Effect of Mycophenolate and Rapamycin on Renal Fibrosis in Lupus Nephritis

Lupus nephritis (LN) leads to chronic kidney disease through progressive fibrosis. Mycophenolate inhibits inosine monophosphate dehydrogenase and is a standard treatment for LN. The mammalian or mechanistic target of rapamycin (mTOR) pathway is activated in LN. Rapamycin inhibits mTOR and is effective in preventing kidney transplant rejection, with the additional merits of reduced incidence of malignancies and viral infections. The effect of mycophenolate or rapamycin on kidney fibrosis in LN has not been investigated. We investigated the effects of mycophenolate and rapamycin in NZB/W F1 murine LN and human mesangial cells (HMC), focusing on mechanisms leading to kidney fibrosis. Treatment of mice with mycophenolate or rapamycin improved nephritis manifestations, decreased anti-double stranded (ds)DNA antibody titre, and reduced IgG deposition in the kidney. Both mycophenolate and rapamycin, especially the latter, decreased glomerular mTOR Ser2448 phosphorylation. Renal histology in untreated mice showed mesangial proliferation and progressive glomerulosclerosis with tubular atrophy, and increased expression of TGF-β1, MCP-1, α-smooth muscle actin, fibronectin and collagen. Both mycophenolate and rapamycin ameliorated the histopathological changes. Results from in vitro experiments showed that both mycophenolate and rapamycin decreased mesangial cell proliferation and their binding by anti-dsDNA antibodies. Mycophenolate and rapamycin also down-regulated mTOR and ...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research

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Abstract Renal disease is a common medical problem in Saudi Arabia. Varieties of renal lesions if not treated properly or not discovered early will lead to a chronic kidney disease. Identifying the types of renal lesions can help in identifying the high-risk patients and appropriate treatment can be provided. Glomerulonephritis (GN) is considered one of the leading causes of end-stage renal disease in Saudi Arabia. The prevalence of different renal lesions were identified by different reports; however, these reports showed inconsistency. One important reason for such differences is related to the lack of unified m...
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
In this study, we therefore examined whether FKN could stimulate the process of EMT, NF-kB, TGFβ, CCL22, F4/80, inflammation, and tubulointerstitial fibrosis in a murine model of LN. We also determined whether FKN was involved in the EMT process of Wnt/β-catenin-expressing HK-2 cells. Mechanistically, we ascertained, for the first time, whether FKN up-regulated EMT-related gene signatures (e.g., vimentin, α-SMA), and hence, renal tubulointerstitial fibrogenesis, and the role of the Wnt/β-catenin signaling pathway in this process. Materials and Methods Cell Culture, Stable Infection, and Grouping HK-...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co-inhibitor...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, 80.4% had some clinical symptomatology. Of the clinical manifestations, 41.3% had polyarthritis, edema (20.7%), and malar rash (17.4%). Anti-nuclear antibody was positive in 80.4% and ds DNA in 70.7%. Renal biopsy showed more number of patients 27 (35%) had Stage IV LN, followed by Stage I, 19 (24%), and Stage II, 16 (20%) LN. Median urinary protein in Class I was 1.05 g, Class II (0.63 g), Class III (1.5 g), Class IV (2.44 g), Class V (3.99 g), and Class VI (4.7 g). Only Stage IV had Kappa of 0.269 {P = 0.003) showing agreement between proteinuria and histological staging which was statistically significant (P
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
Authors: Siemens TA, Riella MC, Moraes TP, Riella CV Abstract There are striking differences in chronic kidney disease between Caucasians and African descendants. It was widely accepted that this occurred due to socioeconomic factors, but recent studies show that apolipoprotein L-1 (APOL1) gene variants are strongly associated with focal segmental glomerulosclerosis, HIV-associated nephropathy, hypertensive nephrosclerosis, and lupus nephritis in the African American population. These variants made their way to South America trough intercontinental slave traffic and conferred an evolutionary advantage to the carrie...
Source: Jornal Brasileiro de Nefrologia - Category: Urology & Nephrology Tags: J Bras Nefrol Source Type: research
Authors: Karasawa K, Uchida K, Takabe T, Moriyama T, Nitta K Abstract Systemic lupus erythematosus (SLE) is an autoimmune chronic inflammatory disease that affects multiple organs and tissues. Lupus nephritis (LN) is a serious complication of SLE, which occurs at a high rate. Conventional treatment strategies of LN have been widely accepted by two concepts such as induction therapy and maintenance therapy. In LN induction therapy until recently, cyclophosphamide in combination with prednisone (PSL) has been the standard method of treatment for proliferative forms of LN. In the latest review, the combination of myco...
Source: Contributions to Nephrology - Category: Urology & Nephrology Tags: Contrib Nephrol Source Type: research
Abstract A significant proportion of individuals with systemic lupus erythematosus (SLE) will have clinical or laboratory evidence of renal involvement at some point in the course of their disease. Lupus nephritis (LN) is one of the more important systemic manifestations of SLE and although progression to end-stage renal disease (ESRD) is not usually the norm, a significant minority of patients will do so, some in a rather dramatic fashion. It is in such instances that LN constitutes a true nephrologic emergency. Gratifyingly, it is rarely a silent emergency and heightened awareness amongst clinicians about its un...
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
Abstract Acute kidney injury (AKI) is common in hospitalized patients with mortality varying from 10% to 80%. It is crucial to know the incidence and etiology of AKI to promote prevention strategies. Our study aimed at obtaining a comprehensive review of the pattern and spectrum of patients who presented for emergency hemodialysis to Kasr Al-Aini Hospital between October 2012 and October 2014. We analyzed clinical and laboratory factors in all such patients. Two thousand twenty three patients were included of which patients with AKI were 728 patients (36%). Cardiac diseases were the cause of AKI in 171 patients, o...
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
This study shows that focal segmental glomerulosclerosis is the most common lesion in renal biopsy in the young age group followed by membranous nephropathy. Diabetic nephropathy and chronic interstitial nephritis were dominant secondary pathological lesions in older age group, whereas lupus nephritis was the most common secondary disease in young age females. PMID: 28352022 [PubMed - in process]
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
Abstract Nearly 20% of SLE corresponds to the pediatric population, and 75% of them have kidney involvement representing an important etiology of chronic kidney disease. A correlation between SLE and ANCA‐associated vasculitis has been identified as an overlapping syndrome. Kidney allograft recurrence is rare in SLE when disease control is achieved and with nowadays immunosuppression treatment. Histologic transformation is unusual, especially when there are negative serologic markers and no immune complex deposition reported in native kidneys. A 17‐year‐old female with crescentic glomerulonephritis, p‐ANCA‐positi...
Source: Pediatric Transplantation - Category: Transplant Surgery Authors: Tags: CASE REPORT Source Type: research
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