Nitric Oxide Levels as a Marker of Intradialytic Hypertension in End-Stage Renal Disease Patients.

Intradialytic hypertension (IDH) is an important emerging complication in hemodialysis patients. No study has examined the diagnostic markers of various risk factors for the occurrence of IDH in chronic hemodialysis patients. Therefore, our study aimed to assess the use of nitric oxide (NO) as a marker of IDH among end-stage renal disease patients. The patients were divided into two groups: Group I (40 patients) with IDH and Group II (40 patients) without IDH. For all participants, a full medical history was taken, followed by laboratory examinations to measure the level of NO and a clinical examination. The dose of erythropoietin per week, the level of intact parathyroid hormone, and platelet count were significantly higher in Group I than in Group II, whereas the mean level of NO (2.10 ± 1.23 pmol/L) was highly significantly lower in patients with IDH (P < 0.001). Multivariate analysis showed that hypertension (odds ratio: 1.824, 95% confidence interval: 1.273-2.982) and the level of NO (odds ratio: 1.68, 95% confidence interval: 1.13-2.97) were independent risk factors for IDH. The receiver operating characteristic curve showed that the cutoff point of NO was 2.52 µmol/L to differentiate between cases with and without IDH (area under the curve = 0.844). Our findings support previous research regarding the involvement of endothelial dysfunction and a higher sodium level in the pathogenesis of IDH. We also found that the NO level had a good diagnostic value for the occurrence of IDH at a cutoff of 2.52 µmol/L.

Long Non-Coding RNA TUG1 Gene Polymorphism and TUG1 Expression Level as Molecular Biomarkers of Systemic Lupus Erythematosus and Lupus Nephritis.

Long non-coding RNA (lncRNA) TUG1 acts as a proto-oncogene, allowing the proliferation of tumor cells, and it has been related to inflammation. Therefore, we aimed in this study to investigate for the first time the role of TUG1 gene polymorphism and the TUG1 level as biomarkers in systemic lupus erythematosus (SLE) and their link to lupus nephritis 145 SLE. A total of 145 healthy controls were subjected to clinical and laboratory evaluation. The disease activity was assessed by the SLE disease activity index (SLEDAI) score. SLE patients were divided into two subgroups according to the presence of lupus nephritis. The TUG1 gene polymorphisms rs5749201 and rs886471 were determined by Sanger sequencing, and TUG1 expression was assessed by qRT-PCR. There was a significant increase in the risk of SLE AA, TA, dominant genotypes, and the A allele of rs5749201 (p < 0.001) by 4.9-, 10.1-, 6.5-, and 2.5-fold in comparison to the relative control. GG and TG, dominant genotypes and the G allele of rs886471 (p < 0.01) increased the risk by 5.09-, 11.9-, 6.5-, and 2.6-fold. AA, A allele, dominant and recessive rs5749201genotypes increased the risk of lupus nephritis by 16.6-, 7.4-, 7.1-, and 12.2-fold, respectively (p < 0.05). GG, dominant and recessive genotypes, and the G allele of rs886471 increased the risk of lupus nephritis by 17.04-, 7.8-, 9.4-, and 6.08-fold, respectively (p < 0.05). Additionally, the AG haplotype increased the risk of SLE and lupus nephritis by 2.7- and 7.8-fold, respectively. The AA rs5749201 and GG rs886471 variants are significantly associated with more severe disease (p < 0.001). TUG1 expression was significantly higher in SLE than in the control and in the lupus nephritis than in non-lupus nephritis cases (p < 0.05). Interestingly, AA rs5749201 and GG rs886471 were significantly associated with higher TUG1 levels (p < 0.001). It was also found that AA rs5749201 and high SLEDAI were predictors of lupus nephritis. Overall, our findings illustrated for the first time that TUG1 gene rs5749201 and rs886471 variants were associated with increased risk of SLE, more severe disease, and lupus nephritis, and the TUG1 level could be used as a diagnostic biomarker of SLE and lupus nephritis.

Potential impact of serpin peptidase inhibitor clade (A) member 4 SERPINA4 (rs2093266) and SERPINA5 (rs1955656) genetic variants on COVID-19 induced acute kidney injury.

