scholarly journals Lupus Nephritis: Role of Serum Complement Levels as Prognostic Marker

2020 ◽  
Vol 6 (1) ◽  
pp. 01-05
Author(s):  
Richmond Gomes

Background: Lupus Nephritis (LN) is one of the most common and serious manifestations in Systemic Lupus Erythematosus (SLE) patients that causes significant morbidity and mortality. Certain biomarkers for LN are sometimes able to assess treatment response of lupus nephritis. Objective: To compare serum complement levels (C3 & C4) as markers of treatment response of LN and their relation to the LN class in renal biopsy. Methods: This prospective observational study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2018 to August 2019. Twenty seven patients who were diagnosed with lupus nephritis after kidney biopsy were included in this study. Serum complement levels (C3 & C4), 24 hours urinary total protein (24-hr UTP) and anti-double-stranded DNA (anti-ds DNA) were measured in all patients at baseline, 3 months and 6 months after treatment. These biomarker values before and after treatment were compared between the treatment response and non response groups. Results: Serum C3 levels were significantly different in patients of proliferative lupus nephritis (Class III & Class IV) than non proliferative lupus nephritis (Class V) at baseline (0.47 ± 0.32 vs0.89 ± 0.43g/l, p = 0.009) and levels changed significantly 6 months after treatment (p <0.001) and likewise for Serum C4 levels (0.10 ± 0.06 vs0.24 ± 0.26g/l, p = 0.040). Serum C3 levels were also found to correlate significantly with SLEDAI and renal SLEDAI. No significant difference was observed for 24-hr UTP levels at baseline between remission and non-remission groups. Conclusion: Serum C3 & C4 levels may be utilized as serological biomarkers to predict and monitor the treatment response of lupus nephritis.

2021 ◽  
Vol 11 (2) ◽  
pp. 97-102
Author(s):  
Saiful Bahar Khan ◽  
Rafi Nazrul Islam ◽  
Md Saif Bin Mizan ◽  
AKM Shahidur Rahman ◽  
Shah Md Zakir Hossain ◽  
...  

Background: Lupus nephritis (LN) is one of the most common and serious manifestations of systemic lupus erythematosus (SLE) that causes significant morbidity and mortality. Certain biomarkers for LN are sometimes able to assess treatment response in lupus nephritis. This study aimed to compare serum complement levels (C3 and C4) as markers of treatment response of LN and their relation to the LN class in renal biopsy. Methods: This prospective observational study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2018 to August 2019. Twenty seven patients who were diagnosed with LN after kidney biopsy were included in this study. Serum complement levels (C3 and C4), 24 hours urinary total protein (24-hr UTP) and anti-double-stranded DNA (anti-ds DNA) were measured in all patients at baseline, 3 months and 6 months after treatment initiation. These biomarker values before and after treatment were compared between the proliferative and non-proliferative LN patients. Results: Serum C3 levels were significantly different between patients with proliferative LN (Class III and Class IV) and non-proliferative LN (Class V) at baseline (0.47 ± 0.32 g/l versus 0.89 ± 0.43 g/l, p=0.009) and levels changed significantly 6 months after treatment initiation (p<0.001) and likewise for serum C4 levels (0.10 ± 0.06 g/l versus 0.24 ± 0.26 g/l, p=0.040). The values of 24-hr UTP and anti-ds-DNA were significantly different 6 months after treatment with p value <0.05 in both groups but C3 (p<0.001) and renal Systemic Lupus Erythematosus Disease Activity Index (rSLEDAI) (p<0.001) were only significant in the proliferative group. On the other hand, after 6 months treatment, C4 levels became relatively higher but that was not significant in both groups (p>0.05). Conclusion: After 6 months of treatment, serum C3 and C4 levels increased towards normal in both LN groups. Serum C3 and C4 levels in patients with LN correlate with disease activity. Therefore, serum complement (C3 and C4) levels may be utilized as serological biomarkers for treatment response of LN. Birdem Med J 2021; 11(2): 97-102


