scholarly journals P0266PREDICTIVE FACTORS OF COMPLETE RENAL RESPONSE IN PROLIFERATIVE LUPUS NEPHRITIS: A COLLABORATIVE STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Beatriz Sanchez Alamo ◽  
Clara Maria Cases Corona ◽  
Serena Gatius ◽  
Patricia Dominguez Torres ◽  
Elena Valdes ◽  
...  

Abstract Background and Aims Proliferative lupus nephritis (class III and IV) is the most severe form of lupus nephritis and requires prompt diagnosis and treatment with immunosuppressive therapy. Since it represents the most serious entity and has the greatest functional consequences there is a need to determine which factors in proliferative lupus nephritis are most predictive of good long-term renal function. Method Methods We analysed the data of 49 biopsy-proven proliferative lupus nephritis (18,4% class III and 81,6% class IV) of three different Spanish hospitals to find prognostic factors for complete renal response (CRR), defined as loss of <25% of eGFR and the absence of proteinuria and microhematuria at the end of the follow up. Sociodemographic, clinical, laboratory, and treatment-related data at the time of kidney biopsy and during follow-up were obtained. We performed univariate analysis and logistic regression to identify independent risk factors. Results The median follow-up was 8 years (IQR: 3-12,5), during which time 18 patients (36,7 %) achieved CRR. In the univariate analysis complete renal response was related to: (1) at the diagnosis to: age [40,52 (11,29) years vs 29,92 (11,93) p=0,004]; (2) in kidney biopsy to less leukocyte infiltration (42,3% p=0,05); (3) during the follow up to: less comorbities (27,8% vs 64,3% p=0,02), less infections (27,8% vs 58,6% p=0,04) and less hospitalizations due to infections (0% vs 33,3% p=0,010), less prevalence of high BP (22,2% vs 60,7% p=0,01), (4) at the end of follow up to : serum albumin [3,97 (0,59) vs 4,31(0,19) mg/dL p=0,03]. In the logistic regression comorbidies (HR : 5,71 95%IC: 1,56-20,93 p=0,008) and age at the moment of diagnosis (HR : 1,046 95%IC:1,001-1,071 p=0,04) were related to complete renal response. We didn´t find any differences concerning treatments. Conclusion Proliferative lupus nephritis is one of the most severe manifestations of lupus nephritis, resulting in increased morbidity and mortality. Traditionally it has been thought that older patients have a worst prognosis, however we demonstrated that they achieved more frequently CRR. In the management of the patients traditional reno protective measures like strict control of BP must be considered since it is a predictive factor of CRR. We shouldn´t forget about the implications of an aggressive immunosuppressive treatment such as hospitalizations due to infections and comorbities.

2021 ◽  
Author(s):  
Subodh Gururani ◽  
Phani Kumar Devarasetti ◽  
Megha Uppin ◽  
Liza Rajasekhar

Abstract Objectives Despite current advances in treatment, refractory lupus nephritis (RLN) continues to pose a challenge. The present paper studies the clinical profile and treatment outcomes in patients with RLN. Methods This was an observational, bidirectional study enrolling consecutive patients of lupus nephritis from August 2018 to January 2019, who either failed to improve within three months, did not achieve partial renal response (PR) at six months, or did not achieve complete renal response (CR) after two years of treatment. Patients were followed every three months; treatment details and outcomes [CR, PR, no renal response (NR)], doubling serum creatinine, and death were recorded. Group comparisons were made using ANOVA and chi-square test. Factors affecting renal response were studied using linear regression. Results Forty-five of forty-eight enrolled patients completed at least nine months of follow-up and were included in outcome analysis. The median (IQR) SLE duration was three years (2–6 years). The majority of patients (n = 25) had proliferative lupus nephritis (LN) (ISN/RPS class III/IV), with nine patients having pure membranous LN (class V). The mean (SD) activity and chronicity indices were 8 (3) and 0. Over a median (IQR) follow-up period of 15 (12–27) months, 28 had CR, 9 had PR, and 8 showed no response to a switch in an immunosuppressive agent. Repeat renal biopsy (n = 8) with a mean (± SD) biopsy interval of 2 (± 1) years showed histological class transformation in more than half of the patients. There was no significant difference in treatment outcome and time to attain response based on individual immunosuppressive (IS) agent or sequence of IS agents used. None of the variables (duration of SLE or nephritis, baseline SLEDAI, leukopenia, hypertension, elevated anti-dsDNA, low complements, serum albumin, 24-hour urinary protein, biopsy class) predicted renal response on univariate analysis. No patient had a doubling of serum creatinine or progression to end-stage renal disease. There were three deaths, all related to infection. Conclusion The present study shows that a change in immunosuppression produces response in most RLN patients while a fifth of them showed no response to therapy. No predictor of renal response was identified. Histologic class switch was frequent. Renal function did not decline over a year of follow-up. Mortality was the direct cause of infection.


