Understanding tubulointerstitial injury and repair mechanisms paves the way for renal outcome improvement in lupus nephritis

2021 ◽  
Author(s):  
Marc Xipell ◽  
Allyson Egan ◽  
Gema Lledó ◽  
Jesús Z. Villarreal ◽  
Gerard Espinosa ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Outcome ◽  
Tubulointerstitial Injury ◽  
Repair Mechanisms ◽  
Outcome Improvement ◽  
Injury And Repair ◽  
The Way

scholarly journals SP184CLINICAL IMPLICATIONS AND PATHOLOGICAL CLASSIFICATION OF TUBULOINTERSTITIAL INJURY FOR THE PREDICTION OF RENAL OUTCOME IN LUPUS NEPHRITIS

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i406-i406
Author(s):  
Lida Maria Rodas Marin ◽  
Claudia Mardones ◽  
Manuel Gomes ◽  
Adriana Garcia Herrera ◽  
Sergio Prieto Gonzalez ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Outcome ◽  
Tubulointerstitial Injury ◽  
Pathological Classification

scholarly journals SAT0211 RENAL INJURY IN SYSTEMIC LUPUS ERYTHEMATOSUS CHARACTERIZED BY THROMBOTIC MICROANGIOPATHY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1048.1-1048
Author(s):  
W. Hu
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Renal Biopsy ◽  
Lupus Erythematosus ◽  
Thrombotic Microangiopathy ◽  
Renal Injury ◽  
Renal Outcome ◽  
Pathological Examination ◽  
Systemic Lupus ◽  
Tubulointerstitial Lesions

Background:Classical lupus nephritis (LN) is characterized by glomerular immune complex(IC) deposition with glomerular proliferation, basement membrane destruction and cell infiltration. Non-IC mediated renal injury with thrombotic microangiopathy (TMA) was also reported in patients with systemic lupus erythematosus (SLE-renal TMA), but most studies were reported in patients with both LN and renal TMA.Objectives:In this study, clinical features and outcomes of SLE-renal TMA in absence of obvious IC in SLE patients were analyzed.Methods:Patients with glomerular TMA and/or vascular TMA in the absence of obvious subendothelial or epithelial immune deposits were screened out from 2332 biopsied in SLE patients who underwent first renal biopsy from January 2005 to August 2016. Their clinical, histological features and outcomes were retrospectively analyzed.Results:In 2332 renal biopsies obtained from SLE patients, 257 (11.0%) showed renal TMA, of which 237 showed both renal TMA and LN, and 20 biopsies had only renal TMA (SLE-renal TMA). There were 2 males and 18 females with an average age of (25 ± 10) years. The median course of SLE and LN were 3.0(1.0, 6.0) and 0.8(0.5, 1.9) months. All 20 patients deserved acute kidney injury, of which 11 (55%) needed renal replacement therapy (RRT) and 12 (60%) were nephrotic syndrome. Blood system involvement was found in all cases, including 13 cases (65.0%) with TMA triad (microvascular hemolytic anemia, thrombocytopenia and elevated lactate dehydrogenase).Pathological examination showed that 17 cases (85.0%) had both glomerular TMA and vascular TMA. Immunofluorescence and electron microscopy showed that 8 cases (40%) had no IC deposition in glomerulus and 12 cases (60%) had only IC deposition in mesangium. Acute tubulointerstitial lesions in patients requiring RRT were more serious than those no needing for RRT((43.6±24.9) %vs(21.7±20.1) %,P=0.047). The fusion range of foot process was positively correlated with proteinuria (r2= 0.347,P=0.006).All patients received high-dose methylprednisolone pulse therapy. Four patients received plasma exchange and three patients received gamma globulin, respectively. Eleven patients requiring RRT all stop RRT in a median time of 16.0 (9.0, 30.0) days. During a median follow-up of 58.0 (36.0, 92.3) months, complete remission (CR) was obtained in 15 cases, partial remission in 4 cases and no remission in 1 case. Six cases (30%) relapsed. No case died or progressed to end stage renal disease.Conclusion:Renal injury characterized by TMA is not uncommon in SLE renal biopsy cases. The clinical manifestation is special and the renal injury is serious. The renal outcome is good by intensive immunosuppressive therapy. It should be considered as a unique type of renal injury in SLE.References:[1]Moake JL. Thrombotic microangiopathies. N Engl J Med. 2002. 347(8): 589-600.[2]Anders HJ, Weening JJ. Kidney disease in lupus is not always ‘lupus nephritis’. Arthritis Res Ther. 2013. 15(2): 108.[3]Song D, Wu LH, Wang FM, et al. The spectrum of renal thrombotic microangiopathy in lupus nephritis. Arthritis Res Ther. 2013. 15(1): R12.[4]Hu WX, Liu ZZ, Chen HP, Zhang HT, Li LS, Liu ZH. Clinical characteristics and prognosis of diffuse proliferative lupus nephritis with thrombotic microangiopathy. Lupus. 2010. 19(14): 1591-8.[5]Tomov S, Lazarchick J, Self SE, Bruner ET, Budisavljevic MN. Kidney-limited thrombotic microangiopathy in patients with SLE treated with romiplostim. Lupus. 2013. 22(5): 504-9.[6]Li C, Yap D, Chan G, et al. Clinical Outcomes and Clinico-pathological Correlations in Lupus Nephritis with Kidney Biopsy Showing Thrombotic Microangiopathy. J Rheumatol. 2019 .[7]Chen MH, Chen MH, Chen WS, et al. Thrombotic microangiopathy in systemic lupus erythematosus: a cohort study in North Taiwan. Rheumatology (Oxford). 2011. 50(4): 768-75.[8]Park MH, AUID- Oho, Caselman N, Ulmer S, Weitz IC, AUID- Oho. Complement-mediated thrombotic microangiopathy associated with lupus nephritis. Blood Adv. 2018. 2(16): 2090-2094.Disclosure of Interests:None declared