2020 ◽  
Vol 103 (8) ◽  
pp. 785-790

Background: Intravenous cyclophosphamide (IVCY) concomitant with corticosteroids demonstrated better outcomes in therapy of proliferative lupus nephritis albeit adverse effects may occur. Mycophenolate mofetil (MMF) is a newer oral medication for treating lupus nephritis. Objective: To compare renal outcomes between IVCY and MMF in conjunction with corticosteroid for induction therapy of proliferative lupus nephritis. Materials and Methods: The authors reviewed the medical records from four university hospitals of children who received prednisolone with either MMF or IVCY for induction therapy of proliferative lupus nephritis between 2005 and 2014 in the present retrospective cohort study. Results: Twenty-eight and 85 patients were included in the MMF and IVCY group, respectively. The respective mean age at MMF and IVCY initiation was 12.36±2.87 and 11.84±3.04 years. Renal remission was not significantly different between the groups (p=0.690). Non-nephrotic range proteinuria (adjusted OR 2.93, 95% CI 1.23 to 6.94, p=0.015), and high initial GFR (adjusted OR 2.93, 95% CI 1.14 to 7.56, p=0.026) were significantly associated with achieving renal remission. Both infectious (82.1%) and non-infectious complications (96.9%) were more common in the IVCY group. Neither death nor end-stage renal disease (ESRD) occurred during the induction therapy. Conclusion: There was no significant difference in renal remission whether children received MMF or IVCY for induction therapy of lupus nephritis; however, adverse events occurred less frequently in the MMF group. Keywords: Children, Lupus nephritis, Systemic lupus erythematosus, Mycophenolate, Cyclophosphamide, Induction


2021 ◽  
Vol 10 (4) ◽  
pp. 793
Author(s):  
Dawn J. Caster ◽  
Erik A. Korte ◽  
Michael L. Merchant ◽  
Jon B. Klein ◽  
Michelle T. Barati ◽  
...  

Kidney involvement in systemic lupus erythematosus (SLE)—termed lupus nephritis (LN)—is a severe manifestation of SLE that can lead to end-stage kidney disease (ESKD). LN is characterized by immune complex deposition and inflammation in the glomerulus. We tested the hypothesis that autoantibodies targeting podocyte and glomerular cell proteins contribute to the development of immune complex formation in LN. We used Western blotting with SLE sera from patients with and without LN to identify target antigens in human glomerular and cultured human-derived podocyte membrane proteins. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified the proteins in the gel regions corresponding to reactive bands observed with sera from LN patients. We identified 102 proteins that were present in both the podocyte and glomerular samples. We identified 10 high-probability candidates, including moesin, using bioinformatic analysis. Confirmation of moesin as a target antigen was conducted using immunohistochemical analysis (IHC) of kidney biopsy tissue and enzyme-linked immunosorbent assay (ELISA) to detect circulating antibodies. By IHC, biopsies from patients with proliferative lupus nephritis (PLN, class III/IV) demonstrated significantly increased glomerular expression of moesin (p < 0.01). By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against moesin (p < 0.01). This suggests that moesin is a target glomerular antigen in lupus nephritis.


2021 ◽  
Vol 15 (9) ◽  
pp. 2343-2344
Author(s):  
Aijaz Z. Khan Chachar ◽  
Miqdad Haider ◽  
Naveed A. Lashari ◽  
M. Mueed Yasin ◽  
Hafiz B. A. Kalhoro ◽  
...  

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder, multisystemic in nature more common in females of childbearing age. There are certain risk factors which predispose to this disease. It affects various organs, kidney is among them. Almost 60% patients having SLE ultimately leads to kidney dysfunction at some stage of the life. Aim: To find out pattern of histopathological findings of lupus nephritis as per WHO classification on kidney biopsy in Pakistan. Methodology: This cross-sectional study was completed in department of Medicine, Fatima Memorial Hospital, Lahore, from March 2016 to May, 2018. Total sample size was 165 patients. Only patients who fulfilled the 2012 SLICC (Systemic Lupus International Collaborating Clinics) criteria were included in the study. SPSS version 25.0 was used data analysis. Results: Age of the patients was between 31-50 years i.e. 114(69.09%), mean and SD was 43.96±4.84 years, females were more commonly affected by calculating 99(59.70%). Patterns of lupus nephritis as per WHO classification and renal biopsy were noted which shows 18(10.91%) had Class I, 53(32.12%) Class II, 43(26.07%) Class III, 35(21.20%) Class IV, 10(6.06%) Class V and 6(3.64%) had Class VI. Conclusion: Class II and Class III Lupus Nephritis are the most common modalities found in patients of SLE. Every patient with Lupus Nephritis should undergo a Renal Biopsy for correct diagnosis of the class of this disease and further management accordingly. Keywords: Lupus Nephritis, SLE, renal biopsy


2021 ◽  
Vol 10 (20) ◽  
pp. 4654
Author(s):  
Tsu-Yi Hsieh ◽  
Yi-Ching Lin ◽  
Wei-Ting Hung ◽  
Yi-Ming Chen ◽  
Mei-Chin Wen ◽  
...  