Lupus ◽  
2021 ◽  
pp. 096120332110339
Author(s):  
Subodh Gururani ◽  
Phani Kumar Devarasetti ◽  
Megha Uppin ◽  
Liza Rajasekhar

Objectives Despite current advances in treatment, refractory lupus nephritis (RLN) continues to pose a challenge. The present paper studies the clinical profile and treatment outcomes in patients with RLN. Methods This observational, bidirectional study enrolled consecutive lupus nephritis (LN) patients from August 2018 to January 2019, who either failed to improve within three months, did not achieve partial renal response (PR) at six months, or did not achieve complete renal response (CR) after two years of treatment. Patients were followed every three months; treatment details and outcomes [CR, PR, no renal response (NR)], doubling serum creatinine, and death were recorded. Group comparisons were made using ANOVA and chi-square test. Factors affecting renal response were studied using linear regression. Results Forty-five of forty-eight enrolled patients completed at least nine months of follow-up and were included in outcome analysis. The median (IQR) SLE duration was three years (2-6 years). The majority of patients (n = 25) had proliferative LN (ISN/RPS class III/IV), with nine patients having pure membranous LN (class V). The mean activity and chronicity indices were 8 and 0. Over a median (IQR) follow-up period of 15 (12-27) months, 28 had CR, 9 had PR, and 8 showed no response to a switch in an immunosuppressive (IS) agent. Repeat renal biopsy (n = 8) with a mean (±SD) biopsy interval of 2 (±1) years showed histological class transformation in more than half of the patients. There was no significant difference in treatment outcome and time to attain response based on individual IS agent or sequence of IS agents used. None of the variables (duration of SLE or nephritis, baseline SLEDAI, leukopenia, hypertension, elevated anti-dsDNA, low complements, serum albumin, 24-hour urinary protein, biopsy class) predicted renal response on univariate analysis. No patient had a doubling of serum creatinine or progression to end-stage renal disease. There were three deaths, all related to infection. Conclusion A change in immunosuppression produces response in most RLN patients while a fifth of them showed no response to therapy. No predictor of renal response was identified. Histologic class switch was frequent. Renal function did not decline over a year of follow-up.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 594-595
Author(s):  
F. Saccon ◽  
M. Gatto ◽  
M. Zen ◽  
M. Fredi ◽  
F. Regola ◽  
...  

