin expression in glomeruli: control mice 31.3 ± 3.7 VS DM mice 21.26 ± 1.22 and DM + EMPA mice 28.22 ± 0.50 VS DM mice 21.26 ± 1.22

Conclusion
Hyperglycemia (DM type II) reduces Podocin-Nephrin and α-Klotho proteins expression in the glomeruli kidney and upregulated by EMPA treatment. SGLT2i (EMPA) treatment in DM patients can significantly reduce progression of DN and onset of ESRD probably through its effect on α-Klotho/Podocin-Nephrin proteins.
#909 Role of cystatin C in the development and progression of chronic heart failure in patients with diabetes
Authors: Vasilkova Volha , Mokhort Tatsiana , Naumenka Elena , Yarets Yulia 
Published: May 2024

Abstract

Background and Aims
It has been known that cystatin C is a marker for early prediction of renal function. In recent years, studies have shown that cystatin C plays an important role in predicting new or worsening cardiovascular diseases. The aim of our study was to investigate the role of cystatin C in the development and progression of chronic heart failure (CHF) in patients with diabetes.

Method
A total of 499 patients with DT1 and DT2, aged 34 to 84 years (60 [60; 72]), were examined. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of the natriuretic peptides (BNP and NTproBNP) in baseline plasma samples. Renal function was assessed based on the levels of serum creatinine and cystatin C. Patients were divided into quartiles according to cystatin C levels: Q1 &lt;0.78 mg/l, Q2 0.78-0.92 mg/l, Q3 0.93-1.38 mg/l, Q4 &gt;1.38 mg/l.

Results
Significant differences in the levels of BNP and NTproBNP were observed in patients with diabetes with cystine C levels ≥0.93 mg/l (32.20 [19.85; 69.35] pg/ml and 104.25 [57.70; 210.08] ng/l, respectively). There were significant correlations between cystatin C and the levels of BNP (r = 0.56, p &lt; 0.05) and NTproBNP (r = 0.58, p &lt; 0.05). Logistic regression analysis showed the prognostic value of cystatin C, and not creatinine, as a predictor of heart failure in patients with diabetes and GFR&gt;60 ml/min/1.73 m2 (1 mg/l increase of cystatin C was associated with 7.085 times increase in CHF odds). ROC analysis revealed that the level of cystatin C ≥0.96 mg/l with a sensitivity of 84% and specificity of 75% predicted increased BNP and NTproBNP in patients with diabetes (ROC AUC = 0.844).

Conclusion
Cystatin C level could be used as a predictive indicator of CHF in patients with diabetes and GFR&gt;60 ml/min/1.73 m2.
#411 Magnesium deficiency abrogates the activation of Insulin-like growth factor-1 signaling pathway in the kidney induced by DPP4 inhibitor
Authors: Iwakura Takamasa , Ema Chiemi , Yasuda Hideo 
Published: May 2024

Abstract

Background and Aims
Dipeptidyl peptidase-4 (DPP-4) inhibitor could attenuate cisplatin nephrotoxicity dependent on the glucagon-like peptide-1 (GLP-1) signaling pathway [1]. We had previously reported that the use of a DPP-4 inhibitor might also attenuate cisplatin nephrotoxicity in diabetic cancer patients [2], and its renoprotective effect was lost under magnesium (Mg) deficiency [3]. However, it remains to be investigated how the GLP-1 signaling pathway changes after the treatment of a DPP-4 inhibitor under Mg deficiency. The purpose of this study was to examine the changes in the downstream pathway of the GLP-1 signaling pathway after the treatment of DPP-4 inhibitor under Mg deficiency.

Method
Sprague Dawley rats received a Mg-deficient diet for 7 days to induce Mg deficiency (low Mg group). Control diet was given to the normal Mg group. Oral administration of a DPP-4 inhibitor was injected 1 day before sacrifice. The changes in serum active GLP-1, insulin, insulin-like growth factor (IGF-1), and the expression of their receptor in the kidney were examined. In addition, the phosphorylation of insulin/IGF-1 receptors in the kidney were investigated.

Results
Serum active GLP-1 increased equally in both groups with DPP-4 inhibitor administration. Renal GLP-1 receptor expression was not observed in the renal tubules. Serum IGF-1 did not change with DPP-4 inhibitor administration in the normal Mg group but increased in the low Mg group. In normal Mg group, renal IGF-1 receptor expression tended to increase with DPP-4 inhibitor administration, and its phosphorylation increased significantly. In contrast, the expression and phosphorylation of the IGF-1 receptor did not change with DPP-4 inhibitor administration in the low Mg group. The increase in serum insulin with the DPP-4 inhibitor was enhanced in the low Mg group, compared to the normal Mg group. The expression and phosphorylation of the insulin receptor did not change with DPP-4 inhibitor administration in both groups.