Background: Lupus nephritis (LN) often lead to end-stage renal disease in systemic lupus erythematosus patients. This study aimed to investigate the clinical application of renal gallium-67 scans for determining renal histological parameters in LN patients. Methods: Between 2006 and 2018, 237 biopsy-proven and 35 repeat biopsies LN patients who underwent renal gallium scans before or after biopsy were included for analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. A delayed 48-h gallium scan was performed and interpreted by semiquantitative methods using left kidney/spine (K/S) ratio. The renal histological results were compared with gallium uptake. Results: Out of 237 participants, 180 (76%) had proliferative LN. Baseline gallium left K/S ratio was significantly higher in class IV LN as compared to class III (median (interquartile range, IQR): 1.16 (1.0–1.3), 0.95 (0.9–1.1), respectively, p < 0.001). Furthermore, changes in gallium uptake between two biopsies were positively correlated with changes activity index (r = 0.357, p = 0.035), endocapillary hypercellularity (r = 0.385, p = 0.032), and neutrophils infiltration (r = 0.390, p = 0.030) in renal pathology. Conclusions: Renal gallium uptake is associated with active inflammation in LN. Changes in renal gallium uptake positively correlated with changes in activity index in renal pathology.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Nermeen Samy Abdel Fattah ◽  
Rania Mahmoud Elhusseiny ◽  
Aml Magdy Darahem

Abstract Background Warts are a common dermatologic complaint resulting from infection with HPV which spread by direct skin-to-skin contact or by autoinoculation. The clinical appearance of warts is variable depends on the type of HPV involved and the site of infection. There are various types of viral warts including common warts, plantar warts, plane warts and genital warts, usually diagnosis of warts is made through clinical examination of the lesions and no laboratory investigations are required. Objective To compare between the therapeutic efficacy and safety of needling versus homologous autoimplantation techniques in treatment of multiple plantar warts and assess their recurrence rate. Patients and Methods Our study included 40 patients with multiple de novo planter warts(3 -10 warts) of (&gt;1 and &lt;3 years duration) divided into 2 groups, 20 patients per group, one group subjected to autoimplantation of wart tissue and the other subjected to needling procedure. Follow up of studied patients was assessed by physician after 2,8 and 12 weeks of procedure through clinical and dermoscopic examination to assess treatment response and after 16 weeks to assess recurrence Results Results of our study reported that there was high statistically significant difference between the 2 studied groups as regard response to treatment after 12 weeks being higher among autoimplantation group (p = 0.001). Moreover, there were no significant relations between treatment response of both patient groups and each of gender, age of patients, number of warts and duration of lesions. Conclusion Autoimplantation technique is more effective and less painful than needling procedure in treatment of multiple plantar warts (both manipulated and remote warts). No significant relations were found between treatment response of either techniques and demographic or clinical characteristics of studied patients.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Andres Ribas ◽  
Isabel Galcerán ◽  
Sara Outón ◽  
Tarek Salman ◽  
Clara Barrios ◽  
...  