Background:LN is still a severe manifestation of Systemic lupus erythematosus (SLE) and multitarget therapy is needed to control the disease especially in refractory cases.Objectives:To evaluate renal response in SLE patients with glomerulonephritis (GN) treated with Belimumab in real-life setting.Methods:Patients with proteinuria >0.5 g/24 h and/or active sediment at baseline enrolled in a multicentre Italian cohort of SLE patients (BeRLiSS study), treated with monthly iv Belimumab 10 mg/kg plus standard of care were considered in this study. Complete renal response (CRR) was defined as proteinuria <0.5 g/24 h, estimated glomerular filtration rate (eGFR)≥90ml/min/1.73m2 and no rescue therapy. Primary efficacy renal response (PERR) was defined as proteinuria ≤0.7 g/24 h, eGFR ≥60ml/min/1.73m2 and no rescue therapy. Prevalence and predictive factors of CRR and PERR at 12 and 24 months after Belimumab initiation were analyzed by multivariate logistic regression analysis.Results:A total of 91 patients were considered in this study, 79 female, mean age 40.51±9.03 years, mean disease duration 12.18±8.15 years, median follow-up time after Belimumab initiation 22 months. Twenty patients had baseline proteinuria ≥0.5 <1 g/day, 17 ≥1 <2 g/day, 13 ≥2 g/day. Belimumab was started at GN onset in 20 (22%) patients and at the time of a renal flare in all other cases. Seventy-five patients underwent a renal biopsy: 1 class I, 4 class II, 14 class III, 47 class IV and 9 class V. Baseline serum creatinine was 82.44±29.26 umol/L; 15 patients showed eGFR<60ml/min/1.73m2 at baseline. Immunosuppresants were taken by 70 (76.9%) patients: 47 micofenolate, 15 azathioprine and 5 ciclosporine. Sixty patients (65.9%) were on antimalarials. During follow-up 34 (37.4%) patients achieved CRR. Among them 5 (14.7%) patients relapsed and 29 (85.3%) patients maintained remission. Mean time to achieved CRR was 9.71±5.91 months.High levels of baseline proteinuria were a negative independent predictor of CRR and PERR at 6 months (OR 0.044 CI95% 0.006-0.320 p=0.002 and OR 0.232 CI95% 0.091-0.596 p=0.002) and 12 months (OR 0.029 CI95% 0.002-0.556 p=0.019 and OR 0.056 CI95% 0.009-0.327 p=0.001). High levels of baseline creatinine were a negative independent predictor of renal response. Renal response at 6 months was a strong predictive factor of renal response at 12 and 24 months.Conclusion:Belimumab is an effective add-on therapy in the treatment of GN in real-life practice setting.Disclosure of Interests:None declared


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Zhongcheng An ◽  
Chen Chen ◽  
Junjie Wang ◽  
Yuchen Zhu ◽  
Liqiang Dong ◽  
...  

Abstract Objective To explore the high-risk factors of augmented vertebra recompression after percutaneous vertebral augmentation (PVA) in the treatment of osteoporotic vertebral compression fracture (OVCF) and analyze the correlation between these factors and augmented vertebra recompression after PVA. Methods A retrospective analysis was conducted on 353 patients who received PVA for a single-segment osteoporotic vertebral compression fracture from January 2017 to December 2018 in our department according to the inclusion criteria. All cases meeting the inclusion and exclusion criteria were divided into two groups: 82 patients in the recompression group and 175 patients in the non-compression group. The following covariates were reviewed: age, gender, body mass index (BMI), injured vertebral segment, bone mineral density (BMD) during follow-up, intravertebral cleft (IVC) before operation, selection of surgical methods, unilateral or bilateral puncture, volume of bone cement injected, postoperative leakage of bone cement, distribution of bone cement, contact between the bone cement and the upper or lower endplates, and anterior height of injured vertebrae before operation, after surgery, and at the last follow-up. Univariate analysis was performed on these factors, and the statistically significant factors were substituted into the logistic regression model to analyze their correlation with the augmented vertebra recompression after PVA. Results A total of 257 patients from 353 patients were included in this study. The follow-up time was 12–24 months, with an average of 13.5 ± 0.9 months. All the operations were successfully completed, and the pain of patients was relieved obviously after PVA. Univariate analysis showed that in the early stage after PVA, the augmented vertebra recompression was correlated with BMD, surgical methods, volume of bone cement injected, preoperative IVC, contact between bone cement and the upper or lower endplates, and recovery of anterior column height. The difference was statistically significant (P < 0.05). Among them, multiple factors logistic regression elucidated that more injected cement (P < 0.001, OR = 0.558) and high BMD (P = 0.028, OR = 0.583) were negatively correlated with the augmented vertebra recompression after PVA, which meant protective factors (B < 0). Preoperative IVC (P < 0.001, OR = 3.252) and bone cement not in contact with upper or lower endplates (P = 0.006, OR = 2.504) were risk factors for the augmented vertebra recompression after PVA. The augmented vertebra recompression after PVP was significantly less than that of PKP (P = 0.007, OR = 0.337). Conclusions The augmented vertebra recompression after PVA is due to the interaction of various factors, such as surgical methods, volume of bone cement injected, osteoporosis, preoperative IVC, and whether the bone cement is in contact with the upper or lower endplates.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 674.1-674
Author(s):  
C. C. Mok ◽  
C. S. Sin ◽  
K. C. Hau ◽  
T. H. Kwan

