Association of Urinary Matrix Metalloproteinase 7 with Incident Renal Flare in Lupus Nephritis

2020 ◽  
Author(s):  
Guobao Wang ◽  
Liling Wu ◽  
Huanjuan Su ◽  
Xiaodan Feng ◽  
Meng Shi ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Matrix Metalloproteinase ◽  
Renal Flare ◽  
Matrix Metalloproteinase 7

scholarly journals OP0165 LONG-TERM OUTCOME OF A RANDOMIZED CONTROLLED TRIAL COMPARING TACROLIMUS WITH MYCOPHENOLATE MOFETIL AS INDUCTION THERAPY OF SEVERE LUPUS NEPHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 104.1-104
Author(s):  
C. C. Mok ◽  
L. Y. Ho ◽  
C. H. To ◽  
K. Y. S. Ying
Keyword(s):  
Lupus Nephritis ◽  
Induction Therapy ◽  
Roc Analysis ◽  
Controlled Trial ◽  
Renal Flare ◽  
Stage 4 ◽  
Ckd Stage ◽  
Renal Prognosis ◽  
The Mean

Background:Objectives:To report the 10-year outcome of a cohort of patients with lupus nephritis (LN) treated with combined glucocorticoids with either mycophenolate mofetil (MMF) or tacrolimus (TAC) as induction in a randomized controlled trial (RCT).Methods:150 patients with active lupus nephritis were randomized to receive either MMF (2-3g/day) (N=76) or TAC (0.1-0.06mg/kg/day) (N=74) in combination with high-dose prednisolone (0.6mg/kg/day for 6-8 weeks and tapered) as induction therapy between 2005 and 2012. Complete renal (CR) or good partial renal responders were switched to azathioprine (AZA) (2mg/kg/day) for maintenance. We hereby report the 10-year outcomes of the patients in terms of renal flares (proteinuric/nephritic), renal function decline (drop in eGFR by ≥30% from baseline), development of chronic kidney disease (CKD) stage 4/5 (eGFR<30ml/min) and mortality. Factors affecting renal prognosis were studied by Cox regression analysis. Renal parameters (urine P/Cr ratio [uPCr], eGFR) at different time points from 6 to 24 months were studied for their predictive value of a poor renal prognosis by ROC analysis.Results:150 patients (92% women) with active LN were studied (ISN/RPS class III±V 36%; IVG/S±V 46%; pure V 19%). The mean age was 35.5±12.8 years and SLE duration was 50.2±62 months. The mean histological activity and chronicity score was 8.2±3.4 and 2.6±1.6, respectively. At baseline, 59(39%) patients were hypertensive, 62(41%) had active urinary casts, 112(75%) had microscopic hematuria and 67% patients had eGFR<90ml/min. As reported previously, the rate of complete renal response (CR) was 59% in the MMF and 62% in the TAC group (p=0.71). Maintenance therapy with AZA was given to 79% patients. After a follow-up of 118.2±42 months, proteinuric and nephritic renal flares occurred in 34% and 37% of patients treated initially with MMF and 53% and 30% in those treated with TAC, respectively. There was a total of 77 renal flares in 43 (57%) patients treated with MMF (0.11/patient-year) and 92 renal flares in 46 (62%) of patients treated with TAC (0.12/patient-year; p=0.44). The cumulative risk of having a renal flare of patients treated with MMF/AZA was 28% at 3 years, 42% at 5 years and 58% at 10 years, whereas the corresponding figures for patients treated with TAC/AZA was 32% at 3 years, 53% in 5 years and 66% in 10 years (p=0.43). For those who achieved CR after induction therapy, the mean time to first renal flare was 70.4±47.1 months in the MMF group and 65.2 ±50 months in the TAC group (p=0.61). The cumulative incidence of a composite outcome of decline of eGFR by ≥30%, development of CKD stage 4/5 or death at 5 and 10 years was 24% and 33%, respectively, in patients treated with MMF, and 17% and 33%, respectively, in those treated with TAC (p=0.90). Factors significantly associated with this outcome were first time lupus nephritis (HR 0.26[0.11-0.59]; p=0.001), uPCR at 6 months (HR 1.33[1.02-1.76]; p=0.04) and eGFR at 6 months (HR 0.98[0.97-0.997]; p=0.02). Exploratory ROC analysis demonstrated that an eGFR cut-off of 80ml/min (AUC 0.70; sensitivity 0.64, specificity 0.66) and uPCR cut-off of 0.75 (AUC 0.73; sensitivity 0.69, specificity 0.74) at month 18 best predicted CKD stage 4/5 or decline of eGFR by ≥30%.Conclusion:Long-term data of our RCT showed that TAC remained non-inferior to MMF as induction therapy of LN in terms of renal flares, renal function decline and mortality. Relapsed renal disease, lower eGFR and more proteinuria post-induction therapy were associated with a poorer outcome. An uPCR ≤0.75 and eGFR of >80ml/min at 18 months best predicted a better outcome at 10 years, and should be considered as a target for induction/consolidation therapy.Acknowledgments:NILDisclosure of Interests:None declared