Abstract Background and Aims Lupus Nephritis (LN) is a severe complication of Systemic Lupus Erytemathosus (SLE). This is the main reason why identifying predisposing factors to differentiate patients at risk of developing LN is so important. Method Retrospective study of patients with SLE diagnosed between years 2008-2018 in our center. Demographic, clinical and analytical data have been collected. Results We included 171 patients, 48 (28%) with diagnose of LN. Age at diagnose of SLE was 39,51 ± 15,40 years, being more frequent in women 151 (87,5%). Time of follow-up since SLE diagnose until development of LN was of 3 ± 5, 3 years. Respectful to the LN classification we found: 4 (8%) class I LN, 6 (12.5%) class II LN, 15 (31.2%) class III LN, 19 (39.5%) class IV LN and 4 (8%) class V LN. At diagnose of SLE, the following variables, where related to developing LN: CH50 [HR: 1,039; CI (95%): 1,004-1,064; p=0,024], C3 [HR: 1,029; CI (95%): 1,016-1,042; p&lt;0,001, titer of Anti- DNACrithidia [HR: 4,364; CI(95%): 1,26-15,064; p=0,02], AntiSM [HR: 4,634, CI (95%) 1,76-12,17, p=0,002], ACA IgG [HR: 7,5; CI (95%): 2,3 -24,449; p=0,001] and Lupus anticoagulant [HR: 4,97; CI (95%): 1,591-15,533; p=0,006]. Treatment with hidroxicloroquine is a protective factor against developing LN [HR: 0,17; CI (95%): 0,063-0,511; p=0.001]. At diagnose of LN, complement factors and titer of anti-DNA crithidia show a positive correlation when compared to the initial determinations: C3 [r= 0,605 (p&lt;0,001]); C1q [r= 0,861 (p=0,006)]; CH50 [r= 0,981 (p&lt;0,001), anti- DNACrithidia [r= 0,529 (p&lt;0,001)], anti-Sm [r=0.8, )p=0.001)]. Conclusion Consumption of complement factors, high titers of anti-DNAcrithidia, Anti-SM, ACA IgG and Lupus anticoagulant are related to a future LN development at SLE diagnose. Moreover, we see an increase of their titer once we diagnose LN. Otherwise, treatment with hidroxicloroquine seems to be a protective factor.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kenneth Kalunian ◽  
Richard Furie ◽  
Jai Radhakrishnan ◽  
Vandana Mathur ◽  
Joel Rothman ◽  
...  

Abstract Background and Aims Lupus nephritis (LN) is a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. T cells are believed to play a central role in the pathogenesis of both SLE and LN. CD6 is a co-stimulatory receptor, predominantly expressed on T cells, that binds to activated leukocyte cell adhesion molecule (ALCAM), a ligand expressed on antigen presenting cells and various epithelial and endothelial tissues. The CD6-ALCAM pathway plays an integral role in modulating T cell activation, proliferation, differentiation and trafficking, and is central to immune mediated inflammation. Itolizumab (EQ001) is a humanized IgG1 monoclonal antibody that binds CD6, blocks the interaction between CD6 and ALCAM, and inhibits both the activation and trafficking of T cells. Inhibiting the CD6-ALCAM pathway with itolizumab potentially represents a promising therapeutic approach for the treatment of LN. The aim of this study is to assess the safety and tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of subcutaneously administered itolizumab in patients with SLE with and without active proliferative lupus nephritis (apLN). Method This cohort-based dose escalation study includes two types of patients: The Type A cohort will enroll ∼24 patients with SLE without apLN (all treated with itolizumab) and the Type B cohort will randomize in a blinded manner ∼36 patients (3:1, itolizumab:placebo) with biopsy-proven ISN/RPS class III or IV (+ V) apLN who have had inadequate response to induction and/or post-induction maintenance treatment, exhibiting urine protein to creatinine ratio [UPCR] ≥1 g/g and active serology. Within both the Type A and Type B cohorts, up to 4 dose groups will be tested (Figure). Background treatments for SLE or LN are allowed. Following 4 weeks of treatment in a new higher dose Type A cohort and recommendation by an independent safety data review committee (DRC), the dose studied in the Type A cohort may then be studied in a Type B Cohort for a 12-week treatment duration (Figure). The primary endpoint is the safety and tolerability of itolizumab. Efficacy endpoints (in the Type B cohorts) include UPCR, estimated glomerular filtration rate, prednisone dose requirements, renal response, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), FACIT Fatigue Scale, serologic markers, and other patient reported outcomes. In Type A cohort patients, clinical responses and pharmacologic activity will be assessed based on changes in serologic markers, SLEDAI-2K, FACIT Fatigue Scale. Pharmacodynamic markers, including markers that may allow future risk stratification, urinary ALCAM and CD6, will be examined in both cohort types. Results The study is ongoing. Six patients have been enrolled in Type A Cohort 1 (0.4 mg/kg dose) and completed both treatment and 4 weeks of post-treatment follow-up. The mean age was 59.5 (12.9) years, 100% were female; 67% were Hispanic/Latino; and 50% were White, and 50% were Black. Duration of SLE ranged from 3 years to 31 years. Concomitant medications for lupus included prednisone (83%, dose range 2.5 mg – 10 mg), methotrexate (33%), and anti-malarials (33%). Baseline SLEDAI-2K (mean 7.5 [2.2]) was based on findings of alopecia (83%); arthritis (67%); mucosal ulcers and rash (50% each); fever, increased dsDNA, and low complement (17% each). There were no adverse events. Additional data from this ongoing study will be presented. Conclusion Itolizumab, a monoclonal antibody blocking the CD6-ALCAM pathway, is a novel experimental treatment for LN. This is the first trial of itolizumab in patients with SLE and apLN. Data from the first cohort of patients suggest that the drug is safe and well-tolerated at a dose of 0.4 mg/kg over a 4-week treatment period. Additional cohorts of patients with SLE and apLN are currently being enrolled.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Phelisa Sogayise ◽  
Udeme Ekrikpo ◽  
Ayanda Gcelu ◽  
Bianca Davidson ◽  
Nicola Wearne ◽  
...  