Background:The goals of treatment of lupus nephritis (LN) are to induce remission, retard the progression of chronic kidney disease, prevent organ complications and ultimately reduce mortality. Previous cohort studies of LN have mainly focused on the risk of mortality and development of end stage renal failure (ESRF) (renal survival). The cumulative frequency of LN patients who survive without organ damage, which correlates better with the balance between treatment efficacy and toxicity, as well as quality of life, has not been well studied.Objectives:To study the organ damage free survival and its predictive factors in patients with active LN.Methods:Consecutive patients who fulfilled ≥4 ACR/SLICC criteria for SLE and with biopsy proven active LN between 2003 and 2018 were retrospectivey analyzed. Those with organ damage before LN onset were excluded. Data on renal parameters and treatment regimens were collected. Complete renal response (CR) was defined as normalization of serum creatinine (SCr), urine P/Cr (uPCR) <0.5 and inactive urinary sediments. Partial renal response (PR) was defined as ≥50% reduction in uPCR and <25% increase in SCr. Organ damage of SLE was assessed by the ACR/SLICC damage index (SDI). The cumulative risk of having any organ damage or mortality since LN was studied by Kaplan-Meier’s analysis. Factors associated with a poor outcome were studied by a forward stepwise Cox regression model, with entry of covariates with p<0.05 and removal with p>0.10.Results:273 LN patients were identified but 64 were excluded (organ damage before LN onset). 211 LN patients were studied (92% women; age at SLE 30.4±13.5 years; SLE duration at LN 1.9±3.1years). 47 (22%) patients had nephrotic syndrome and 60 (29%) were hypertensive. Histological LN classes was: III/IV±V (75.1%), I/II (7.8%) and pure V (17.1%) (histologic activity and chronicity score 7.0±4.2 and 1.8±1.5, respectively). Induction regimens were: prednisolone (33.1±17.5mg/day) in combination with intravenous cyclophosphamide (CYC) (21.4%; 1.0±0.2g per pulse), oral CYC (8.6%; 96.4±37.8mg/day), azathioprine (AZA) (14.3%; 78.6±25.2mg/day), mycophenolate mofetil (MMF) (22.8%; 1.9±0.43g/day) and tacrolimus (TAC) (17.1%; 4.3±1.1mg/day). After a follow-up of 8.6±5.4 years, 94(45%) patient developed organ damage (SDI≥1) and 21(10%) patients died. The commonest organ damage was renal (36.3%) and musculoskeletal (17.9%), and the causes of death were: infection (38.1%), malignancy (19.0%), cardiovascular events (9.5%) and ESRF complications (9.5%). At last visit, 114 (55%) patients survived without any organ damage. The cumulative organ damage free survival at 5, 10 and 15 years after renal biopsy was 73.5%, 59.6% and 48.3%, respectively. The 5, 10 and 15-year renal survival rate were 95.2%, 92.0% and 84.1% respectively. In a Cox regression model, nephritic relapse (HR 3.72[1.78-7.77]), proteinuric relapse (HR 2.30[1.07-4.95]) and older age (HR 1.89[1.05-3.37]) were associated with either organ damage or mortality, whereas CR (HR 0.25[0.12-0.50]) at month 12 were associated with organ damage free survival. Baseline SCr, uPCR and histological LN classes were not significantly associated with a poor outcome. Among patients with class III/IV LN, the long-term organ damage free survival were not significantly different in users of MMF (reference) from CYC (IV/oral) (HR 1.45[0.76- 2.75]) or TAC (HR 1.03[0.26-1.62]) as induction therapy.Conclusion:Organ damage free survival is achieved in 55% of patients with active LN upon 9 years of follow-up. CYC/MMF/TAC based induction regimens did not differ for the long-term outcome of LN. Targeting complete renal response and preventing renal relapses remain important goals of LN treatment.Acknowledgments:NILDisclosure of Interests:None declared


2021 ◽  
Author(s):  
Gema Ariceta ◽  
Fadi Fakhouri ◽  
Lisa Sartz ◽  
Benjamin Miller ◽  
Vasilis Nikolaou ◽  
...  

