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  • 1
    In: Biomarkers in Medicine, Future Medicine Ltd, Vol. 14, No. 16 ( 2020-11), p. 1521-1536
    Abstract: Aim: An advanced proteomics platform for protein biomarker discovery in diabetic chronic kidney disease (DKD) was developed, validated and implemented. Materials & methods: Three Type 2 diabetes mellitus patients and three control subjects were enrolled. Urinary peptides were extracted, samples were analyzed on a hybrid LTQ-Orbitrap Velos Pro instrument. Raw data were searched using the SEQUEST algorithm and integrated into Proteome Discoverer platform. Results & discussion: Unique peptide sequences, resulted sequence coverage, scoring of peptide spectrum matches were reported to albuminuria and databases. Five proteins that can be associated with early DKD were found: apolipoprotein AI, neutrophil gelatinase-associated lipocalin, cytidine deaminase, S100-A8 and hemoglobin subunit delta. Conclusion: Urinary proteome analysis could be used to evaluate mechanisms of pathogenesis of DKD.
    Type of Medium: Online Resource
    ISSN: 1752-0363 , 1752-0371
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2020
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  • 2
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Interactions among multiple molecules and signalling pathways contribute to the pathogenesis and progression of diabetic kidney disease (DKD). Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aim of the study was to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients. The molecular mechanisms of lncRNAs intervention were evaluated in relation to a particular miRNA profile. Method A total of 136 patients with type 2 DM and 25 healthy subjects were enrolled in a cross-sectional case series study and assessed concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), and urinary miRNA21, 124, 93, 29a (quantified by a real-time PCR System). Results Multivariable regression analysis yielded models in which urinary lncRNA MALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93 and 29a (p & lt;0.0001; R2=0.727); urinary lncRNA NEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, and 29a (p & lt;0.0001; R2=0.702); urinary lncRNA MIAT correlated directly with miRNA93 and 29a, and eGFR (p & lt;0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, and 124 (p & lt;0.0001; R2=0.654); urinary lncRNA TUG1 correlated directly with eGFR, miRNA93 and 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, and 124 (p & lt;0.0001; R2=0.748). The results provided document upregulated lncRNA MALAT1 and NEAT1, as well as miRNA21 and 124. By contrast, lncRNA MIAT and TUG1, and miRNA93 and 29a were downregulated. Conclusion In patients with type 2 DM lncRNAs exert distinct functions in different cell types, either deleterious or protective, at both glomerular and tubular level. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1465709-0
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  • 3
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Hypokalemia is associated with progression of chronic kidney disease (CKD), although the possible underlying mechanisms are not well established. Several observational studies showed that low or even low to normal serum potassium levels predict the decline of kidney function in the general population. However, this hypothesis has not been yet investigated in patients with reduced nephron number as are congenital single kidney (cSK) patients. Our aim was to prospectively examine the association of plasma potassium with risk of rapid kidney function decline in a cSK patients’ cohort. Method A cohort of 67 consecutive patients with cSK (mean age = 44.4+/-15.7 years; males 29p (43.28%)), with a mean estimated glomerular filtration rate (eGFR) = 65.2+/-28 ml/min/1.73m2, were enrolled in this longitudinal observational study. We evaluated the associations of plasma potassium levels with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). The eGFR was assessed with CKD-EPI formula. The rapid kidney function decline was defined as a fall in eGFR of more than 5 ml/min/1.73 m2/year, according to the KDIGO guidelines. Results During a mean follow-up time of 20.16+/-9.3 months, 31.34% (21p) of patients presented decline of eGFR, with a fall of mean – 11.6+/-5.43 ml/min/1.73m2/year. In univariable regression analysis, the decline of eGFR was associated with baseline eGFR (R2=0.09, p=0.013), age (R2=0.31, p & lt;0.001), male gender (R2=0.14, p=0.001), arterial hypertension (R2=0.17, p=0.001), diabetes mellitus (R2=0.13, p=0.003), coronary artery disease (R2=0.12, p=0.005), uric acid (R2=0.23, p & lt;0.001), C-reactive protein (R2=0.09, p=0.011), proteinuria/24h (R2=0.14, p=0.002) and serum potassium (R2=0.29, p & lt;0.001). The serum potassium levels were significantly lower in the group with rapid decline of eGFR, with a mean of 3.62+/-0.41 mmol/L vs. 4.51+/-0.74 mmol/L, p & lt;0.001. In multivariable regression analysis, the association between lower serum potassium levels and risk of rapid eGFR decline remained significant (HR=1.65; 95%CI, 1.105-2.49; p=0.015). Conclusion These results suggest that lower serum potassium levels may play a role in rapid kidney function decline in the cSK population. Further research is required to assess whether the higher risk of kidney function decline in cSK individuals could be diminished when optimised serum potassium levels strictly.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1465709-0
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  • 4
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 36, No. Supplement_1 ( 2021-05-29)
    Abstract: To date, endoscopic retrograde colangio-pancreatography (ERCP) represents a major advance in gastro-intestinal endoscopy. The ERCP is a safe and minimally invasive therapy for pancreatic-biliary diseases. Adverse events (AEs) associated to ERCP are well described. However, little is known about acute kidney injury (AKI) associated to ERCP. The aim of this study was to evaluate the incidence of post-ERCP AKI and the risk factors for AKI development. The prognostic implication of ERCP-associated AKI in in-hospital mortality has been also assessed. Method In this prospective observational study, we evaluated 396 patients who underwent ERCP, from the 3rd January 2019 through the 27th January 2020. AKI was defined as an increase in serum creatinine (SCr) ≥ 0.3 mg/dl or an increase in SCr ≥ 50% and/or by a decrease in urine output to 0.5 ml/kg/hour for 6 hours, in the first 48 hours following ERCP. Logistic uni- and multivariable regression methods were used to determine predictors of AKI and in-hospital mortality. A two-tailed value & lt;0.05 was considered significant. Results In the studied group, median age was 69 years, interquartile range [IQ =17], 183 (46.21%) patients being males. ERCP-associated AKI was detected in 103 patients (26%). Univariable regression analysis showed that AKI was associated with baseline eGFR (r=0.246, P & lt;0.001), age (r=0.108, P=0.04), Charlson Comorbidity Index (CCI) (r=0.239, P & lt;0.001), and with the following pre-ERCP parameters: systemic inflammatory response syndrome (SIRS) (r=0.125, P=0.012), serum albumin (r= -0.232, P & lt;0.001), C-reactive protein (r=0.246, P & lt;0.001), hematocrit (r= -0.130, P=0.009), platelet count (r=-0.155, P=0.001), total bilirubin level (r=0.230; P & lt;0.001), alaninamino transferase level (r= -0.101, P=0.044), and alcaline phosphatase level (r=0.286, P & lt;0.001). In the multivariable regression analysis, the independent predictors of AKI were: baseline eGFR (adjusted odds ratio (OR) 0.941, 95% confidence interval (CI): 0.927–0.956, P & lt;0.001), CCI score (OR=1.17, 95%CI: 1.05-1.32, P=0.005), SIRS (OR=2.02, 95%CI: 1.009-4.036, P=0.047), total bilirubin (OR=1.08, 95%CI: 1.036-1.123, P & lt;0.001), and alcaline phosphatase (OR=1.002, 95%CI:1.001-1.002, P & lt;0.001). AKI was associated with increased in-hospital mortality (7.76 % versus 0.34 %, P & lt;0.001). In our group, AKI was an independent predictor of in-hospital mortality (OR=9.98 , 95% CI: 1.19-83.26, P=0.03). Conclusion In patients undergoing ERCP, AKI was a common complication and an independent risk factor for in-hospital mortality. These findings highlight the importance of early AKI and AKI-related risk factors recognition, in order to minimise the risk for ERCP-associated AKI and to improve the post-ERCP outcome of patients.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1465709-0
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  • 5
    In: International Journal of Medical Sciences, Ivyspring International Publisher, Vol. 18, No. 10 ( 2021), p. 2093-2101
    Type of Medium: Online Resource
    ISSN: 1449-1907
    Language: English
    Publisher: Ivyspring International Publisher
    Publication Date: 2021
    detail.hit.zdb_id: 2151424-0
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