Background. Lupus nephritis (LN) can be complicated with requirement for kidney replacement therapy and death. Efficacy of induction therapies using mycophenolate mofetil (MMF) or intravenous cyclophosphamide (IVCYC) has been reported from studies, but there is limited data in Africans comparing both treatments in patients with proliferative LN. Methods. This was a retrospective study of patients with biopsy-proven proliferative LN diagnosed and treated with either MMF or IVCYC in a single centre in Cape Town, South Africa, over a 5-year period. The primary outcome was attaining complete remission after completion of induction therapy. Results. Of the 84 patients included, mean age was 29.6 ± 10.4 years and there was a female preponderance (88.1%). At baseline, there were significant differences in estimated glomerular filtration rate (eGFR) and presence of glomerular crescents between both groups ( p ≤ 0.05 ). After completion of induction therapy, there was no significant difference in remission status (76.0% versus 87.5%; p = 0.33 ) or relapse status (8.1% versus 10.3%; p = 0.22 ) for the IVCYC and MMF groups, respectively. Mortality rate for the IVCYC group was 5.5 per 10,000 person-days of follow-up compared to 1.5 per 10,000 person-days of follow-up for the MMF group ( p = 0.11 ), and there was no significant difference in infection-related adverse events between both groups. Estimated GFR at baseline was the only predictor of death (OR: 1.0 [0.9–1.0]; p = 0.001 ). Conclusion. This study shows similar outcomes following induction treatment with MMF or IVCYC in patients with biopsy-proven proliferative LN in South Africa. However, a prospective and randomized study is needed to adequately assess these outcomes.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marwa Omrane ◽  
Raja Aoudia ◽  
Mondher Ounissi ◽  
Mariem Najar ◽  
Mouna Jerbi ◽  
...  

Abstract Background and Aims Hypertension is a common manifestation during systemic lupus erythematosus (SLE). Its mechanism is multifactorial and microthromboses of renal arterioles seem to be the most important mechanism. The objective of our study is to identify the histological and evolutionary characteristics of patients with lupus nephritis (LN) presenting with hypertension. Method A retrospective study of 85 patients followed for LES with lupus nephritis documented by a renal biopsy collected in 17 years and presenting with hypertension. Results Among 174 patients with LN, eighty-five (48.58%) are hypertensive. A sex ratio F / H of 6.08. The mean age of LN diagnosis was 36.4 years old [13 -75 years old]. The average time to onset of hypertension was 25.8 months [0-204 months]. Malignant hypertension was present in 12% of patients. Antiphospholipid Antibody Syndrome (APLS) was found in 35.3% of cases. Renal biopsy showed LN class II in 2 cases, class III in 8 cases, class IV in 43 cases, class V isolated in 8 cases and class VI in 3 cases. Vascular lesions were arteriolosclerosis in 40% of cases and thrombotic microangiopathy (TMA) lesions in 17.6% of cases. The treatment was essentially based on blockers of the renin angiotensin system, either as monotherapy or in combination with calcium channel blockers, beta blockers or central antihypertensives. The evolution was marked by the occurrence of cerebrovascular accidents associated in 7 cases with APLS and coronary artery disease in 2 cases. Renal evolution was marked by total and durable remission in 27.5%, chronic renal disease in 31.7%, and end-stage renal failure in 40.8% of cases. Blood pressure was balanced in 40,5 % of cases and unbalanced in 59,5% of cases. Conclusion In our lupus patients, hypertension was common, associated with severe glomerular and vascular lesions and a rather severe renal prognosis.


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