ABSTRACT Background Eculizumab modifies the course of disease in patients with atypical hemolytic uremic syndrome (aHUS), but data evaluating whether eculizumab discontinuation is safe are limited. Methods Patients enrolled in the Global aHUS Registry who received ≥1 month of eculizumab before discontinuing, demonstrated hematologic or renal response prior to discontinuation and had ≥6 months of follow-up were analyzed. The primary endpoint was the proportion of patients suffering thrombotic microangiopathy (TMA) recurrence after eculizumab discontinuation. Additional endpoints included: eGFR changes following eculizumab discontinuation to last available follow-up; number of TMA recurrences; time to TMA recurrence; proportion of patients restarting eculizumab; and changes in renal function. Results We analyzed 151 patients with clinically diagnosed aHUS who had evidence of hematologic or renal response to eculizumab, before discontinuing. Thirty-three (22%) experienced a TMA recurrence. Univariate analysis revealed that patients with an increased risk of TMA recurrence after discontinuing eculizumab were those with a history of extrarenal manifestations prior to initiating eculizumab, pathogenic variants, or a family history of aHUS. Multivariate analysis showed an increased risk of TMA recurrence in patients with pathogenic variants and a family history of aHUS. Twelve (8%) patients progressed to end-stage renal disease after eculizumab discontinuation; 7 (5%) patients eventually received a kidney transplant. Forty (27%) patients experienced an extrarenal manifestation of aHUS after eculizumab discontinuation. Conclusions Eculizumab discontinuation in patients with aHUS is not without risk, potentially leading to TMA recurrence and renal failure. A thorough assessment of risk factors prior to the decision to discontinue eculizumab is essential.


2015 ◽  
Vol 75 (3) ◽  
pp. 526-531 ◽  
Author(s):  
Farah Tamirou ◽  
David D'Cruz ◽  
Shirish Sangle ◽  
Philippe Remy ◽  
Carlos Vasconcelos ◽  
...  

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.


2021 ◽  
pp. ASN.2020081181 ◽  
Author(s):  
Aishwarya Ravindran ◽  
Marta Casal Moura ◽  
Fernando C. Fervenza ◽  
Samih H. Nasr ◽  
Mariam P. Alexander ◽  
...  

BackgroundIn patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1/EXT2 findings in a large cohort of membranous lupus nephritis.MethodsWe conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1/EXT2-positive versus EXT1/EXT2-negative patients were compared.ResultsOur study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1/EXT2-positive and 252 (67.4%) were EXT1/EXT2-negative. EXT1/EXT2-positive patients were significantly younger (P=0.01), had significantly lower serum creatinine levels (P=0.02), were significantly more likely to present with proteinuria ≥3.5 g/24 h (P=0.009), and had significantly less chronicity features (glomerulosclerosis, P=0.001 or interstitial fibrosis and tubular atrophy, P<0.001) on kidney biopsy. Clinical follow-up data were available for 160 patients, of which 64 (40%) biopsy results were EXT1/EXT2-positive and 96 (60%) were EXT1/EXT2-negative. The proportion of patients with class 3/4 lupus nephritis coexisting with membranous lupus nephritis was not different between the EXT1/EXT2-positive and EXT1/EXT2-negative groups (25.0% versus 32.3%; P=0.32). The patients who were EXT1/EXT2-negative evolved to ESKD faster and more frequently compared with EXT1/EXT2-positive patients (18.8% versus 3.1%; P=0.003).ConclusionsThe prevalence of EXT1/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1/EXT2-negative membranous lupus nephritis, EXT1/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1/EXT2-positive.


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.


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