BMC Nephrology最新文献

Background: Activated leukocyte cell adhesion molecule (ALCAM) serves as an important effector that activates and traffics lymphocytes into tissues. The expression and role of ALCAM in IgA nephropathy (IgAN) remain unclear. Here, we aim to evaluate the expression and effect of ALCAM in IgAN patients.

Methods: We performed a prospective study including 71 IgAN patients, and 41 controls. Serum and uALCAM levels were evaluated. Renal expression of ALCAM and its ligand S100B were measured. The correlation of serum ALCAM with clinical data, renal pathology, and prognosis was analyzed. Cox regression analysis was conducted to identify independent factors associated with prognosis. Kaplan-Meier survival analysis was performed to explore the role of serum ALCAM.

Results: Circulating ALCAM levels were higher in IgAN patients than in controls. Serum ALCAM levels showed a positive correlation with proteinuria and renal pathology. Renal ALCAM expression was also elevated in IgAN patients. IgAN patients were divided into low and high ALCAM groups (< 4.76, and ≥ 4.76 ng/mL) based on the optimal cut-off value for predicting renal progression. The high ALCAM group exhibited more severe clinical parameters and renal pathology. High serum ALCAM level was an independent risk factor for IgAN progression. IgAN patients with high ALCAM level exhibited a lower cumulative renal survival rate compared to the low-level group.

Conclusions: In summary, serum ALCAM level in IgAN patients was elevated, which was consistent with clinical and pathological severity, and served as an independent risk factor and a promising novel predictor for the progression of IgAN.

Clinical trial number: Not applicable.

Background: Autosomal dominant tubulointerstitial kidney disease caused by uromodulin mutation (ADTKD-UMOD) is a hereditary condition characterized by progressive renal dysfunction, often requiring renal replacement therapy by middle age. A notable feature is a strong family history of chronic kidney disease (CKD) and hyperuricemia; however, the absence of urinary abnormalities often delays diagnosis. To facilitate early CKD management, a diagnostic method that is simpler than genetic analysis yet strongly indicative of ADTKD-UMOD is needed.

Methods: Serum and urinary UMOD levels were measured in patients with ADTKD-UMOD, healthy controls, and patients with other diseases. We investigated whether reduced UMOD levels are a distinctive feature of ADTKD-UMOD.

Results: In 13 cases of ADTKD-UMOD, the serum UMOD (sUMOD) was 24.5 ± 13.9 ng/ml, the serum UMOD/GFR (sUMOD/GFR) was 1.23 ± 0.96, and the urinary UMOD/Cr (uUMOD/Cr) was 1.8 ± 0.9 mg/gcr. In the ADTKD-UMOD dataset, the sUMOD values were significantly lower than those in the other disease datasets. The UMOD/Cr and sUMOD/eGFR values also tended to be lower, although statistically significant differences were observed only in limited comparisons. The ROC analysis revealed that a serum UMOD concentration of < 56.4 ng/ml or sUMOD/GFR of < 1.71 is strongly suggestive of ADTKD-UMOD.

Conclusions: Measurement of UMOD protein levels is a useful tool for the diagnosis of　ADTKD-UMOD. Considering the stability of the procedure, serum UMOD may be more reliable than urinary UMOD measurement.

Background: Monocyte chemoattractant protein-1 (MCP-1) has been implicated in the pathogenesis of chronic kidney disease (CKD); however, its clinical significance in CKD remains unclear. This study investigated the association between plasma MCP-1 levels and kidney and cardiovascular outcomes in patients with CKD.

Methods: This multicenter, prospective, observational analysis used data from the BRIGHTEN study. Participants with anemia and CKD (eGFR < 60 mL/min/1.73 m²) were classified into four groups based on quartiles of their baseline plasma MCP-1 levels. The primary outcomes included kidney outcomes (a composite of initiation of maintenance dialysis, kidney transplantation, 50% decline in eGFR, or eGFR ≤ 6 mL/min/1.73 m²), the annual rate of eGFR decline, cardiovascular outcomes, and all-cause mortality. Associations were assessed using Cox proportional hazard and linear mixed-effects models.

Results: This study included 1,447 participants with advanced CKD (median eGFR 17.9 mL/min/1.73 m²). The group with the lowest MCP-1 level (< 324.5 pg/mL) had the highest baseline eGFR. In the univariable analyses, higher MCP-1 levels were associated with an increased risk of kidney and cardiovascular outcomes (log-rank p < 0.01 and p = 0.03, respectively), although these associations were not significant after multivariable adjustment. Analysis of the annual eGFR decline using a multivariable linear mixed-effects model revealed that higher MCP-1 levels were associated with an additional eGFR decline of approximately 1.0 mL/min/1.73 m² per year compared to the lowest MCP-1 group. MCP-1 levels were not associated with mortality.

Conclusions: In patients with CKD, higher plasma MCP-1 levels are associated with a more rapid decline in kidney function but not with the composite outcome of kidney failure. MCP-1 was not associated with cardiovascular outcomes or mortality in this population cohort.

Background: Renal ischemia-reperfusion injury (IRI) is a common clinical condition that triggers a complex cascade of biological responses, including inflammation, oxidative stress, and apoptosis. These responses can lead to impaired renal function and acute kidney injury (AKI). Despite advancements in therapeutic agents, there is still a need for safe and effective drugs. In this study, we investigated the therapeutic effects and mechanisms of Gancao Xiexin Decoction (GCXXD), an herbal compound known for its anti-inflammatory, antioxidant, and immunomodulatory properties, in treating renal IRI.

Methods: We utilized network pharmacology to identify the intersection targets of the active ingredients in GCXXD and AKI. Cytoscape software was used to obtain core targets, and the String database was used to map the interaction network of these targets. GO and KEGG enrichment analyses were conducted to assess the biological functions and potential pathways involved. Molecular docking simulations were performed to examine the binding of the main active components of GCXXD to the key pathways. Validation experiments were conducted using an IRI mouse model and a hypoxia-reoxygenation-mediated HK2 injury model.

Results: A total of 11 core targets of GCXXD for the treatment of AKI were identified. GO and KEGG analyses revealed enrichment in biological functions related to oxidative stress, apoptosis, and the PI3K/AKT signaling pathway. Molecular docking results indicated strong binding affinity between the key active components (baicalein, ginsenoside Rh2, quercetin, and wogonin) of GCXXD and the PI3K/AKT pathway. In both in vivo and ex vivo experiments, GCXXD activated the PI3K/AKT pathway and ameliorated renal IRI.

Conclusion: This study demonstrated that GCXXD effectively improved ischemia-reperfusion-induced renal injury primarily via activating the PI3K/AKT pathway. These findings provided a scientific basis for the clinical application of GCXXD and paved the way for the development of new drugs and therapeutic strategies.