scholarly journals Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma

2009 ◽  
Vol 10 (5) ◽  
pp. 496-503 ◽  
Author(s):  
Sangeeta Goswami ◽  
Pornpimon Angkasekwinai ◽  
Ming Shan ◽  
Kendra J Greenlee ◽  
Wade T Barranco ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Matrix Metalloproteinase ◽  
Airway Epithelial ◽  
Matrix Metalloproteinase 7

scholarly journals Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

2020 ◽  
Vol 7 ◽  
Author(s):  
Mark Nomden ◽  
Leonie Beljaars ◽  
Henkjan J. Verkade ◽  
Jan B. F. Hulscher ◽  
Peter Olinga
Keyword(s):  
Immune Response ◽  
Liver Fibrosis ◽  
Pulmonary Fibrosis ◽  
Matrix Metalloproteinase ◽  
Biliary Atresia ◽  
Adaptive Immune Response ◽  
Cell Contact ◽  
T Helper 1 ◽  
Matrix Metalloproteinase 7

Biliary atresia (BA) is a rare cholangiopathy of infancy in which the bile ducts obliterate, leading to profound cholestasis and liver fibrosis. BA is hypothesized to be caused by a viral insult that leads to over-activation of the immune system. Patients with BA are surgically treated with a Kasai portoenterostomy (KPE), which aims to restore bile flow from the liver to the intestines. After KPE, progressive liver fibrosis is often observed in BA patients, even despite surgical success and clearance of their jaundice. The innate immune response is involved during the initial damage to the cholangiocytes and further differentiation of the adaptive immune response into a T-helper 1 cell (Th1) response. Multiple studies have shown that there is continuing elevation of involved cytokines that can lead to the progressive liver fibrosis. However, the mechanism by which the progressive injury occurs is not fully elucidated. Recently, matrix metalloproteinase-7 (MMP-7) has been investigated to be used as a biomarker to diagnose BA. MMPs are involved in extracellular matrix (ECM) turnover, but also have non-ECM related functions. The role of MMP-7 and other MMPs in liver fibrosis is just starting to be elucidated. Multiple studies have shown that serum MMP-7 measurements are able to accurately diagnose BA in a cohort of cholestatic patients while hepatic MMP-7 expression correlated with BA-related liver fibrosis. While the mechanism by which MMP-7 can be involved in the pathophysiology of BA is unclear, MMP-7 has been investigated in other fibrotic pathologies such as renal and idiopathic pulmonary fibrosis. MMP-7 is involved in Wnt/β-catenin signaling, reducing cell-to-cell contact by shedding of E-cadherin, amplifying inflammation and fibrosis via osteopontin (OPN) and TNF-α while it also appears to play a role in induction of angiogenesis This review aims to describe the current understandings of the pathophysiology of BA. Subsequently, we describe how MMP-7 is involved in other pathologies, such as renal and pulmonary fibrosis. Then, we propose how MMP-7 can potentially be involved in BA. By doing this, we aim to describe the putative role of MMP-7 as a prognostic biomarker in BA and to provide possible new therapeutic and research targets that can be investigated in the future.

scholarly journals Early achievement of deep remission predicts low incidence of renal flare in lupus nephritis class III or IV

2018 ◽  
Vol 20 (1) ◽  
Author(s):  
Hironari Hanaoka ◽  
Harunobu Iida ◽  
Tomofumi Kiyokawa ◽  
Yukiko Takakuwa ◽  
Kimito Kawahata
Keyword(s):  
Lupus Nephritis ◽  
Class Iii ◽  
Renal Flare ◽  
Low Incidence

The Role of Matrix Metalloproteinase-7 in Redefining the Gastric Microenvironment in Response to Helicobacter pylori

2006 ◽  
Vol 130 (6) ◽  
pp. 1754-1763 ◽  
Author(s):  
Catherine McCaig ◽  
Cedric Duval ◽  
Elaine Hemers ◽  
Islay Steele ◽  
D. Mark Pritchard ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 7
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