Background: SARS-CoV-2 has a number of targets, including the kidneys. Acute Kidney Injury (AKI) might develop in up to a quarter of SARS-CoV-2 patients. In the clinical environment, AKI is linked to a high rate of death and leads to the progression of AKI to chronic renal disease. Aim: We aimed to investigate rs2093266 and rs1955656 polymorphisms in SERPINA4 and SERPINA5 genes, respectively, as risk factors for COVID-19 induced AKI. Subjects and methods: A case-control study included 227 participants who were divided into three groups: 81 healthy volunteers who served as controls, 76 COVID-19 patients without AKI and 70 COVID -19 patients with AKI. The TaqMan assay was used for genotyping the SERPINA4 (rs2093266) and SERPINA5 (rs1955656) polymorphisms by real-time PCR technique. Results: Lymphocytes and eGFR showed a significantly decreasing trend across the three studied groups, while CRP, d-Dimer, ferritin, creatinine, KIM-1and NGAL showed a significantly increasing trend across the three studied groups (P < 0.001). Rs2093266 (AG and AA) genotypes were significant risk factors among non-AKI and AKI groups in comparison to controls. Rs1955656 (AG and AA) were significant risk factors among the AKI group, while AA was the only significant risk factor among the non-AKI group. Recessive, dominant, co-dominant, and over-dominant models for genotype combinations were demonstrated. The GG v AA, GG + AG v AA, and GG v AG + AA models of the rs2093266 were all significant predictors of AKI, whilst only the GG v AA model of the rs1955656 SNP was a significant predictor. The logistic regression model was statistically significant, χ2 = 56.48, p < 0.001. AKI was associated with progressed age (OR = 0.95, 95% CI: 0.91-0.98, p = 0.006), suffering from chronic diseases (OR = 3.25, 95% CI: 1.31-8.01, p = 0.010), increased BMI (OR = 0.89, 95% CI: 0.81-0.98, p = 0.018), immunosuppressive (OR = 4.61, 95% CI: 1.24-17.16, p = 0.022) and rs2093266 (AG + AA) (OR = 3.0, 95% CI: 1.11-8.10, p = 0.030). Conclusion: Single nucleotide polymorphisms (rs2093266) at SERPINA4 gene and (rs1955656) at SERPINA5 gene were strongly linked to the development of AKI in COVID-19 patients.

TCF7L2 gene polymorphism as a risk for type 2 diabetes mellitus and diabetic microvascular complications.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic condition with various genetics and environmental influences that affects the capacity of the body to produce or use insulin resulting in hyperglycemia, which may lead to variable complications. It is one of the world's rising health problems. There is emerging evidence that some genetic polymorphisms can impact the risk of evolving T2DM. We try to determine the relationship of (rs7903146) variant of the Transcription factor 7-like 2 (TCF7L2) gene with T2DM and its microvascular complications. METHODS AND RESULTS: This case-control study included 180 subjects: 60 diabetic patients without complications, 60 diabetic patients with microvascular complications and 60 matched healthy controls. Genotypes of rs7903146 (C/T) SNP in the TCF7L2 gene were evaluated by real-time polymerase chain reaction via TaqMan allelic discrimination. Logistic regression was used to detect the most independent factor for development of diabetes and diabetic microvascular complications. Variant homozygous TT and heterozygous CT genotypes were significantly increased in diabetic without complications and diabetic with complications groups than controls (p = 0.003, 0.001) respectively. The T allele was more represented in both patient groups than controls with no significant difference between patient groups. TT genotype as well as T allele was significantly associated with increased T2DM risk. CONCLUSION: The T allele of rs7903146 polymorphism of TCF7L2 confers susceptibility to development of T2DM. However, no significant association was found for diabetic complications.

Developing and validating a risk score model for prediction of acute kidney injury in non-ICU hospitalized patients.