Conclusion
DPP-4 inhibitor activated the renal IGF-1 signaling pathway, but this effect disappeared under Mg deficiency. Further investigation is needed to determine whether the renal protective effect of DPP-4 inhibitor is dependent on the IGF-1 signaling pathway.
#2977 Pregnancy-related acute kidney injury in a second level care hospital in Merida, Yucatan, Mexico
Authors: Cruz Julio Ismael Pech , Alejandra Álvarez Zapata Naomi , Yah Anhialy Yaniré Collí 
Published: May 2024

Abstract

Background and Aims
Pregnancy-related acute kidney injury (PRAKI) is a public health problem associated with an increased risk of adverse maternal and fetal outcomes. The causes of PRAKI varies according to the age of gestation. Mexico lacks a national acute kidney injury (AKI) registry, and the access to AKI treatment is limited due to lack of financial coverage, lack of nephrologists, and poor infrastructure. The General Hospital Dr. Agustín O'Horán is a second level unit that attends to the uninsured pregnant population from the southeast of Mexico. The aim of this study was to investigate the prevalence, clinical characteristics, and outcomes of PRAKI in a Mexican population.

Method
This was a retrospective study in an obstetric intensive care unit (OICU) in the General Hospital Dr. Agustín O'Horán in Merida, Yucatan, Mexico. Women during pregnancy and postpartum periods admitted to the OICU between January to December 2023 were included. Demographical, clinical and laboratory data were collected from medical records, and AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. We evaluated the prevalence, clinical characteristics, and outcomes of PRAKI.

Results
During the study period, 188 women were admitted to the OICU, and the mean age was 24.9 years. Eight women presented in the first trimester, 19 in the second trimester, 21 in the third trimester, and 140 in the postpartum period. Fifty-five women met AKI creatinine criteria: 31 (56.3%) had stage 1, 15 (27.3%) had stage 2, and 9 (16.4%) had stage 3. The most common causes of PRAKI were obstetric hemorrhage (27.3%), eclampsia (21.8%), and preeclampsia (18.2%) (Table 1). There was no difference in vital signs on admission and baseline creatinine level between both groups. Women who developed PRAKI had a longer stay in the OICU (4.2 days vs 2.3 days, p &lt; 0.001), and greater use of vasopressor (30.9% vs 9.0%, p &lt; 0.001), and mechanical ventilation (34.5% vs 11.3%, p &lt; 0.001). Women with AKI had higher mortality (9.1% vs 1.5%, p = 0.012), and perinatal mortality (9.1% vs 2.3%, p = 0.035) (Table 2).

Conclusion
Women during pregnancy and postpartum periods who developed PRAKI had more adverse clinical and obstetric outcomes (maternal and perinatal mortality). Hence, women in pregnancy and postpartum periods admitted to an intensive care unit should be closely monitored and implement strategies for early diagnosis and aggressive therapy of PRAKI regardless of KDIGO stage.
#557 Seraph® 100 affinity blood cartridge as a potential adjunctive blood purification strategy for S. aureus-induced septic shock
Authors: De Rosa Silvia , de Cal Massimo , Lorenzin Anna , Ronco Claudio , Zanella Monica 
Published: May 2024

Abstract

Background and Aims
S. aureus infections, particularly methicillin-resistant strains, can induce severe conditions, provoking an overwhelming immune response and contributing to systemic inflammation and organ failure. Effective antibiotic therapy and meticulous supportive care are crucial in the ICU to manage S. aureus-induced septic shock. In this context, blood purification strategies aim to target the microorganism and associated toxins, contributing to the systemic inflammatory cascade. The objective of this in-vitro study was to analyze the potential removal, through adsorption, by the Seraph100 Affinity Blood Cartridge (S100ABC) against S. aureus. Subsequently, the study assessed whether the adsorptive capabilities toward bacteria were maintained, and if so, whether the bacteria retained its bactericidal activity.

Method
The study employed an in vitro model of hemoadsorption to characterize the adsorption performed by the S100ABC on a circulating bacterial load inoculated in blood. A volume of 150 ml of blood served as a negative control (CTR-). The remaining 650 mL were enriched with a concentration of S. aureus bacteria equal to 1×106 and incubated for 4 h at 37°C. At 4 h, the blood was divided into 2 glass bowls and stirred at 37°C: 500 mL were circulated at a speed of 120 mL/min via a dedicated test platform (Galileo) with Seraph100, while another 150 mL was stirred and used as a positive control (CTR+). The experiment was performed twice. Samples were taken from circulating blood and the two controls for blood cultures and placement on CNA agar.

