Serum galactose-deficient immunoglobulin A1 in recurrent immunoglobulin a nephropathy after kidney transplantation: A meta-analysis.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a main cause of end stage renal disease (ESRD). Many IgAN patients with ESRD accept kidney allograft for renal replacement. However, disease recurrence occurs after transplantation. Galactose-deficient immunoglobulin A1(Gd-IgA1) has been proved to be a crucial biomarker in the primary IgAN population. METHODS: This meta-analysis aimed to explore the association between serum Gd-IgA1 and IgAN recurrence after renal transplantation and was registered on PROSPERO: CRD42022356952; A literature search was performed and relevant studies were retrieved from the PubMed, Embase and Cochrane library databases from inception to April 27, 2023. The inclusion criteria were: 1) full-text studies; 2) patients with histological diagnosis of IgAN of their native kidneys who underwent kidney transplantation; 3) studies exploring the relationship between serum Gd-IgA1 and IgAN recurrence after kidney transplantation. The exclusion criteria were: 1) reviews, case reports, or non-clinical studies. 2) studies with insufficient original data or incomplete data. 3) studies with duplicated data. Study quality was assessed using Newcastle Ottawa Scale (NOS). Data were pooled using a random-effects model. RESULTS: 8 full-text studies including 515 patients were identified. The Newcastle-Ottawa Scale (NOS) score ranged from 6 to 8. The standard mean difference (SMD) of the level of Gd-IgA1 was significantly higher in recurrence group than in non-recurrence group (SMD = 0.50，95%CI = 0.15-0.85, p = 0.005). Furthermore, Gd-IgA1 levels were higher in recurrence patients than in non-recurrence in both Europe subgroup (SMD 0.45, 95%CI: 0.08-0.82, p = 0.02) and Asia subgroup (SMD 0.90, 95%CI: 0.10-1.70, p = 0.03). However, pretransplant Gd-IgA1 levels showed no significant difference between recurrence and non-recurrence group (SMD 0.46, 95%CI: 0.06-0.99, p = 0.08) in anther subgroup analysis while posttransplant Gd-IgA1 levels were significantly higher in recurrence population than in non-recurrence (SMD 0.57, 95%CI 0.21 to 0.92, p = 0.002). CONCLUSIONS: This meta-analysis showed that posttransplant serum Gd-IgA1 levels are associated with IgAN recurrence after kidney transplantation; however, pretransplant serum Gd-IgA1 levels are not.

Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise.

Moderate-intensity exercise training has been regarded a healthy way to alleviate kidney fibrosis by the transforming growth factor-beta (TGFß) signaling pathway. However, the impact of different intensity exercise training on renal function is unknown, and the underlying mechanism is also unclear. The purpose of this study is to explore the effect of lactic acid in different intensity exercise training on renal fibrosis in spontaneous hypertension. Masson's trichrome staining, immunohistochemistry, lactic acid kit, and Western blotting were applied on the excised renal tissue from six male Wistar-Kyoto rats (WKY) and 18 male spontaneously hypertensive rats (SHR), which were randomly divided into a sedentary hypertensive group (SHR), moderate-intensity exercise hypertensive group (SHR-M), and high-intensity exercise hypertensive group (SHR-H). The results revealed that renal and blood lactic acid, as well as the key fibrotic protein levels of transient receptor potential vanilloid 4 (TRPV4), TGFß-1, phospho-Smad2/3 (p-Smad2/3), and connective tissue growth factor (CTGF), were significantly decreased in the SHR-M group when compared with the SHR and SHR-H groups. In further in vitro experiments, we selected normal rat kidney interstitial fibroblast (NRK-49F) cells. By immunofluorescence and Western blotting techniques, we found that TRPV4 antagonists (RN-1734) markedly inhibited lactate-induced fibrosis. In conclusion, compared with previous studies, high-intensity exercise training (HIET) can cause adverse effects (renal damage and fibrosis). High concentrations of lactic acid can aggravate renal fibrosis conditions via activating TRPV4-TGFß1-SMAD2/3-CTGF-mediated renal fibrotic pathways in spontaneous hypertension. This finding might provide new ideas for treating hypertensive nephropathy with different intensity exercise in the future.

Diagnostic Value of Urine Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Acute Kidney Injury: A Meta-Analysis.

BACKGROUND: Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP7) are both involved in renal tubular epithelial cell cycle arrest in acute kidney injury (AKI). Several recent studies showed that urine TIMP-2 times IGFBP7 ([TIMP-2]*[IGFBP7]) is a promising biomarker to predict AKI. METHODS: The aim of this meta-analysis was to assess the diagnostic value of urine [TIMP-2]*[IGFBP7] for early diagnosis of AKI. Relevant studies were retrieved from the PubMed, EMBASE, and Cochrane Library databases. The sensitivity and specificity were determined, and summary receiver operating characteristic (SROC) curves were constructed. RESULTS: Ten full-text prospective studies were included in this meta-analysis. The estimated sensitivity of urine [TIMP-2]*[IGFBP7] for the early diagnosis of AKI was 0.84 (95% CI = 0.80-0.88) and the specificity was 0.57 (95%CI = 0.55-0.60). The SROC analysis showed an area under the curve of 0.8813. LIMITATION: The limited number of included studies, small sample size, unpublished negative results and language limitation might have affected the evaluation. CONCLUSION: Urine [TIMP-2]*[IGFBP7] is a promising candidate for early detection of AKI, especially in ruling-out AKI. However, the potential of this biomarker should be validated in larger studies with a broader spectrum of clinical settings.