BACKGROUND: Acute kidney injury (AKI) is a common complication in hospitalized patients. Several risk score models have been designed for intensive care unit (ICU) patients. We aim to establish a new risk prediction score for AKI patients in general wards. MATERIALS AND METHODS: All hospitalized ward patients who developed AKI were included in our study. To develop a new prediction score model we used the data collected from 107 patients who developed AKI. We used our prospective validation cohort (122 patients) to develop and validate this prediction score model of AKI. RESULTS: Of 10,243 patients, 107 (1%) patients developed AKI 24 hours after admission to the general wards. Mortality rate was 26.2%. A score model of 15 points, based on clinical and laboratory data, was developed for prediction of AKI. We demonstrated a cutoff value ≥ 4 out of 15 as a predictor of AKI in non-ICU patients. The area under the receiver operating characteristic (AUC ROC) value of the score model was 0.950, 95% CI (confidence interval) and the p-value < 0.001 with sensitivity of 94.39 and specificity of 81.43. On applying this score model on a prospective group of patients (validation group n = 122), the AUC ROC value was 0.826. CONCLUSION: We developed and validated a new risk score model with a cutoff value ≥ 4 out of 15 for prediction of AKI in non-ICU patients. It will help in the early prediction of AKI in non-ICU patients.

Cell-free long non-coding RNAs (LY86-AS1 & HCG27_201and GAS5) as biomarkers for pre-diabetes and type 2 DM in Egypt.

BACKGROUND: Increasing interest has been focused on lncRNAs as potential markers in the pathogenesis and progression of numerous diseases. AIM: We aimed to investigate the expression pattern and role of cell-free lncRNAs (GAS5, HCG27_201 and LY86-AS1) in pre-diabetic, diabetic and T2DM groups. SUBJECTS & METHODS: Quantification of the expression level of cell-free lncRNAs (GAS5, HCG27_201 and LY86-AS1) was performed by real-time PCR in 210 individuals classified in diabetic (T2DM), pre-diabetic and control groups. RESULTS: Significant differences were observed in the relative expression level of lncRNAs (GAS5, LY86-AS1 and HCG27_201) among the three studied groups. The LncRNA expression levels decreased gradually from the control to the pre-diabetic group and reached the lowest values in the T2DM group. The A receiver operating characteristic curve (ROC) was applied to identify a cut-off value for each of the three genes among our groups. The three lncRNAs showed promising results in discriminating between the diabetic patients and controls, with HCG27_201 gene expression having the best performance. Furthermore, lncRNA expression was able to predict the future development of DM in the pre-diabetics because ROC analysis among diabetics and pre-diabetics revealed considerable results. GAS5 gene expression showed the best performance. Additionally, HCG27_201 expression was the most valuable biomarker for differentiating between pre-diabetics and controls and presented a sensitivity of 91% and specificity of 64%. CONCLUSIONS: We concluded that cell free lncRNAs (GAS5, LY86-AS1 and HCG27_201) could be considered promising diagnostic and predictive biomarkers for DM and that HCG27_201 could act as a potential diagnostic biomarker for pre-diabetes.

Leptin receptor gene (A/G) polymorphism rs1137101 and renal cell carcinoma.

Leptin plays an important role in carcinogenesis as leptin/leptin receptor signaling promotes the angiogenesis, proliferation, and inhibits epithelial cell apoptosis. Variants in the leptin receptor gene have potential associations with renal cell carcinoma (RCC). We aimed to investigate association of rs1137101 (A/G) polymorphism at LEPR gene with risk of RCC and patients survival. 123 individuals were classified into group I: 73 RCC patients and group II: 50 healthy controls. Genotyping of the Gln223Arg (A/G) polymorphism rs1137101 at LEPR gene was analyzed using allelic discrimination assay by Real-Time PCR technique. GG genotype was the most frequent among RCC patients (67.1%), while AA genotype was the most frequent in controls (60%); (p < 0.001). By univariate cox regression: gene polymorphism (GG versus GA +AA), stage, histopathologic subtype, and grade were found to affect survival significantly; however, the multivariate analysis showed that only gene polymorphism (GG versus GA +AA) and tumor stage significantly affect survival. LEPR gene variants rs1137101 might be a candidate risk factor for RCC in Egypt. GG genotype is associated with more aggressive tumor behavior and shorter survival compared with GA & AA genotypes so, genotyping of Gln223Arg (A/G) rs1137101 could also predict RCC outcome.