Fabry disease, a rare genetic disorder affecting multiple organs, has understudied correlations among enzyme activity, genotype, and clinical manifestations in patients of different sexes with classical and late-onset phenotypes. In this study, clinical data, α-Gal A activity, and GLA gene test results of 311 patients, who were categorized by classical and late-onset phenotypes, ⩽5% and > 5% of the normal mean value of enzyme activity, and truncated and nontruncated mutation groups, were collected. The common clinical manifestations of Fabry disease included acroparesthesia, hypohidrosis/anhidrosis, neuropsychiatric system, and renal and cardiovascular involvement. Multiorgan involvement was higher in males and classical phenotype patients. In both sexes, classical patients commonly presented with acroparesthesia and multiorgan involvement, whereas late-onset patients showed renal, neuropsychiatric, and cardiovascular involvement. Male and classical patients had lower enzyme activity than female and late-onset patients, respectively. Classical males with enzyme activity of ⩽5% of the normal mean level showed higher multiorgan involvement frequency than those with enzyme activity of > 5%, whereas no significant difference was observed among females. Ninety-five gene mutation sites were detected, with significant phenotype heterogeneity in patients with the same mutation. No significant difference in enzyme activity or clinical manifestations was observed between truncated and nontruncated mutations. Overall, male patients with Fabry disease, regardless of classical or late-onset phenotype, have a higher frequency of multiple-organ involvement and lower α-Gal A activity than female patients. α-Gal A activity was closely correlated with clinical symptoms in males but weakly correlated with clinical manifestations in females. The clinical manifestations of patients with the same mutation are heterogeneous, and the correlation between gene mutation and enzyme activity or clinical manifestation is weak.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Age of Onset ; alpha-Galactosidase/metabolism* ; China ; Fabry Disease/enzymology* ; Genotype ; Mutation ; Phenotype ; Sex Factors ; East Asian People/genetics*

Humans ; Blood Pressure/physiology* ; Renal Insufficiency, Chronic ; Hypertension/drug therapy* ; Antihypertensive Agents/therapeutic use*

Objective:To explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in different regions of the kidney in distinguishing IgA nephropathy (IgAN) patients from healthy volunteers.Methods:This study was a cross-sectional study. Eighty-four patients diagnosed with IgAN (IgAN group) who underwent renal biopsy (lower pole of the left kidney) and were pathologically confirmed at the First Medical Center of PLA General Hospital from February 2022 to September 2023 and thirty-four healthy volunteers (control group) were included prospectively. The regions of interest were outlined in the right renal cortex, medulla, and parenchyma for all subjects, and the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D *), and perfusion fraction (f) were measured in the corresponding regions. The differences in IVIM-DWI parameters between the IgAN group and the control group were compared using the student′s t-test or the Mann-Whitney U test. Receiver operating characteristic curve analysis was performed on the parameters with statistically significant differences, and the area under the curve (AUC) was calculated. Results:There were statistically significant differences in renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values between the IgAN group and the control group ( Z=-3.03, -2.21, -2.62, -2.03, -2.03; P=0.002, 0.027, 0.009, 0.043, 0.042). The AUCs (95% CI) for diagnosing IgAN using renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values were 0.679 (0.586-0.762), 0.630 (0.537-0.717), 0.654 (0.535-0.774), 0.619 (0.497-0.742), and 0.620 (0.495-0.745), respectively. There were no statistically significant differences in renal medullary ADC, D, renal cortex, medulla and parenchyma D *, renal cortical and renal parenchymal f values between the two groups ( P>0.05). Conclusion:The quantitative parameters of renal IVIM-DWI are influenced by different measurement regions, among which the ADC, D of renal cortex and parenchyma, and f of renal medulla can be used for the initial diagnosis of IgAN.

The risk factors of acute kidney injury caused by strenuous exercise include dehydration of the body, elevated body temperature, and intake of large amounts of sugary drinks after exercise, etc. The possible mechanism of the injury may be the inflammatory reaction of the body or the kidney itself, and the accumulation of various metabolites causing damage to the structure and function of the kidney under the induction of various risk factors. Repeated exposure to those risk factors not only increase the risk of acute kidney disease, but also may lead to chronic kidney disease. The paper reviews the definition, epidemiology, clinical manifestations, pathogenesis, and prevention measures of exercise-related kidney injury, to provide guidance for the formulation of appropriate exercise programs.

