Recurrence Of IgA Nephropathy After Kidney Transplantation

Click Here to know more info about How Cistanche Fix IgA nephropathy

1 Pathogenesis of IgAN recurrence after renal transplantation
At this stage, the pathogenesis of IgAN has not been fully clarified, and it is currently believed that the occurrence of IgAN is mediated by multiple factors such as genetics, environment, and immunity[4]. More accepted is the pathogenesis of multiple hits: (1) excessive production of galactose-deficient IgA1 (Gd-IgA1) is the initial stage of IgAN; (2) autoantibodies against glycans or glycopeptides are therefore (3) Anti-glycan antibody recognizes and forms an immune complex with Gd-IgA1 and deposits in the mesangial area; (4) Activates mesangial cells, induces the secretion of cytokines, chemokines and extracellular matrix proteins, and then leads to kidney damage [5-6].

The study of molecular markers in the pathogenesis of multiple hits may help to predict the recurrence and progression of IgAN after renal transplantation and provide potential therapeutic targets. Berthelot et al. [7] showed that higher levels of serum Gd-IgA1 and IgA-IgG immune complexes and lower levels of circulating IgA-sCD89 (myeloid cell receptor for IgA) complexes before transplantation were predictive of kidney transplantation. recurrence of post-IgAN. However, Berthoux et al. [8] found that IgG autoantibodies to serum Gd-IgA1 after transplantation were associated with a higher risk of IgAN recurrence compared with healthy subjects.
In the past decade, genome-wide association studies (GWAS) have made significant contributions to the study of the genetic basis of IgAN, and found nearly 20 independent risk allelic loci of IgAN, but further clarification of related molecules is still needed mechanism [9]. A large GWAS of 20 612 IgAN patients of European and East Asian ancestry, in addition to identifying major histocompatibility complex (MHC), complement factor H (complement factor H, CFH), tumor necrosis factor ligand family members 13 (tumor necrosis factor ligand super family member 13, TNFSF13), HORMAD2 and DEFA loci, multiple new IgAN loci were identified [such as ITGAM-ITGAX, VAV3, CARD9, human leukocyte antigen
(human leukocyte antigen, HLA)-DQB1, DEFA] in the intestinal mucosa, with most loci associated with inflammatory bowel disease, maintenance of the intestinal epithelial barrier, and responses to mucosal pathogens [10]. Dysregulation of the complement system has also been associated with IgAN relapse. Research by Zhang Chunyun et al. [11] showed that most patients with recurrent IgAN after kidney transplantation were accompanied by deposition of complement C3, while deposition of C1q and C4 was rare. Studies have also confirmed that the mannose-binding lectin (MBL) pathway is involved in the relapse process of IgAN, and is associated with increased proteinuria and renal damage, and the prognosis of patients with C4d deposition is poor [12]. The deposition of C1q on the mesangium also has a high predictive value for the recurrence of IgAN after renal transplantation [13].

Recent studies have shown that several other non-specific biomarkers predicted the risk of IgAN recurrence after renal transplantation, but their clinical relevance needs to be further validated in a larger independent population cohort. For example Garnier et al [14] found that serum IgA levels were associated with the recurrence of IgAN after renal transplantation and could be used as a marker for the recurrence of IgAN. Wu et al [15] have outlined the role of tumor necrosis factor (tNF) in the development of a new study. outlined that tumor necrosis factor (TNF) B cell activating factor (B cell activating factor) and proliferation factor (BAFF) in the superfamily. BAFF) and a proliferation-inducing ligand (APRIL) in the tumor necrosis factor (TNF) superfamily. ligand (APRIL) can be involved in glomerular inflammation by reducing serum IgA levels and IgA deposition in Martín-Penagos et al. et al [16-17] found a higher correlation between APRIL and IgAN compared to BAFF. The early and sustained elevation of APRIL after renal transplantation may The early and sustained elevation of APRIL after renal transplantation may induce overproduction of Gd-IgA1 and accelerate the recurrence of IgAN, but since However, because of the heterogeneity of IgAN, the conclusion is not clear. A clinical study of 69 patients with Data from a clinical study of 69 patients with IgAN before and after transplantation showed that high pre-transplant serum APRIL levels were associated with high transplantation levels. A clinical study of 69 IgAN patients before and after transplantation showed that high serum APRIL levels before transplantation were associated with IgAN recurrence after transplantation [18]. In addition, Lee et al [19] used proteomics to identify serine protease inhibitors (SER) in urine. In addition, Lee et al. [19] used proteomics to determine the presence of serine protease inhibitor (SERPIN) A1, transthyretin, apolipoprotein (APRIL), and serotonin in urine. (SERPIN), apolipoprotein (APO) A4, and retinol-binding protein (RTP) in urine. Retinol binding protein (RBP)4 can be used to monitor IgAN after renal transplantation. They can be used as biomarkers to monitor the recurrence of IgAN after renal transplantation.
The study of the pathogenesis of IgAN can better identify patients at high risk of recurrence and help improve the sensitivity of diagnosis. patients at high risk of recurrence, which can help to improve the sensitivity and specificity of diagnosis and The study of the pathogenesis of IgAN can better identify patients with high risk of recurrence, help improve the sensitivity and specificity of diagnosis, and have clinical implications for improving the treatment plan and prognosis.