scholarly journals Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis

2021 ◽  
Vol 11 (8) ◽  
pp. 693
Author(s):  
Corina Daniela Ene ◽  
Simona Roxana Georgescu ◽  
Mircea Tampa ◽  
Clara Matei ◽  
Cristina Iulia Mitran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lupus Nephritis ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Control Group ◽  
Dna Repair Mechanisms ◽  
Glycation End Products ◽  
Repair Mechanisms ◽  
Low Levels ◽  
Defective Dna Repair

The interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydrocarbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Our study included 38 SLE patients with lupus nephritis (LN group), 44 SLE patients without renal impairment (non-LN group) and 40 healthy volunteers as control group. In the present paper, we evaluated serum lipid peroxidation, DNA oxidation, oxidized proteins, carbohydrate oxidation, and endogenous protective systems. We detected defective DNA repair mechanisms via 8-oxoguanine-DNA-glycosylase (OGG1), the reduced regulatory effect of soluble receptor for advanced glycation end products (sRAGE) in the activation of AGE-RAGE axis, low levels of thiols, disulphide bonds formation and high nitrotyrosination in lupus nephritis. All these data help us to identify more molecular mechanisms to counteract oxidative stress in LN that could permit a more precise assessment of disease prognosis, as well as developing new therapeutic targets.

Association of coexisting anti-ribosomal P and anti-dsDNA antibodies with histology and renal prognosis in lupus nephritis patients

Lupus ◽  
2021 ◽  
pp. 096120332098390
Author(s):  
Ayako Wakamatsu ◽  
Hiroe Sato ◽  
Yoshikatsu Kaneko ◽  
Takamasa Cho ◽  
Yumi Ito ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Renal Outcome ◽  
Class V ◽  
Double Stranded Dna ◽  
Number Of Patients ◽  
Renal Histology ◽  
Renal Prognosis ◽  
Incidence Of Ckd ◽  
Ribosomal P

Objectives Anti-ribosomal P protein autoantibodies (anti-P) specifically develop in patients with systemic lupus erythematosus. Associations of anti-P with lupus nephritis (LN) histological subclass and renal outcome remain inconclusive. We sought to determine the association of anti-P and anti-double-stranded DNA antibody (anti-dsDNA) with renal histology and prognosis in LN patients. Methods Thirty-four patients with LN, having undergone kidney biopsy, were included. The 2018 revised ISN/RPS classification system was used for pathophysiological evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 for > 3 months. Results Six patients (17.6%) were positive for anti-P and 26 (76.5%) for anti-dsDNA. Among the six patients with anti-P, one did not have anti-dsDNA, but did have anti-Sm antibody, and showed a histological subtype of class V. This patient maintained good renal function for over 14 years. The remaining five patients, who had both anti-P and anti-dsDNA, exhibited proliferative nephritis and were associated with prolonged hypocomplementemia, and the incidence of CKD did not differ from patients without anti-P. Conclusion Although this study included a small number of patients, the results indicated that histology class and renal prognosis associated with anti-P depend on the coexistence of anti-dsDNA. Further studies with a large number of patients are required to confirm this conclusion.

scholarly journals Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

2015 ◽  
Vol 75 (3) ◽  
pp. 526-531 ◽  
Author(s):  
Farah Tamirou ◽  
David D'Cruz ◽  
Shirish Sangle ◽  
Philippe Remy ◽  
Carlos Vasconcelos ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Lupus Nephritis ◽  
Positive Predictive Value ◽  
Maintenance Therapy ◽  
Early Response ◽  
Renal Outcome ◽  
Proliferative Lupus Nephritis ◽  
Long Term Follow Up

ObjectiveTo report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome.MethodsIn 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up.ResultsDeath (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker.ConclusionsThe long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome.Trial registration numberNCT00204022.