Objective:To investigate the association between ambulatory arterial stiffness index (AASI) and renal poor prognosis in patients with chronic kidney disease (CKD).Methods:A prospective study was conducted to enroll 117 non-dialysis patients with CKD who volunteered for receiving ambulatory blood pressure monitoring test from December 2017 to December 2018 in the Department of Nephropathy of the First Medical Center of Chinese PLA General Hospital. According to the AASI tertiles, patients were divided into low AASI group (≤0.414, n=38), medium AASI group (0.414-0.517, n=40), and high AASI group (≥0.517, n=39). The differences of clinical baseline information among the three groups were compared. The follow-up time was until August 2020. Kaplan-Meier curve and Cox proportional hazard regression model were used to explore the effect of AASI on renal poor prognosis. Results:The median age of 117 patients was 61(49, 65) years old. There were 80 males (68.4%) and patients with hypertension accounted for 77.8%(91 cases). After a median follow-up of 27 months, 34 cases had composite endpoint events [renal replacement therapy (dialysis or kidney transplantation), 40% estimated glomerular filtration rate (eGFR) decline, and death], of which 10 patients were on dialysis, 19 patients had 40% eGFR decline, and 5 patients died. There were significant differences in age, hemoglobin, body mass index, eGFR, 24 h systolic blood pressure (SBP), daytime SBP, nighttime SBP, morning SBP, 24 h mean arterial pressure and 24 h pulse pressure among the three groups (all P<0.05). Kaplan-Meier survival analysis indicated that higher AASI was associated with lower cumulative survival rate in patients (Log-rank test χ2=13.111, P=0.001). Univariate Cox regression analysis showed that high AASI was an influencing factor for renal endpoint events ( P<0.05), and after adjusting for age, gender, mean arterial pressure, eGFR, 24 h urine protein, diabetes and body mass index, high AASI was an independent influencing factor for renal poor prognosis in classification and continuous variable analysis models ( HR=2.88, 95% CI 1.00-8.26, P=0.050; HR=1.50, 95% CI 1.02-2.21, P=0.039). Conclusion:High AASI is an independent influencing factor for renal poor prognosis in CKD patients.

Netrin-1, an axon guidance factor, and its receptor UNC5B play important roles in axonal development and angiogenesis. This study examined netrin-1 and UNC5B expression in kidneys with diabetic kidney disease (DKD) and investigated their roles in angiogenesis. Netrin-1 and UNC5B were upregulated in streptozotocininduced DKD Wistar rats, and their expression was compared with that in healthy controls. However, exogenous netrin-1 in UNC5B-depleted human renal glomerular endothelial cells (HRGECs) inhibited cell migration and tubulogenesis. This effect was likely associated with SRC pathway deactivation. Netrin-1 treatment also eliminated the pro-angiogenic effects of exogenous VEGF-165 on UNC5B-silenced HRGECs. These results indicate that UNC5B antagonizes netrin-1 and that UNC5B upregulation contributes partly to enhancing angiogenesis in DKD. Therefore, introducing exogenous netrin-1 and depleting endogenous UNC5B are potential strategies for reducing the incidence of early angiogenesis and mitigating kidney injury in DKD.

This study aimed to compare clinical features between membranous nephropathy (MN) and nonmembranous nephropathy (non-MN), to explore the clinically differential diagnosis of these two types, and to establish a diagnostic model of MN. After renal biopsy was obtained, 798 patients were divided into two groups based on their examination results: primary MN group (n = 248) and non-MN group (n = 550). Their data were statistically analyzed. Logistic regression analysis indicated that anti-PLA2R antibodies, IgG, and Cr were independently correlated with MN, and these three parameters were then used to establish the MN diagnostic model. A receiver operating characteristic (ROC) curve confirmed that our diagnostic model could distinguish between patients with and without MN, and their corresponding sensitivity, specificity, and AUC were 79.9%, 89.4%, and 0.917, respectively. The cutoff value for this combination in MN diagnosis was 0.34. The established diagnostic model that combined multiple factors shows a potential for broad clinical applications in differentiating primary MN from other kidney diseases and provides reliable evidence supporting the feasibility of noninvasive diagnosis of kidney diseases.

Objective:To explore the role and mechanism of the B7-H1 expressed by auto-keratinocytes in the intermingled skin grafting model in vitro(MELC). Methods:The intermingled skin grafting model(MELC) was established in vitro. Flow cytometry was performed to detect the expressions of B7-H1 in keratinocytes. The expressions of PD-1 in lymphocytes were measured at the same time. The levels of IL-10,Foxp3 and GATA-3 mRNA in lymphocytes were detected by Real-time quantitative PCR. Results: Through flow eytometry,in the MELC with auto-keratinocytes,the expression of B7-H1 in auto-keratinocytes and the PD-1 in lymphocytes were rising trend and the rising rate was in time-dependent manners(P<0. 01). RT-PCR assay indicated that the relative levels of IL-10, Foxp3,GATA-3mRNA expression were significant raised and the rising rate was in time-dependent manners (P<0. 01). Conclusion:In the intermingled skin grafting model,the auto-keratinocytes could express B7-H1 to enhance the expression of PD-1 in T cells. When B7-H1 combined with PD-1,the Th2 cells and Foxp3+Tregs were induced and suppressed the immune response in the intermingled skin grafting model.