2 Diagnosis of IgAN recurrence after renal transplantation

IgAN recurrence can be defined as clinical recurrence and histopathological recurrence. Clinical recurrence is highly heterogeneous and may not show obvious clinical symptoms. It is characterized by asymptomatic microscopic hematuria, proteinuria and progressive decline in the function of the transplanted kidney. The main features are asymptomatic microscopic hematuria, proteinuria and progressive decline in graft kidney function. The main features are asymptomatic microscopic hematuria, proteinuria and progressive decline in graft kidney function. Histopathologic recurrence is characterized by thylakoid
Histopathologic recurrence is characterized by thylakoid IgA deposition with or without thylakoid hyperplasia and, in a few cases, crescentic features [20]. Histopathologic recurrence often precedes clinical recurrence, as shown by Ortiz et al [21 [21] showed that histologic recurrence occurred in approximately 52% of patients within 2 years after renal transplantation The study by Ortiz et al [21] showed that histological recurrence without proteinuria or hematuria occurred in approximately 52% of patients within 2 years after renal transplantation. Therefore, the main diagnostic tool for the recurrence of IgAN after renal transplantation relies on the renal transplantation. The main diagnostic tool for post-transplant IgAN recurrence (biopsy), including optical, immunofluorescence, and electron microscopy, to differentiate recurrent IgAN from recurrent IgAN. This allows differentiation of recurrent IgAN from chronic rejection, drug toxicity, infection, etc. Infections and other factors causing glomerular disease. The diagnostic criteria include.
(1) pre-transplantation renal biopsy to confirm the diagnosis of IgAN as the primary disease; (2) post-transplantation renal biopsy to determine the same pathological type of recurrence; and (3) zero-point puncture biopsy of the transplanted kidney to exclude donor IgAN (partial study) [4]. However, it is difficult to have the above 3 elements in actual clinical practice, and many patients are already in the ESRD stage when the disease is detected, have difficulty in identifying the primary disease, or are reluctant to perform renal biopsy due to mild symptoms at the time of recurrence, as well as differences in biopsy indications, diagnostic criteria, and follow-up time, and the existing literature reports a recurrence rate of IgAN of 4.5% to 70.5% [22-23].
Furthermore, the recurrence of IgAN is time-dependent. A retrospective analysis of renal transplant recipients in the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) found that among 2,501 renal transplant recipients with biopsy-confirmed IgAN as the primary disease, recurrence of disease at 5, 10, and 15 years postoperatively was more common than in other countries.
The disease recurrence rates were 5.1%, 10.1%, and 15.0% at 10 and 15 years postoperatively, respectively, and the recurrence rate increased with the duration of transplantation [24].
The pathological manifestations of IgAN recurrence after renal transplantation are more diverse than those of IgAN in the general population due to the long-term immunosuppressive state and combined rejection [25]. endocapillary ypercellularity, E), and Segmental glomerulosclerosis/ adhesion (S) and glomerular sclerosis (S). adhesion (S) and tubular atrophy/interstitial fibrosis (TIA). atrophy/interstitial fibrosis (T), which is important for the standardization of the diagnosis of IgAN [26
It is important to standardize the diagnosis of IgAN [26]. It has been found that recurrent IgAN with crescent formation The incidence of transplant renal failure in recurrent IgAN with crescent formation was found to be 88.8%, suggesting that neonatal The incidence of transplant renal failure in recurrent IgAN with crescent formation was found to be 88.8%, suggesting that neonatal formation has an important value in the prognosis of recurrent IgAN [27]. Therefore, the In 2017, cellular and/or fibrocellular crescents (cellular/ fibrocellular crescents (C) were also included as a prognostic parameter in 2017, and IgAN Oxford pathological typing was updated to MEST-C [28]. The specific IgAN Oxford pathology pathological typing is shown in Table 1 [28].