Traumatic meningeal injury and repair mechanisms

2018 ◽  
Vol 19 (5) ◽  
pp. 431-432
Author(s):  
David J. Loane ◽  
Alan I. Faden
Keyword(s):  
Repair Mechanisms ◽  
Injury And Repair

scholarly journals P0418LUPUS NEPHRITIS: A MONOCENTRIC STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marwa Omrane ◽  
Raja Aoudia ◽  
Mondher Ounissi ◽  
Soumaya Chargui ◽  
Mouna Jerbi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Renal Failure ◽  
Lupus Nephritis ◽  
Renal Biopsy ◽  
Predictive Factors ◽  
Lupus Erythematosus ◽  
Renal Outcome ◽  
Sustained Remission ◽  
Systemic Lupus ◽  
Therapeutic Protocols

Abstract Background and Aims Systemic lupus erythematosus is a multi-visceral autoimmune disease. Renal involvement is one of the most common and serious manifestations of this disease. The histological lesions are highly polymorphic and the renal biopsy remains crucial for the therapeutic management of lupus nephritis (LN). The aim of our investigation was to study the epidemiological, clinical, biological and histological characteristics, outcomes and to evaluate the therapeutic protocols used for lupus nephritis’ treatment and to identify predictive factors of renal prognosis in patients with lupus nephritis. Method It was a retrospective study including patients over 16 years old with lupus nephritis proved by kidney biopsy and followed up over a period of 17 years in our department. Results We collected 155 women and 19 men with a sex ratio F / H of 8.2. The mean age at the time of the discovery of LN was 32.6 years with a maximum between 15 years and 45 years. The most frequent extra-renal manifestations were articular and dermatological manifestations (79%). Renal symptomatology was dominated by proteinuria noted in all patients, associated to a nephrotic syndrome in 68% of patients. At the time of diagnosis of LN, hematuria was present in 69% of patients and renal failure was present in half of cases. Immunologically, antinuclear antibody were positive in 89.1% of cases, anti DNA positive in 73.4% of cases, anti Sm positive in 79.8% of cases and Antiphospholipids were positive in 50% of cases, associated with an antiphospholipid syndrome in 14.9% of cases. We performed 243 renal biopsies with 174 initial and 69 iterative biopsies. The histological lesions were polymorphic dominated by LN class IV (36.6%) isolated or associated with LN class V (17.7%). All patients received a corticosteroid for induction or maintenance treatment. It was associated with immunosuppressive treatment according to different treatment regimens. The median duration of follow-up was 81.2 months. Renal outcome was marked by complete and sustained remission in 36.7% of cases, incomplete remission with chronic kidney disease in 34.5% of cases, chronic renal failure in 28.7% of cases. At univariate analysis, we identified the young age below 35 years at the time of the discovery of LN, the male sex, increased serum creatinine at the time of biopsy, proliferative forms, the presence of histological signs of chronicity and lesions of thrombotic microangiopathy as predictive factors of poor renal outcomes. Conclusion Lupus nephritis is one of the most common and serious manifestations of Systemic lupus erythematosus. The generalization of renal biopsy, the use of early codified therapeutic protocols and regular monitoring and evaluation of disease activity according to the appropriate scores can improve management and survival of patients with renal impairment.

scholarly journals Improvement of Outcomes in Patients with Lupus Nephritis: Management Evolution in Chinese Patients from 1994 to 2010

2019 ◽  
Vol 46 (8) ◽  
pp. 912-919 ◽  
Author(s):  
Si-Jia Shao ◽  
Jin-Hua Hou ◽  
Guo-Tong Xie ◽  
Wen Sun ◽  
Dan-Dan Liang ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Activity Index ◽  
Survival Rates ◽  
Standard Of Care ◽  
Chinese Patients ◽  
Renal Outcome ◽  
Therapeutic Effects ◽  
Endstage Renal Disease ◽  
Renal Relapse ◽  
Chronicity Index

Objective.To assess how the longterm outcomes have changed over the past decades in Chinese patients with lupus nephritis (LN). The trends in patient manifestation at presentation, treatment pattern, and therapeutic effects were evaluated.Methods.A cohort of biopsy-proven patients with LN (n = 1945) from January 1994 to December 2010 was analyzed. Treatment regimens, treatment response, renal relapse, and renal outcome were compared at different time periods (1994–1998, 1999–2004, and 2005–2010).Results.Patients in the later periods had shorter duration of disease, lower serum creatinine value and chronicity at biopsy, and more frequent followup. They were more likely to receive standard-of-care therapies, which included cyclophosphamide, mycophenolate mofetil, and combination therapy. Patients in the later periods had higher probabilities of achieving remission (p < 0.001) and lower probabilities of experiencing renal flare (p = 0.007). The 5-year renal survival rates were 92.6%, 90.6%, and 94.3% in 1994–1998, 1999–2004, and 2005–2010, respectively. The 5-year risk of endstage renal disease (ESRD) did not differ between 1994–1998 and 1999–2004, but was significantly lower in 2005–2010 (HR 0.40, 95% CI 0.19–0.85 vs 1999–2004). In multivariable Cox analysis, standard therapy was independently associated with lower risk of ESRD (adjusted HR 0.72, 95% CI 0.52–0.98, p = 0.04). Variables of renal damage at biopsy (renal function, activity index, and chronicity index) were independently associated with poor outcome.Conclusion.The outcomes of Chinese patients with LN have improved from 1994 to 2010. With the increased use of standard therapies, the remission rates have increased and renal relapse has decreased.

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