Results
This study demonstrated that the S100ABC reduces the circulating bacterial load (from 1x106 at T0 to 0.25x106 at T6 h), leading to the adsorption of bacteria onto the cartridge. Bacteria were found adhering to the beads contained in the cartridge.

Conclusion
Our preliminary data show that the S100ABC effectively reduces the circulating bacterial load. The S100ABC could be an adjunct sorbent for reducing S. aureus in human blood, supporting antibiotic therapy in patients with S. aureus-induced septic shock.
#102 Increased expression of carbonic anhydrase 4 in megalin deficiency
Authors: Klahn Peter Andreasen , Berg Peder Matzen , Svendsen Samuel Levi Svinth , Tan Yifan , Sørensen Mads Vaarby , Weyer Kathrin , Damkier Helle Hasager , Rinschen Markus , Leipziger Jens , Nielsen Rikke 
Published: May 2024

Abstract

Background and Aims
Megalin is an endocytic receptor located in the apical membrane of proximal tubule (PT) cells. It prevents low molecular-weight proteinuria by reuptake of a variety of proteins from the filtrate. Megalin is required for normal uptake of Cubilin-bound proteins, but it is unknown if the receptor is important for other apical PT proteins. Carbonic anhydrase 4 (CA4) is an enzyme crucial for PT bicarbonate reuptake. Our aim was to investigate the relationship between the expression patterns of these two proteins.

Method
A mouse model of kidney-specific mosaic megalin-knockout (M-KO). Liquid chromatography-mass spectrometry (LC-MS) on mouse kidney cortex. Immunohistochemistry (IHC), electron microscopy (EM) and Western blotting (WB) of mouse kidney. Biochemical analysis of mouse blood and urine.

Results
LC-MS revealed a 4.23-fold increase in CA4 abundance in M-KO mice together with smaller but also statistically significant alterations in other acid-base-associated proteins. IHC shows that the increase in CA4 abundance specifically was in the cells lacking megalin, while cells with megalin retained normal abundance. The same pattern was observed in a biopsy from a patient lacking megalin. WB revealed increased shedding of CA4 in urine from M-KO mice and EM showed mislocalization of CA4.

Conclusion
We show a hitherto unknown relationship where the expression and subcellular localization of CA4 is altered in PT-cells lacking megalin and show that M-KO mice have altered acid-base handling. Comparable blood parameters at baseline are maintained despite differences in urinary excretion and when challenged with acetazolamide the urinary excretion of the groups becomes alike, however blood parameters become different. While the mechanisms and full extend are unknown, this links megalin to the acid-base regulating systems of the PT.
#1715 Role of T cell profile (Th1/Th2/Th17/Treg) and podocyturia in the peripheral blood of patients with preeclampsia versus normal pregnancy
Authors: Kaul Anupma , Agarwal Vikas , Pandey Amita 
Published: May 2024

Abstract

Background and Aims
The concept of the balance between Th17/Treg cell immunity plays important role in determining pregnancy outcomes. Does Treg/TH17 play a role in pathogenesis of preeclampsia associated proteinuria and its implication on irreversible renal damage was the research question.

Method
This hospital based prospective study conducted in the Department of obstetrics and gynecology at a tertiary care medical college between October 2018 till October 2020 and assessment of T cell profiling and urinary podocyturia among all pregnancies with clinical evidence of preeclampsia and compared it with normal pregnancy monitoring for maternal and foetal outcomes. Repeat assessment of Th profiling and podocyturia was done after 3 months post partum to look for any residual effect.

Results
A total of 40 patients of preeclampsia and 40 control were enrolled in the study with median age group (24.58 ± 1.22 vs 25.16 ± 1.01). The percentage of Th1 and Th2 were higher for the preeclampsia group as compared to the control group with no change in the percentage of Th17 subsets while Th17 1 were found higher and percentage of Treg (8.1 ± 3.19 vs 2.3 ± 1,05, p = 0.001) lower in the peripheral blood of the preeclampsia group at time of delivery however the ratio of Th1/Treg, Th2/Treg, Th17/Treg and Th17.1/Treg were found significantly lowered after 6 weeks of delivery among those with preeclampsia nearly comparable to the normal pregnancy group The quantitative assessment of podocyte in urine using antinephrin showed increase numbers among preeclamptic pregnancies compared to normal yet it settled within 6 weeks of delivery.

Conclusion
Women with preeclampsia per se does not increase the risk to exacerbation of kidney disease however greater research mandates to assess the women at greatest risk of kidney disease after pre-eclampsia to have good maternal and foetal outcomes.